2024-03-28T11:37:51Zhttps://escholarship.org/oaioai:escholarship.org:ark:/13030/qt2679s83k2024-03-02T20:25:00Zqt2679s83kSystemic cisplatin exposure during infancy and adolescence causes impaired cognitive function in adulthoodJohn, TamiLomeli, NaomiBota, Daniela A2017-02-01Cancer survivors diagnosed during infancy and adolescence may be at risk for chemotherapy-related cognitive impairments (CRCI), however the effects of pediatric chemotherapy treatment on adulthood cognitive function are not well understood. Impairments in memory, attention and executive function affect 15-50% of childhood leukemia survivors related to methotrexate exposure. Systemic cisplatin is used to treat a variety of childhood and adult cancers, yet the risk and extent of cognitive impairment due to platinum-based chemotherapy in pediatric patients is unknown. Systemic cisplatin penetrates the CNS, induces hippocampal synaptic damage, and leads to neuronal and neural stem/progenitor cell (NSC) loss. Survivors of non-leukemic cancers may be at risk for significant cognitive impairment related to cisplatin-driven neurotoxicity. We sought to examine the long-term effects of systemic cisplatin administration on cognitive function when administered during infancy and adolescence in a rat model. We performed cognitive testing in adult rats exposed to systemic cisplatin during either infancy or adolescence. Rats treated as adolescents showed significantly poor retrieval of a novel object as compared to controls. Further, cisplatin-treated infants and adolescents showed poor contextual discrimination as compared to controls, and an impaired response to cued fear conditioning. Ultimately, systemic cisplatin exposure resulted in more profound impairments in cognitive function in rats treated during adolescence than in those treated during infancy. Further, exposure to cisplatin during adolescence affected both hippocampus and amygdala dependent cognitive function, suggesting a more global cognitive dysfunction at this age.Biological PsychologyBiomedical and Clinical SciencesPsychologyBehavioral and Social SciencePediatric Research InitiativeBasic Behavioral and Social SciencePediatricMental HealthBrain DisordersChildhood LeukemiaRare DiseasesNeurosciencesCancerStem Cell ResearchAcquired Cognitive ImpairmentHematologyPediatric CancerAetiology2.1 Biological and endogenous factorsMental healthAge FactorsAgingAnimalsAntineoplastic AgentsCisplatinCognition DisordersConditioningPsychologicalDiscriminationPsychologicalFearMaleRatsRatsSprague-DawleyRecognitionPsychologyChemotherapy-related cognitive impairmentMemoryMedical and Health SciencesPsychology and Cognitive SciencesNeurology & NeurosurgeryBiological psychologyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/2679s83karticleoai:escholarship.org:ark:/13030/qt24s9g6nv2024-02-12T19:51:59Zqt24s9g6nvA call for action: Conceptualizing assets-based inclusive design as a social movement to address systemic inequities.Ahumada-Newhart, VeronicaMaya Hernandez, J.Badillo-Urquiola, Karla2022-08-01application/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/24s9g6nvarticleoai:escholarship.org:ark:/13030/qt4b08q1cz2024-01-18T21:39:36Zqt4b08q1czPrenatal maternal mood patterns predict child temperament and adolescent mental healthGlynn, Laura MHowland, Mariann ASandman, Curt ADavis, Elysia PPhelan, MichaelBaram, Tallie ZStern, Hal S2018-03-01BackgroundThis study quantifies the dynamics of maternal mood focusing on unpredictability, and to assess ifgreater unpredictability of prenatal maternal mood predicts child temperament and internalizingsymptoms through early adolescence.MethodsThe association between prenatal mood predictability and child internalizing symptoms were assessedin two longitudinal cohorts (N’s = 227 and 180). Maternal mood was assessed repeatedly duringpregnancy as early as 15 weeks’ gestation. Predictability of maternal mood was calculated by applyingShannon’s entropy to the distribution of responses on mood questionnaires. Maternal reports of childnegative affectivity (a predictor of later internalizing) were collected at 6, 12, 24 months and 7 years ofage. Child self-reports of anxiety symptoms were collected at 10 years and reports of depressionsymptoms at 13 years.ResultsFetal exposure to more elevated maternal mood entropy predicted higher levels of child negativeaffectivity at 12 months (r = .36; p < 01), 24 months (r = .31; p < 01) and 7 years (r = .32; p < 01) of age.In addition, children exposed to higher prenatal maternal mood entropy, reported higher levels ofanxiety symptoms at 10 years (r = .24; p < 01) and elevated depressive symptoms at 13 years (r = .29; p< .01). These associations persisted after adjusting for maternal pre and postnatal mood valence (e.g.depression levels) and for other relevant demographic characteristics.ConclusionsOur findings provide strong support for the notion that patterns of maternal mood influence thedeveloping brain. More specifically, they suggest that prenatal maternal mood predictability may be acritical predictor of developmental mental health trajectories and should be considered whenassessing early life influences on lifespan mental health.PrenatalPostpartumPregnancyDepressionAnxietyTemperamentChild DevelopmentEntropyInternalizing DisordersAdolescenceEmotion Regulationapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/4b08q1czarticleoai:escholarship.org:ark:/13030/qt4xz5r5xj2024-01-18T21:39:00Zqt4xz5r5xjAn assets-based design approach to promote digital equity for Latino youth and their communitiesAhumada-Newhart, VeronicaHernandez, J. Maya2020-01-01application/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/4xz5r5xjarticleoai:escholarship.org:ark:/13030/qt6vv2v0rn2024-01-18T21:35:21Zqt6vv2v0rnWearable speckle plethysmography (SPG) for characterizing microvascular flow and resistance.Ghijsen, MichaelRice, Tyler BYang, BruceWhite, Sean MTromberg, Bruce J2018-08-01In this work we introduce a modified form of laser speckle imaging (LSI) referred to as affixed transmission speckle analysis (ATSA) that uses a single coherent light source to probe two physiological signals: one related to pulsatile vascular expansion (classically known as the photoplethysmographic (PPG) waveform) and one related to pulsatile vascular blood flow (named here the speckle plethysmographic (SPG) waveform). The PPG signal is determined by recording intensity fluctuations, and the SPG signal is determined via the LSI dynamic light scattering technique. These two co-registered signals are obtained by transilluminating a single digit (e.g. finger) which produces quasi-periodic waveforms derived from the cardiac cycle. Because PPG and SPG waveforms probe vascular expansion and flow, respectively, in cm-thick tissue, these complementary phenomena are offset in time and have rich dynamic features. We characterize the timing offset and harmonic content of the waveforms in 16 human subjects and demonstrate physiologic relevance for assessing microvascular flow and resistance.application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/6vv2v0rnarticleBiomedical optics express, vol 9, iss 83937 - 3952oai:escholarship.org:ark:/13030/qt78s5f7nv2024-01-18T21:35:03Zqt78s5f7nvMaternal Stress Potentiates the Effect of an Inflammatory Diet in Pregnancy on Maternal Concentrations of Tumor Necrosis Factor Alpha.Lindsay, Karen LBuss, ClaudiaWadhwa, Pathik DEntringer, Sonja2018-09-06Maternal inflammation during pregnancy is known to adversely impact fetal development, birth outcomes, and offspring physical and mental health. Diet and stress have been identified as important determinants of inflammation, yet their combined effects have not been examined in the context of pregnancy. The aim of this study was to examine the relationship between maternal diet with inflammatory potential and psychological stress, and to determine their interaction effect on concentrations of tumor necrosis factor (TNF)-α across pregnancy. We conducted a prospective longitudinal study of n = 202 women with three assessments during pregnancy, which included: ecological momentary assessment (EMA) of maternal stress using the perceived stress scale (PSS) short version; 24-h dietary recalls from which the dietary inflammatory index (DII) was computed; and serum measurements of TNF-α. Across pregnancy, higher perceived stress was associated with consumption of a more pro-inflammatory diet (r = 0.137; p < 0.05). In a linear regression model adjusted for covariates, DII was positively associated with TNF-α (B = 0.093, p = 0.010). The effect of the pro-inflammatory diet on concentrations of TNF-α was more pronounced in women reporting higher levels of stress (B = 0.134, p = 0.018 for DII*PSS interaction). These results highlight the need to consider nutrition and stress concurrently in the context of inflammation during pregnancy.AdultBiomarkers: bloodDiet: adverse effectsFemaleHumansInflammation: blooddiagnosisimmunologyInflammation Mediators: bloodLongitudinal StudiesMaternal Nutritional Physiological PhenomenaNutritional StatusPregnancyPregnancy Complications: blooddiagnosisimmunologyProspective StudiesRisk FactorsStressPsychological: blooddiagnosisimmunologyTumor Necrosis Factor-alpha: bloodYoung Adultapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/78s5f7nvarticleNutrients, vol 10, iss 9oai:escholarship.org:ark:/13030/qt7m86r4cn2024-01-18T21:34:35Zqt7m86r4cnHippocampal CA1 gamma power predicts the precision of spatial memory judgments.Stevenson, Rebecca FZheng, JieMnatsakanyan, LilitVadera, SumeetKnight, Robert TLin, Jack JYassa, Michael A2018-10-02The hippocampus plays a critical role in spatial memory. However, the exact neural mechanisms underlying high-fidelity spatial memory representations are unknown. We report findings from presurgical epilepsy patients with bilateral hippocampal depth electrodes performing an object-location memory task that provided a broad range of spatial memory precision. During encoding, patients were shown a series of objects along the circumference of an invisible circle. At test, the same objects were shown at the top of the circle (0°), and patients used a dial to move the object to its location shown during encoding. Angular error between the correct location and the indicated location was recorded as a continuous measure of performance. By registering pre- and postimplantation MRI scans, we were able to localize the electrodes to specific hippocampal subfields. We found a correlation between increased gamma power, thought to reflect local excitatory activity, and the precision of spatial memory retrieval in hippocampal CA1 electrodes. Additionally, we found a similar relationship between gamma power and memory precision in the dorsolateral prefrontal cortex and a directional relationship between activity in this region and in the CA1, suggesting that the dorsolateral prefrontal cortex is involved in postretrieval processing. These results indicate that local processing in hippocampal CA1 and dorsolateral prefrontal cortex supports high-fidelity spatial memory representations.AdultCA1 RegionHippocampal: diagnostic imagingphysiologyFemaleHumansMagnetic Resonance ImagingMaleMiddle AgedPrefrontal Cortex: diagnostic imagingphysiologySpatial Memory: physiologyapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/7m86r4cnarticleProceedings of the National Academy of Sciences of the United States of America, vol 115, iss 4010148 - 10153oai:escholarship.org:ark:/13030/qt8d0539sb2024-01-18T21:32:03Zqt8d0539sbTele-Exercise as a Promising Tool to Promote Exercise in Children With Cystic Fibrosis.Chen, Jen JenCooper, Dan MHaddad, FadiaSladkey, AnnaNussbaum, EliezerRadom-Aizik, Shlomit2018-09-28Introduction: Cross-infection risk from contact exposure limits exercise opportunities in children with cystic fibrosis (CF). The purpose of this study is to evaluate the feasibility of a new live-streamed platform which delivered supervised and interactive group exercise sessions to CF children via digital devices while avoiding contact exposure. Methods: Ten CF children participated in a 6-week tele-exercise program. The program consisted of three 30-min sessions per week for a total of 18 sessions and included aerobic, resistance, and flexibility exercises. Sessions were streamed via a HIPAA compliant VSee telemedicine platform. Instructors and participants were able to interact in real-time online. Heart rate (HR) monitors were used to evaluate exercise intensity with a goal of moderate-vigorous physical activity ≥10 min, 70% of the sessions. System usability scale (SUS) and qualitative questionnaires were used to gauge participants' satisfaction and feedback. Results: On average participants attended 85% of the sessions. For the overall sessions participants exercise 21.1 ± 6.9 min at moderate-vigorous physical activity. Nine out of 10 participants used the exercise platform without parental guidance. Qualitative questionnaire and System Usability Scale (SUS) indicated that all participants enjoyed the tele-exercise program and highly rated the exercise platform 90.8 out of 100 (passing > 68). Conclusions: Tele-exercise platform is a promising new approach to promote exercise in children with CF. The online platform allows supervised virtual group exercise experience with optimal participation and no risk for cross-infection. This approach might prove to be useful in enhancing the use of exercise as therapy in children with CF.application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/8d0539sbarticleoai:escholarship.org:ark:/13030/qt1wr558qk2024-01-18T21:29:37Zqt1wr558qkComparative transcriptome analysis and RNA interference reveal CYP6A8 and SNPs related to pyrethroid resistance in Aedes albopictus.Xu, JiabaoSu, XinghuaBonizzoni, MariangelaZhong, DaibinLi, YijiZhou, GuofaNguyen, HoanTong, SarahYan, GuiyunChen, Xiao-Guang2018-11-12Wide and improper application of pyrethroid insecticides for mosquito control has resulted in widespread resistance in Aedes albopictus mosquitoes, an important dengue vector. Therefore, understanding the molecular regulation of insecticide resistance is urgently needed to provide a basis for developing novel resistance diagnostic methods and vector control approaches. We investigated the transcriptional profiles of deltamethrin-resistant and -susceptible Ae. albopictus by performing paired-end sequencing for RNA expression analysis. The analysis used 24 independent libraries constructed from 12 wild-caught resistant and 12 susceptible Ae. albopictus female adults. A total of 674,503,592 and 612,512,034 reads were obtained, mapped to the Ae. albopictus genome and assembled into 20,091 Ae. albopictus transcripts. A total of 1,130 significantly differentially expressed genes included 874 up-regulated genes and 256 down-regulated genes in the deltamethrin-resistant individuals. These differentially expressed genes code for cytochrome P450s, cuticle proteins, glutathione S-transferase, serine proteases, heat shock proteins, esterase, and others. We selected three highly differentially expressed candidate genes, CYP6A8 and two genes of unknown function (CCG013931 and CCG000656), to test the association between these 3 genes and deltamethrin resistance using RNAi through microinjection in adult mosquitoes and oral feeding in larval mosquitoes. We found that expression knockdown of these three genes caused significant changes in resistance. Further, we detected 1,162 single nucleotide polymorphisms (SNPs) with a frequency difference of more than 50%. Among them, 5 SNPs in 4 cytochrome P450 gene families were found to be significantly associated with resistance in a genotype-phenotype association study using independent field-collected mosquitoes of known resistance phenotypes. Altogether, a combination of novel individually based transcriptome profiling, RNAi, and genetic association study identified both differentially expressed genes and SNPs associated with pyrethroid resistance in Ae. albopictus mosquitoes, and laid a useful foundation for further studies on insecticide resistance mechanisms.Aedes: geneticsvirologyAnimalsChina: epidemiologyCytochrome P-450 Enzyme System: drug effectsgeneticsDengue: epidemiologyprevention & controltransmissionFemaleGene Expression Profiling: methodsInsect Proteins: geneticsInsecticide Resistance: geneticsInsecticides: adverse effectspharmacologyLarva: drug effectsmetabolismMosquito ControlMosquito Vectors: geneticsPolymorphismSingle Nucleotide: drug effectsgeneticsPyrethrins: adverse effectspharmacologyRNA Interferenceapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/1wr558qkarticlePLoS neglected tropical diseases, vol 12, iss 11e0006828 - e00068e0006828oai:escholarship.org:ark:/13030/qt78f9t9w52023-12-11T16:45:27Zqt78f9t9w5Differential responses of human dendritic cells to metabolites from the oral/airway microbiomeWhiteson, KAgrawal, SAgrawal, A2017-05-09Small molecule metabolites that are produced or altered by host-associated microbial communities are emerging as significant immune response modifiers. However, there is a key gap in our knowledge of how oral microbial metabolites affect the immune response. Here, we examined the effects of metabolites from five bacterial strains found commonly in the oral/airway microbial communities of humans. The five strains, each isolated from cystic fibrosis patient sputum, were Pseudomonas aeruginosa FLR01 non-mucoid (P1) and FLR02 mucoid (P2) forms, Streptococcus pneumoniae (Sp), S. salivarius (Ss) and Rothia mucilaginosa (Rm). The effect of bacterial metabolites on dendritic cell (DC) activation, T cell priming and cytokine secretion was determined by exposing DCs to bacterial supernatants and individual metabolites of interest. Supernatants from P1 and P2 induced high levels of tumour necrosis factor (TNF)-α, interleukin (IL)-12 and IL-6 from DCs and primed T cells to secrete interferon (IFN)-γ, IL-22 compared to supernatants from Sp, Ss and Rm. Investigations into the composition of supernatants using gas chromatography-mass spectroscopy (GC-MS) revealed signature metabolites for each of the strains. Supernatants from P1 and P2 contained high levels of putrescine and glucose, while Sp and Ss contained high levels of 2,3-butanediol. The individual metabolites replicated the results of whole supernatants, although the magnitudes of their effects were reduced significantly. Altogether, our data demonstrate for the first time that the signature metabolites produced by different bacteria have different effects on DC functions. The identification of signature metabolites and their effects on the host immune system can provide mechanistic insights into diseases and may also be developed as biomarkers.Biomedical and Clinical SciencesImmunologyLungInfectious DiseasesAetiology2.2 Factors relating to the physical environmentInflammatory and immune systemInfectionBacteriaButylene GlycolsCell DifferentiationCellsCulturedCystic FibrosisCytokinesDendritic CellsGas Chromatography-Mass SpectrometryHumansLymphocyte ActivationMicrobiotaRespiratory SystemSputumTh1 Cellsbutanediolbutanedionedendritic cellsglucoseoral microbiomeputrescineapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/78f9t9w5articleClinical & Experimental Immunology, vol 188, iss 3371 - 379oai:escholarship.org:ark:/13030/qt0d6071h72023-12-11T15:56:41Zqt0d6071h7Attitudes toward Potential Participant RegistriesGrill, Joshua DHolbrook, AndrewPierce, AimeeHoang, DanGillen, Daniel LSwerdlow, Russell2017-01-01Difficult participant recruitment is a consistent barrier to successful medical research. Potential participant registries represent an increasingly common intervention to overcome this barrier. A variety of models for registries exist, but few data are available to instruct their design and implementation. To provide such data, we surveyed 110 cognitively normal research participants enrolled in a longitudinal study of aging and dementia. Seventy-four (67%) individuals participated in the study. Most (78%, CI: 0.67, 0.87) participants were likely to enroll in a registry. Willingness to participate was reduced for registries that required enrollment through the Internet using a password (26%, CI: 0.16, 0.36) or through email (38%, CI: 0.27, 0.49). Respondents acknowledged their expectations that researchers share information about their health and risk for disease and their concerns that their data could be shared with for-profit companies. We found no difference in respondent preferences for registries that shared contact information with researchers, compared to honest broker models that take extra precautions to protect registrant confidentiality (28% versus 30%; p = 0.46). Compared to those preferring a shared information model, respondents who preferred the honest broker model or who lacked model preference voiced increased concerns about sharing registrant data, especially with for-profit organizations. These results suggest that the design of potential participant registries may impact the population enrolled, and hence the population that will eventually be enrolled in clinical studies. Investigators operating registries may need to offer particular assurances about data security to maximize registry enrollment but also must carefully manage participant expectations.Biomedical and Clinical SciencesBiological PsychologyClinical SciencesNeurosciencesPsychologyBasic Behavioral and Social ScienceClinical ResearchBehavioral and Social ScienceAgedAgingAttitudeBiomedical ResearchConfidentialityDementiaFemaleFollow-Up StudiesHumansInternetLongitudinal StudiesMaleRegistriesSurveys and QuestionnairesClinical trialrecruitmentregistriesCognitive SciencesNeurology & NeurosurgeryClinical sciencesBiological psychologyapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/0d6071h7articleJournal of Alzheimer's Disease, vol Preprint, iss Preprint1 - 8oai:escholarship.org:ark:/13030/qt9hm0j0kw2023-12-11T14:00:53Zqt9hm0j0kwPharmacological Rescue of Long-Term Potentiation in Alzheimer Diseased SynapsesPrieto, G AlephTrieu, Brian HDang, Cindy TBilousova, TinaGylys, Karen HBerchtold, Nicole CLynch, GaryCotman, Carl W2017-02-01Long-term potentiation (LTP) is an activity-dependent and persistent increase in synaptic transmission. Currently available techniques to measure LTP are time-intensive and require highly specialized expertise and equipment, and thus are not well suited for screening of multiple candidate treatments, even in animal models. To expand and facilitate the analysis of LTP, here we use a flow cytometry-based method to track chemically induced LTP by detecting surface AMPA receptors in isolated synaptosomes: fluorescence analysis of single-synapse long-term potentiation (FASS-LTP). First, we demonstrate that FASS-LTP is simple, sensitive, and models electrically induced LTP recorded in intact circuitries. Second, we conducted FASS-LTP analysis in two well-characterized Alzheimer's disease (AD) mouse models (3xTg and Tg2576) and, importantly, in cryopreserved human AD brain samples. By profiling hundreds of synaptosomes, our data provide the first direct evidence to support the idea that synapses from AD brain are intrinsically defective in LTP. Third, we used FASS-LTP for drug evaluation in human synaptosomes. Testing a panel of modulators of cAMP and cGMP signaling pathways, FASS-LTP identified vardenafil and Bay-73-6691 (phosphodiesterase-5 and -9 inhibitors, respectively) as potent enhancers of LTP in synaptosomes from AD cases. These results indicate that our approach could provide the basis for protocols to study LTP in both healthy and diseased human brains, a previously unattainable goal.Significance statementLearning and memory depend on the ability of synapses to strengthen in response to activity. Long-term potentiation (LTP) is a rapid and persistent increase in synaptic transmission that is thought to be affected in Alzheimer's disease (AD). However, direct evidence of LTP deficits in human AD brain has been elusive, primarily due to methodological limitations. Here, we analyze LTP in isolated synapses from AD brain using a novel approach that allows testing LTP in cryopreserved brain. Our analysis of hundreds of synapses supports the idea that AD-diseased synapses are intrinsically defective in LTP. Further, we identified pharmacological agents that rescue LTP in AD, thus opening up a new avenue for drug screening and evaluation of strategies for alleviating memory impairments.Biomedical and Clinical SciencesNeurosciencesAlzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD)Acquired Cognitive ImpairmentNeurodegenerativeDementiaAlzheimer's DiseaseAgingBrain DisordersAetiology2.1 Biological and endogenous factorsNeurologicalAlzheimer DiseaseAnimalsCyclic AMPCyclic GMPElectric StimulationFlow CytometryHumansLong-Term PotentiationMaleMiceMiceInbred C57BLPhosphodiesterase InhibitorsRatsSprague-DawleyReceptorsAMPASignal TransductionSynapsesSynaptosomesAlzheimer's diseaseflow cytometryGluA1LTPphosphodiesterase inhibitorssynaptosomesMedical and Health SciencesPsychology and Cognitive SciencesNeurology & Neurosurgeryapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/9hm0j0kwarticleJournal of Neuroscience, vol 37, iss 51197 - 1212oai:escholarship.org:ark:/13030/qt8vp2d2p82023-12-11T13:02:38Zqt8vp2d2p8Rho-associated kinase 1 inhibition is synthetically lethal with von Hippel-Lindau deficiency in clear cell renal cell carcinomaThompson, JMNguyen, QHSingh, MPavesic, MWNesterenko, INelson, LJLiao, ACRazorenova, OV2017-02-23Clear cell renal cell carcinoma (CC-RCC) is the most lethal of all genitourinary cancers. The functional loss of the von Hippel-Lindau (VHL) gene occurs in 90% of CC-RCC, driving cancer progression. The objective of this study was to identify chemical compounds that are synthetically lethal with VHL deficiency in CC-RCC. An annotated chemical library, the library of pharmacologically active compounds (LOPAC), was screened in parallel on VHL-deficient RCC4 cells and RCC4VHL cells with re-introduced VHL. The ROCK inhibitor, Y-27632, was identified and validated for selective targeting of VHL-deficient CC-RCC in multiple genetic backgrounds by clonogenic assays. Downregulation of ROCK1 by small interfering RNA (siRNA) selectively reduced the colony-forming ability of VHL-deficient CC-RCC, thus mimicking the effect of Y-27632 treatment, whereas downregulation of ROCK2 had no effect. In addition, two other ROCK inhibitors, RKI 1447 and GSK 429286, selectively targeted VHL-deficient CC-RCC. CC-RCC treatment with ROCK inhibitors is cytotoxic and cytostatic based on bromodeoxyuridine (BrdU) assay, propidium iodide (PI) staining and growth curves, and blocks cell migration based on transwell assay. On the one hand, knockdown of hypoxia-inducible factor (HIF) β in the VHL-deficient CC-RCC had a protective effect against Y-27632 treatment, mimicking VHL reintroduction. On the other hand, CC-RCCVHL cells were sensitized to Y-27632 treatment in hypoxia (2% O2). These results suggest that synthetic lethality between ROCK inhibition and VHL deficiency is dependent on HIF activation. Moreover, HIF1α or HIF2α overexpression in CC-RCCVHL cells is sufficient to sensitize them to ROCK inhibition. Finally, Y-27632 treatment inhibited growth of subcutaneous 786-OT1 CC-RCC tumors in mice. Thus, ROCK inhibitors represent potential therapeutics for VHL-deficient CC-RCC.Biochemistry and Cell BiologyBiomedical and Clinical SciencesOncology and CarcinogenesisBiological SciencesRare DiseasesCancerKidney DiseaseDevelopment of treatments and therapeutic interventions5.1 PharmaceuticalsAmidesAnimalsApoptosisBiomarkersTumorCarcinomaRenal CellCell CycleCell ProliferationEnzyme InhibitorsGene Expression RegulationNeoplasticHumansHypoxia-Inducible Factor 1alpha SubunitKidney NeoplasmsMicePyridinesRNASmall InterferingTumor CellsCulturedVon Hippel-Lindau Tumor Suppressor ProteinXenograft Model Antitumor Assaysrho-Associated KinasesClinical SciencesOncology & CarcinogenesisBiochemistry and cell biologyOncology and carcinogenesisapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/8vp2d2p8articleOncogene, vol 36, iss 81080 - 1089oai:escholarship.org:ark:/13030/qt1sd6s65b2023-12-08T16:40:43Zqt1sd6s65bPhosphorylation of a constrained azacyclic FTY720 analog enhances anti-leukemic activity without inducing S1P receptor activationMcCracken, ANMcMonigle, RJTessier, JFransson, RPerryman, MSChen, BKeebaugh, ASelwan, EBarr, SAKim, SMRoy, SGLiu, GFallegger, DSernissi, LBrandt, CMoitessier, NSnider, AJClare, SMüschen, MHuwiler, AKleinman, MTHanessian, SEdinger, AL2017-03-01The frequency of poor outcomes in relapsed leukemia patients underscores the need for novel therapeutic approaches. The Food and Drug Administration-approved immunosuppressant FTY720 limits leukemia progression by activating protein phosphatase 2A and restricting nutrient access. Unfortunately, FTY720 cannot be re-purposed for use in cancer patients due to on-target toxicity associated with S1P receptor activation at the elevated, anti-neoplastic dose. Here we show that the constrained azacyclic FTY720 analog SH-RF-177 lacks S1P receptor activity but maintains anti-leukemic activity in vitro and in vivo. SH-RF-177 was not only more potent than FTY720, but killed via a distinct mechanism. Phosphorylation is dispensable for FTY720's anti-leukemic actions. However, chemical biology and genetic approaches demonstrated that the sphingosine kinase 2 (SPHK2)-mediated phosphorylation of SH-RF-177 led to engagement of a pro-apoptotic target and increased potency. The cytotoxicity of membrane-permeant FTY720 phosphonate esters suggests that the enhanced potency of SH-RF-177 stems from its more efficient phosphorylation. The tight inverse correlation between SH-RF-177 IC50 and SPHK2 mRNA expression suggests a useful biomarker for SH-RF-177 sensitivity. In summary, these studies indicate that FTY720 analogs that are efficiently phosphorylated but fail to activate S1P receptors may be superior anti-leukemic agents compared to compounds that avoid cardiotoxicity by eliminating phosphorylation.Biomedical and Clinical SciencesCardiovascular Medicine and HaematologyClinical SciencesOncology and CarcinogenesisHematologyCancer5.1 PharmaceuticalsDevelopment of treatments and therapeutic interventionsAnimalsAntineoplastic AgentsApoptosisCell LineTumorDisease ModelsAnimalDrug ResistanceNeoplasmFemaleFingolimod HydrochlorideHumansLeukemiaMicePhosphorylationPhosphotransferases (Alcohol Group Acceptor)ReceptorsLysosphingolipidXenograft Model Antitumor AssaysImmunologyCardiovascular medicine and haematologyClinical sciencesOncology and carcinogenesisapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/1sd6s65barticleLeukemia, vol 31, iss 3669 - 677oai:escholarship.org:ark:/13030/qt2fz1w9n82023-10-07T23:30:25Zqt2fz1w9n8Impact of a personalized versus moderate-intensity exercise prescription: a randomized controlled trialSchneider, MargaretSchmalbach, PrielGodkin, Sophia2017-04-01Effective approaches to promote adolescent physical activity are needed. Moreover, a one-size-fits-all approach has been minimally successful to date. This randomized controlled trial evaluates a theory-based personalized exercise prescription to enhance motivation for being active and physical activity participation among adolescent reluctant exercisers. Adolescents were characterized by affective style as reluctant (predisposed to negative affect during exercise) or latent (predisposed to positive affect during exercise) exercisers based on their affective response to an acute exercise task, and then randomly assigned to an exercise prescription of either a personalized or a moderate intensity. Assignment was double-blind. Assessments were pre- and post- the 8-week intervention. Participants were an ethnically diverse group of adolescents (19 % non-Latino White) in a public middle-school. The exercise intensity manipulation and assessments took place at the school site during regular Physical Education. Participants were assigned to either a moderate-intensity exercise prescription [target heart rate (HR) range 60-80 % of HR max] or a personalized exercise prescription corresponding to an intensity that "feels good" to the individual for 8 weeks during daily Physical Education. Outcome measures included exercise-related intrinsic motivation (via questionnaire), and daily moderate-to-vigorous physical activity (MVPA; via accelerometer). The exercise intensity manipulation did not yield actual differences in exercise intensity during PE, and had no effect on either Intrinsic Motivation or MVPA. There was no significant interaction between affective style and group assignment in predicting Intrinsic Motivation or MVPA. This study did not find support for a link between affective experiences during exercise and physical activity participation. Providing adolescents with a personalized exercise intensity prescription and asking them to follow the prescription during PE was not an effective strategy to manipulate their affective experience of exercise. A more rigorous test of affective manipulation may require supervised exercise sessions during which exercise intensity can be directly observed and controlled.Public HealthHealth SciencesMind and BodyBehavioral and Social SciencePreventionPediatricClinical ResearchClinical Trials and Supportive Activities6.7 PhysicalEvaluation of treatments and therapeutic interventionsAdolescentDouble-Blind MethodExerciseFemaleHealth BehaviorHealth PromotionHumansMaleMotivationPhysical Education and TrainingSchoolsPhysical EducationSchool-basedEnjoymentMedical and Health SciencesPsychology and Cognitive SciencesClinical PsychologyPublic healthSocial and personality psychologyapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/2fz1w9n8articleJournal of Behavioral Medicine, vol 40, iss 2239 - 248oai:escholarship.org:ark:/13030/qt6n40v1qr2023-09-28T00:52:51Zqt6n40v1qrProof-of-Concept Randomized Trial of the Monoclonal Antibody GSK249320 Versus Placebo in Stroke PatientsCramer, Steven CEnney, Lori ARussell, Colleen KSimeoni, MonicaThompson, Thomas R2017-03-01Background and purposeOne class of poststroke restorative therapy focuses on promoting axon outgrowth by blocking myelin-based inhibitory proteins such as myelin-associated glycoprotein. The purpose of the current study was to extend preclinical and clinical findings of GSK249320, a humanized monoclonal antibody to myelin-associated glycoprotein with disabled Fc region, to explore effects on motor outcomes poststroke.MethodsIn this phase IIb double-blind, randomized, placebo-controlled study, patients at 30 centers with ischemic stroke 24 to 72 hours prior and gait deficits were randomized to 2 IV infusions of GSK249320 or placebo. Primary outcome measure was change in gait velocity from baseline to day 90.ResultsA total of 134 subjects were randomized between May 2013 and July 2014. The 2 groups were overall well matched at baseline. The study was stopped at the prespecified interim analysis because the treatment difference met the predefined futility criteria cutoff; change in gait velocity to day 90 was 0.55±0.46 (mean±SD) in the GSK249320 group and 0.56±0.50 for placebo. Secondary end points including upper extremity function were concordant. The 2 IV infusions of GSK249320 were well tolerated. No neutralizing antibodies to GSK249320 were detected.ConclusionsGSK249320, within 72 hours of stroke, demonstrated no improvement on gait velocity compared with placebo. Possible reasons include challenges translating findings into humans and no direct evidence that the therapy reached the biological target. The antibody was well tolerated and showed low immunogenicity, findings potentially useful to future studies aiming to use a monoclonal antibody to modify activity in specific biological pathways to improve recovery from stroke.Clinical trial registrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT01808261.Biomedical and Clinical SciencesHealth SciencesSports Science and ExerciseClinical Trials and Supportive ActivitiesClinical ResearchRehabilitationStrokeBrain DisordersNeurosciencesEvaluation of treatments and therapeutic interventions6.1 PharmaceuticalsAgedAntibodiesMonoclonalHumanizedDouble-Blind MethodFemaleHumansInfusionsIntravenousMaleMyelin-Associated GlycoproteinPlacebo EffectTreatment Outcomeaxonbrainclinical trialgaitstrokeCardiorespiratory Medicine and HaematologyClinical SciencesNeurology & NeurosurgeryClinical sciencesAllied health and rehabilitation scienceapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/6n40v1qrarticleStroke, vol 48, iss 3692 - 698oai:escholarship.org:ark:/13030/qt7156v39q2023-09-27T20:36:06Zqt7156v39qActivation of PKC&agr; and PI3K Kinases in Hypertrophic and Nodular Port Wine Stain LesionsYin, RongGao, LinTan, WenbinGuo, WeiZhao, TaoNelson, Jhon StuartWang, Gang2017-10-01Port wine stain (PWS) is a congenital, progressive vascular malformation. Many patients with PWS develop hypertrophy and discrete nodularity during their adult life, but the mechanism(s) remain incompletely understood. In this study, we attempted to investigate activation status of PKCα, PI3K, PDPK1 and PLC-γ and protein levels of PP2A and DAG to explore their potential roles in the formation of hypertrophic and nodular PWS lesions. We found phosphorylated levels of PKCα, PI3K, PDPK1, and PLC-γ and protein levels of PP2A and DAG showed moderate increases in the endothelial cells of hypertrophic PWS as compared to the adjacent normal skin. These increases extended throughout the entire stroma of blood vessels in PWS nodules. Many proliferating cells, such as fibroblasts, also showed strong activation of PKCα, PI3K, PDPK1 and PLC-γ and upregulations of PP2A and DAG in nodular PWS lesions. Our data showed that there is aberrant activation of PKCα, PI3K, PDPK1 and PLC-γ and upregulation of PP2A and DAG mainly in endothelial cells in hypertrophic PWS areas, but presenting in the entire vasculatures and surrounding fibroblasts in PWS nodules. Our data suggest that both PKCα and PI3K signaling pathways contribute to the development of hypertrophy and nodularity in adult PWS.Biomedical and Clinical SciencesClinical SciencesClinical ResearchPediatricAetiology2.1 Biological and endogenous factorsCardiovascularAdultFemaleHumansHypertrophyMalePhosphatidylinositol 3-KinasesPort-Wine StainProtein Kinase C-alphaport wine stainPI3KPKC alphaPLC-gammaPDPK1vascular malformationDermatology & Venereal DiseasesClinical sciencesapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/7156v39qarticleAmerican Journal of Dermatopathology, vol 39, iss 10747 - 752oai:escholarship.org:ark:/13030/qt2vf3x5892023-09-27T17:50:20Zqt2vf3x589Changes in urine volume and serum albumin in incident hemodialysis patientsEriguchi, RiekoObi, YoshitsuguRhee, Connie MChou, Jason ATortorici, Amanda RMathew, Anna TKim, TaeheeSoohoo, MelissaStreja, ElaniKovesdy, Csaba PKalantar‐Zadeh, Kamyar2017-10-01IntroductionHypoalbuminemia is a predictor of poor outcomes in dialysis patients. Among hemodialysis patients, there has not been prior study of whether residual kidney function or decline over time impacts serum albumin levels. We hypothesized that a decline in residual kidney function is associated with an increase in serum albumin levels among incident hemodialysis patients.MethodsIn a large national cohort of 38,504 patients who initiated hemodialysis during 1/2007-12/2011, we examined the association of residual kidney function, ascertained by urine volume and renal urea clearance, with changes in serum albumin over five years across strata of baseline residual kidney function, race, and diabetes using case-mix adjusted linear mixed effects models.FindingsSerum albumin levels increased over time. At baseline, patients with greater urine volume had higher serum albumin levels: 3.44 ± 0.48, 3.50 ± 0.46, 3.57 ± 0.44, 3.59 ± 0.45, and 3.65 ± 0.46 g/dL for urine volume groups of <300, 300-<600, 600-<900, 900-<1,200, and ≥1,200 mL/day, respectively (Ptrend < 0.001). Over time, urine volume and renal urea clearance declined and serum albumin levels rose, while the baseline differences in serum albumin persisted across groups of urinary volume. In addition, the rate of decline in residual kidney function was not associated with the rate of change in albumin.DiscussionHypoalbuminemia in hemodialysis patients is associated with lower residual kidney function. Among incident hemodialysis patients, there is a gradual rise in serum albumin that is independent of the rate of decline in residual kidney function, suggesting that preservation of residual kidney function does not have a deleterious impact on serum albumin levels.Biomedical and Clinical SciencesClinical SciencesAssistive TechnologyBioengineeringKidney DiseaseClinical ResearchRenal and urogenitalCohort StudiesFemaleHumansKidney FailureChronicMaleMiddle AgedRenal DialysisRetrospective StudiesSerum AlbuminUrineResidual kidney functionhypoalbuminemiaurine volumehemodialysisUrology & NephrologyClinical sciencesapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/2vf3x589articleHemodialysis International, vol 21, iss 4507 - 518oai:escholarship.org:ark:/13030/qt3cj9841h2023-09-27T15:20:25Zqt3cj9841hHeart‐hand syndrome IV: a second family with LMNA‐related cardiomyopathy and brachydactylyZaragoza, MVHakim, SAHoang, VElliott, AM2017-03-01[Image: see text]Biological SciencesBiomedical and Clinical SciencesClinical SciencesGeneticsBrachydactylyCardiomyopathyDilatedHumansLamin Type AMutationPedigreeSyndromeGenetics & HeredityClinical sciencesapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/3cj9841harticleClinical Genetics, vol 91, iss 3499 - 500oai:escholarship.org:ark:/13030/qt6dm509hr2023-09-22T11:43:29Zqt6dm509hrThe Herpes Simplex Virus Type 1 Latency-Associated Transcript Inhibits Phenotypic and Functional Maturation of Dendritic CellsChentoufi, Aziz AlamiDervillez, XavierDasgupta, GargiNguyen, ChelseaKabbara, Khaled WJiang, XianzhiNesburn, Anthony BWechsler, Steven LBenMohamed, Lbachir2012-06-01We recently found that the herpes simplex virus-1 (HSV-1) latency-associated transcript (LAT) results in exhaustion of virus-specific CD8⁺ T cells in latently-infected trigeminal ganglia (TG). In this study we sought to determine if this impairment may involve LAT directly and/or indirectly interfering with DC maturation. We found that a small number of HSV-1 antigen-positive DCs are present in the TG of latently-infected CD11c/eYFP mice; however, this does not imply that these DCs are acutely or latently infected. Some CD8⁺ T cells are adjacent to DCs, suggesting possible interactions. It has previously been shown that wild-type HSV-1 interferes with DC maturation. Here we show for the first time that this is associated with LAT expression, since compared to LAT⁻ virus: (1) LAT⁺ virus interfered with expression of MHC class I and the co-stimulatory molecules CD80 and CD86 on the surface of DCs; (2) LAT⁺ virus impaired DC production of the proinflammatory cytokines IL-6, IL-12, and TNF-α; and (3) DCs infected in vitro with LAT⁺ virus had significantly reduced the ability to stimulate HSV-specific CD8⁺ T cells. While a similar number of DCs was found in LAT⁺ and LAT⁻ latently-infected TG of CD11c/eYFP transgenic mice, more HSV-1 Ag-positive DCs and more exhausted CD8 T cells were seen with LAT⁺ virus. Consistent with these findings, HSV-specific cytotoxic CD8⁺ T cells in the TG of mice latently-infected with LAT⁺ virus produced less IFN-γ and TNF-α than those from TG of LAT⁻-infected mice. Together, these results suggest a novel immune-evasion mechanism whereby the HSV-1 LAT increases the number of HSV-1 Ag-positive DCs in latently-infected TG, and interferes with DC phenotypic and functional maturation. The effect of LAT on TG-resident DCs may contribute to the reduced function of HSV-specific CD8⁺ T cells in the TG of mice latently infected with LAT⁺ virus.Medical MicrobiologyBiomedical and Clinical SciencesImmunologyInfectious DiseasesSexually Transmitted InfectionsInfectionAnimalsCD8-Positive T-LymphocytesCell DifferentiationDendritic CellsHerpes SimplexHerpesvirus 1HumanImmune EvasionMiceMiceInbred C57BLMiceTransgenicMicroRNAsPhenotypeTrigeminal GanglionVirus LatencyVirologyapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/6dm509hrarticleViral Immunology, vol 25, iss 3204 - 215oai:escholarship.org:ark:/13030/qt9nt504n32023-08-20T21:53:23Zqt9nt504n3The changing landscape of diabetes prevalence among first-generation Asian immigrants in California from 2003 to 2013Fan, WenjunLee, Debora HBillimek, JohnChoi, SarahWang, Ping H2017-01-01ObjectiveThe prevalence of diabetes mellitus (DM) is increasing rapidly, particularly in Asia. Asian immigrants in Western countries are a fast-growing population who carry both intrinsic risks due to their genetic background and extrinsic risks associated with Western lifestyles. However, recent trends in diabetes prevalence and associated risk factors among Asian immigrants in the USA are not well understood.Research design and methodsWe examined adults aged 18 and older from the recent California Health Interview Survey data sets from 2003 to 2013 to determine prevalence of known DM among first-generation Asian immigrants and whites. The impact of various DM risk factors in Asian immigrants relative to whites was analyzed and multivariable regression models were constructed to obtain adjusted DM risk in Asian immigrants versus in whites.ResultsAcross the study span, we identified 2007 first-generation Asian immigrants and 14 668 whites as having known DM or prediabetes mellitus (pre-DM). From 2003 to 2013, the prevalence of DM and pre-DM combined rose from 6.8% to 12.4% in Asian immigrants and 5.5% to 6.9% in whites. Much of the increase could be attributed to pre-DM, which rose from 0.7% to 3.2% in Asian immigrants during the study period. The impacts of age and body mass index on DM risk were consistently greater in Asian immigrants than in whites. Non-DM Asian immigrants were found less likely to engage in physical activity than were non-DM whites. After adjustment of various associated factors, Asian immigrants were more likely than whites to have DM and this relative risk for DM gradually increased across the study period.ConclusionsA rising prevalence of known DM and particularly pre-DM among Asian immigrants in California was observed during the previous decade. To reduce the burden of diabetes and its complications, future strategies should consider specific risk factors for this ethnic group, including encouraging physical activity.PreventionDiabetesAgingMetabolic and endocrineImmigrationMinorityPre-DiabetesSurvey AnalysisClinical Sciencesapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/9nt504n3articleBMJ Open Diabetes Research & Care, vol 5, iss 1e000327oai:escholarship.org:ark:/13030/qt99j2t2dq2023-08-18T00:11:45Zqt99j2t2dqHigh-throughput screen detects calcium signaling dysfunction in typical sporadic autism spectrum disorderSchmunk, GalinaNguyen, Rachel LFerguson, David LKumar, KennyParker, IanGargus, J Jay2017-01-01Autism spectrum disorder (ASD) is a heterogeneous group of neurodevelopmental disorders without any defined uniting pathophysiology. Ca2+ signaling is emerging as a potential node in the genetic architecture of the disorder. We previously reported decreased inositol trisphosphate (IP3)-mediated Ca2+ release from the endoplasmic reticulum in several rare monogenic syndromes highly comorbid with autism - fragile X and tuberous sclerosis types 1 and 2 syndromes. We now extend those findings to a cohort of subjects with sporadic ASD without any known mutations. We developed and applied a high throughput Fluorometric Imaging Plate Reader (FLIPR) assay to monitor agonist-evoked Ca2+ signals in human primary skin fibroblasts. Our results indicate that IP3 -mediated Ca2+ release from the endoplasmic reticulum in response to activation of purinergic receptors is significantly depressed in subjects with sporadic as well as rare syndromic forms of ASD. We propose that deficits in IP3-mediated Ca2+ signaling represent a convergent hub function shared across the spectrum of autistic disorders - whether caused by rare highly penetrant mutations or sporadic forms - and holds promise as a biomarker for diagnosis and novel drug discovery.PediatricBrain DisordersMental HealthAutismNeurosciencesClinical ResearchIntellectual and Developmental Disabilities (IDD)Aetiology2.1 Biological and endogenous factorsMental healthAdenosine TriphosphateAdolescentAdultAutism Spectrum DisorderCalciumCalcium SignalingCase-Control StudiesChildChildPreschoolFemaleFibroblastsGene Expression ProfilingHigh-Throughput Screening AssaysHumansMaleMolecular ImagingROC CurveTranscriptomeYoung Adultapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/99j2t2dqarticleScientific Reports, vol 7, iss 140740oai:escholarship.org:ark:/13030/qt8rs2051r2023-08-03T15:40:41Zqt8rs2051rAssociation of ultrasound-based measures of fetal body composition with newborn adiposity.Ikenoue, SWaffarn, FSumiyoshi, KOhashi, MIkenoue, CBuss, CGillen, DLSimhan, HNEntringer, SWadhwa, PD2017-08-01BackgroundNewborns exhibit substantial variation in gestational age-adjusted and sex-adjusted fat mass proportion. The antecedent characteristics of fetal body composition that are associated with newborn fat mass proportion are poorly understood.ObjectiveThe aim of this study was to determine whether a composite measure of fetal fat mass is prospectively associated with newborn adiposity.MethodsIn a longitudinal study of 109 low-risk pregnancies, fetal ultrasonography was performed at approximately 12, 20 and 30 weeks gestation. Estimated fetal adiposity (EFA) was derived by integrating cross-sectional arm and thigh per cent fat area and anterior abdominal wall thickness. Newborn per cent body fat was quantified by Dual Energy X-Ray Absorptiometry. The association between EFA and newborn per cent body fat was determined by multiple linear regression.ResultsAfter controlling for confounding factors, EFA at 30 weeks was significantly associated with newborn per cent body fat (standardized β = 0.41, p < 0.001) and explained 24.0% of its variance, which was substantially higher than that explained by estimated fetal weight (8.1%). The observed effect was driven primarily by arm per cent fat area.ConclusionsA composite measure of fetal adiposity at 30 weeks gestation may constitute a better predictor of newborn per cent body fat than estimated fetal weight by conventional fetal biometry. Fetal arm fat deposition may represent an early indicator of newborn adiposity. After replication, these findings may provide a basis for an improved understanding of the ontogeny of fetal fat deposition, thereby contributing to a better understanding of its intrauterine determinants and the development of potential interventions.HumansAbsorptiometryPhotonUltrasonographyPrenatalLongitudinal StudiesProspective StudiesBody CompositionGestational AgePregnancyAdultInfantNewbornFemaleMaleAdiposityfetal body compositionfetal fat massnewborn adiposityper cent body fatNutritionPreventionClinical ResearchObesityPerinatal Period - Conditions Originating in Perinatal PeriodPediatricReproductive health and childbirthCardiovascularMedical and Health SciencesEndocrinology & Metabolismapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/8rs2051rarticlePediatric obesity, vol 12 Suppl 1, iss Suppl 186 - 93oai:escholarship.org:ark:/13030/qt42r503cr2023-07-09T01:56:36Zqt42r503crMaternal Cortisol During Pregnancy and Infant Adiposity: A Prospective Investigation.Entringer, SonjaBuss, ClaudiaRasmussen, Jerod MLindsay, KarenGillen, Daniel LCooper, Dan MWadhwa, Pathik D2017-04-01ContextGlucocorticoids play a key role during intrauterine development in cellular growth and differentiation. Evidence suggests that exposure to inappropriate concentrations of glucocorticoids during sensitive developmental periods may produce alterations in physiological systems that impact obesity risk.ObjectiveTo elucidate the magnitude and stage-of-gestation-specific association of maternal cortisol concentrations during pregnancy with infant adiposity.Design, participants, and settingSixty-seven mother-child dyads recruited in early pregnancy at university-based obstetric clinics in Southern California were followed with serial assessments from early gestation through birth until 6 months postnatal age. Maternal cumulative cortisol production was assessed over each of 4 consecutive days in early (≅13 weeks), mid (≅24 weeks), and late pregnancy (≅30 weeks) (5 saliva samples/d × 4 days × 3 trimesters = 60 saliva samples/subject). Infant body composition was serially assessed in newborns (at ∼25 days postnatal age) and at ∼6 months age with dual-energy X-ray absorptiometry imaging.ResultsAfter adjusting for key prenatal, birth, and postnatal covariates, higher maternal cortisol during the early third trimester (conditioned on prior early and midgestation cortisol concentrations) was significantly associated with a greater change in infant percent body fat from 1 to 6 months of age [partial r (adjusted for covariates) = 0.379, P = 0.007], accounting for ∼14% of the variance in this measure of childhood obesity risk.ConclusionThe present findings suggest a stage-of-gestation-specific effect of maternal cortisol on infant adiposity gain in early postnatal life and provide evidence in humans to support the role of glucocorticoids in fetal programming of childhood obesity risk.HumansObesityHydrocortisoneAbsorptiometryPhotonProspective StudiesChild DevelopmentFetal DevelopmentPregnancyPregnancy TrimesterThirdAdultInfantInfantNewbornFemaleAdiposityYoung AdultPreventionClinical ResearchPerinatal Period - Conditions Originating in Perinatal PeriodNutritionPediatricConditions Affecting the Embryonic and Fetal PeriodsMetabolic and endocrineCardiovascularReproductive health and childbirthGood Health and Well BeingClinical SciencesPaediatrics and Reproductive MedicineEndocrinology & Metabolismapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/42r503crarticleThe Journal of clinical endocrinology and metabolism, vol 102, iss 41366 - 1374oai:escholarship.org:ark:/13030/qt7fw4b66c2023-04-15T12:27:35Zqt7fw4b66cAssociation of Serum Triglyceride to HDL Cholesterol Ratio with All-Cause and Cardiovascular Mortality in Incident Hemodialysis Patients.Chang, Tae IkStreja, ElaniSoohoo, MelissaKim, Tae WooRhee, Connie MKovesdy, Csaba PKashyap, Moti LVaziri, Nosratola DKalantar-Zadeh, KamyarMoradi, Hamid2017-04-01Background and objectivesElevated serum triglyceride/HDL cholesterol (TG/HDL-C) ratio has been identified as a risk factor for cardiovascular (CV) disease and mortality in the general population. However, the association of this important clinical index with mortality has not been fully evaluated in patients with ESRD on maintenance hemodialysis (MHD). We hypothesized that the association of serum TG/HDL-C ratio with all-cause and CV mortality in patients with ESRD on MHD is different from the general population.Design, setting, participants, & measurementsWe studied the association of serum TG/HDL-C ratio with all-cause and CV mortality in a nationally representative cohort of 50,673 patients on incident hemodialysis between January 1, 2007 and December 31, 2011. Association of baseline and time-varying TG/HDL-C ratios with mortality was assessed using Cox proportional hazard regression models, with adjustment for multiple variables, including statin therapy.ResultsDuring the median follow-up of 19 months (interquartile range, 11-32 months), 12,778 all-cause deaths and 4541 CV deaths occurred, respectively. We found that the 10th decile group (reference: sixth deciles of TG/HDL-C ratios) had significantly lower risk of all-cause mortality (hazard ratio, 0.91 [95% confidence interval, 0.83 to 0.99] in baseline and 0.86 [95% confidence interval, 0.79 to 0.94] in time-varying models) and CV mortality (hazard ratio, 0.83 [95% confidence interval, 0.72 to 0.96] in baseline and 0.77 [95% confidence interval, 0.66 to 0.90] in time-varying models). These associations remained consistent and significant across various subgroups.ConclusionsContrary to the general population, elevated TG/HDL-C ratio was associated with better CV and overall survival in patients on hemodialysis. Our findings provide further support that the nature of CV disease and mortality in patients with ESRD is unique and distinct from other patient populations. Hence, it is vital that future studies focus on identifying risk factors unique to patients on MHD and decipher the underlying mechanisms responsible for poor outcomes in patients with ESRD.HumansKidney FailureChronicCardiovascular DiseasesTriglyceridesRenal DialysisCause of DeathSurvival RateProportional Hazards ModelsFollow-Up StudiesAgedMiddle AgedFemaleMaleCholesterolHDLRepublic of KoreaCholesterolConfidence IntervalsHydroxymethylglutaryl-CoA Reductase InhibitorsLipidsLipoproteinsHDLhemodialysishigh-density lipoprotein cholesterolmortalityrenal dialysisrisk factorstriglycerideCardiovascularBioengineeringKidney DiseaseAssistive TechnologyClinical ResearchGood Health and Well BeingClinical SciencesUrology & Nephrologyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/7fw4b66carticleClinical journal of the American Society of Nephrology : CJASN, vol 12, iss 4591 - 602oai:escholarship.org:ark:/13030/qt6dv5z7cx2023-03-15T19:06:15Zqt6dv5z7cxSelective stimulation of facial muscles with a penetrating electrode array in the feline model.Sahyouni, RonaldBhatt, JayDjalilian, Hamid RTang, William CMiddlebrooks, John CLin, Harrison W2017-02-01Objectives/hypothesisPermanent facial nerve injury is a difficult challenge for both patients and physicians given its potential for debilitating functional, cosmetic, and psychological sequelae. Although current surgical interventions have provided considerable advancements in facial nerve rehabilitation, they often fail to fully address all impairments. We aim to introduce an alternative approach to facial nerve rehabilitation.Study designAcute experiments in animals with normal facial function.MethodsThe study included three anesthetized cats. Four facial muscles (levator auris longus, orbicularis oculi, nasalis, and orbicularis oris) were monitored with a standard electromyographic (EMG) facial nerve monitoring system with needle electrodes. The main trunk of the facial nerve was exposed, and a 16-channel penetrating electrode array was placed into the nerve. Electrical current pulses were delivered to each stimulating electrode individually. Elicited EMG voltage outputs were recorded for each muscle.ResultsStimulation through individual channels selectively activated restricted nerve populations, resulting in selective contraction of individual muscles. Increasing stimulation current levels resulted in increasing EMG voltage responses. Typically, selective activation of two or more distinct muscles was successfully achieved via a single placement of the multi-channel electrode array by selection of appropriate stimulation channels.ConclusionWe have established in the animal model the ability of a penetrating electrode array to selectively stimulate restricted fiber populations within the facial nerve and to selectively elicit contractions in specific muscles and regions of the face. These results show promise for the development of a facial nerve implant system.Level of evidenceN/A.Laryngoscope, 2016 127:460-465, 2017.Facial MusclesNeuronsNerve FibersFacial NerveAnimalsCatsFacial ParalysisDisease ModelsAnimalElectromyographyElectric StimulationElectrodesImplantedMuscle ContractionComputer GraphicsSignal ProcessingComputer-AssistedVideo RecordingFacial nervefacial nerve implantfacial stimulationmulti-channel electrode arrayRehabilitationNeurosciencesClinical SciencesOtorhinolaryngologyapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/6dv5z7cxarticleThe Laryngoscope, vol 127, iss 2460 - 465oai:escholarship.org:ark:/13030/qt6fn6f65h2023-02-09T23:05:08Zqt6fn6f65hRadiative transport in the diffusion approximation: An extension for highly absorbing media and small source-detector separationsVenugopalan, V.You, J. STromberg, B. J1998-08-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/6fn6f65harticlePhysical Review E, vol 58, iss 22395 - 2407oai:escholarship.org:ark:/13030/qt5gv7q75h2022-08-01T21:26:14Zqt5gv7q75hStudy of the Carrier-Aided Thin Film Electrode Array Design for Cochlear Insertion.Xu, YuchenLuo, ChuanZeng, Fan-GangMiddlebrooks, John CLin, Harrison WYou, Zheng2018-04-27The micro-fabricated thin film electrode array (TFEA) has been a promising design for cochlear implants (CIs) because of its cost-effectiveness and fabrication precision. The latest polymer-based cochlear TFEAs have faced difficulties for cochlear insertion due to the lack of structural stiffness. To stiffen the TFEA, dissolvable stiffening materials, TFEAs with different structures, and TFEAs with commercial CIs as carriers have been invested. In this work, the concept of enhancing a Parylene TFEA with Kapton tape as a simpler carrier for cochlear insertion has been proved to be feasible. The bending stiffness of the Kapton-aided TFEA was characterized with an analytical model, a finite element model, and a cantilever bending experiment, respectively. While the Kapton tape increased the bending stiffness of the Parylene TFEA by 10³ times, the 6-μm-thick TFEA with a similar Young's modulus, as a polyimide, in turn significantly increased the bending stiffness of the 170-μm-thick Kapton carrier by 60%. This result indicated that even the TFEA is ultra-flexible and that its bending stiffness should not be neglected in the design or selection of its carrier.application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/5gv7q75harticleMicromachines, vol 9, iss 5oai:escholarship.org:ark:/13030/qt4030887c2022-08-01T21:25:13Zqt4030887cDistinct Patterns of Reduced Prefrontal and Limbic Gray Matter Volume in Childhood General and Internalizing PsychopathologySnyder, Hannah RHankin, Benjamin LSandman, Curt AHead, KevinDavis, Elysia P2017-07-26Reduced grey matter volume (GMV) is widely implicated in psychopathology, but studies have found mostly overlapping areas of GMV reduction across disorders rather than unique neural signatures, potentially due to pervasive comorbidity. GMV reductions may be associated with broader psychopathology dimensions rather than specific disorders. We used an empirically supported bifactor model consisting of common psychopathology and internalizing- and externalizing-specific factors to evaluate whether latent psychopathology dimensions yield a clearer, more parsimonious pattern of GMV reduction in prefrontal and limbic/paralimbic areas implicated in individual disorders. A community sample of children (n=254, ages 6–10) was used to to evaluate whether GMV reductions could constitute early neural risk factors. The common psychopathology factor was associated with reduced GMV in prefrontal areas (dorsal, orbitofrontal, ventrolateral). The internalizing-specific factor was related to reduced GMV in limbic/paralimbic areas (hippocampus, amygdala, insula). No significant associations were found between GMV and the externalizing-specific factor after accounting for common psychopathology.p factorinternalizingexternalizingmiddle childhoodgrey matter volumeapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/4030887carticleClinical Psychological Science, vol 5, iss 61001 - 1013oai:escholarship.org:ark:/13030/qt1qs962jg2022-08-01T21:24:29Zqt1qs962jgMobile Computing: The Role of Autonomous Features in Robot-Mediated Virtual LearningNewhart, Veronica AhumadaWarschauer, Mark2021-01-01application/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/1qs962jgchapteroai:escholarship.org:ark:/13030/qt3xz542w12022-08-01T21:23:50Zqt3xz542w1Telerobots for Informal Learning in Schools.Ahumada-Newhart, VeronicaRiek, Laurel2022-08-01application/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/3xz542w1articleoai:escholarship.org:ark:/13030/qt7pz432xz2021-08-13T01:15:24Zqt7pz432xzComparison of speckleplethysmographic (SPG) and photoplethysmographic (PPG) imaging by Monte Carlo simulations and in vivo measurements.Dunn, Cody ELertsakdadet, BenCrouzet, ChristianBahani, AdrianChoi, Bernard2018-09-01Noncontact photoplethysmography (PPG) is limited by a poor signal-to-noise ratio (SNR). A solution to this limitation is the use of alternate sources of optical contrast to generate a complementary pulsatile waveform. One such source is laser speckle contrast, which is modulated in biological tissues by the flow rate of red blood cells. Averaging a region of interest from a speckle contrast image over time allows for the calculation of a speckleplethysmogram (SPG). Similar to PPG, SPG enables monitoring of heart rate and respiratory rate. A gap in the knowledge base exists as to the precise spatiotemporal relationship between PPG and SPG signals. We have developed an eight-layer tissue model to simulate both PPG and SPG signals in a reflectance geometry via Monte Carlo methods. We modeled PPG by compression of the upper and lower blood nets due to expansion of the larger arterial layer below. The in silico PPG peak-to-peak amplitude percent was greater at 532 nm than at 860 nm (5.6% vs. 3.0%, respectively), which matches trends from the literature. We modeled SPG by changing flow speeds of red blood cells in both the capillaries and arterioles over the cardiac cycle. The in silico SPG peak-to-peak amplitude percent was 24% at 532 nm and 40% at 860 nm. In silico results are similar to in vivo results measured with a two-camera set up for simultaneous imaging of PPG and SPG. Both in silico and in vivo data suggest SPG has a much larger SNR than PPG, which may prove beneficial for noncontact, wide-field optical monitoring of cardiovascular health.application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/7pz432xzarticleBiomedical optics express, vol 9, iss 94306 - 4316oai:escholarship.org:ark:/13030/qt9ds8664s2021-08-13T01:14:09Zqt9ds8664sStudy partners: essential collaborators in discovering treatments for Alzheimer's disease.Largent, Emily AKarlawish, JasonGrill, Joshua D2018-09-27Global leaders have set an ambitious goal of developing interventions to effectively treat or prevent Alzheimer's disease by 2025.Achieving this goal will require clinical trials to test promising interventions, yet Alzheimer's researchers are confronting a clinical trial recruitment crisis. One reason for this is that Alzheimer's disease trials must enroll "dyads" composed of both a participant and his or her study partner.In this article, we argue that it is essential to identify ways to facilitate study partner participation, such as removing logistical barriers, offering payment, and providing paid, protected time off for study visits. Facilitating participation, particularly among non-spousal study partners, should offer a twofold benefit: faster accrual and greater generalizability of results.application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/9ds8664sarticleAlzheimer's research & therapy, vol 10, iss 1101 - 101oai:escholarship.org:ark:/13030/qt9wd7n51b2021-08-13T01:13:43Zqt9wd7n51bSupporting the Education of Homebound Children Through Semi-autonomous Telepresence Robots.Newhart, Veronica Ahumada2019-07-01We used the Toyota Human Support Robot (HSR) to be an advanced telepresence robot with object manipulation, autonomous navigation, and an intuitive user interface.We tested the telepresence HSR with homebound children who have used other types of telepresence robots to compare the features and usability.publiceScholarship, University of Californiahttps://escholarship.org/uc/item/9wd7n51bmultimediaoai:escholarship.org:ark:/13030/qt895904mj2021-04-09T19:56:02Zqt895904mjParticulate air pollution, ambulatory heart rate variability, and cardiac arrhythmia in retirement community residents with coronary artery disease.Bartell, Scott MLonghurst, JohnTjoa, ThomasSioutas, ConstantinosDelfino, Ralph J2013-10-08Decreased heart rate variability (HRV) has been associated with future cardiac morbidity and mortality and is often used as a marker of altered cardiac autonomic balance in studies of health effects of airborne particulate matter. Fewer studies have evaluated associations between air pollutants and cardiac arrhythmia.We examined relationships between cardiac arrhythmias, HRV, and exposures to airborne particulate matter.We measured HRV and arrhythmia with ambulatory electrocardiograms in a cohort panel study for up to 235 hr per participant among 50 nonsmokers with coronary artery disease who were ≥ 71 years of age and living in four retirement communities in the Los Angeles, California, Air Basin. Exposures included hourly outdoor gases, hourly traffic-related and secondary organic aerosol markers, and daily size-fractionated particle mass. We used repeated measures analyses, adjusting for actigraph-derived physical activity and heart rate, temperature, day of week, season, and community location.Ventricular tachycardia was significantly increased in association with increases in markers of traffic-related particles, secondary organic carbon, and ozone. Few consistent associations were observed for supraventricular tachycardia. Particulates were significantly associated with decreased ambulatory HRV only in the 20 participants using ACE (angiotensin I-converting enzyme) inhibitors.Although these data support the hypothesis that particulate exposures may increase the risk of ventricular tachycardia for elderly people with coronary artery disease, HRV was not associated with exposure in most of our participants. These results are consistent with previous findings in this cohort for systemic inflammation, blood pressure, and ST segment depression.application/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/895904mjarticleEnvironmental health perspectives, vol 121, iss 101135 - 1141oai:escholarship.org:ark:/13030/qt244477x12019-04-10T23:11:17Zqt244477x1Disparities in Caregivers’ Experiences at the Dentist with their Young Child.Reich, SOchoa, WGaona, ASalcedo, YBardales, GNewhart, Veronica AhumadaLin, JDiaz, G2019-03-01application/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/244477x1articleoai:escholarship.org:ark:/13030/qt5cv709cx2018-05-07T21:09:34Zqt5cv709cxThe interactive effects of maternal stress and diet in pregnancy on markers of inflammationLindsay, Karen L.Buss, ClaudiaWadhwa, Pathik D.Entringer, Sonja2018-05-04Introduction:Excess inflammation during pregnancy may exert adverse effects on fetal development and birth outcomes, including prematurity, intrauterine growth restriction, and preeclampsia. Maternal nutrition and stress are two of the most frequently but independently studied factors for their influence on prenatal inflammatory status, but their interaction in the context of pregnancy has been significantly understudied.The Dietary Inflammatory Index (DII) is a validated method to characterize and quantify the cumulative inflammatory potential of an individual diet,1 and has been previously used in prenatal populations.2,3 Ecological Momentary Assessment (EMA) methods are an effective way to assess psychosocial states in real-time, ambulatory, naturalistic settings, reducing the potential for recall and saliency bias associated with traditional retrospective questionnaires.4 Objective: The aim of this study is to investigate the combined effects of perceived stress (PSS) and dietary inflammatory index (DII) across pregnancy on markers of maternal inflammation.Financial Support: NIH grants R01 HD-060628, HD-065825 & MH-091351; European Commission FP7 289346 Project Early NutritionPoster presented at the ICTS Translational Science Day at University of California Irvine on May 4, 2018pregnancymaternalnutritioninflammatoryinflammationexercisetestingstressdietnon-diabeticICTS Translational Science DayICTSposterCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/5cv709cxmultimediaoai:escholarship.org:ark:/13030/qt7q24j5bb2018-04-25T17:57:37Zqt7q24j5bbThe effects of water and lipids on NIR optical breast measurementsCerussi, AEBevilacqua, FShah, NJakubowski, DBerger, AJLanning, RTromberg, BJ2001-01-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/7q24j5bbarticleProceedings of SPIE - The International Society for Optical Engineering, vol 4250419 - 428oai:escholarship.org:ark:/13030/qt5142j0hw2018-04-25T17:57:16Zqt5142j0hwTwo-photon imaging of collagen remodeling in RAFT tissue culturesWallace, VPColeno, MLYomo, TSun, CHTromberg, BJ2001-01-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/5142j0hwarticleProceedings of SPIE - The International Society for Optical Engineering, vol 4262118 - 124oai:escholarship.org:ark:/13030/qt9592n9qg2018-04-25T17:56:12Zqt9592n9qgFluence rate effects in human glioma spheroids: Implications for photodynamic therapy of brain tumorsMadsen, SJSun, CHTromberg, BJHirschberg, H2001-01-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/9592n9qgarticleProceedings of SPIE - The International Society for Optical Engineering, vol 4248150 - 156oai:escholarship.org:ark:/13030/qt93c4h0vb2018-04-25T17:56:01Zqt93c4h0vbEffects of low-fluence rate PDT on glioma spheroidsMadsen, SJRodenbush, RMSun, CHTromberg, BJHirschberg, H2002-01-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/93c4h0vbarticleProceedings of SPIE - The International Society for Optical Engineering, vol 4612190 - 195oai:escholarship.org:ark:/13030/qt90j6b55n2018-04-25T17:55:49Zqt90j6b55nCombined multiphoton and optical coherence microscopyTang, SKrasieva, TBChen, ZTromberg, BJ2005-01-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/90j6b55narticleProgress in Biomedical Optics and Imaging - Proceedings of SPIE, vol 5700286 - 293oai:escholarship.org:ark:/13030/qt7d98v4v92018-04-25T17:55:36Zqt7d98v4v9JBO to Begin "e-First" Publication in 2005Tromberg, Bruce J2004-01-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/7d98v4v9articleJournal of Biomedical Optics, vol 9, iss 61120oai:escholarship.org:ark:/13030/qt6mx7j1s22018-04-25T17:53:07Zqt6mx7j1s2Broadband absorption spectroscopy by combining frequency-domain and steady-state techniquesBerger, AJBevilacqua, FJakubowski, DBCerussi, AEButler, JHsiang, DTromberg, BJ2001-01-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/6mx7j1s2articleProceedings of SPIE - The International Society for Optical Engineering, vol 4250437 - 442oai:escholarship.org:ark:/13030/qt5vp1m12g2018-04-25T17:52:46Zqt5vp1m12gTwo-photon excited imaging of photosensitizers in tissuesColeno, MLWallace, VPSun, CHDunn, AKBerns, MWTromberg, BJ1999-01-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/5vp1m12garticlePROCEEDINGS OF OPTICAL DIAGNOSTICS AND LIVING CELLS II, vol 360467 - 73oai:escholarship.org:ark:/13030/qt58g1j7bz2018-04-25T17:52:22Zqt58g1j7bzMultipoint Thermal Sensors Associated with Improved Oncologic Outcomes Following Cryoablation.Martin, Jeremy WPatel, Roshan MOkhunov, ZhamshidVyas, AashayVajgrt, DuaneClayman, Ralph V2017-04-17Cryoablation (CA) is a minimally invasive modality for the management of small renal cortical neoplasms (RCN). Effective ablation is dependent on achieving target temperatures during CA that result in tumor cell death. We investigated long-term oncologic outcomes following CA using multipoint thermal sensors (MTS), which allow precise temperature determination at four points along the needle.We performed a retrospective review of 20 patients with <4 cm RCN who underwent de novo CA from 2005 to 2009. In 11 procedures, MTS needles were deployed with the goal of obtaining -20°C at the tumor margin, while 9 were done without MTS. Patient demographics, tumor characteristics, and CA procedure data were retrieved and analyzed. Follow-up CT or MRI was used to assess recurrence status.With a mean follow-up of 45 months, none of the 11 patients experienced a recurrence in the MTS group, compared with 4 of 9 (44.4%) patients in the non-MTS group (p = 0.026). Of the biopsy-confirmed renal cancers, none of the 6 in the MTS group, compared with 3 of 6 (50%) in the non-MTS group, recurred (p = 0.182). Age, tumor size, surgical approach, tumor histopathology, grade, follow-up time, and skin-to-tumor distance were similar between the MTS and non-MTS groups. The MTS group was also associated with increased total length of freeze (p = 0.041), procedure time (p = 0.020), cryoprobe utilization (p = 0.049), and a greater ratio of cryoprobes used per cm diameter of tumor (p = 0.003).In this small renal mass pilot study, the use of MTS needles to monitor temperature and guide cryoneedle deployment was associated with improved oncologic outcomes.AgedAged80 and overCarcinomaRenal Cell: surgeryCryosurgery: instrumentationmethodsFemaleHumansKidney Neoplasms: surgeryMagnetic Resonance ImagingMaleMiddle AgedNeedlesNeoplasm RecurrenceLocal: diagnostic imagingepidemiologyPilot ProjectsRetrospective StudiesTomographyX-Ray Computedapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/58g1j7bzarticleJournal of endourology, vol 31, iss 4355 - 360oai:escholarship.org:ark:/13030/qt3wx0b7g12018-04-25T17:51:51Zqt3wx0b7g1Quality control and assurance for validation of DOS/I measurementsCerussi, ADurkin, AKwong, RQuang, THill, BTromberg, BJMacKinnon, NMantulin, WW2010-01-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/3wx0b7g1articleProgress in Biomedical Optics and Imaging - Proceedings of SPIE, vol 7567oai:escholarship.org:ark:/13030/qt3s0090dc2018-04-25T17:51:40Zqt3s0090dcDevelopment of an in vivo model for the study of photodynamic therapy and anti-angiogenic treatmentsMadsen, SJSun, CHTromberg, BJHirschberg, H2003-02-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/3s0090dcarticleProceedings of SPIE - The International Society for Optical Engineering, vol 495217 - 22oai:escholarship.org:ark:/13030/qt3nf208jk2018-04-25T17:51:30Zqt3nf208jkSyndrome of selective IgM deficiency with severe T cell deficiency associated with disseminated cutaneous mycobacterium avium intracellulaire infection.Gharib, AsalLouis, Ankmalika GuptaAgrawal, SudhanshuGupta, Sudhir2015-10-12Cutaneous non-disseminated, non-tuberculous mycobacterial infections have been reported in both immunocompetent and immunocompromised subjects. Systemic Mycobacterium avium intracellulaire (MAI) have been reported in non-HIV patients with Idiopathic CD4 lymphocytopenia. We report a comprehensive immunological analysis in syndrome of selective IgM deficiency and T lymphocytopenia (both CD4+ and CD8+) with disseminated cutaneous MAI infection. Naïve (TN) and Central memory (TCM) subsets of both CD4+ and CD8+ T cells were decreased, whereas terminally differentiated effector memory (TEMRA) subset of CD4+ and CD8+ T cells were markedly increased. IFN-γ producing T cells were markedly decreased. Although CD14(high)CD16- proinflammatory monocytes were modestly increased, IFN-γR+ monocytes were markedly decreased. The expression of TLR3, TLR5, TLR7, and TLR9 on monocytes was decreased. Germinal center B cells (CD19+IgD-CD38+CD27(lo)) and B1 cells (CD20+CD27+CD43+CD70-) were markedly decreased. A role of immune alterations, including B cells and antibodies in disseminated cutaneous MAI infection is discussed.application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/3nf208jkarticleAmerican journal of clinical and experimental immunology, vol 4, iss 215 - 27oai:escholarship.org:ark:/13030/qt3jg6g9tx2018-04-25T17:51:20Zqt3jg6g9txCharacterization of optical and thermal distributions from an intracranial balloon applicator for photodynamic therapyMadsen, SJSvaasand, LOTromberg, BJHirschberg, H2001-01-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/3jg6g9txarticleProceedings of SPIE - The International Society for Optical Engineering, vol 425741 - 49oai:escholarship.org:ark:/13030/qt2q9857fp2018-04-25T17:50:48Zqt2q9857fpCombined two-photon excited fluorescence and second-harmonic generation backscattering microscopy of turbid tissuesZoumi, AYeh, ATTromberg, BJ2002-01-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/2q9857fparticleProceedings of SPIE - The International Society for Optical Engineering, vol 4620175 - 181oai:escholarship.org:ark:/13030/qt0h20b8c32018-04-25T17:50:22Zqt0h20b8c3Scheme for efficient fiber-based CARS probeBalu, MLui, GChen, ZTromberg, BJPotma, EO2010-01-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/0h20b8c3articleProceedings in Biomedical Optics and Imaging - Proceedings in SPIE, vol 7569oai:escholarship.org:ark:/13030/qt3cc910mg2018-04-17T18:27:46Zqt3cc910mgNoninvasive in vivo monitoring of cyanide toxicity and treatment using diffuse optical spectroscopy in a rabbit model.Lee, JangwoenKeuter, Kelly AKim, JaeTran, AndrewUppal, AmitMukai, DavidMahon, Sari BrennerCancio, Leopoldo CBatchinsky, AndriyTromberg, Bruce JBrenner, Matthew2009-06-01Currently, no reliable noninvasive methods exist for monitoring the severity of in vivo cyanide (CN) toxicity, treatment, and resulting physiological changes. We developed a broadband diffuse optical spectroscopy (DOS) system to measure bulk tissue absorption and scattering. DOS was used to optically monitor CN toxicity and treatment with sodium nitrite (NaNO2). To perform experiments, the DOS probe was placed on the hind leg of rabbits. A sodium CN solution was infused intravenously. DOS and concurrent physiologic measurements were obtained. After completion of CN infusion, NaNO2 was infused to induce methemoglobinemia (MetHb). During infusion of CN, blood gas measurements showed an increase in venous partial pressure of oxygen (pO2), and following reversal, venous pO2 values decreased. DOS measurements demonstrated corresponding changes in hemoglobin oxygenation states and redox states of cytochrome-c oxidase (CcO) during CN infusion and NaNO2 treatment. Therefore, DOS enables detection and monitoring of CN toxicity and treatment with NaNO2.AnimalsBlood Gas Analysis: methodsElectron Transport Complex IV: metabolismFeasibility StudiesHematinics: therapeutic useHemoglobins: analysisHydroxocobalamin: therapeutic useIndicators and Reagents: therapeutic useMaleMethemoglobin: analysisModelsAnimalOximetryOxyhemoglobins: analysisPoisoning: blooddrug therapyPotassium Cyanide: bloodtoxicityRabbitsSodium Nitrite: therapeutic useSpectrophotometryInfrared: methodsSpectrum Analysis: methodsStatistics as TopicToxicity TestsAcute: methodsapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/3cc910mgarticleMilitary medicine, vol 174, iss 6615 - 621oai:escholarship.org:ark:/13030/qt8kz5r66c2018-04-17T18:25:21Zqt8kz5r66cDifferential pathlength factor informs evoked stimulus response in a mouse model of Alzheimer's disease.Lin, Alexander JPonticorvo, AdrienDurkin, Anthony JVenugopalan, VasanChoi, BernardTromberg, Bruce J2015-10-12Baseline optical properties are typically assumed in calculating the differential pathlength factor (DPF) of mouse brains, a value used in the modified Beer-Lambert law to characterize an evoked stimulus response. We used spatial frequency domain imaging to measure in vivo baseline optical properties in 20-month-old control ([Formula: see text]) and triple transgenic APP/PS1/tau (3xTg-AD) ([Formula: see text]) mouse brains. Average [Formula: see text] for control and 3xTg-AD mice was [Formula: see text] and [Formula: see text], respectively, at 460 nm; and [Formula: see text] and [Formula: see text], respectively, at 530 nm. Average [Formula: see text] for control and 3xTg-AD mice was [Formula: see text] and [Formula: see text], respectively, at 460 nm; and [Formula: see text] and [Formula: see text], respectively, at 530 nm. The calculated DPF for control and 3xTg-AD mice was [Formula: see text] and [Formula: see text] OD mm, respectively, at 460 nm; and [Formula: see text] and [Formula: see text] OD mm, respectively, at 530 nm. In hindpaw stimulation experiments, the hemodynamic increase in brain tissue concentration of oxyhemoglobin was threefold larger and two times longer in the control mice compared to 3xTg-AD mice. Furthermore, the washout of deoxyhemoglobin from increased brain perfusion was seven times larger in controls compared to 3xTg-AD mice ([Formula: see text]). application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/8kz5r66carticleNeurophotonics, vol 2, iss 4045001 - 0450045001oai:escholarship.org:ark:/13030/qt51w7f7bb2018-04-17T18:21:35Zqt51w7f7bbDiffuse optical spectroscopic imaging of subcutaneous adipose tissue metabolic changes during weight loss.Ganesan, GWarren, R VLeproux, ACompton, MCutler, KWittkopp, STran, GO'Sullivan, TMalik, SGalassetti, P RTromberg, B J2016-08-22Changes in subcutaneous adipose tissue (AT) structure and metabolism have been shown to correlate with the development of obesity and related metabolic disorders. Measurements of AT physiology could provide new insight into metabolic disease progression and response to therapy. An emerging functional imaging technology, diffuse optical spectroscopic imaging (DOSI), was used to obtain quantitative measures of near infrared (NIR) AT optical and physiological properties.Ten overweight or obese adults were assessed during 3 months on calorie-restricted diets. DOSI-derived tissue concentrations of hemoglobin, water and lipid and the wavelength-dependent scattering amplitude (A) and slope (b) obtained from 30 abdominal locations and three time points (T0, T6, T12) were calculated and analyzed using linear mixed-effects models and were also used to form 3D surface images.Subjects lost a mean of 11.7±3.4% of starting weight, while significant changes in A (+0.23±0.04 mm(-1), adj. P<0.001),b (-0.17±0.04, adj. P<0.001), tissue water fraction (+7.2±1.1%, adj. P<0.001) and deoxyhemoglobin (1.1±0.3 μM, adj. P<0.001) were observed using mixed-effect model analysis.Optical scattering signals reveal alterations in tissue structure that possibly correlate with reductions in adipose cell volume, while water and hemoglobin dynamics suggest improved AT perfusion and oxygen extraction. These results suggest that DOSI measurements of NIR optical and physiological properties could be used to enhance understanding of the role of AT in metabolic disorders and provide new strategies for diagnostic monitoring of obesity and weight loss.AdultAgedCaloric RestrictionEnergy IntakeFemaleHumansMagnetic Resonance ImagingMaleMiddle AgedMonte Carlo MethodObesity: epidemiologymetabolismphysiopathologyOptical ImagingScatteringRadiationSubcutaneous Fat: diagnostic imagingmetabolismphysiopathologyUnited States: epidemiologyWeight Lossapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/51w7f7bbarticleInternational journal of obesity (2005), vol 40, iss 81292 - 12300oai:escholarship.org:ark:/13030/qt91z1g0f22018-04-17T18:19:18Zqt91z1g0f2Real-time simultaneous single snapshot of optical properties and blood flow using coherent spatial frequency domain imaging (cSFDI)Ghijsen, MichaelChoi, BernardDurkin, Anthony JGioux, SylvainTromberg, Bruce J2016-02-16application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/91z1g0f2articleBiomedical Optics Express, vol 7, iss 3870oai:escholarship.org:ark:/13030/qt6xb390wn2018-04-17T18:18:08Zqt6xb390wnImaging in breast cancer: diffuse optics in breast cancer: detecting tumors in pre-menopausal women and monitoring neoadjuvant chemotherapy.Tromberg, Bruce JCerussi, AlbertShah, NatashaCompton, MontanaDurkin, AmandaHsiang, DavidButler, JohnMehta, Rita2005-11-28Diffuse optical spectroscopy (DOS) and diffuse optical imaging (DOI) are non-invasive diagnostic techniques that employ near-infrared (NIR) light to quantitatively characterize the optical properties of centimeter-thick, multiple-scattering tissues. Although NIR was first applied to breast diaphanography more than 70 years ago, quantitative optical methods employing time- or frequency-domain 'photon migration' technologies have only recently been used for breast imaging. Because their performance is not limited by mammographic density, optical methods can provide new insight regarding tissue functional changes associated with the appearance, progression, and treatment of breast cancer, particularly for younger women and high-risk subjects who may not benefit from conventional imaging methods. This paper reviews the principles of diffuse optics and describes the development of broadband DOS for quantitatively measuring the optical and physiological properties of thick tissues. Clinical results are shown highlighting the sensitivity of diffuse optics to malignant breast tumors in 12 pre-menopausal subjects ranging in age from 30 to 39 years and a patient undergoing neoadjuvant chemotherapy for locally advanced breast cancer. Significant contrast was observed between normal and tumor regions of tissue for deoxy-hemoglobin (p = 0.005), oxy-hemoglobin (p = 0.002), water (p = 0.014), and lipids (p = 0.0003). Tissue hemoglobin saturation was not found to be a reliable parameter for distinguishing between tumor and normal tissues. Optical data were converted into a tissue optical index that decreased 50% within 1 week in response to neoadjuvant chemotherapy. These results suggest a potential role for diffuse optics as a bedside monitoring tool that could aid the development of new strategies for individualized patient care.AdultBreast Neoplasms: drug therapypathologyClinical Trials as TopicFemaleHumansNeoadjuvant TherapyOptics and PhotonicsPatient Care PlanningPoint-of-Care SystemsPremenopauseRisk FactorsSensitivity and SpecificitySpectroscopyNear-InfraredTreatment Outcomeapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/6xb390wnarticleBreast cancer research : BCR, vol 7, iss 6279 - 285oai:escholarship.org:ark:/13030/qt12q1023t2018-04-17T18:12:48Zqt12q1023tImaging breast cancer chemotherapy response with light. Commentary on Soliman et al., p. 2605.Tromberg, Bruce JCerussi, Albert E2010-05-01Diffuse optical spectroscopy (DOS), which is used to image tumor metabolic response to neoadjuvant chemotherapy (NAC), shows large changes in tumor functional parameters with significant reductions in oxy- and deoxyhemoglobin for responders versus nonresponders. Although investigational, DOS may provide a cost-effective, risk-free method for optimizing NAC drug and dosing strategies for individual patients.Antineoplastic Combined Chemotherapy Protocols: therapeutic useBreast Neoplasms: drug therapymetabolismpathologyChemotherapyAdjuvantDiagnostic Imaging: methodsFemaleHemoglobins: metabolismHumansMiddle AgedNeoadjuvant TherapyOxyhemoglobins: metabolismPrognosisReproducibility of ResultsTime FactorsTreatment Outcomeapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/12q1023tarticleClinical cancer research : an official journal of the American Association for Cancer Research, vol 16, iss 92486 - 2488oai:escholarship.org:ark:/13030/qt9xn5h4hj2018-04-17T18:11:02Zqt9xn5h4hjDiffuse optical spectroscopy measurements of healing in breast tissue after core biopsy: case study.Tanamai, WendyChen, CynthiaSiavoshi, SaraCerussi, AlbertHsiang, DavidButler, JohnTromberg, Bruce2009-01-01Diffuse optical spectroscopy (DOS) has been used to monitor and predict the effects of neoadjuvant (i.e., presurgical) chemotherapy in breast cancer patients in several pilot studies. Because patients with suspected breast cancers undergo biopsy prior to treatment, it is important to understand how biopsy trauma influences DOS measurements in the breast. The goal of this study was to measure the effects of a standard core breast biopsy on DOS measurements of tissue deoxyhemoglobin, hemoglobin, water, and bulk lipid concentrations. We serially monitored postbiopsy effects in the breast tissue in a single subject (31-year-old premenopausal female) with a 37x18x20 mm fibroadenoma. A baseline measurement and eight weekly postbiopsy measurements were taken with a handheld DOS imaging instrument. Our instrument used frequency domain photon migration combined with broadband steady-state spectroscopy to characterize tissues via quantitative measurements of tissue absorption and reduced scattering coefficients from 650 to 1000 nm. The concentrations of significant near-infrared (NIR) absorbers were mapped within a 50 cm(2) area over the biopsied region. A 2-D image of a contrast function called the tissue optical index (TOI=deoxyhemoglobinxwaterbulk lipid) was generated and revealed that a minimum of 14 days postbiopsy was required to return TOI levels in the biopsied area to their prebiopsy levels. Changes in the TOI images of the fibroadenoma also reflected the progression of the patient's menstrual cycle. DOS could therefore be useful in evaluating both wound-healing response and the effects of hormone and hormonal therapies in vivo.BiopsyBreast: metabolismpathologyBreast Neoplasms: metabolismpathologyFemaleHemoglobins: analysisHumansLipids: analysisSpectroscopyNear-Infrared: methodsWater: analysisWound HealingYoung Adultapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/9xn5h4hjarticleJournal of biomedical optics, vol 14, iss 1014024 - 0140014024oai:escholarship.org:ark:/13030/qt7p36f9tc2018-04-17T18:07:11Zqt7p36f9tcCelebrating Britton ChanceYodh, Arjun GTromberg, Bruce J2000-01-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/7p36f9tcarticleJournal of Biomedical Optics, vol 5, iss 2115oai:escholarship.org:ark:/13030/qt6tr4w04h2018-04-13T19:58:51Zqt6tr4w04hChemically modified peptides based on the membrane-proximal external region of the HIV-1 envelope induce high-titer, epitope-specific nonneutralizing antibodies in rabbits.Venditto, Vincent JWieczorek, LindsayMolnar, SebastianTeque, FernandoLanducci, GaryWatson, Douglas SForthal, DonaldPolonis, Victoria RLevy, Jay ASzoka, Francis C, Jr2014-08-28Broadly neutralizing monoclonal antibodies (bNAbs) 2F5 and 4E10 bind to the membrane proximal external region (MPER) of gp41 and also cross-react with phospholipids. In this study, we investigated if chemical modifications on the MPER adjacent to 2F5 and 4E10 epitopes using mimetics of inflammation-associated posttranslational modifications to induce 2F5- and 4E10-like bNAbs can break tolerance. We synthesized a series of chemically modified peptides spanning the MPER. The serine, threonine, and tyrosine residues in the peptides were modified with sulfate, phosphate, or nitrate moieties and presented in liposomes for rabbit immunizations. All immunizations resulted in high antisera titers directed toward both the modified and unmodified immunogens. Tyrosine modification was observed to significantly suppress antiepitope responses. Sera with strong anti-gp140 titers were purified by affinity chromatography toward the MPER peptide and found to possess a higher affinity toward the MPER than did the bNAbs 2F5 and 4E10. Modest neutralization was observed in the H9 neutralization assay, but neutralization was not observed in the TZM-bl cell or peripheral blood mononuclear cell (PBMC) neutralization assay platforms. Although neutralizing antibodies were not induced by this approach, we conclude that chemical modifications can increase the immune responses to poorly immunogenic antigens, suggesting that chemical modification in an appropriate immunization protocol should be explored further as an HIV-1 vaccine strategy. AIDS Vaccines: chemistryimmunologyAnimalsAntibodiesMonoclonal: immunologyAntibodiesNeutralizing: immunologyAntibody Affinity: immunologyCell LineChromatographyAffinityCross Reactions: immunologyEpitopes: chemistryimmunologyHIV Antibodies: immunologyHIV Envelope Protein gp41: chemistryimmunologyHIV-1: immunologyNeutralization TestsRabbitsenv Gene ProductsHuman Immunodeficiency Virus: immunologyapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/6tr4w04harticleClinical and vaccine immunology : CVI, vol 21, iss 81086 - 1093oai:escholarship.org:ark:/13030/qt6cb2813b2018-04-13T19:57:39Zqt6cb2813bSyndrome of selective IgM deficiency with severe T cell deficiency associated with disseminated cutaneous mycobacterium avium intracellulaire infection.Gharib, AsalLouis, Ankmalika GuptaAgrawal, SudhanshuGupta, Sudhir2015-10-12Cutaneous non-disseminated, non-tuberculous mycobacterial infections have been reported in both immunocompetent and immunocompromised subjects. Systemic Mycobacterium avium intracellulaire (MAI) have been reported in non-HIV patients with Idiopathic CD4 lymphocytopenia. We report a comprehensive immunological analysis in syndrome of selective IgM deficiency and T lymphocytopenia (both CD4+ and CD8+) with disseminated cutaneous MAI infection. Naïve (TN) and Central memory (TCM) subsets of both CD4+ and CD8+ T cells were decreased, whereas terminally differentiated effector memory (TEMRA) subset of CD4+ and CD8+ T cells were markedly increased. IFN-γ producing T cells were markedly decreased. Although CD14(high)CD16- proinflammatory monocytes were modestly increased, IFN-γR+ monocytes were markedly decreased. The expression of TLR3, TLR5, TLR7, and TLR9 on monocytes was decreased. Germinal center B cells (CD19+IgD-CD38+CD27(lo)) and B1 cells (CD20+CD27+CD43+CD70-) were markedly decreased. A role of immune alterations, including B cells and antibodies in disseminated cutaneous MAI infection is discussed. application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/6cb2813barticleAmerican journal of clinical and experimental immunology, vol 4, iss 215 - 27oai:escholarship.org:ark:/13030/qt96h7p63r2018-04-13T19:54:45Zqt96h7p63rEvaluating visual perception for assessing reconstructed flap health.Ponticorvo, AdrienTaydas, ErenMazhar, AmaanEllstrom, Christopher LRimler, JonathanScholz, ThomasTong, JuneEvans, Gregory R DCuccia, David JDurkin, Anthony J2015-07-04Detecting failing tissue flaps before they are clinically apparent has the potential to improve postoperative flap management and salvage rates. This study demonstrates a model to quantitatively compare clinical appearance, as recorded via digital camera, with spatial frequency domain imaging (SFDI), a noninvasive imaging technique using patterned illumination to generate images of total hemoglobin and tissue oxygen saturation (stO2).Using a swine pedicle model in which blood flow was carefully controlled with occlusion cuffs and monitored with ultrasound probes, throughput was reduced by 25%, 50%, 75%, and 100% of baseline values in either the artery or the vein of each of the flaps. The color changes recorded by a digital camera were quantified to predict which occlusion levels were visible to the human eye. SFDI was also used to quantify the changes in physiological parameters including total hemoglobin and oxygen saturation associated with each occlusion.There were no statistically significant changes in color above the noticeable perception levels associated with human vision during any of the occlusion levels. However, there were statistically significant changes in total hemoglobin and stO2 levels detected at the 50%, 75%, and 100% occlusion levels for arterial and venous occlusions.As demonstrated by the color imaging data, visual flap changes are difficult to detect until significant occlusion has occurred. SFDI is capable of detecting changes in total hemoglobin and stO2 as a result of partial occlusions before they are perceivable, thereby potentially improving response times and salvage rates.AnimalsBiomarkers: bloodColor PerceptionFree Tissue Flaps: blood supplyphysiologyHemoglobins: metabolismOptical ImagingOxygen: bloodPhotographySwineapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/96h7p63rarticleThe Journal of surgical research, vol 197, iss 1210 - 217oai:escholarship.org:ark:/13030/qt01k2d4492018-04-13T19:53:05Zqt01k2d449Defining the optimal window for cranial transplantation of human induced pluripotent stem cell-derived cells to ameliorate radiation-induced cognitive impairment.Acharya, Munjal MMartirosian, VahanChristie, Lori-AnnRiparip, LaraStrnadel, JanParihar, Vipan KLimoli, Charles L2015-01-12Past preclinical studies have demonstrated the capability of using human stem cell transplantation in the irradiated brain to ameliorate radiation-induced cognitive dysfunction. Intrahippocampal transplantation of human embryonic stem cells and human neural stem cells (hNSCs) was found to functionally restore cognition in rats 1 and 4 months after cranial irradiation. To optimize the potential therapeutic benefits of human stem cell transplantation, we have further defined optimal transplantation windows for maximizing cognitive benefits after irradiation and used induced pluripotent stem cell-derived hNSCs (iPSC-hNSCs) that may eventually help minimize graft rejection in the host brain. For these studies, animals given an acute head-only dose of 10 Gy were grafted with iPSC-hNSCs at 2 days, 2 weeks, or 4 weeks following irradiation. Animals receiving stem cell grafts showed improved hippocampal spatial memory and contextual fear-conditioning performance compared with irradiated sham-surgery controls when analyzed 1 month after transplantation surgery. Importantly, superior performance was evident when stem cell grafting was delayed by 4 weeks following irradiation compared with animals grafted at earlier times. Analysis of the 4-week cohort showed that the surviving grafted cells migrated throughout the CA1 and CA3 subfields of the host hippocampus and differentiated into neuronal (∼39%) and astroglial (∼14%) subtypes. Furthermore, radiation-induced inflammation was significantly attenuated across multiple hippocampal subfields in animals receiving iPSC-hNSCs at 4 weeks after irradiation. These studies expand our prior findings to demonstrate that protracted stem cell grafting provides improved cognitive benefits following irradiation that are associated with reduced neuroinflammation. AnimalsCognition Disorders: etiologysurgeryCranial Irradiation: adverse effectsHeterograftsHippocampus: surgeryHumansImmunohistochemistryInduced Pluripotent Stem Cells: transplantationMicroscopyConfocalRadiation InjuriesExperimental: surgeryRatsRatsNudeStem Cell Transplantation: methodsapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/01k2d449articleStem cells translational medicine, vol 4, iss 174 - 83oai:escholarship.org:ark:/13030/qt20c4c1wp2018-04-06T20:07:13Zqt20c4c1wpAging in Down Syndrome and the Development of Alzheimer's Disease Neuropathology.Head, ElizabethLott, Ira TWilcock, Donna MLemere, Cynthia A2016-01-01Chromosome 21, triplicated in Down Syndrome, contains several genes that are thought to play a critical role in the development of AD neuropathology. The overexpression of the gene for the amyloid precursor protein (APP), on chromosome 21, leads to early onset beta-amyloid (Aβ) plaques in DS. In addition to Aβ accumulation, middle-aged people with DS develop neurofibrillary tangles, cerebrovascular pathology, white matter pathology, oxidative damage, neuroinflammation and neuron loss. There is also evidence of potential compensatory responses in DS that benefit the brain and delay the onset of dementia after there is sufficient neuropathology for a diagnosis of AD. This review describes some of the existing literature and also highlights gaps in our knowledge regarding AD neuropathology in DS. It will be critical in the future to develop networked brain banks with standardized collection procedures to fully characterize the regional and temporal pathological events associated with aging in DS. As more information is acquired regarding AD evolution in DS, there will be opportunities to develop interventions that are age-appropriate to delay AD in DS.Age FactorsAging: pathologyAlzheimer Disease: pathologyAmyloid beta-Protein Precursor: geneticsmetabolismAnimalsDown Syndrome: pathologyHumansNeurofibrillary Tangles: geneticsmetabolismmicrobiologyNeuropathologytau Proteins: metabolismapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/20c4c1wparticleCurrent Alzheimer research, vol 13, iss 118 - 29oai:escholarship.org:ark:/13030/qt16q0g0br2018-04-06T20:05:05Zqt16q0g0brAsymptomatic memory CD8+ T cells: from development and regulation to consideration for human vaccines and immunotherapeutics.Khan, Arif AzamSrivastava, RuchiLopes, Patricia PradoWang, ChristinePham, Thanh TCochrane, JustinThai, Nhi Thi UyenGutierrez, LucasBenmohamed, Lbachir2014-02-05Generation and maintenance of high quantity and quality memory CD8(+) T cells determine the level of protection from viral, bacterial, and parasitic re-infections, and hence constitutes a primary goal for T cell epitope-based human vaccines and immunotherapeutics. Phenotypically and functionally characterizing memory CD8(+) T cells that provide protection against herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2) infections, which cause blinding ocular herpes, genital herpes, and oro-facial herpes, is critical for better vaccine design. We have recently categorized 2 new major sub-populations of memory symptomatic and asymptomatic CD8(+) T cells based on their phenotype, protective vs. pathogenic function, and anatomical locations. In this report we are discussing a new direction in developing T cell-based human herpes vaccines and immunotherapeutics based on the emerging new concept of "symptomatic and asymptomatic memory CD8(+) T cells."CD8-Positive T-Lymphocytes: immunologyHerpesvirus Vaccines: immunologyHumansImmunologic MemoryImmunotherapy: methodsT-Lymphocyte Subsets: immunologyapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/16q0g0brarticleHuman vaccines & immunotherapeutics, vol 10, iss 4945 - 963oai:escholarship.org:ark:/13030/qt0rm238hc2018-04-06T20:02:52Zqt0rm238hcAF710B, a Novel M1/σ1 Agonist with Therapeutic Efficacy in Animal Models of Alzheimer’s Disease.Fisher, AbrahamBezprozvanny, IlyaWu, LiliRyskamp, Daniel ABar-Ner, NiraNatan, NivaBrandeis, RachelElkon, HanochNahum, VictoriaGershonov, EitanLaFerla, Frank MMedeiros, Rodrigo2016-01-01We previously developed orthosteric M1 muscarinic agonists (e.g. AF102B, AF267B and AF292), which act as cognitive enhancers and potential disease modifiers. We now report on a novel compound, AF710B, a highly potent and selective allosteric M1 muscarinic and σ1 receptor agonist. AF710B exhibits an allosteric agonistic profile on the M1 muscarinic receptor; very low concentrations of AF710B significantly potentiated the binding and efficacy of carbachol on M1 receptors and their downstream effects (p-ERK1/2, p-CREB). AF710B (1-30 µg/kg, p.o.) was a potent and safe cognitive enhancer in rats treated with the M1 antagonist trihexyphenidyl (passive avoidance impairment). These effects of AF710B involve σ1 receptor activation. In agreement with its antiamnesic properties, AF710B (at 30 nM), via activation of M1 and a possible involvement of σ1 receptors, rescued mushroom synapse loss in PS1-KI and APP-KI neuronal cultures, while AF267B (1 µM) was less potent in PS1-KI and ineffective in APP-KI models, respectively. In female 3xTg-AD mice, AF710B (10 µg/kg, i.p./daily/2 months) (i) mitigated cognitive impairments in the Morris water maze; (ii) decreased BACE1, GSK3β activity, p25/CDK5, neuroinflammation, soluble and insoluble Aβ40, Aβ42, plaques and tau pathologies. AF710B differs from conventional σ1 and M1 muscarinic (orthosteric, allosteric or bitopic) agonists. These results highlight AF710B as a potential treatment for Alzheimer's disease (e.g. improving cognitive deficits, synaptic loss, amyloid and tau pathologies, and neuroinflammation) with a superior profile over a plethora of other therapeutic strategies.Allosteric RegulationAlzheimer Disease: drug therapymetabolismpathologyAnimalsAvoidance Learning: drug effectsphysiologyCerebral Cortex: drug effectsmetabolismpathologyDisease ModelsAnimalDrug EvaluationPreclinicalFemaleHippocampus: drug effectsmetabolismpathologyHumansMaleMaze Learning: drug effectsphysiologyMiceTransgenicNootropic Agents: chemistrypharmacologyPC12 CellsRatsRatsSprague-DawleyRatsWistarReceptorMuscarinic M1: agonistsmetabolismReceptorssigma: agonistsmetabolismSpiro Compounds: chemistrypharmacologySynapses: drug effectsmetabolismpathologyThiazolidines: chemistrypharmacologyapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/0rm238hcarticleNeuro-degenerative diseases, vol 16, iss 1-295 - 110oai:escholarship.org:ark:/13030/qt9454c25h2018-04-06T20:00:16Zqt9454c25hThe Suitability of Propofol Compared with Urethane for Anesthesia during Urodynamic Studies in Rats.Moheban, Adam AChang, Huiyi HHavton, Leif A2016-01-01Urethane anesthesia preserves many reflex functions and is often the preferred anesthetic for urodynamic studies in rats. Because of the toxicity profile of urethane, its use as an anesthetic typically is limited to acute and terminal investigations. Alternative anesthetic options are needed for longitudinal studies of micturition reflexes in rats. In this study, we evaluated propofol anesthesia administered at constant rate infusion at different planes of anesthesia in rats for combined cystometrography and external urethral sphincter (EUS) EMG in rats. No reflex micturition was noted after rats received 100%, 80%, or 60% of a previously reported anesthetic dose of propofol. At 40% of the standard propofol dose, a subset of rats showed reflex voiding, with bladder contractions and associated EUS EMG activity. In contrast, urethane anesthesia at a surgical plane allowed for reflex voiding with bladder contractions and EUS activation. Latency to leaking or voiding was longer in rats under propofol anesthesia than in those under urethane anesthesia. In a subset of rats with reflex voiding under propofol anesthesia, voiding efficiency was decreased compared with that of rats anesthetized with urethane. We conclude that propofol anesthesia suppresses micturition reflexes in rats more efficiently than did urethane. Propofol is a suitable anesthetic for longitudinal studies in rats, but its use for urodynamic evaluations is limited in these animals due to its marked suppression of both bladder contractions and EUS EMG activation.AnesthesiaAnesthetics: pharmacologyAnimalsElectromyographyLaboratory Animal ScienceMaleMuscle ContractionPropofol: pharmacologyRatsRatsSprague-DawleyReflex: drug effectsUrethane: pharmacologyUrinary BladderUrination: drug effectsUrodynamics: drug effectsapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/9454c25harticleJournal of the American Association for Laboratory Animal Science : JAALAS, vol 55, iss 189 - 94oai:escholarship.org:ark:/13030/qt6k05w5wt2018-04-06T19:58:49Zqt6k05w5wtAn Examination of Changes in Emotion Co-Regulation Among Mother and Child Dyads During the Strange Situation.Guo, YuqingLeu, Szu-YunBarnard, Kathryn EThompson, Elaine ASpieker, Susan J2015-05-14The present study applied State Space Grid analysis to describe how preschooler-mother dyads co-regulate emotion in the Strange Situation. Second-to-second mother and child affect during pre-separation play (baseline) and the final reunion (post perturbation) episodes of the Strange Situation were coded for 80 dyads. Change in emotion co-regulation across the two Strange Situation episodes was examined with linear mixed models for groups with secure and insecure classifications. The groups did not differ at baseline. Change in content-specific emotion co-regulation but not content-free emotion co-regulation was found to be significantly different within and between groups. Both secure and insecure dyads reduced the time spent in positive interaction but increased the time in negative interaction across two episodes; the change in secure dyads was less pronounced than in the insecure dyads. After the separation, secure dyads had more positive interactions and fewer negative interactions compared to insecure dyads. Results highlight how secure dyads adapted to the stressful change, whereas insecure dyads were more reactive and less resilient to the stress of the study's brief imposed separation.application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/6k05w5wtarticleInfant and child development, vol 24, iss 3256 - 273oai:escholarship.org:ark:/13030/qt5gd7s0gh2018-04-06T19:50:23Zqt5gd7s0ghPrevalence of restless legs syndrome and sleep quality in carriers of the fragile X premutation.Summers, S MCogswell, JGoodrich, J EMu, YNguyen, D VBrass, S DHagerman, R J2014-08-01This study examined the relationship between the fragile X premutation and restless legs syndrome (RLS). Demographic, medical history and survey responses related to sleep were collected from 213 participants (127 carriers and 86 age matched controls). Subjects were asked about the presence of the four formal diagnostic criteria for RLS. Individuals with the premutation were 1.9 times as likely to meet criteria for RLS (95% CI 1.1–3.2, p=0.025) as controls. Premutation carriers with RLS also experienced significantly worse symptoms than matched controls with adjusted mean scores of 15.1±8.8 vs 7.9±4.4, respectively on the International Restless Legs Scale (IRLS). As markers for domains of sleep disturbance, all subjects completed the Epworth Sleepiness Scale (ESS), the Insomnia Severity Index (ISA) and the Pittsburgh Sleep Quality Index (PSQI). Premutation carriers demonstrated significantly more pathology on these tests except for the ESS where there was a trend towards increased daytime sleepiness in carriers. RLS joins a host of other conditions that should be carefully screened for in those carrying the fragile X premutation and sleep should be a focus for clinicians providing care to them.Age FactorsCase-Control StudiesDemographyFemaleFragile X Mental Retardation Protein: geneticsHumansMaleMiddle AgedMutation: geneticsPrevalenceRestless Legs Syndrome: epidemiologygeneticsphysiopathologySeverity of Illness IndexSleepSleep Initiation and Maintenance Disorders: geneticsapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/5gd7s0gharticleClinical genetics, vol 86, iss 2181 - 184oai:escholarship.org:ark:/13030/qt9pg280gp2018-04-06T19:46:56Zqt9pg280gpConcurrent exercise on a gravity-independent device during simulated microgravity.Cotter, Joshua AYu, AlvinHaddad, FadiaKreitenberg, ArthurBaker, Michael JTesch, Per ABaldwin, Kenneth MCaiozzo, Vincent JAdams, Gregory R2015-05-01The objective of this study is to examine the effect of a high-intensity concurrent training program using a single gravity-independent device on maintaining skeletal muscle function and aerobic capacity during short-term unilateral lower limb suspension (ULLS).Nineteen subjects (10 males and 9 females; 21.0 ± 2.5 yr, 65.4 ± 12.2 kg) were separated into two groups: 1) 10-d ULLS only (n = 9) and 2) 10-d ULLS plus aerobic and resistance training (ULLS + EX, n = 10). Exercise was performed on a single gravity-independent Multi-Mode Exercise Device (M-MED) with alternating days of high-intensity interval aerobic training and maximal exertion resistance training.Aerobic capacity increased by 7% in ULLS + EX (P < 0.05). Knee extensor and ankle plantar flexor three-repetition maximum increased in the ULLS + EX group (P < 0.05), but this change was only different from ULLS in the plantar flexors (P < 0.05). Peak torque levels decreased with ULLS but were increased for the knee extensors and attenuated for the ankle plantar flexors with ULLS + EX (P < 0.05). A shift toward type IIx myosin heavy-chain mRNA occurred with ULLS and was reversed with ULLS + EX in the vastus lateralis (P < 0.05) but not the soleus. Myostatin and atrogin increased with ULLS in both the vastus lateralis and soleus, but this change was mitigated with ULLS + EX only in the vastus lateralis (P = 0.0551 for myostatin, P < 0.05 for atrogin). Citrate synthase was decreased in the soleus during ULLS but was increased with ULLS + EX (P < 0.05).These results indicate that an M-MED class countermeasure device appears to be effective at mitigating the deconditioning effects of microgravity simulated during a modified ULLS protocol.AgedAtrophyExercise: physiologyFemaleHumansMaleMiddle AgedMuscle Fatigue: physiologyMuscle Strength: physiologyMuscleSkeletal: growth & developmentpathologyphysiologyOxygen ConsumptionPhysical Education and Training: methodsRNAMessenger: metabolismResistance TrainingWeightlessness Simulation: instrumentationYoung Adultapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/9pg280gparticleMedicine and science in sports and exercise, vol 47, iss 5990 - 1000oai:escholarship.org:ark:/13030/qt7dm2f69c2018-04-06T19:43:20Zqt7dm2f69cDefining the optimal window for cranial transplantation of human induced pluripotent stem cell-derived cells to ameliorate radiation-induced cognitive impairment.Acharya, Munjal MMartirosian, VahanChristie, Lori-AnnRiparip, LaraStrnadel, JanParihar, Vipan KLimoli, Charles L2015-01-12Past preclinical studies have demonstrated the capability of using human stem cell transplantation in the irradiated brain to ameliorate radiation-induced cognitive dysfunction. Intrahippocampal transplantation of human embryonic stem cells and human neural stem cells (hNSCs) was found to functionally restore cognition in rats 1 and 4 months after cranial irradiation. To optimize the potential therapeutic benefits of human stem cell transplantation, we have further defined optimal transplantation windows for maximizing cognitive benefits after irradiation and used induced pluripotent stem cell-derived hNSCs (iPSC-hNSCs) that may eventually help minimize graft rejection in the host brain. For these studies, animals given an acute head-only dose of 10 Gy were grafted with iPSC-hNSCs at 2 days, 2 weeks, or 4 weeks following irradiation. Animals receiving stem cell grafts showed improved hippocampal spatial memory and contextual fear-conditioning performance compared with irradiated sham-surgery controls when analyzed 1 month after transplantation surgery. Importantly, superior performance was evident when stem cell grafting was delayed by 4 weeks following irradiation compared with animals grafted at earlier times. Analysis of the 4-week cohort showed that the surviving grafted cells migrated throughout the CA1 and CA3 subfields of the host hippocampus and differentiated into neuronal (∼39%) and astroglial (∼14%) subtypes. Furthermore, radiation-induced inflammation was significantly attenuated across multiple hippocampal subfields in animals receiving iPSC-hNSCs at 4 weeks after irradiation. These studies expand our prior findings to demonstrate that protracted stem cell grafting provides improved cognitive benefits following irradiation that are associated with reduced neuroinflammation.AnimalsCognition Disorders: etiologysurgeryCranial Irradiation: adverse effectsHeterograftsHippocampus: surgeryHumansImmunohistochemistryInduced Pluripotent Stem Cells: transplantationMicroscopyConfocalRadiation InjuriesExperimental: surgeryRatsRatsNudeStem Cell Transplantation: methodsapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/7dm2f69carticleStem cells translational medicine, vol 4, iss 174 - 83oai:escholarship.org:ark:/13030/qt83w7j0wj2018-04-06T19:40:41Zqt83w7j0wjFunctions of Antibodies.Forthal, Donald N2014-08-15application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/83w7j0wjarticleMicrobiology spectrum, vol 2, iss 41 - 17oai:escholarship.org:ark:/13030/qt4fj1n9fx2018-04-06T19:35:13Zqt4fj1n9fxSynaptophysin and synaptojanin-1 in Down syndrome are differentially affected by Alzheimer's disease.Martin, Sarah BDowling, Amy L SLianekhammy, JoannLott, Ira TDoran, EricMurphy, M PaulBeckett, Tina LSchmitt, Frederick AHead, Elizabeth2014-01-01Adults with Down syndrome (DS) develop Alzheimer's disease (AD) neuropathology by 40 years of age. Synaptophysin (SYN) consistently declines with age and is further reduced with sporadic AD. Thus, we hypothesized that SYN would be reduced in DS with AD. The gene for synaptojanin-1 (SYNJ1), involved in synaptic vesicle recycling, is on chromosome 21. We measured SYN and SYNJ1 in an autopsy series of 39 cases with DS and 28 without DS, along with 7 sporadic AD cases. SYN was significantly lower in DSAD compared with DS alone and similar to sporadic AD. Reduced SYN is associated with AD neuropathology and with Aβ levels in DS, as is seen in sporadic AD. SYNJ1 was significantly higher in DS and correlated with several measures of Aβ. SYNJ1 was higher in DSAD and significantly higher than SYNJ1 in sporadic AD. Although significantly higher in DS, SYNJ1 is further increased with AD neuropathology suggesting interesting differences in a synapse-associated protein that is overexpressed in trisomy 21.AdolescentAdultAge FactorsAgedAged80 and overAlzheimer Disease: complicationspathologyAmyloid beta-Peptides: metabolismAutopsyBrain: metabolismChildChildPreschoolDown Syndrome: complicationspathologyFemaleHumansInfantMaleMiddle AgedNerve Tissue Proteins: geneticsmetabolismPhosphoric Monoester Hydrolases: geneticsmetabolismSynaptophysin: geneticsmetabolismYoung Adultapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/4fj1n9fxarticleJournal of Alzheimer's disease : JAD, vol 42, iss 3767 - 775oai:escholarship.org:ark:/13030/qt47n3q1wd2018-04-05T00:02:07Zqt47n3q1wdTGF-β mediated DNA methylation in prostate cancer.Lee, ChungZhang, QiangZi, XaolinDash, AtreyaSoares, Marcelo BRahmatpanah, FarahnazJia, ZhenyuMcClelland, MichaelMercola, Dan2012-06-01Almost all tumors harbor a defective negative feedback loop of signaling by transforming growth factor-β (TGF-β). Epigenetic mechanisms of gene regulation, including DNA methylation, are fundamental to normal cellular function and also play a major role in carcinogenesis. Recent evidence demonstrated that TGF-β signaling mediates cancer development and progression. Many key events in TGF-β signaling in cancer included auto-induction of TGF-β1 and increased expression of DNA methyltransferases (DNMTs), suggesting that DNA methylation plays a significant role in cancer development and progression. In this review, we performed an extensive survey of the literature linking TGF-β signaling to DNA methylation in prostate cancer. It appeared that almost all DNA methylated genes detected in prostate cancer are directly or indirectly related to TGF-β signaling. This knowledge has provided a basis for our future directions of prostate cancer research and strategies for prevention and therapy for prostate cancer.application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/47n3q1wdarticleTranslational andrology and urology, vol 1, iss 278 - 88oai:escholarship.org:ark:/13030/qt6zx0b7jn2018-04-04T23:56:43Zqt6zx0b7jnSuction-modified needle biopsy technique for the human soleus muscle.Cotter, Joshua AYu, AlvinKreitenberg, ArthurHaddad, Fadia HBaker, Michael JFox, John CAdams, Gregory R2013-10-01The needle biopsy technique for the soleus muscle is of particular interest because of the muscle's unique fiber type distribution, contractile properties, and sensitivity to unloading. Unlike other commonly biopsied muscles, the soleus is not fully superficial and is in close proximity to neurovascular structures, resulting in a more challenging biopsy. Because of this, a standardized protocol for performing needle biopsies on the human soleus muscle that is safe, reliable, and repeatable is presented.Ultrasonography was used on an initial set of 12 subjects to determine the optimal biopsy zone, thereby guiding the location of the incision site. There were 45 subjects recruited who attended 2 separate biopsy sessions. Each biopsy session incorporated 3 passes of the biopsy needle proximal, posterior, and distal using suction from a portable vacuum source producing 3 separate muscle specimens.There were 84 soleus muscle biopsy procedures which were successfully conducted yielding 252 total samples without complication. Ultrasonography was used to confirm biopsy needle infiltration of the soleus muscle. Average sample weight obtained per pass was 61.5 +/- 15.7 mg. Histochemistry and molecular analyses demonstrated a considerably higher amount of slow type I MHC in comparison to the vastus lateralis, providing verification for the successful sampling of the soleus muscle.The procedure presented consists of a detailed protocol to accurately and consistently obtain muscle biopsy samples from the human soleus muscle. We have demonstrated that the human soleus biopsy is a safe, reliable, and repeatable procedure providing ample tissue for multiple types of analyses.AdultBiopsyNeedle: instrumentationmethodsFemaleHumansMaleMuscleSkeletal: pathologySuctionYoung Adultapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/6zx0b7jnarticleAviation, space, and environmental medicine, vol 84, iss 101066 - 1073oai:escholarship.org:ark:/13030/qt3nm4t3v42018-04-04T23:53:56Zqt3nm4t3v4Satellite cells say NO to radiation.Cho-Lim, Jennie JCaiozzo, Vincent JTseng, Bertrand PGiedzinski, ErichBaker, Mike JLimoli, Charles L2011-05-14Skeletal muscles are commonly exposed to radiation for diagnostic procedures and the treatment of cancers and heterotopic bone formation. Few studies have considered the impact of clinical doses of radiation on the ability of satellite cells (myogenic stem cells) to proliferate, differentiate and contribute to recovering/maintaining muscle mass. The primary objective of this study was to determine whether the proliferation of irradiated satellite cells could be rescued by manipulating NO levels via pharmacological approaches and mechanical stretch (which is known to increase NO levels). We used both SNP (NO donor) and PTIO (NO scavenger) to manipulate NO levels in satellite cells. We observed that SNP was highly effective in rescuing the proliferation of irradiated satellite cells, especially at doses less than 5 Gy. The potential importance of NO was further illustrated by the effects of PTIO, which completely inhibited the rescue effect of SNP. Mechanical cyclic stretch was found to produce significant increases in NO levels of irradiated satellite cells, and this was associated with a robust increase in satellite cell proliferation. The effects of both radiation and NO on two key myogenic regulatory factors (MyoD and myogenin) were also explored. Irradiation of satellite cells produced a significant increase in both MyoD and myogenin, effects that were mitigated by manipulating NO levels via SNP. Given the central role of myogenic regulatory factors in the proliferation and differentiation of satellite cells, the findings of the current study underscore the need to more fully understand the relationship between radiation, NO and the functionality of satellite cells.AnimalsBiomechanical PhenomenaCell CountCell Differentiation: drug effectsradiation effectsCell Proliferation: drug effectsradiation effectsCyclic N-Oxides: pharmacologyDose-Response RelationshipRadiationFree Radical Scavengers: pharmacologyGamma RaysImidazoles: pharmacologyMaleMyogenic Regulatory Factors: metabolismNitric Oxide: biosynthesismetabolismNitroprusside: pharmacologyRatsRatsSprague-DawleySatellite CellsSkeletal Muscle: cytologydrug effectsmetabolismradiation effectsapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/3nm4t3v4articleRadiation research, vol 175, iss 5561 - 568oai:escholarship.org:ark:/13030/qt612944kx2018-04-04T23:51:49Zqt612944kxFrequency of elevated hepatocellular carcinoma (HCC) biomarkers in patients with advanced hepatitis C.Sterling, Richard KWright, Elizabeth CMorgan, Timothy RSeeff, Leonard BHoefs, John CDi Bisceglie, Adrian MDienstag, Jules LLok, Anna S2012-01-20Prospective studies of serum hepatocellular carcinoma (HCC) biomarkers in patients with advanced hepatitis C are lacking. The aim of this study was to determine the frequencies and performance of elevated α-fetoprotein (AFP), AFP-L3, and des-γ-carboxy prothrombin (DCP) levels as HCC biomarkers in advanced hepatitis C.Patients in the HALT-C Trial were tested every 3 months for 42 months. Screening ultrasound was performed every 12 months. Levels of biomarkers were compared in patients in whom HCC did or did not develop.In all, 855 patients were evaluated; HCC developed in 46. Among patients without HCC, 73.2% had AFP consistently <20, 24.5% had at least one AFP between 20 and 199, and 2.3% had at least one AFP value ≥200 ng/ml; 73.7% had DCP consistently <90, 11.6% had at least one DCP between 90 and 149, and 14.7% had at least one DCP value ≥150 mAU/ml. AFP-L3 ≥10% was present at least once in 9.0% and in 17.1% of those with AFP ≥20 ng/ml. Among all patients with elevated biomarkers, a diagnosis of HCC was made in 0-31.6% (depending on the biomarker and cutoff) during the subsequent 24 months. AFP ≥200 ng/ml had the highest specificity (99%), but sensitivity was ≤20%. DCP ≥40 mAU/ml had the highest sensitivity (76%), but specificity was ≤58%. Independent predictors of elevated AFP were gender (female), race (Black), more advanced disease, and HCC. Elevated DCP was associated with more advanced disease and HCC.Mild-moderate elevations in total AFP and DCP but not in AFP-L3 occur frequently in patients with chronic hepatitis C and advanced fibrosis, are related to factors other than HCC, and are poor predictors of HCC.Biomarkers: bloodCarcinomaHepatocellular: bloodcomplicationsDisease ProgressionFemaleHepatitis C: complicationsHumansLiver Neoplasms: bloodcomplicationsMaleMiddle AgedPredictive Value of TestsProspective StudiesProtein Isoforms: bloodProtein Precursors: bloodProthrombinalpha-Fetoproteins: analysisapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/612944kxarticleThe American journal of gastroenterology, vol 107, iss 164 - 74oai:escholarship.org:ark:/13030/qt31s9s40f2018-04-04T23:47:10Zqt31s9s40fEnhancing the Construct and Content Validity of Rating Scales for Clinical Research: Using Qualitative Methods to Develop a Rating Scale to Assess Parental Perceptions of Their Role in Promoting Infant Exercise.Olshansky, EllenLakes, Kimberley DVaughan, JessicaGravem, DanaRich, Julia KDavid, MarissaNguyen, HeatherCooper, Dan2012-04-01With a focus on the early stages of developing new assessment tools, we present an example of how researchers can apply qualitative data to the development of conceptual domains and specific items representing those domains for quantitative instruments. Specifically, our previous research examining mothers' perceptions and experiences of engaging in assisted exercise with their infants provided the foundation for the development of the Perceptions of Pediatric Activity Scale (PPAS). We describe the process we used to develop the PPAS as an exemplar for the process of incorporating qualitative data in instrument development. In addition, we address instrument development for diverse populations, and we provide examples illustrating how we extracted concepts using a concept-indicator model to construct the items in the PPAS. We conclude by noting that we are currently in the process of pilot-testing the PPAS to evaluate its utility and reliability.application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/31s9s40farticleThe International journal of educational and psychological assessment, vol 10, iss 136 - 50oai:escholarship.org:ark:/13030/qt9mt452962018-04-04T23:43:26Zqt9mt45296A sample selection strategy to boost the statistical power of signature detection in cancer expression profile studies.Jia, ZhenyuWang, YipengHu, YuanjieMcLaren, ChristineYu, YingyanYe, KaiXia, Xiao-QinKoziol, James ALernhardt, WaldemarMcClelland, MichaelMercola, Dan2013-02-01In case-control profiling studies, increasing the sample size does not always improve statistical power because the variance may also be increased if samples are highly heterogeneous. For instance, tumor samples used for gene expression assay are often heterogeneous in terms of tissue composition or mechanism of progression, or both; however, such variation is rarely taken into account in expression profiles analysis. We use a prostate cancer prognosis study as an example to demonstrate that solely recruiting more patient samples may not increase power for biomarker detection at all. In response to the heterogeneity due to mixed tissue, we developed a sample selection strategy termed Stepwise Enrichment by which samples are systematically culled based on tumor content and analyzed with t-test to determine an optimal threshold for tissue percentage. The selected tissue-percentage threshold identified the most significant data by balancing the sample size and the sample homogeneity; therefore, the power is substantially increased for identifying the prognostic biomarkers in prostate tumor epithelium cells as well as in prostate stroma cells. This strategy can be generally applied to profiling studies where the level of sample heterogeneity can be measured or estimated.BiomarkersTumor: geneticsData InterpretationStatisticalGene Expression ProfilingHumansMaleProstatic Neoplasms: geneticspathologyapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/9mt45296articleAnti-cancer agents in medicinal chemistry, vol 13, iss 2203 - 211oai:escholarship.org:ark:/13030/qt0f72w5042018-04-04T23:40:34Zqt0f72w504Rate of progression of hepatic fibrosis in patients with chronic hepatitis C: results from the HALT-C Trial.Hoefs, John CShiffman, Mitchell LGoodman, Zachary DKleiner, David EDienstag, Jules LStoddard, Anne M2011-09-12The gradual accumulation of hepatic fibrosis in chronic liver disease results in clinical complications. The rate of hepatic fibrosis score progression (RFSP) in predicting clinical outcomes was assessed by extending the 4-year Hepatitis C Antiviral Long-term Treatment Against Cirrhosis (HALT-C) Trial to include preenrollment liver biopsies.The RFSP was calculated from the linear regression slope of Ishak fibrosis score vs time in 457 patients with liver biopsies (≥10-mm length) prior to the HALT-C Trial (575 biopsies) plus 1101 on-study biopsies (total 1676 biopsies). Individual slopes were calculated if duration from first to last biopsy was > 4 years.The RFSP as average fibrosis score vs average time in intervals (0-3 and >3 years prestudy, screening, month 24 and 48 on-study) in 455 patients in cohorts of baseline Ishak score ranged from 0.005 with Ishak score 2 to 0.124 with Ishak 6. The RFSP in individual patients (-0.35 to +0.97 Ishak units/year) had a mean of 0.12 ± 0.23 in 344 patients with prestudy and on-study biopsies (group A) and only 0.17 ± 0.22 in 169 with prestudy and screening biopsies (group B). Group A patients with RFSP slope ≥ 0.2 (95 patients, 27.6%) had higher 7-year cumulative rates of non-hepatocellular carcinoma outcomes (46% vs 8%, respectively) and with a hepatocellular carcinoma (10% vs 3%, respectively) than RFSP slope < 02 (249 patients, 72.4%) (P < .0001). RFSP and screening Ishak score correlated independently (P <.0001) with clinical outcomes in multivariate analysis.Rapid RFSP (>0.2), which occurred in 26.7% of HALT-C Trial patients, correlated strongly with clinical outcomes.AdultAntiviral Agents: therapeutic useBiopsyCarcinomaHepatocellular: epidemiologypathologyDisease ProgressionDrug TherapyCombinationFemaleFibrosisHepatitis CChronic: diagnosisdrug therapypathologyHumansInterferon-alpha: therapeutic useLiver: pathologyLiver Cirrhosis: pathologyprevention & controlLiver Neoplasms: epidemiologypathologyMaleMiddle AgedPolyethylene Glycols: therapeutic usePrevalencePrognosisRecombinant Proteins: therapeutic useRibavirin: therapeutic useTime FactorsTreatment Outcomeapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/0f72w504articleGastroenterology, vol 141, iss 3900 - 902oai:escholarship.org:ark:/13030/qt1sm5c4pf2018-04-04T23:35:57Zqt1sm5c4pfExpression of HER2 in Breast Cancer Promotes a Massive Reorganization of Gene Activity and Suggests a Role for Epigenetic Regulation.Rahmatpanah, FarahnazJia, ZhenyuChen, XinJones, Frank EMcClelland, MichaelMercola, Dan2012-01-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/1sm5c4pfarticleJournal of data mining in genomics & proteomics, vol 3oai:escholarship.org:ark:/13030/qt7m9817182018-04-04T23:30:01Zqt7m981718Age-Dependent Resistance to Excitotoxicity in Htt CAG140 Mice and the Effect of Strain Background.Strong, Melissa KSouthwell, Amber LYonan, Jennifer MHayden, Michael RMacgregor, Grant RThompson, Leslie MSteward, Oswald2012-01-01Mouse strain background can influence vulnerability to excitotoxic neuronal cell death and potentially modulate phenotypes in transgenic mouse models of human disease. Evidence supports a contribution of excitotoxicity to the selective death of medium spiny neurons in Huntington's disease (HD). Here, we assess whether strain differences in excitotoxic vulnerability influence striatal cell death in a knock-in mouse model of HD. Previous studies that evaluated resistance to excitotoxic lesions in several mouse models of HD had variable outcomes. In the present study, we directly compare one model on two different background strains to test the contribution of strain to excitotoxicity-mediated neurodegeneration. Mice of the FVB/N strain, which are highly vulnerable to excitotoxicity, become extremely resistant to quinolinic acid-induced striatal neurodegeneration with age, when carrying a huntingtin (Htt) allele expressing a HD transgene (CAG140). The resistance is much greater than the age-dependent resistance that has been previously reported in YAC128 mice. By 12 months of age, both heterozygous and homozygous FVB.CAG140 mice displayed virtually complete resistance to quinolinic acid-induced striatal neurodegeneration. A similar resistance develops in CAG140 mice on a C57BL/6N background although the effect size is smaller because C57BL/6N mice are already resistant due to genetic background. In a direct comparison with the YAC128 mice, FVB.CAG140 mice have greater resistance. FVB.CAG140 mice are also resistant to neurodegeneration following kainic acid-induced status epilepticus suggesting the existence of a common cellular mechanism that provides protection against multiple types of excitotoxic insult. These findings establish FVB.CAG140 mice as a useful model to investigate the cellular and molecular mechanisms that confer neuroprotection against excitotoxicity.Aging: pathologyAnimalsCorpus Striatum: drug effectspathologyDisease ModelsAnimalDose-Response RelationshipDrugHuntingtin ProteinHuntington Disease: chemically inducedpathologyMaleMiceMiceInbred C57BLMiceTransgenicNerve Tissue Proteins: geneticsNuclear Proteins: geneticsQuinolinic AcidSpecies Specificityapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/7m981718articleJournal of Huntington's disease, vol 1, iss 2221 - 241oai:escholarship.org:ark:/13030/qt96n2h86b2018-04-04T23:23:27Zqt96n2h86bStroke-related translational research.Caplan, Louis RArenillas, JuanCramer, Steven CJoutel, AnneLo, Eng HMeschia, JamesSavitz, SeanTournier-Lasserve, Elizabeth2011-09-09Stroke-related translational research is multifaceted. Herein, we highlight genome-wide association studies and genetic studies of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, COL4A1 mutations, and cerebral cavernous malformations; advances in molecular biology and biomarkers; newer brain imaging research; and recovery from stroke emphasizing cell-based and other rehabilitative modalities.AnimalsCerebral Arterial Diseases: geneticsmetabolismpathologyGenome-Wide Association Study: methodstrendsHumansMutation: geneticsStroke: geneticsmetabolismpathologyTranslational Medical Research: methodstrendsapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/96n2h86barticleArchives of neurology, vol 68, iss 91110 - 1123oai:escholarship.org:ark:/13030/qt6f6331jc2018-04-04T23:18:34Zqt6f6331jcCurrent trends in negative immuno-synergy between two sexually transmitted infectious viruses: HIV-1 and HSV-1/2.Chentoufi, Aziz AlamiDervillez, XavierRubbo, Pierre-AlainKuo, TiffanyZhang, XiuliNagot, NicolasTuaillon, EdouardVan De Perre, PhilippeNesburn, Anthony BBenmohamed, Lbachir2012-01-01In the current era of effective anti-retroviral therapy, immuno-compromised patients with HIV-1 infection do live long enough to suffer diseases caused by many opportunistic infections, such as herpes simplex virus type 1 and/or type 2 (HSV-1/2). An estimated two-third of the 40 million individuals that have contracted HIV-1 worldwide are co-infected with HSV-1/2 viruses, the causative agents of ocular oro-facial and genital herpes. The highest prevalence of HIV and HSV-1/2 infections are confined to the same regions of Sub-Saharan Africa. HSV-1/2 infections affect HIV-1 immunity, and vice versa. While important research gains have been made in understanding herpes and HIV immunity, the cellular and molecular mechanisms underlying the crosstalk between HSV-1/2 and HIV co-infection remain to be fully elucidated. Understanding the mechanisms behind the apparent HSV/HIV negative immuno-synergy maybe the key to successful HSV and HIV vaccines; both are currently unavailable. An effective herpes immunotherapeutic vaccine would in turn - indirectly - contribute in reducing HIV epidemic. The purpose of this review is: (i) to summarize the current trends in understanding the negative immuno-crosstalk between HIV and HSV-1/2 infections; and (ii) to discuss the possibility of developing a novel mucosal herpes immunotherapeutic strategy or even a combined or chimeric immunotherapeutic vaccine that simultaneously targets HIV and HSV-1/2 infections. These new trends in immunology of HSV-1/2 and HIV co-infections should become part of current efforts in preventing sexually transmitted infections. The alternative is needed to balance the ethical and financial concerns associated with the rising number of unsuccessful mono-valent clinical vaccine trials.application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/6f6331jcarticleCurrent trends in immunology, vol 1351 - 68oai:escholarship.org:ark:/13030/qt8xm0n7p92018-04-04T22:55:05Zqt8xm0n7p9A parenting group in general practice.Ruel, AAdams, G R1981-08-01We describe the organization and experience of a discussion-support group for young mothers. The group, of seven women, met on 21 occasions over a period of six months. We found that certain themes and anxieties to do with parenting recurred and that discussing topics within the group was of help to the participants.ChildEnglandFamily PracticeFemaleHumansMother-Child RelationsMothers: psychologyRoleSensitivity Training Groupsapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/8xm0n7p9articleThe Journal of the Royal College of General Practitioners, vol 31, iss 229496 - 499oai:escholarship.org:ark:/13030/qt5bk0s2vr2018-04-04T22:50:14Zqt5bk0s2vrSequence-specific binding of luzopeptin to DNA.Fox, K RDavies, HAdams, G RPortugal, JWaring, M J1988-03-25We have examined the binding of luzopeptin, an antitumor antibiotic, to five DNA fragments of varying base composition. The drug forms a tight, possibly covalent, complex with the DNA causing a reduction in mobility on nondenaturing polyacrylamide gels and some smearing of the bands consistent with intramolecular cross-linking of DNA duplexes. DNAase I and micrococcal nuclease footprinting experiments suggest that the drug binds best to regions containing alternating A and T residues, although no consensus di- or trinucleotide sequence emerges. Binding to other sites is not excluded and at moderate ligand concentrations the DNA is almost totally protected from enzyme attack. Ligand-induced enhancement of DNAase I cleavage is observed at both AT and GC-rich regions. The sequence selectivity and characteristics of luzopeptin binding are quite different from those of echinomycin, a bifunctional intercalator of related structure.AntibioticsAntineoplastic: metabolismBase SequenceBinding SitesDNA-Binding Proteins: metabolismDeoxyribonuclease I: pharmacologyEchinomycin: metabolismHydroxyquinolinesIntercalating AgentsMicrococcal Nuclease: pharmacologyQuinolines: metabolismapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/5bk0s2vrarticleNucleic acids research, vol 16, iss 62489 - 2507oai:escholarship.org:ark:/13030/qt86m3q82t2018-04-04T22:46:57Zqt86m3q82tMuscle buffer capacity estimated from pH changes during rest-to-work transitionsAdams, G. RFoley, J. MMeyer, R. A1990-09-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/86m3q82tarticleJournal of Applied Physiology, vol 69, iss 3968 - 972oai:escholarship.org:ark:/13030/qt9dq8m6k92018-04-04T22:45:08Zqt9dq8m6k9Skeletal muscle responses to lower limb suspension in humansHather, B. MAdams, G. RTesch, P. ADudley, G. A1992-04-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/9dq8m6k9articleJournal of Applied Physiology, vol 72, iss 41493 - 1498oai:escholarship.org:ark:/13030/qt3n51k68c2018-04-04T22:43:27Zqt3n51k68cMagnetic resonance imaging and electromyography as indexes of muscle functionAdams, G. RDuvoisin, M. RDudley, G. A1992-10-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/3n51k68carticleJournal of Applied Physiology, vol 73, iss 41578 - 1583oai:escholarship.org:ark:/13030/qt94m7p3m92018-04-04T22:42:09Zqt94m7p3m9Mapping of electrical muscle stimulation using MRIAdams, G. RHarris, R. TWoodard, D.Dudley, G. A1993-02-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/94m7p3m9articleJournal of Applied Physiology, vol 74, iss 2532 - 537oai:escholarship.org:ark:/13030/qt3ts625tx2018-04-04T22:37:35Zqt3ts625txSkeletal muscle myosin heavy chain composition and resistance trainingAdams, G. RHather, B. MBaldwin, K. MDudley, G. A1993-02-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/3ts625txarticleJournal of Applied Physiology, vol 74, iss 2911 - 915oai:escholarship.org:ark:/13030/qt5jb1c92t2018-04-04T22:32:49Zqt5jb1c92tMyosin heavy chain expression in rodent skeletal muscle: effects of exposure to zero gravityHaddad, F.Herrick, R. EAdams, G. RBaldwin, K. M1993-12-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/5jb1c92tarticleJournal of Applied Physiology, vol 75, iss 62471 - 2477oai:escholarship.org:ark:/13030/qt17v4w7m42018-04-04T22:29:43Zqt17v4w7m4Interaction of chronic creatine depletion and muscle unloading: effects on postural locomotor muscles.Adams, G RHaddad, FBaldwin, K M1994-09-01In some rodent skeletal muscles, hindlimb non-weight-bearing activity induces a shift in the expression of myosin heavy chains (MHCs) that favors the type II isoforms at the expense of type I. Chemically induced chronic creatine depletion results in isomyosin shifts favoring expression of type I MHCs. In this study, creatine depletion was induced separately and in combination with non-weight-bearing activity to determine if the response to lowering this metabolite would counter the MHC transitions expected from non-weight bearing. Creatine depletion was induced by feeding rats a diet supplemented with the creatine analogue beta-guanidinopropionic acid (beta-GPA). Female Sprague-Dawley rats weighing 247 +/- 8 g were randomly assigned to four groups: 1) normal diet control, 2) beta-GPA control (BC), 3) normal diet suspended (NS), and 4) beta-GPA suspended (BS). BC and BS animals were fed a diet containing the creatine analogue for 68 days. Hindlimb non-weight bearing in BS and NS animals was accomplished by tail suspension for the final 30 days of this period. beta-GPA feeding lowered the creatine content of muscles sampled by 65%. Creatine depletion resulted in a 16% increase in citrate synthase activity in the soleus (SOL) and a 24% increase in the plantaris (PLN). In two postural muscles, the SOL and vastus intermedius (VI), tail suspension resulted in large decreases in the type I MHC expression and increases in type IIx and IIb MHCs. In two locomotor muscles, the PLN and medial gastrocnemius, type I MHC declined and type IIb increased with suspension.(ABSTRACT TRUNCATED AT 250 WORDS)AnimalsBase SequenceCitrate (si)-Synthase: metabolismCreatine: deficiencyFemaleGuanidines: pharmacologyHindlimbMolecular Sequence DataMuscle FibersSkeletal: physiologyMuscle Proteins: biosynthesischemistryMuscleSkeletal: metabolismMyosins: biosynthesisgeneticsPhenotypePropionates: pharmacologyRNAMessenger: biosynthesischemistryRatsRatsSprague-DawleyWeight-Bearingapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/17v4w7m4articleJournal of applied physiology (Bethesda, Md. : 1985), vol 77, iss 31198 - 1205oai:escholarship.org:ark:/13030/qt6qs1n0cd2018-04-04T22:04:03Zqt6qs1n0cdAge dependence of myosin heavy chain transitions induced by creatine depletion in rat skeletal muscle.Adams, G RBaldwin, K M1995-01-01This study was designed to test the hypothesis that myosin heavy chain (MHC) plasticity resulting from creatine depletion is an age-dependent process. At weaning (age 28 days), rat pups were placed on either standard rat chow (normal diet juvenile group) or the same chow supplemented with 1% wt/wt of the creatine analogue beta-guanidinopropionic acid [creatine depletion juvenile (CDJ) group]. Two groups of adult rats (age approximately 8 wk) were placed on the same diet regimens [normal diet adult and creatine depletion adult (CDA) groups]. After 40 days (CDJ and normal diet juvenile groups) and 60 days (CDA and normal diet adult groups), animals were killed and several skeletal muscles were removed for analysis of creatine content or MHC distribution. In the CDJ group, creatine depletion (78%) was accompanied by significant shifts toward expression of slower MHC isoforms in two slow and three fast skeletal muscles. In contrast, creatine depletion in adult animals did not result in similar shifts toward slow MHC isoform expression in either muscle type. The results of this study indicate that there is a differential effect of creatine depletion on MHC transitions that appears to be age dependent. These results strongly suggest that investigators contemplating experimental designs involving the use of the creatine analogue beta-guanidinopropionic acid should consider the age of animals to be used.Aging: metabolismAnimalsBody Weight: physiologyCreatine: antagonists & inhibitorsdeficiencymetabolismFemaleGuanidines: pharmacologyMaleMuscleSkeletal: metabolismMyofibrils: metabolismphysiologyMyosin Subfragments: metabolismOrgan Size: physiologyPropionates: pharmacologyRatsRatsSprague-Dawleyapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/6qs1n0cdarticleJournal of applied physiology (Bethesda, Md. : 1985), vol 78, iss 1368 - 371oai:escholarship.org:ark:/13030/qt2m1311222018-04-04T22:01:49Zqt2m131122Running performance and cardiovascular capacity are not impaired in creatine-depleted rats.Adams, G RBodell, P WBaldwin, K M1995-09-01Several published reports have indicated that derangement of the phosphocreatine/creatine (Cr) energy-buffering system via Cr analogue feeding results in cardiomyopathy when cardiac performance is assessed in vitro. The present study was designed to examine indexes of cardiac performance in rats that have been chronically Cr depleted. Adult (180 +/- 4 g) rats were assigned to a normal diet (ND) (n = 8) or a Cr-depletion diet (CD) group (n = 10). After 61 +/- 1 days of ad libitum feeding, measurements of steady-state exercise O2 consumption were made. Hemodynamic indexes were then assessed during incremental running to peak sustained levels. Rats were then killed and the left ventricle was excised. In the CD group Cr was depleted 82% and V1 isomyosin decreased while V2 increased. O2 consumption during steady-state running was not different in CD rats. The respiratory exchange ratios of CD rats reflected a bias toward fat utilization during the latter stages of prolonged exercise. The exercise heart rates and peak systolic blood pressures of CD rats were slightly lower than those of ND rats. Both negative and positive rates of left ventricular pressure development were significantly reduced at all running speeds in the CD rats. CD rats were capable of exercise performance equal to that of ND animals. The hemodynamic and metabolic data suggest that the adaptations seen in the CD animals may be similar to those reported after endurance training. These results indicate that chronic Cr depletion does not impair either the circulatory or exercise capacity of rodents.AnimalsCreatine: deficiencyDietFemaleGuanidines: administration & dosageHeart: physiologyHemodynamics: physiologyMuscleSkeletal: metabolismMyosins: metabolismOxygen Consumption: physiologyPhysical ConditioningAnimal: physiologyPropionates: administration & dosageRatsRatsSprague-DawleyRegression Analysisapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/2m131122articleJournal of applied physiology (Bethesda, Md. : 1985), vol 79, iss 31002 - 1007oai:escholarship.org:ark:/13030/qt8s28h0gw2018-04-04T21:59:55Zqt8s28h0gwThe relationships among IGF-1, DNA content, and protein accumulation during skeletal muscle hypertrophyAdams, G. RHaddad, F.1996-12-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/8s28h0gwarticleJournal of Applied Physiology, vol 81, iss 62509 - 2516oai:escholarship.org:ark:/13030/qt0655k7rr2018-04-04T21:58:36Zqt0655k7rrLocalized infusion of IGF-I results in skeletal muscle hypertrophy in ratsAdams, Gregory RMcCue, Samuel A1998-05-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/0655k7rrarticleJournal of Applied Physiology, vol 84, iss 51716 - 1722oai:escholarship.org:ark:/13030/qt58v429qj2018-04-04T21:55:54Zqt58v429qjTime course of changes in markers of myogenesis in overloaded rat skeletal musclesAdams, Gregory RHaddad, FadiaBaldwin, Kenneth M1999-11-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/58v429qjarticleJournal of Applied Physiology, vol 87, iss 51705 - 1712oai:escholarship.org:ark:/13030/qt4hj9w55p2018-04-04T21:53:52Zqt4hj9w55pEffects of spaceflight and thyroid deficiency on hindlimb development. I. Muscle mass and IGF-I expression.Adams, G RMcCue, S ABodell, P WZeng, MBaldwin, K M2000-03-01Thyroid deficiency (TD) in neonatal rats causes reduced growth of skeletal muscle that is disproportionately greater than that for other tissues (G. R. Adams, S. A. McCue, M. Zeng, and K. M. Baldwin. Am. J. Physiol. Regulatory Integrative Comp. Physiol. 276: R954-R961, 1999). TD depresses plasma insulin-like growth factor I (IGF-I) levels, suggesting a mechanism for this effect. We hypothesized that TD and exposure to spaceflight (SF) would interact to reduce skeletal muscle growth via a reduction in IGF-I levels. Neonatal rats were flown in space for 16 days. There was a similar, nonadditive reduction in the growth of the body ( approximately 50%) and muscle weight (fast muscles, approximately 60%) with either TD or SF. In the soleus muscle, either SF or TD alone resulted in growth reductions that were augmented by SF-TD interactions. There were strong correlations between 1) muscle mass and muscle IGF-I levels and 2) circulating IGF-I and body weight. These results indicate that either hypothyroidism or exposure to SF will limit the somatic and muscle-specific growth of neonatal rats. The impact of these perturbations on skeletal muscle growth is relatively greater than the effect on somatic growth. The mechanisms by which either TD or SF impact growth appear to have a common pathway involving the control of plasma and muscle IGF-I concentrations.AnimalsAnimalsNewbornBody WeightFemaleHindlimb: growth & developmentHypothyroidism: metabolismpathologyInsulin-Like Growth Factor I: metabolismMaleMuscle DevelopmentMuscleSkeletal: growth & developmentmetabolismpathologyOrgan SizePregnancyRatsThyroid Hormones: deficiencyWeightlessness: adverse effectsapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/4hj9w55particleJournal of applied physiology (Bethesda, Md. : 1985), vol 88, iss 3894 - 903oai:escholarship.org:ark:/13030/qt5hk7s1mt2018-04-04T21:52:02Zqt5hk7s1mtEffects of spaceflight and thyroid deficiency on rat hindlimb development. II. Expression of MHC isoforms.Adams, G RHaddad, FMcCue, S ABodell, P WZeng, MQin, LQin, A XBaldwin, K M2000-03-01Both slow-twitch and fast-twitch muscles are undifferentiated after birth as to their contractile protein phenotype. Thus we examined the separate and combined effects of spaceflight (SF) and thyroid deficiency (TD) on myosin heavy chain (MHC) gene expression (protein and mRNA) in muscles of neonatal rats (7 and 14 days of age at launch) exposed to SF for 16 days. Spaceflight markedly reduced expression of the slow, type I MHC gene by approximately 55%, whereas it augmented expression of the fast IIx and IIb MHCs in antigravity skeletal muscles. In fast muscles, SF caused subtle increases in the fast IIb MHC relative to the other adult MHCs. In contrast, TD prevented the normal expression of the fast MHC phenotype, particularly the IIb MHC, whereas TD maintained expression of the embryonic/neonatal MHC isoforms; this response occurred independently of gravity. Collectively, these results suggest that normal expression of the type I MHC gene requires signals associated with weight-bearing activity, whereas normal expression of the IIb MHC requires an intact thyroid state acting independently of the weight-bearing activities typically encountered during neonatal development of laboratory rodents. Finally, MHC expression in developing muscles is chiefly regulated by pretranslational processes based on the tight relationship between the MHC protein and mRNA data.AnimalsAnimalsNewbornBase SequenceDNA Primers: geneticsFemaleGene ExpressionHindlimb: growth & developmentHypothyroidism: geneticsmetabolismpathologyMaleMuscle FibersFast-Twitch: metabolismMuscle FibersSlow-Twitch: metabolismMuscleSkeletal: metabolismMyocardium: metabolismMyosin Heavy Chains: geneticsmetabolismPregnancyProtein Isoforms: geneticsmetabolismRNAMessenger: geneticsmetabolismRatsThyroid Hormones: deficiencyWeightlessness: adverse effectsapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/5hk7s1mtarticleJournal of applied physiology (Bethesda, Md. : 1985), vol 88, iss 3904 - 916oai:escholarship.org:ark:/13030/qt1mh828h22018-04-04T21:50:11Zqt1mh828h2Insulin-like growth factor in muscle growth and its potential abuse by athletesAdams, G R2000-12-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/1mh828h2articleBritish Journal of Sports Medicine, vol 34, iss 6412 - 413oai:escholarship.org:ark:/13030/qt38k1j42h2018-04-04T21:46:20Zqt38k1j42hInsulin-like growth factor in muscle growth and its potential abuse by athletesAdams, G. R2001-07-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/38k1j42harticleWestern Journal of Medicine, vol 175, iss 17 - 9oai:escholarship.org:ark:/13030/qt4sx4w7x42018-04-04T21:44:20Zqt4sx4w7x4Effects of microgravity on myogenic factor expressions during postnatal development of rat skeletal muscleInobe, ManabuInobe, IkukoAdams, Gregory RBaldwin, Kenneth MTakeda, Shin'Ichi2002-05-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/4sx4w7x4articleJournal of Applied Physiology, vol 92, iss 51936 - 1942oai:escholarship.org:ark:/13030/qt0s5121wv2018-04-04T21:41:15Zqt0s5121wvExercise effects on muscle insulin signaling and action - Selected Contribution: Acute cellular and molecular responses to resistance exerciseHaddad, FadiaAdams, Gregory R2002-07-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/0s5121wvarticleJournal of Applied Physiology, vol 93, iss 1394 - 403oai:escholarship.org:ark:/13030/qt1fz902m02018-04-04T21:38:10Zqt1fz902m0Exercise Effects on Muscle Insulin Signaling and Action - Invited Review: Autocrine/paracrine IGF-I and skeletal muscle adaptationAdams, Gregory R2002-09-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/1fz902m0articleJournal of Applied Physiology, vol 93, iss 31159 - 1167oai:escholarship.org:ark:/13030/qt5nw9v85h2018-04-04T21:35:48Zqt5nw9v85hAutocrine and/or paracrine insulin-like growth factor-I activity in skeletal muscle.Adams, Gregory R2002-10-01Similar to bone, skeletal muscle responds and adapts to changes in loading state via mechanisms that appear to be intrinsic to the muscle. One of the mechanisms modulating skeletal muscle adaptation it thought to involve the autocrine and/or paracrine production of insulinlike growth factor-I. This brief review outlines components of the insulinlike growth factor-I system as it relates to skeletal muscle and provides the rationale for the theory that insulinlike growth factor-I is involved with muscle adaptation.1-Phosphatidylinositol 4-Kinase: physiologyAdaptationPhysiologicalAnimalsAutocrine Communication: physiologyHumansHypertrophyInsulin-Like Growth Factor I: physiologyMuscle FibersSkeletal: pathologyMuscleSkeletal: physiologyParacrine Communication: physiologySatellite CellsSkeletal Muscle: physiologySignal Transduction: physiologyapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/5nw9v85harticleClinical orthopaedics and related research, vol Suppl, iss 403S188 - S196oai:escholarship.org:ark:/13030/qt9sg699q32018-04-04T21:32:42Zqt9sg699q3Cellular and molecular responses to increased skeletal muscle loading after irradiationAdams, Gregory RCaiozzo, Vincent JHaddad, FadiaBaldwin, Kenneth M2002-10-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/9sg699q3articleAmerican Journal of Physiology-Cell Physiology, vol 283, iss 4C1182 - C1195oai:escholarship.org:ark:/13030/qt838774wf2018-04-04T21:30:38Zqt838774wfEffects of distraction on muscle length: mechanisms involved in sarcomerogenesis.Caiozzo, Vincent JUtkan, AliChou, RichardKhalafi, AfshinChandra, HeenaBaker, MichaelRourke, BryanAdams, GregBaldwin, KenGreen, Stuart2002-10-01Although a great deal of interest has been given to understanding the mechanisms involved in regulating the radial growth that occurs because of resistance training, much less has been given to studying the longitudinal growth of skeletal muscle that occurs because of passive stretch. The current authors provide a brief overview of key issues relevant to the longitudinal growth of skeletal muscle that occurs during distraction osteogenesis. Specifically, five key issues are addressed: (1) the pattern of sarcomerogenesis during distraction; (2) sarcomerogenesis and altered expression of sarcomeric and nonsarcomeric genes; (3) the satellite cell hypothesis; (4) mitogenic factors; and (5) new approaches for studying the longitudinal growth of skeletal muscle. A discussion is provided that revolves around the concept of a negative feedback loop. One of the most interesting issues to be resolved in muscle biology is the role of satellite cells in regulating the growth of skeletal muscle. Currently, it is not known whether satellite cell activation is a prerequisite for the longitudinal growth of skeletal muscle. Gene chip analyses provide a paradoxical view, showing that distraction osteogenesis results in the upregulation of a gene, GADD45, involved with growth arrest and deoxyribonucleic acid destruction.AnimalsHumansInsulin-Like Growth Factor I: physiologyModelsAnimalMuscle FibersSkeletal: physiologyMuscleSkeletal: metabolismpathologyphysiopathologyOligonucleotide Array Sequence AnalysisOsteogenesisDistractionProtein IsoformsSarcomeres: physiologySatellite CellsSkeletal Muscle: physiologyapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/838774wfarticleClinical orthopaedics and related research, vol Suppl, iss 403S133 - S145oai:escholarship.org:ark:/13030/qt8xb388nb2018-04-04T21:22:49Zqt8xb388nbGender differences in resistance-training-induced myofiber hypertrophy among older adults.Bamman, Marcas MHill, Vernishia JAdams, Gregory RHaddad, FadiaWetzstein, Carla JGower, Barbara AAhmed, AliHunter, Gary R2003-02-01We tested the hypothesis that older men (n = 9, 69 +/- 2 years) would experience greater resistance-training-induced myofiber hypertrophy than older women (n = 5, 66 +/- 1 years) following knee extensor training 3 days per week at 65-80% of one-repetition maximum for 26 weeks. Vastus lateralis biopsies were analyzed for myofiber areas, myosin heavy chain isoform distribution, and levels of mRNA for insulin-like growth factor 1 (IGF-1), IGFR1, and myogenin. Gender x Training interactions (p <.05) indicate greater myofiber hypertrophy for all three primary fiber types (I, IIa, IIx) and enhanced one-repetition maximum strength gain in men compared with women (p <.05). Covarying for serum IGF-1, dehydroepiandrosterone sulfate, or each muscle mRNA did not negate these interactions. In both genders, type IIx myofiber area distribution and myosin heavy chain type IIx distribution decreased with a concomitant increase in type IIa myofiber area distribution (p <.05). In summary, gender differences in load-induced myofiber hypertrophy among older adults cannot be explained by levels of circulating IGF-1 or dehydroepiandrosterone sulfate, or by expression of the myogenic transcripts examined.AgedAnalysis of VarianceBody Composition: physiologyBody Mass IndexCohort StudiesExerciseFemaleHumansImmunohistochemistryInsulin-Like Growth Factor I: analysismetabolismMaleMiddle AgedMuscle FibersSkeletal: metabolismphysiologyMuscleSkeletal: anatomy & histologyphysiologyMyogenin: analysismetabolismPhysical Education and TrainingReference ValuesSensitivity and SpecificitySex Factorsapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/8xb388nbarticleThe journals of gerontology. Series A, Biological sciences and medical sciences, vol 58, iss 2108 - 116oai:escholarship.org:ark:/13030/qt6wk9m1fg2018-04-04T21:20:22Zqt6wk9m1fgAcute molecular responses of skeletal muscle to resistance exercise in able-bodied and spinal cord-injured subjectsBickel, C. ScottSlade, Jill MHaddad, FadiaAdams, Gregory RDudley, Gary A2003-06-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/6wk9m1fgarticleJournal of Applied Physiology, vol 94, iss 62255 - 2262oai:escholarship.org:ark:/13030/qt1436j9ms2018-04-04T21:17:48Zqt1436j9msSkeletal muscle unweighting: spaceflight and ground-based modelsAdams, Gregory RCaiozzo, Vincent JBaldwin, Kenneth M2003-12-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/1436j9msarticleJournal of Applied Physiology, vol 95, iss 62185 - 2201oai:escholarship.org:ark:/13030/qt8rn3x0ch2018-04-04T21:14:21Zqt8rn3x0chInhibition of MAP/ERK kinase prevents IGF-I-induced hypertrophy in rat musclesHaddad, FadiaAdams, Gregory R2004-01-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/8rn3x0charticleJournal of Applied Physiology, vol 96, iss 1203 - 210oai:escholarship.org:ark:/13030/qt9bw8h7772018-04-04T21:12:21Zqt9bw8h777Skeletal muscle hypertrophy in response to isometric, lengthening, and shortening training bouts of equivalent durationAdams, Gregory RCheng, Daniel CHaddad, FadiaBaldwin, Kenneth M2004-05-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/9bw8h777articleJournal of Applied Physiology, vol 96, iss 51613 - 1618oai:escholarship.org:ark:/13030/qt7tb2r3162018-04-04T21:08:31Zqt7tb2r316Time course of molecular responses of human skeletal muscle to acute bouts of resistance exerciseBickel, C. ScottSlade, JillMahoney, EdHaddad, FadiaDudley, Gary AAdams, Gregory R2005-02-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/7tb2r316articleJournal of Applied Physiology, vol 98, iss 2482 - 488oai:escholarship.org:ark:/13030/qt719972x22018-04-04T21:07:03Zqt719972x2IL-6-induced skeletal muscle atrophyHaddad, F.Zaldivar, F.Cooper, D. MAdams, G. R2005-03-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/719972x2articleJournal of Applied Physiology, vol 98, iss 3911 - 917oai:escholarship.org:ark:/13030/qt1x8813vn2018-04-04T21:05:11Zqt1x8813vnIsometric resistance exercise fails to counteract skeletal muscle atrophy processes during the initial stages of unloadingHaddad, F.Adams, G. RBodell, P. WBaldwin, K. M2006-02-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/1x8813vnarticleJournal of Applied Physiology, vol 100, iss 2433 - 441oai:escholarship.org:ark:/13030/qt5k3502n72018-04-04T21:03:05Zqt5k3502n7Aging-sensitive cellular and molecular mechanisms associated with skeletal muscle hypertrophyHaddad, FadiaAdams, Gregory R2006-04-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/5k3502n7articleJournal of Applied Physiology, vol 100, iss 41188 - 1203oai:escholarship.org:ark:/13030/qt5k01w9n22018-04-04T21:00:48Zqt5k01w9n2Skeletal muscle dysfunction in chronic renal failure: effects of exerciseAdams, Gregory RVaziri, Nosratola D2006-04-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/5k01w9n2articleAmerican Journal of Physiology-Renal Physiology, vol 290, iss 4F753 - F761oai:escholarship.org:ark:/13030/qt0x75t58m2018-04-04T20:58:48Zqt0x75t58mSatellite cell proliferation and skeletal muscle hypertrophyAdams, Gregory R2006-12-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/0x75t58marticleApplied Physiology, Nutrition, and Metabolism, vol 31, iss 6782 - 790oai:escholarship.org:ark:/13030/qt7647m3h02018-04-04T20:55:48Zqt7647m3h0Similar acute molecular responses to equivalent volumes of isometric, lengthening, or shortening mode resistance exerciseGarma, T.Kobayashi, C.Haddad, F.Adams, G. RBodell, P. WBaldwin, K. M2007-01-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/7647m3h0articleJournal of Applied Physiology, vol 102, iss 1135 - 143oai:escholarship.org:ark:/13030/qt0mq6z7122018-04-04T20:48:33Zqt0mq6z712Combined isometric, concentric, and eccentric resistance exercise prevents unloading-induced muscle atrophy in ratsAdams, G. RHaddad, F.Bodell, P. WTran, P. DBaldwin, K. M2007-11-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/0mq6z712articleJournal of Applied Physiology, vol 103, iss 51644 - 1654oai:escholarship.org:ark:/13030/qt4x9118vr2018-04-04T20:41:11Zqt4x9118vrEffect of Exercise Training on Aortic Tone in Chronic Renal InsufficiencyShelkovnikov, S.Summers, S. MElahimehr, R.Adams, G.Purdy, R. EVaziri, N. D2008-05-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/4x9118vrarticleAmerican Journal of Hypertension, vol 21, iss 5564 - 569oai:escholarship.org:ark:/13030/qt0s45w8jd2018-04-04T20:37:32Zqt0s45w8jdEffect of Exercise on Cardiac Tissue Oxidative and Inflammatory Mediators in Chronic Kidney DiseaseBai, Y.Sigala, W.Adams, G.R.Vaziri, N.D.2009-01-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/0s45w8jdarticleAmerican Journal of Nephrology, vol 29, iss 3213 - 221oai:escholarship.org:ark:/13030/qt8c9820bg2018-04-04T20:33:08Zqt8c9820bgSkeletal muscle growth in young rats is inhibited by chronic exposure to IL-6 but preserved by concurrent voluntary endurance exerciseBodell, P. WKodesh, E.Haddad, F.Zaldivar, F. PCooper, D. MAdams, G. R2009-02-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/8c9820bgarticleJournal of Applied Physiology, vol 106, iss 2443 - 453oai:escholarship.org:ark:/13030/qt4v2607bw2018-04-04T20:29:30Zqt4v2607bwIncreased rat neonatal activity influences adult cytokine levels and relative muscle mass.Buchowicz, BryceYu, TiffanyNance, Dwight MZaldivar, Frank PCooper, Dan MAdams, Gregory R2010-07-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/4v2607bwarticlePediatric Research, vol 68, iss 5399 - 404oai:escholarship.org:ark:/13030/qt58f4006r2018-04-04T20:25:05Zqt58f4006rSuction-Modified Needle Biopsy Technique for the Human Soleus MuscleCotter, Joshua AYu, AlvinKreitenberg, ArthurHaddad, Fadia HBaker, Michael JFox, John CAdams, Gregory R2013-10-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/58f4006rarticleAviation, Space, and Environmental Medicine, vol 84, iss 101066 - 1073oai:escholarship.org:ark:/13030/qt06h9884p2018-04-04T20:21:59Zqt06h9884pConcurrent exercise on a gravity-independent device during simulated microgravity.Cotter, Joshua AYu, AlvinHaddad, FadiaKreitenberg, ArthurBaker, Michael JTesch, Per ABaldwin, Kenneth MCaiozzo, Vincent JAdams, Gregory R2015-05-01The objective of this study is to examine the effect of a high-intensity concurrent training program using a single gravity-independent device on maintaining skeletal muscle function and aerobic capacity during short-term unilateral lower limb suspension (ULLS).Nineteen subjects (10 males and 9 females; 21.0 ± 2.5 yr, 65.4 ± 12.2 kg) were separated into two groups: 1) 10-d ULLS only (n = 9) and 2) 10-d ULLS plus aerobic and resistance training (ULLS + EX, n = 10). Exercise was performed on a single gravity-independent Multi-Mode Exercise Device (M-MED) with alternating days of high-intensity interval aerobic training and maximal exertion resistance training.Aerobic capacity increased by 7% in ULLS + EX (P < 0.05). Knee extensor and ankle plantar flexor three-repetition maximum increased in the ULLS + EX group (P < 0.05), but this change was only different from ULLS in the plantar flexors (P < 0.05). Peak torque levels decreased with ULLS but were increased for the knee extensors and attenuated for the ankle plantar flexors with ULLS + EX (P < 0.05). A shift toward type IIx myosin heavy-chain mRNA occurred with ULLS and was reversed with ULLS + EX in the vastus lateralis (P < 0.05) but not the soleus. Myostatin and atrogin increased with ULLS in both the vastus lateralis and soleus, but this change was mitigated with ULLS + EX only in the vastus lateralis (P = 0.0551 for myostatin, P < 0.05 for atrogin). Citrate synthase was decreased in the soleus during ULLS but was increased with ULLS + EX (P < 0.05).These results indicate that an M-MED class countermeasure device appears to be effective at mitigating the deconditioning effects of microgravity simulated during a modified ULLS protocol.AgedAtrophyExercise: physiologyFemaleHumansMaleMiddle AgedMuscle Fatigue: physiologyMuscle Strength: physiologyMuscleSkeletal: growth & developmentpathologyphysiologyOxygen ConsumptionPhysical Education and Training: methodsRNAMessenger: metabolismResistance TrainingWeightlessness Simulation: instrumentationYoung Adultapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/06h9884particleMedicine and science in sports and exercise, vol 47, iss 5990 - 1000oai:escholarship.org:ark:/13030/qt6x84t2mz2018-04-04T19:05:46Zqt6x84t2mzCytokines and cytokine networks target neurons to modulate long-term potentiation.Prieto, G AlephCotman, Carl W2017-04-29Cytokines play crucial roles in the communication between brain cells including neurons and glia, as well as in the brain-periphery interactions. In the brain, cytokines modulate long-term potentiation (LTP), a cellular correlate of memory. Whether cytokines regulate LTP by direct effects on neurons or by indirect mechanisms mediated by non-neuronal cells is poorly understood. Elucidating neuron-specific effects of cytokines has been challenging because most brain cells express cytokine receptors. Moreover, cytokines commonly increase the expression of multiple cytokines in their target cells, thus increasing the complexity of brain cytokine networks even after single-cytokine challenges. Here, we review evidence on both direct and indirect-mediated modulation of LTP by cytokines. We also describe novel approaches based on neuron- and synaptosome-enriched systems to identify cytokines able to directly modulate LTP, by targeting neurons and synapses. These approaches can test multiple samples in parallel, thus allowing the study of multiple cytokines simultaneously. Hence, a cytokine networks perspective coupled with neuron-specific analysis may contribute to delineation of maps of the modulation of LTP by cytokines.AnimalsCellsCulturedCytokines: geneticsmetabolismpharmacologyHippocampus: physiologyHumansInflammationLearningLong-Term PotentiationMemoryMetabolic Networks and PathwaysMiceNeurons: drug effectsphysiologyReceptorsCytokine: geneticsimmunologySignal TransductionSynapses: physiologySynaptic TransmissionSynaptosomes: drug effectsphysiologyapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/6x84t2mzarticleCytokine & growth factor reviews, vol 3427 - 33oai:escholarship.org:ark:/13030/qt2p07z3sj2018-04-04T19:03:44Zqt2p07z3sjMultipoint Thermal Sensors Associated with Improved Oncologic Outcomes Following Cryoablation.Martin, Jeremy WPatel, Roshan MOkhunov, ZhamshidVyas, AashayVajgrt, DuaneClayman, Ralph V2017-04-17Cryoablation (CA) is a minimally invasive modality for the management of small renal cortical neoplasms (RCN). Effective ablation is dependent on achieving target temperatures during CA that result in tumor cell death. We investigated long-term oncologic outcomes following CA using multipoint thermal sensors (MTS), which allow precise temperature determination at four points along the needle.We performed a retrospective review of 20 patients with <4 cm RCN who underwent de novo CA from 2005 to 2009. In 11 procedures, MTS needles were deployed with the goal of obtaining -20°C at the tumor margin, while 9 were done without MTS. Patient demographics, tumor characteristics, and CA procedure data were retrieved and analyzed. Follow-up CT or MRI was used to assess recurrence status.With a mean follow-up of 45 months, none of the 11 patients experienced a recurrence in the MTS group, compared with 4 of 9 (44.4%) patients in the non-MTS group (p = 0.026). Of the biopsy-confirmed renal cancers, none of the 6 in the MTS group, compared with 3 of 6 (50%) in the non-MTS group, recurred (p = 0.182). Age, tumor size, surgical approach, tumor histopathology, grade, follow-up time, and skin-to-tumor distance were similar between the MTS and non-MTS groups. The MTS group was also associated with increased total length of freeze (p = 0.041), procedure time (p = 0.020), cryoprobe utilization (p = 0.049), and a greater ratio of cryoprobes used per cm diameter of tumor (p = 0.003).In this small renal mass pilot study, the use of MTS needles to monitor temperature and guide cryoneedle deployment was associated with improved oncologic outcomes.AgedAged80 and overCarcinomaRenal Cell: surgeryCryosurgery: instrumentationmethodsFemaleHumansKidney Neoplasms: surgeryMagnetic Resonance ImagingMaleMiddle AgedNeedlesNeoplasm RecurrenceLocal: diagnostic imagingepidemiologyPilot ProjectsRetrospective StudiesTomographyX-Ray Computedapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/2p07z3sjarticleJournal of endourology, vol 31, iss 4355 - 360oai:escholarship.org:ark:/13030/qt62b187nn2018-03-28T01:03:42Zqt62b187nnCell context-dependent dual effects of EFEMP1 stabilizes subpopulation equilibrium in responding to changes of in vivo growth environmentHu, YuanjieKe, ChaoRu, NingChen, YumayYu, LipingSiegel, Eric RLinskey, Mark EWang, PingZhou, Yi-Hong2015-08-20Conflicting functions of EFEMP1 in cancer have been reported. Using two syngeneic glioma cell lines (U251 and U251-NS) carrying two different principal cell subpopulations that express high or low EGFR, and that are able to interconvert via mis-segregation of chromosome 7 (Chr7), we studied EFEMP1's cell-context-dependent functions in regulating subpopulation equilibrium, here defined by the percentage of cells carrying different copies of Chr7. We found that EFEMP1 attenuated levels of EGFR and cellular respiration in high-EGFR-expressing cells, but increased levels of NOTCH1, MMP2, cell invasiveness, and both oxidative phosphorylation and glycolytic respiration in low-EGFR-expressing cells. Consistently, EFEMP1 suppressed intracranial xenograft formation in U251 and promoted its formation in U251-NS. Interestingly, subpopulation equilibria in xenografts of U251-NS without EFEMP1 overexpression were responsive to inoculum size (1, 10 and 100 thousand cells), which may change the tumor-onset environment. It was not observed in xenografts of U251-NS with EFEMP1 overexpression. The anti-EGFR function of EFEMP1 suppressed acceleration of growth of U251-NS, but not the subpopulation equilibrium, when serially passed under a different (serum-containing adherent) culture condition. Overall, the data suggest that the orthotopic environment of the brain tumor supports EFEMP1 in carrying out both its anti-EGFR and pro-invasive/cancer stem cell-transforming functions in the two glioma cell subpopulations during formation of a single tumor, where EFEMP1 stabilizes the subpopulation equilibrium in response to alterations of the growth environment. This finding implies that EFEMP1 may restrain cancer plasticity in coping with ever-changing tumor microenvironments and/or therapeutic-intervention stresses.EFEMP1cell invasivenessgliomatumor cell subpopulationstumor subpopulation equilibriumapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/62b187nnarticleOncotarget, vol 6, iss 3130762 - 30772oai:escholarship.org:ark:/13030/qt5509r4gz2018-03-28T00:55:41Zqt5509r4gzClinical Word Sense Disambiguation with Interactive Search and ClassificationWang, YueZheng, KaiXu, HuaMei, Qiaozhu2017-02-10Resolving word ambiguity in clinical text is critical for many natural language processing applications. Effective word sense disambiguation (WSD) systems rely on training a machine learning based classifier with abundant clinical text that is accurately annotated, the creation of which can be costly and time-consuming. We describe a double-loop interactive machine learning process, named ReQ-ReC (ReQuery-ReClassify), and demonstrate its effectiveness on multiple evaluation corpora. Using ReQ-ReC, a human expert first uses her domain knowledge to include sense-specific contextual words into the ReQuery loops and searches for instances relevant to the senses. Then, in the ReClassify loops, the expert only annotates the most ambiguous instances found by the current WSD model. Even with machine-generated queries only, the framework is comparable with or faster than current active learning methods in building WSD models. The process can be further accelerated when human experts use their domain knowledge to guide the search process.application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/5509r4gzarticleoai:escholarship.org:ark:/13030/qt79k0b5fj2018-03-28T00:54:06Zqt79k0b5fjRefractive outcomes of intraoperative wavefront aberrometry versus optical biometry alone for intraocular lens power calculation.Zhang, ZinaThomas, Logan WilliamLeu, Szu-YenCarter, StevenGarg, Sumit2017-09-01To compare the outcomes of intraoperative wavefront aberrometry versus optical biometry alone for intraocular lens (IOL) power calculation in eyes undergoing cataract surgery with monofocal IOL implantation.Preoperative data were obtained with the IOLMaster. Intraoperative aphakic measurements and IOL power calculations were obtained in some patients with the optiwave refractive analysis (ORA) system. Analysis was performed to determine the accuracy of monofocal IOL power prediction and postoperative manifest refraction at 1 month of the ORA versus IOLMaster.Two hundred and ninety-five eyes reviewed, 61 had only preoperative IOLMaster measurements and 234 had both IOLMaster and ORA measurements. Of these 234 eyes, 6 were excluded, 107 had the same recommended IOL power by ORA and IOLMaster. Sixty-four percent of these eyes were within ±0.5D. 95 eyes had IOL power implantation based on ORA instead of IOLMaster. Seventy percent of these eyes were within ±0.5D of target refraction. 26 eyes had IOL power chosen based on IOLMaster predictions instead of ORA. Sixty-five percent were within ±0.5D. In the group with IOLMaster without ORA measurements, 80% of eyes were within ±0.5D of target refraction. The absolute error was statistically smaller in those eyes where the ORA and IOLMaster recommended the same IOL power based on preoperative target refraction compared to instances in which IOL selection was based on ORA or IOLMaster alone. Neither prediction errors were statistically different between the ORA and IOLMaster alone.Intraoperative wavefront aberrometry with the ORA system provides postoperative refractive results comparable to conventional biometry with the IOLMaster for monofocal IOL selection.Aberrometry: methodsAdultAgedAged80 and overBiometry: methodsCataract ExtractionFemaleHumansIntraoperative PeriodLensesIntraocularMaleMiddle AgedRefractionOcularVisual AcuityYoung Adultapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/79k0b5fjarticleIndian journal of ophthalmology, vol 65, iss 9813 - 8817oai:escholarship.org:ark:/13030/qt0r60n6692018-03-22T21:52:39Zqt0r60n669Predictive Accuracy of Serial Transvaginal Cervical Lengths and Quantitative Vaginal Fetal Fibronectin Levels for Spontaneous Preterm Birth Among Nulliparous Women.Esplin, M SeanElovitz, Michal AIams, Jay DParker, Corette BWapner, Ronald JGrobman, William ASimhan, Hyagriv NWing, Deborah AHaas, David MSilver, Robert MHoffman, Matthew KPeaceman, Alan MCaritis, Steve NParry, SamuelWadhwa, PathikForoud, TatianaMercer, Brian MHunter, Shannon MSaade, George RReddy, Uma M2017-03-14Spontaneous preterm birth is a leading cause of infant mortality. Prediction, largely based on prior pregnancy outcomes, is not possible in women pregnant for the first time.To assess the accuracy of universal screening to predict spontaneous preterm birth in nulliparous women using serial measurements of vaginal fetal fibronectin levels and cervical length.A prospective observational cohort study of nulliparous women with singleton pregnancies, from 8 clinical sites across the United States between October 2010 and May 2014. Women and clinicians were blinded to results unless cervical shortening less than 15 mm was identified.Transvaginal cervical length and quantitative vaginal fetal fibronectin levels were reviewed at 2 study visits 4 or more weeks apart.Spontaneous preterm birth at less than 37 weeks was the primary outcome. Cervical length and quantitative fetal fibronectin were considered independently and together at each visit. Measurement distributions were compared for spontaneous preterm birth vs all other births. Spontaneous preterm birth before 32 weeks was a secondary outcome.The study included 9410 women (median age, 27.0 [interquartile range, 9.0] years; 60.7% non-Hispanic white, 13.8% non-Hispanic black, 16.5% Hispanic, 4.0% Asian, and 5.1% other), of whom 474 (5.0%) had spontaneous preterm births, 335 (3.6%) had medically indicated preterm births, and 8601 (91.4%) had term births. Among women with spontaneous preterm birth, cervical length of 25 mm or less occurred in 35 of 439 (8.0%) at 16 to 22 weeks' gestation and in 94 of 403 (23.3%) at 22 to 30 weeks' gestation. Fetal fibronectin levels of 50 ng/mL or greater at 16 to 22 weeks identified 30 of 410 women (7.3%) with spontaneous preterm birth and 31 of 384 (8.1%) at 22 to 30 weeks. The area under the receiver operating characteristic curve for screening between 22 and 30 weeks for fetal fibronectin level alone was 0.59 (95% CI, 0.56-0.62), for transvaginal cervical length alone was 0.67 (95% CI, 0.64-0.70), and for the combination as continuous variables was 0.67 (95% CI, 0.64-0.70).Among nulliparous women with singleton pregnancies, quantitative vaginal fetal fibronectin and serial transvaginal ultrasound cervical length had low predictive accuracy for spontaneous preterm birth. These findings do not support routine use of these tests in such women.AdolescentAdultArea Under CurveBiomarkers: analysisCervical Length Measurement: methodsCervix Uteri: anatomy & histologyFemaleFetusFibronectins: analysisGestational AgeHumansParityPredictive Value of TestsPregnancyPremature Birth: diagnosisethnologyProspective StudiesROC CurveVagina: chemistryYoung Adultapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/0r60n669articleJAMA, vol 317, iss 101047 - 1056oai:escholarship.org:ark:/13030/qt1299n2kb2018-03-22T21:50:33Zqt1299n2kbA Randomized, Double-Blind, Placebo-Controlled, Phase II Study of Oral ELND005 (scyllo-Inositol) in Young Adults with Down Syndrome without Dementia.Rafii, Michael SSkotko, Brian GMcDonough, Mary EllenPulsifer, MargaretEvans, CaseyDoran, EricMuranevici, GabrielaKesslak, PatrickAbushakra, SusanLott, Ira T2017-01-01ELND005 (scyllo-Inositol; cyclohexane-1,2,3,4,5,6-hexol) has been evaluated as a potential disease-modifying treatment for Alzheimer's disease (AD). Individuals with Down syndrome (DS) have an increased risk for developing AD dementia.To evaluate the safety and tolerability of ELND005 and to determine its pharmacokinetics (PK) and relationship between PK parameters, safety outcome measures, and exploratory efficacy outcome measures in young adults with DS without dementia.This was a prospective, randomized, double-blind, placebo-controlled, parallel-group, three-arm, multicenter Phase II study of the safety and pharmacokinetics of ELND005 administered orally for 4 weeks (ClinicalTrials.gov NCT01791725). Participants who met study eligibility criteria were randomly assigned in a 2 : 1:1 ratio to receive ELND005 at either 250 mg twice daily (BID) or 250 mg once daily (QD) or matching placebo for 4 weeks.There were no apparent treatment group-related trends on cognitive or behavioral measures and there were no SAEs and no deaths in the study. Overall, mean changes from baseline in clinical laboratory parameters, vital sign measurements, electrocardiogram results, and other physical findings were unremarkable. ELND005 accumulation averaged approximately 2-fold with QD dosing, and 3- to 4-fold with BID dosing.Overall, treatment of adults with DS with ELND005 at both doses was well tolerated, achieved measurable blood levels and demonstrated no safety findings. Further studies will be needed to test efficacy.AdministrationOralAdolescentAdultCognition Disorders: etiologyDouble-Blind MethodDown Syndrome: complicationsdiagnostic imagingdrug therapyElectrocardiographyFemaleHumansInositol: administration & dosagepharmacokineticsMagnetic Resonance ImagingMaleMental Disorders: etiologyProspective StudiesPsychiatric Status Rating ScalesTreatment OutcomeYoung Adultapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/1299n2kbarticleJournal of Alzheimer's disease : JAD, vol 58, iss 2401 - 411oai:escholarship.org:ark:/13030/qt0ms4c5mx2018-03-22T21:48:20Zqt0ms4c5mxIntermittent Ca2+signals mediated by Orai1 regulate basal T cell motility.Dong, Tobias XOthy, ShivashankarGreenberg, Milton LJairaman, AmitAkunwafo, ChijiokeLeverrier, SabrinaYu, YingParker, IanDynes, Joseph LCahalan, Michael D2017-12-14Ca2+influx through Orai1 channels is crucial for several T cell functions, but a role in regulating basal cellular motility has not been described. Here, we show that inhibition of Orai1 channel activity increases average cell velocities by reducing the frequency of pauses in human T cells migrating through confined spaces, even in the absence of extrinsic cell contacts or antigen recognition. Utilizing a novel ratiometric genetically encoded cytosolic Ca2+indicator, Salsa6f, which permits real-time monitoring of cytosolic Ca2+along with cell motility, we show that spontaneous pauses during T cell motility in vitro and in vivo coincide with episodes of cytosolic Ca2+signaling. Furthermore, lymph node T cells exhibited two types of spontaneous Ca2+transients: short-duration 'sparkles' and longer duration global signals. Our results demonstrate that spontaneous and self-peptide MHC-dependent activation of Orai1 ensures random walk behavior in T cells to optimize immune surveillance.application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/0ms4c5mxarticleeLife, vol 6oai:escholarship.org:ark:/13030/qt74p8805k2018-03-22T21:46:12Zqt74p8805kDevelopmental Emergence of Phenotypes in the Auditory Brainstem Nuclei ofFmr1Knockout Mice.Rotschafer, Sarah ECramer, Karina S2017-12-27Fragile X syndrome (FXS), the most common monogenic cause of autism, is often associated with hypersensitivity to sound. Several studies have shown abnormalities in the auditory brainstem in FXS; however, the emergence of these auditory phenotypes during development has not been described. Here, we investigated the development of phenotypes in FXS model [Fmr1knockout (KO)] mice in the ventral cochlear nucleus (VCN), medial nucleus of the trapezoid body (MNTB), and lateral superior olive (LSO). We studied features of the brainstem known to be altered in FXS orFmr1KO mice, including cell size and expression of markers for excitatory (VGLUT) and inhibitory (VGAT) synapses. We found that cell size was reduced in the nuclei with different time courses. VCN cell size is normal until after hearing onset, while MNTB and LSO show decreases earlier. VGAT expression was elevated relative to VGLUT in theFmr1KO mouse MNTB by P6, before hearing onset. Because glial cells influence development and are altered in FXS, we investigated their emergence in the developingFmr1KO brainstem. The number of microglia developed normally in all three nuclei inFmr1KO mice, but we found elevated numbers of astrocytes inFmr1KO in VCN and LSO at P14. The results indicate that some phenotypes are evident before spontaneous or auditory activity, while others emerge later, and suggest that Fmr1 acts at multiple sites and time points in auditory system development.application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/74p8805karticleeNeuro, vol 4, iss 6oai:escholarship.org:ark:/13030/qt5513221p2018-03-22T21:44:14Zqt5513221pPhase IIa trial of fingolimod for amyotrophic lateral sclerosis demonstrates acceptable acute safety and tolerability.Berry, James DPaganoni, SabrinaAtassi, NazemMacklin, Eric AGoyal, NamitaRivner, MichaelSimpson, ErickaAppel, StanleyGrasso, Daniela LMejia, Nicte IMateen, FarrahGill, AlanVieira, FernandoTassinari, ValeriePerrin, Steven2017-12-29Immune activation has been implicated in progression of amytrophic lateral sclerosis (ALS). Oral fingolimod reduces circulating lymphocytes. The objective of this phase IIa, randomized, controlled trial was to test the short-term safety, tolerability, and target engagement of fingolimod in ALS.Randomization was 2:1 (fingolimod:placebo). Treatment duration was 4 weeks. Primary outcomes were safety and tolerability. Secondary outcomes included circulating lymphocytes and whole-blood gene expression.Thirty participants were randomized; 28 were administered a drug (fingolimod 18, placebo 10). No serious adverse events occurred. Adverse events were similar by treatment arm, as was study discontinuation (2 fingolimod vs. 0 placebo, with no statistical difference). Forced expiratory volume in 1 second (FEV1) and FEV1/slow vital capacity changes were similar in the fingolimod and placebo arms. Circulating lymphocytes decreased significantly in the fingolimod arm (P < 0.001). Nine immune-related genes were significantly downregulated in the fingolimod arm, including forkhead box P3 (P < 0.001) and CD40 ligand (P = 0.003).Fingolimod is safe and well-tolerated and can reduce circulating lymphocytes in ALS patients. Muscle Nerve 56: 1077-1084, 2017.AdultAgedAmyotrophic Lateral Sclerosis: diagnosisdrug therapyBradycardia: chemically inducedFatigue: chemically inducedFemaleFingolimod Hydrochloride: adverse effectstherapeutic useHumansImmunosuppressive Agents: adverse effectstherapeutic useMaleMiddle AgedSingle-Blind Methodapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/5513221particleMuscle & nerve, vol 56, iss 61077 - 1084oai:escholarship.org:ark:/13030/qt9211r9d62018-03-22T21:43:02Zqt9211r9d6Usages of Computers and Smartphones to Develop Dementia Care Education Program for Asian American Family Caregivers.Lee, Jung-AhNguyen, HannahPark, JoanTran, LinhNguyen, TrangHuynh, Yen2017-10-31Families of ethnic minority persons with dementia often seek help at later stages of the disease. Little is known about the effectiveness of various methods in supporting ethnic minority dementia patients' caregivers. The objective of the study was to identify smartphone and computer usage among family caregivers of dementia patients (i.e., Korean and Vietnamese Americans) to develop dementia-care education programs for them.Participants were asked various questions related to their computer or smartphone usage in conjunction with needs-assessment interviews. Flyers were distributed at two ethnic minority community centers in Southern California. Snowball recruitment was also utilized to reach out to the families of dementia patients dwelling in the community.Thirty-five family caregivers, including 20 Vietnamese and 15 Korean individuals, participated in this survey. Thirty participants (30 of 35, 85.7%) were computer users. Among those, 76.7% (23 of 30) reported daily usage and 53% (16 of 30) claimed to use social media. A majority of the participants (31 of 35, 88.6%) reported that they owned smartphones. More than half of smartphone users (18 of 29, 62%) claimed to use social media applications. Many participants claimed that they could not attend in-class education due to caregiving and/or transportation issues.Most family caregivers of dementia patients use smartphones more often than computers, and more than half of those caregivers communicate with others through social media apps. A smartphone-app-based caregiver intervention may serve as a more effective approach compared to the conventional in-class method. Multiple modalities for the development of caregiver interventions should be considered.application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/9211r9d6articleHealthcare informatics research, vol 23, iss 4338 - 342oai:escholarship.org:ark:/13030/qt2xf600dm2018-03-22T21:41:52Zqt2xf600dmAssociation between supraclavicular brown adipose tissue composition at birth and adiposity gain from birth to 6 months of age.Entringer, SonjaRasmussen, JerodCooper, Dan MIkenoue, SatoruWaffarn, FeizalWadhwa, Pathik DBuss, Claudia2017-12-30BackgroundBrown adipose tissue (BAT) is associated with higher energy expenditure and lower adiposity in adults. However, the relationship between BAT composition and adiposity in early life is unknown. The objective of this study was to test the hypothesis that brown fat composition at birth is prospectively associated with adiposity gain during the first 6 months of postnatal life.MethodsN=35 healthy infants were followed up prospectively from intrauterine life and birth through 6 months of age. Dixon magnetic resonance imaging (MRI) scans were conducted during the neonatal period to characterize supraclavicular BAT composition. Dual-energy X-ray absorptiometry to assess total body composition was performed within the first and sixth months of life.ResultsAfter adjusting for potential confounding factors, a more brown-like composition (smaller fat fraction) of the supraclavicular BAT depot was associated with a smaller increase in percent body fat over the first 6 months of postnatal life.ConclusionsA more brown-like BAT composition at birth appears to be protective against excess adiposity gain in early life. Newborn BAT tissue may constitute a target for prevention strategies against the subsequent development of obesity.application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/2xf600dmarticlePediatric research, vol 82, iss 61017 - 1021oai:escholarship.org:ark:/13030/qt8fp0g5962018-03-22T21:39:19Zqt8fp0g596Systemic Neutrophil Depletion Modulates the Migration and Fate of Transplanted Human Neural Stem Cells to Rescue Functional Repair.Nguyen, Hal XHooshmand, Mitra JSaiwai, HirokazuMaddox, JakeSalehi, ArjangLakatos, AnitaNishi, Rebecca ASalazar, DesireeUchida, NobukoAnderson, Aileen J2017-09-20The interaction of transplanted stem cells with local cellular and molecular cues in the host CNS microenvironment may affect the potential for repair by therapeutic cell populations. In this regard, spinal cord injury (SCI), Alzheimer's disease, and other neurological injuries and diseases all exhibit dramatic and dynamic changes to the host microenvironment over time. Previously, we reported that delayed transplantation of human CNS-derived neural stem cells (hCNS-SCns) at 9 or 30 d post-SCI (dpi) resulted in extensive donor cell migration, predominantly neuronal and oligodendrocytic donor cell differentiation, and functional locomotor improvements. Here, we report that acute transplantation of hCNS-SCns at 0 dpi resulted in localized astroglial differentiation of donor cells near the lesion epicenter and failure to produce functional improvement in an all-female immunodeficient mouse model. Critically, specific immunodepletion of neutrophils (polymorphonuclear leukocytes) blocked hCNS-SCns astroglial differentiation near the lesion epicenter and rescued the capacity of these cells to restore function. These data represent novel evidence that a host immune cell population can block the potential for functional repair derived from a therapeutic donor cell population, and support targeting the inflammatory microenvironment in combination with cell transplantation after SCI.SIGNIFICANCE STATEMENTThe interaction of transplanted cells with local cellular and molecular cues in the host microenvironment is a key variable that may shape the translation of neurotransplantation research to the clinical spinal cord injury (SCI) human population, and few studies have investigated these events. We show that the specific immunodepletion of polymorphonuclear leukocyte neutrophils using anti-Ly6G inhibits donor cell astrogliosis and rescues the capacity of a donor cell population to promote locomotor improvement after SCI. Critically, our data demonstrate novel evidence that a specific host immune cell population can block the potential for functional repair derived from a therapeutic donor cell population.AnimalsCell CommunicationCell Differentiation: immunologyCell MovementFemaleMiceMiceSCIDNerve Regeneration: immunologyNeural Stem Cells: immunologytransplantationNeurogenesis: immunologyNeutrophils: immunologypathologyRecovery of FunctionSpinal Cord Injuries: pathologytherapyStem Cell Nicheapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/8fp0g596articleThe Journal of neuroscience : the official journal of the Society for Neuroscience, vol 37, iss 389269 - 9287oai:escholarship.org:ark:/13030/qt9183g35f2018-03-22T21:37:40Zqt9183g35fTime-Restricted Feeding Shifts the Skin Circadian Clock and Alters UVB-Induced DNA Damage.Wang, Hongvan Spyk, ElyseLiu, QiangGeyfman, MikhailSalmans, Michael LKumar, VivekIhler, AlexanderLi, NingTakahashi, Joseph SAndersen, Bogi2017-08-01The epidermis is a highly regenerative barrier protecting organisms from environmental insults, including UV radiation, the main cause of skin cancer and skin aging. Here, we show that time-restricted feeding (RF) shifts the phase and alters the amplitude of the skin circadian clock and affects the expression of approximately 10% of the skin transcriptome. Furthermore, a large number of skin-expressed genes are acutely regulated by food intake. Although the circadian clock is required for daily rhythms in DNA synthesis in epidermal progenitor cells, RF-induced shifts in clock phase do not alter the phase of DNA synthesis. However, RF alters both diurnal sensitivity to UVB-induced DNA damage and expression of the key DNA repair gene, Xpa. Together, our findings indicate regulation of skin function by time of feeding and emphasize a link between circadian rhythm, food intake, and skin health.application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/9183g35farticleCell reports, vol 20, iss 51061 - 1072oai:escholarship.org:ark:/13030/qt92g806mz2018-03-22T21:34:59Zqt92g806mzTissue Elasticity Bridges Cancer Stem Cells to the Tumor Microenvironment Through microRNAs: Implications for a "Watch-and-Wait" Approach to Cancer.Li, Shengwen CalvinVu, Long TLuo, Jane JianyingZhong, Jiang FLi, ZhongjunDethlefs, Brent ALoudon, William GKabeer, Mustafa H2017-01-01Targeting the tumor microenvironment (TME) through which cancer stem cells (CSCs) crosstalk for cancer initiation and progression, may open new treatments different from those centered on the original hallmarks of cancer genetics thereby implying a new approach for suppression of TME driven activation of CSCs. Cancer is dynamic, heterogeneous, evolving with the TME and can be influenced by tissue-specific elasticity. One of the mediators and modulators of the crosstalk between CSCs and mechanical forces is miRNA, which can be developmentally regulated, in a tissue- and cellspecific manner.Here, based on our previous data, we provide a framework through which such gene expression changes in response to external mechanical forces can be understood during cancer progression. Recognizing the ways mechanical forces regulate and affect intracellular signals with applications in cancer stem cell biology. Such TME-targeted pathways shed new light on strategies for attacking cancer stem cells with fewer side effects than traditional gene-based treatments for cancer, requiring a "watchand- wait" approach. We attempt to address both normal brain microenvironment and tumor microenvironment as both works together, intertwining in pathology and physiology - a balance that needs to be maintained for the "watch-and-wait" approach to cancer.This review connected the subjects of tissue elasticity, tumor microenvironment, epigenetic of miRNAs, and stem-cell biology that are very relevant in cancer research and therapy. It attempts to unify apparently separate entities in a complex biological web, network, and system in a realistic and practical manner, i.e., to bridge basic research with clinical application.application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/92g806mzarticleCurrent stem cell research & therapy, vol 12, iss 6455 - 470oai:escholarship.org:ark:/13030/qt8n27s5k52018-03-22T21:33:01Zqt8n27s5k5Bundle in the Bronx: Impact of a Transition-of-Care Outpatient Parenteral Antibiotic Therapy Bundle on All-Cause 30-Day Hospital Readmissions.Madaline, TheresaNori, PriyaMowrey, WenzhuZukowski, ElisabethGohil, ShrutiSarwar, UzmaWeston, GregoryUrrely, RiganniPalombelli, MatthewPierino, Vinnie FrankParsons, VanessaEhrlich, AmyOstrowsky, BelindaCorpuz, MarilouPirofski, Liise-Anne2017-06-29A streamlined transition from inpatient to outpatient care can decrease 30-day readmissions. Outpatient parenteral antibiotic therapy (OPAT) programs have not reduced readmissions; an OPAT bundle has been suggested to improve outcomes. We implemented a transition-of-care (TOC) OPAT bundle and assessed the effects on all-cause, 30-day hospital readmission.Retrospectively, patients receiving postdischarge intravenous antibiotics were evaluated before and after implementation of a TOC-OPAT program in Bronx, New York, between July, 2015 and February, 2016. Pearson's χ2test was used to compare 30-day readmissions between groups, and logistic regression was used to adjust for covariates. Time from discharge to readmission was analyzed to assess readmission risk, using log-rank test to compare survival curves and Cox proportional hazards model to adjust for covariates. Secondary outcomes, 30-day emergency department (ED) visits, and mortality were analyzed similarly.Compared with previous standard care (n = 184), the TOC-OPAT group (n = 146) had significantly lower 30-day readmissions before (13.0% vs 26.1%,P< .01) and after adjustment for covariates (odds ratio [OR] = 0.51; 95% confidence interval [CI], 0.27-0.94;P= .03). In time-dependent analyses, TOC-OPAT patients were at significantly lower risk for readmission (log-rank test,P< .01; hazard ratio = 0.56; 95% CI, 0.32-0.97;P= .04). Propensity-matched sensitivity analysis showed lower readmissions in the TOC-OPAT group (13.6% vs 24.6%,P= .04), which was attenuated after adjustment (OR = 0.51; 95% CI, 0.25-1.05;P= .07). Mortality and ED visits were similar in both groups.Our TOC-OPAT patients had reduced 30-day readmissions compared with the previous standard of care. An effective TOC-OPAT bundle can successfully improve patient outcomes in an economically disadvantaged area.application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/8n27s5k5articleOpen forum infectious diseases, vol 4, iss 2ofx097 - ofx0ofx097oai:escholarship.org:ark:/13030/qt1bd3t8dt2018-03-22T21:17:59Zqt1bd3t8dtBundle in the Bronx: Impact of a Transition-of-Care Outpatient Parenteral Antibiotic Therapy Bundle on All-Cause 30-Day Hospital Readmissions.Madaline, TheresaNori, PriyaMowrey, WenzhuZukowski, ElisabethGohil, ShrutiSarwar, UzmaWeston, GregoryUrrely, RiganniPalombelli, MatthewPierino, Vinnie FrankParsons, VanessaEhrlich, AmyOstrowsky, BelindaCorpuz, MarilouPirofski, Liise-Anne2017-06-29A streamlined transition from inpatient to outpatient care can decrease 30-day readmissions. Outpatient parenteral antibiotic therapy (OPAT) programs have not reduced readmissions; an OPAT bundle has been suggested to improve outcomes. We implemented a transition-of-care (TOC) OPAT bundle and assessed the effects on all-cause, 30-day hospital readmission.Retrospectively, patients receiving postdischarge intravenous antibiotics were evaluated before and after implementation of a TOC-OPAT program in Bronx, New York, between July, 2015 and February, 2016. Pearson's χ2test was used to compare 30-day readmissions between groups, and logistic regression was used to adjust for covariates. Time from discharge to readmission was analyzed to assess readmission risk, using log-rank test to compare survival curves and Cox proportional hazards model to adjust for covariates. Secondary outcomes, 30-day emergency department (ED) visits, and mortality were analyzed similarly.Compared with previous standard care (n = 184), the TOC-OPAT group (n = 146) had significantly lower 30-day readmissions before (13.0% vs 26.1%,P< .01) and after adjustment for covariates (odds ratio [OR] = 0.51; 95% confidence interval [CI], 0.27-0.94;P= .03). In time-dependent analyses, TOC-OPAT patients were at significantly lower risk for readmission (log-rank test,P< .01; hazard ratio = 0.56; 95% CI, 0.32-0.97;P= .04). Propensity-matched sensitivity analysis showed lower readmissions in the TOC-OPAT group (13.6% vs 24.6%,P= .04), which was attenuated after adjustment (OR = 0.51; 95% CI, 0.25-1.05;P= .07). Mortality and ED visits were similar in both groups.Our TOC-OPAT patients had reduced 30-day readmissions compared with the previous standard of care. An effective TOC-OPAT bundle can successfully improve patient outcomes in an economically disadvantaged area.application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/1bd3t8dtarticleOpen forum infectious diseases, vol 4, iss 2ofx097 - ofx0ofx097oai:escholarship.org:ark:/13030/qt2jw7m0372018-03-22T21:15:21Zqt2jw7m037Design and synthesis of formononetin-dithiocarbamate hybrids that inhibit growth and migration of PC-3 cells via MAPK/Wnt signaling pathways.Fu, Dong-JunZhang, LiSong, JianMao, Ruo-WangZhao, Ruo-HanLiu, Ying-ChaoHou, Yu-HuiLi, Jia-HuanYang, Jia-JiaJin, Cheng-YunLi, PingZi, Xiao-LinLiu, Hong-MinZhang, Sai-YangZhang, Yan-Bing2017-02-15A series of novel formononetin-dithiocarbamate derivatives were designed, synthesized and evaluated for antiproliferative activity against three selected cancer cell line (MGC-803, EC-109, PC-3). The first structure-activity relationship (SAR) for this formononetin-dithiocarbamate scaffold is explored in this report with evaluation of 14 variants of the structural class. Among these analogues, tert-butyl 4-(((3-((3-(4-methoxyphenyl)-4-oxo-4H-chromen-7-yl)oxy)propyl)thio)carbonothioyl)piperazine-1-carboxylate (8i) showed the best inhibitory activity against PC-3 cells (IC50 = 1.97 μM). Cellular mechanism studies elucidated 8i arrests cell cycle at G1 phase and regulates the expression of G1 checkpoint-related proteins in concentration-dependent manners. Furthermore, 8i could inhibit cell growth via MAPK signaling pathway and inhibit migration via Wnt pathway in PC-3 cells.Antineoplastic Agents: chemical synthesischemistrypharmacologyApoptosis: drug effectsCell LineTumorCell Movement: drug effectsCell Proliferation: drug effectsChemistry TechniquesSyntheticDose-Response RelationshipDrugDrug DesignDrug Screening AssaysAntitumorDrug SynergismG1 Phase Cell Cycle Checkpoints: drug effectsHumansIsoflavones: chemical synthesischemistrypharmacologyMAP Kinase Signaling System: drug effectsStructure-Activity RelationshipThiocarbamates: chemistryWnt Signaling Pathway: drug effectsapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/2jw7m037articleoai:escholarship.org:ark:/13030/qt7fh5s0m02018-03-22T21:12:59Zqt7fh5s0m0Psychometric properties of stress and anxiety measures among nulliparous women.Bann, Carla MParker, Corette BGrobman, William AWillinger, MarianSimhan, Hyagriv NWing, Deborah AHaas, David MSilver, Robert MParry, SamuelSaade, George RWapner, Ronald JElovitz, Michal AMiller, Emily SReddy, Uma M2017-03-10To examine the psychometric properties of three measures, the perceived stress scale (PSS), pregnancy experience scale (PES), and state trait anxiety inventory (STAI), for assessing stress and anxiety during pregnancy among a large sample of nulliparous women.The sample included 10,002 pregnant women participating in the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nMoM2b). Internal consistency reliability was assessed with Cronbach's alpha and factorial validity with confirmatory factor analyses. Intraclass correlations (ICCs) were calculated to determine stability of PSS scales over time. Psychometric properties were examined for the overall sample, as well as subgroups based on maternal age, race/ethnicity and language.All three scales demonstrated good internal consistency reliability. Confirmatory factor analyses supported the factor structures of the PSS and the PES. However, a one-factor solution of the trait-anxiety subscale from the STAI did not fit well; a two-factor solution, splitting the items into factors based on direction of item wording (positive versus negative) provided a better fit. Scores on the PSS were generally stable over time (ICC = 0.60). Subgroup analyses revealed a few items that did not perform well on Spanish versions of the scales.Overall, the scales performed well, suggesting they could be useful tools for identifying women experiencing high levels of stress and anxiety during pregnancy and allowing for the implementation of interventions to help reduce maternal stress and anxiety.AdultAnxiety: diagnosisFemaleHumansParityPregnancyPregnancy Complications: diagnosisPregnant Women: psychologyPsychiatric Status Rating Scales: standardsPsychometrics: instrumentationStressPsychological: diagnosisYoung Adultapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/7fh5s0m0articleJournal of psychosomatic obstetrics and gynaecology, vol 38, iss 153 - 62oai:escholarship.org:ark:/13030/qt5210t7p12018-03-22T21:11:42Zqt5210t7p1Functional and Histological Effects of Chronic Neural Electrode Implantation.Sahyouni, RonaldChang, David TMoshtaghi, OmidMahmoodi, AminDjalilian, Hamid RLin, Harrison W2017-04-06Permanent injury to the cranial nerves can often result in a substantial reduction in quality of life. Novel and innovative interventions can help restore form and function in nerve paralysis, with bioelectric interfaces among the more promising of these approaches. The foreign body response is an important consideration for any bioelectric device as it influences the function and effectiveness of the implant. The purpose of this review is to describe tissue and functional effects of chronic neural implantation among the different categories of neural implants and highlight advances in peripheral and cranial nerve stimulation.Data Sources: PubMed, IEEE, and Web of Science literature search.Review Methods: A review of the current literature was conducted to examine functional and histologic effects of bioelectric interfaces for neural implants.Bioelectric devices can be characterized as intraneural, epineural, perineural, intranuclear, or cortical depending on their placement relative to nerves and neuronal cell bodies. Such devices include nerve-specific stimulators, neuroprosthetics, brainstem implants, and deep brain stimulators. Regardless of electrode location and interface type, acute and chronic histological, macroscopic and functional changes can occur as a result of both passive and active tissue responses to the bioelectric implant.A variety of chronically implantable electrodes have been developed to treat disorders of the peripheral and cranial nerves, to varying degrees of efficacy. Consideration and mitigation of detrimental effects at the neural interface with further optimization of functional nerve stimulation will facilitate the development of these technologies and translation to the clinic.3.application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/5210t7p1articleLaryngoscope investigative otolaryngology, vol 2, iss 280 - 93oai:escholarship.org:ark:/13030/qt4kd194vp2018-03-22T21:09:47Zqt4kd194vpPorcine Neural Progenitor Cells Derived from Tissue at Different Gestational Ages Can Be Distinguished by Global Transcriptome.Yang, JingMenges, StevenGu, PingTongbai, RonaldSamuel, MelissaPrather, Randall SKlassen, Henry2017-09-01The impact of gestational age on mammalian neural progenitor cells is potentially important for both an understanding of neural development and the selection of donor cells for novel cell-based treatment strategies. In terms of the latter, it can be problematic to rely entirely on rodent models in which the gestational period is significantly shorter and the brain much smaller than is the case in humans. Here, we analyzed pig brain progenitor cells (pBPCs) harvested at 2 different gestational ages (E45 and E60) using gene expression profiles, obtained by microarray analysis and quantitative polymerase chain reaction (qPCR), across time in culture. Comparison of the global transcriptome of pBPCs from age-matched transgenic green flourescent protein (GFP)-expressing fetuses versus non- GFP-expressing fetuses did not reveal significant differences between the 2 cell types, whereas comparison between E45 and E60 pBPCs did show separation between the data sets by principle component analysis. Further examination by qPCR showed evidence of relative downregulation of proliferation markers and upregulation of glial markers in the gestationally older (E60) cells. Additional comparisons were made. This study provides evidence of age-related changes in the gene expression of cultured fetal porcine neural progenitors that are potentially relevant to the role of these cells during development and as donor cells for transplantation studies.application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/4kd194vparticleCell transplantation, vol 26, iss 91582 - 1595oai:escholarship.org:ark:/13030/qt7j43175k2018-03-22T21:08:21Zqt7j43175kCompartmentalized Culture of Perivascular Stroma and Endothelial Cells in a Microfluidic Model of the Human Endometrium.Gnecco, Juan SPensabene, VirginiaLi, David JDing, TianbingHui, Elliot EBruner-Tran, Kaylon LOsteen, Kevin G2017-07-20The endometrium is the inner lining of the uterus. Following specific cyclic hormonal stimulation, endometrial stromal fibroblasts (stroma) and vascular endothelial cells exhibit morphological and biochemical changes to support embryo implantation and regulate vascular function, respectively. Herein, we integrated a resin-based porous membrane in a dual chamber microfluidic device in polydimethylsiloxane that allows long term in vitro co-culture of human endometrial stromal and endothelial cells. This transparent, 2-μm porous membrane separates the two chambers, allows for the diffusion of small molecules and enables high resolution bright field and fluorescent imaging. Within our primary human co-culture model of stromal and endothelial cells, we simulated the temporal hormone changes occurring during an idealized 28-day menstrual cycle. We observed the successful differentiation of stroma into functional decidual cells, determined by morphology as well as biochemically as measured by increased production of prolactin. By controlling the microfluidic properties of the device, we additionally found that shear stress forces promoted cytoskeleton alignment and tight junction formation in the endothelial layer. Finally, we demonstrated that the endometrial perivascular stroma model was sustainable for up to 4 weeks, remained sensitive to steroids and is suitable for quantitative biochemical analysis. Future utilization of this device will allow the direct evaluation of paracrine and endocrine crosstalk between these two cell types as well as studies of immunological events associated with normal vs. disease-related endometrial microenvironments.Cell Culture TechniquesEndometrium: blood supplycytologymetabolismFemaleHuman Umbilical Vein Endothelial Cells: cytologymetabolismHumansMembranesArtificialModelsCardiovascularPorosityTissue Engineering: methodsapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/7j43175karticleAnnals of biomedical engineering, vol 45, iss 71758 - 1769oai:escholarship.org:ark:/13030/qt4w33g62k2018-03-22T21:06:22Zqt4w33g62kCXCL10/CXCR3-Dependent Mobilization of Herpes Simplex Virus-Specific CD8+TEMand CD8+TRMCells within Infected Tissues Allows Efficient Protection against Recurrent Herpesvirus Infection and Disease.Srivastava, RuchiKhan, Arif AChilukuri, SravyaSyed, Sabrina ATran, Tien TFurness, JulieBahraoui, ElmostafaBenMohamed, Lbachir2017-07-15Herpes simplex virus 1 (HSV-1) establishes latency within the sensory neurons of the trigeminal ganglia (TG). HSV-specific memory CD8+T cells play a critical role in preventing HSV-1 reactivation from TG and subsequent virus shedding in tears that trigger recurrent corneal herpetic disease. The CXC chemokine ligand 10 (CXCL10)/CXC chemokine receptor 3 (CXCR3) chemokine pathway promotes T cell immunity to many viral pathogens, but its importance in CD8+T cell immunity to recurrent herpes has been poorly elucidated. In this study, we determined how the CXCL10/CXCR3 pathway affects TG- and cornea-resident CD8+T cell responses to recurrent ocular herpesvirus infection and disease using a well-established murine model in which HSV-1 reactivation was induced from latently infected TG by UV-B light. Following UV-B-induced HSV-1 reactivation, a significant increase in both the number and function of HSV-specific CXCR3+CD8+T cells was detected in TG and corneas of protected C57BL/6 (B6) mice, but not in TG and corneas of nonprotected CXCL10-/-or CXCR3-/-deficient mice. This increase was associated with a significant reduction in both virus shedding and recurrent corneal herpetic disease. Furthermore, delivery of exogenous CXCL10 chemokine in TG of CXCL10-/-mice, using the neurotropic adeno-associated virus type 8 (AAV8) vector, boosted the number and function of effector memory CD8+T cells (TEM) and tissue-resident memory CD8+T cells (TRM), but not of central memory CD8+T cells (TCM), locally within TG, and improved protection against recurrent herpesvirus infection and disease in CXCL10-/-deficient mice. These findings demonstrate that the CXCL10/CXCR3 chemokine pathway is critical in shaping CD8+T cell immunity, locally within latently infected tissues, which protects against recurrent herpesvirus infection and disease.IMPORTANCEWe determined how the CXCL10/CXCR3 pathway affects CD8+T cell responses to recurrent ocular herpesvirus infection and disease. Using a well-established murine model, in which HSV-1 reactivation in latently infected trigeminal ganglia was induced by UV-B light, we demonstrated that lack of either CXCL10 chemokine or its CXCR3 receptor compromised the mobilization of functional CD8+TEMand CD8+TRMcells within latently infected trigeminal ganglia following virus reactivation. This lack of T cell mobilization was associated with an increase in recurrent ocular herpesvirus infection and disease. Inversely, augmenting the amount of CXCL10 in trigeminal ganglia of latently infected CXCL10-deficient mice significantly restored the number of local antiviral CD8+TEMand CD8+TRMcells associated with protection against recurrent ocular herpes. Based on these findings, a novel "prime/pull" therapeutic ocular herpes vaccine strategy is proposed and discussed.AnimalsCD8-Positive T-Lymphocytes: immunologyChemokine CXCL10: deficiencymetabolismCornea: immunologyvirologyDisease ModelsAnimalHerpes Simplex: immunologyprevention & controlImmunologic MemoryMiceInbred C57BLMiceKnockoutReceptorsCXCR3: deficiencymetabolismRecurrenceSimplexvirus: immunologyTrigeminal Ganglion: immunologyvirologyapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/4w33g62karticleJournal of virology, vol 91, iss 14oai:escholarship.org:ark:/13030/qt7k72k2jj2018-03-22T21:04:17Zqt7k72k2jjDendritic Cell-Airway Epithelial Cell Cross-Talk Changes with Age and Contributes to Chronic Lung Inflammatory Diseases in the Elderly.Agrawal, Anshu2017-06-06Age-associated dysregulated immune and inflammatory responses are one of the major factors responsible for the prevalence of chronic respiratory diseases in the older population. Pulmonary dendritic cells (DCs) are present below the airway epithelial cells (AECs) and are critical in initiating effective immune responses to harmful pathogens while maintaining tolerance against harmless antigens. The interaction between DCs and AECs plays a crucial role in lung immunity at homeostasis and during infections. The functions of both DCs and AECs are impacted with age. The present report reviews how the potential crosstalk between pulmonary DCs and AECs is dysregulated in the elderly impairing the capacity to maintain tolerance at the respiratory surfaces, which results in severe and chronic respiratory inflammatory diseases. We also discuss how such DC-AECs crosstalk will provide insight into the mechanisms underlying the increased susceptibility of the elderly to pulmonary inflammatory diseases.Age FactorsAgingAnimalsChronic DiseaseDendritic Cells: immunologypathologyHumansInflammation: epidemiologyimmunologypathologyLung: immunologypathologyLung Diseases: epidemiologyimmunologypathologyRespiratory Mucosa: immunologypathologyapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/7k72k2jjarticleInternational journal of molecular sciences, vol 18, iss 6oai:escholarship.org:ark:/13030/qt65p7w38f2018-03-22T21:01:09Zqt65p7w38fActivation of PKCα and PI3K Kinases in Hypertrophic and Nodular Port Wine Stain Lesions.Yin, RongGao, LinTan, WenbinGuo, WeiZhao, TaoNelson, Jhon StuartWang, Gang2017-10-01Port wine stain (PWS) is a congenital, progressive vascular malformation. Many patients with PWS develop hypertrophy and discrete nodularity during their adult life, but the mechanism(s) remain incompletely understood. In this study, we attempted to investigate activation status of PKCα, PI3K, PDPK1 and PLC-γ and protein levels of PP2A and DAG to explore their potential roles in the formation of hypertrophic and nodular PWS lesions. We found phosphorylated levels of PKCα, PI3K, PDPK1, and PLC-γ and protein levels of PP2A and DAG showed moderate increases in the endothelial cells of hypertrophic PWS as compared to the adjacent normal skin. These increases extended throughout the entire stroma of blood vessels in PWS nodules. Many proliferating cells, such as fibroblasts, also showed strong activation of PKCα, PI3K, PDPK1 and PLC-γ and upregulations of PP2A and DAG in nodular PWS lesions. Our data showed that there is aberrant activation of PKCα, PI3K, PDPK1 and PLC-γ and upregulation of PP2A and DAG mainly in endothelial cells in hypertrophic PWS areas, but presenting in the entire vasculatures and surrounding fibroblasts in PWS nodules. Our data suggest that both PKCα and PI3K signaling pathways contribute to the development of hypertrophy and nodularity in adult PWS.application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/65p7w38farticleThe American Journal of dermatopathology, vol 39, iss 10747 - 752oai:escholarship.org:ark:/13030/qt36w1z6tw2018-03-22T20:58:28Zqt36w1z6twA survey of current practices for genomic sequencing test interpretation and reporting processes in US laboratories.O'Daniel, Julianne MMcLaughlin, Heather MAmendola, Laura MBale, Sherri JBerg, Jonathan SBick, DavidBowling, Kevin MChao, Elizabeth CChung, Wendy KConlin, Laura KCooper, Gregory MDas, SomaDeignan, Joshua LDorschner, Michael OEvans, James PGhazani, Arezou AGoddard, Katrina AGornick, MicheleFarwell Hagman, Kelly DHambuch, TinaHegde, MadhuriHindorff, Lucia AHolm, Ingrid AJarvik, Gail PKnight Johnson, AmyMighion, LindseyMorra, MassimoPlon, Sharon EPunj, SumitRichards, C SueSantani, AvniShirts, Brian HSpinner, Nancy BTang, ShaWeck, Karen EWolf, Susan MYang, YapingRehm, Heidi L2017-05-03While the diagnostic success of genomic sequencing expands, the complexity of this testing should not be overlooked. Numerous laboratory processes are required to support the identification, interpretation, and reporting of clinically significant variants. This study aimed to examine the workflow and reporting procedures among US laboratories to highlight shared practices and identify areas in need of standardization.Surveys and follow-up interviews were conducted with laboratories offering exome and/or genome sequencing to support a research program or for routine clinical services. The 73-item survey elicited multiple choice and free-text responses that were later clarified with phone interviews.Twenty-one laboratories participated. Practices highly concordant across all groups included consent documentation, multiperson case review, and enabling patient opt-out of incidental or secondary findings analysis. Noted divergence included use of phenotypic data to inform case analysis and interpretation and reporting of case-specific quality metrics and methods. Few laboratory policies detailed procedures for data reanalysis, data sharing, or patient access to data.This study provides an overview of practices and policies of experienced exome and genome sequencing laboratories. The results enable broader consideration of which practices are becoming standard approaches, where divergence remains, and areas of development in best practice guidelines that may be helpful.Genet Med advance online publication 03 Novemeber 2016.DisclosureGenetic Testing: methodsstandardsHumansIncidental FindingsInformation DisseminationLaboratories: ethicsstandardsPractice Guidelines as TopicResearch ReportSample SizeSequence AnalysisDNA: methodsstandardsSurveys and Questionnairesapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/36w1z6twarticleGenetics in medicine : official journal of the American College of Medical Genetics, vol 19, iss 5575 - 582oai:escholarship.org:ark:/13030/qt7k08p0372018-03-22T20:57:03Zqt7k08p037Feasibility of common bibliometrics in evaluating translational science.Schneider, MKane, C MRainwater, JGuerrero, LTong, GDesai, S RTrochim, W2017-01-31A pilot study by 6 Clinical and Translational Science Awards (CTSAs) explored how bibliometrics can be used to assess research influence.Evaluators from 6 institutions shared data on publications (4202 total) they supported, and conducted a combined analysis with state-of-the-art tools. This paper presents selected results based on the tools from 2 widely used vendors for bibliometrics: Thomson Reuters and Elsevier.Both vendors located a high percentage of publications within their proprietary databases (>90%) and provided similar but not equivalent bibliometrics for estimating productivity (number of publications) and influence (citation rates, percentage of papers in the top 10% of citations, observed citations relative to expected citations). A recently available bibliometric from the National Institutes of Health Office of Portfolio Analysis, examined after the initial analysis, showed tremendous potential for use in the CTSA context.Despite challenges in making cross-CTSA comparisons, bibliometrics can enhance our understanding of the value of CTSA-supported clinical and translational research.application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/7k08p037articleJournal of clinical and translational science, vol 1, iss 145 - 52oai:escholarship.org:ark:/13030/qt77w3t1p62018-03-22T20:54:27Zqt77w3t1p6Correlation of focal adhesion assembly and disassembly with cell migration on nanotopography.Liang, Elena IMah, Emma JYee, Albert FDigman, Michelle A2017-02-20Selective cell adhesion is desirable to control cell growth and migration on biomedical implants. Mesenchymal cell migration is regulated through focal adhesions (FAs) and can be modulated by their microenvironment, including changes in surface topography. We use the Number and Molecular Brightness (N&B) imaging analysis to provide a unique perspective on FA assembly and disassembly. This imaging analysis generates a map of real-time fluctuations of protein monomers, dimers, and higher order aggregates of FA proteins, such as paxillin during assembly and disassembly. We show a dynamic view of how nanostructured surfaces (nanoline gratings or nanopillars) regulate single molecular dynamics. In particular, we report that the smallest nanopillars (100 nm spacing) gave rise to a low population of disassembling adhesion clusters of ∼2 paxillin proteins whereas the larger nanopillars (380 nm spacing) gave rise to a much larger population of larger disassembling clusters of ∼3-5 paxillin proteins. Cells were more motile on the smaller nanopillars (spaced 100-130 nm apart) compared to all other surfaces studied. Thus, physical nanotopography influences cell motility, adhesion size, and adhesion assembly and disassembly. We report for the first time, with single molecular detection, how nanotopography influences cell motility and protein reorganization in adhesions.Cell Adhesion: physiologyCell Movement: physiologyFocal Adhesions: physiologyMechanotransductionCellular: physiologyNanoparticles: chemistryultrastructureStatistics as TopicSurface Propertiesapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/77w3t1p6articleIntegrative biology : quantitative biosciences from nano to macro, vol 9, iss 2145 - 155oai:escholarship.org:ark:/13030/qt4zf6179z2018-03-22T20:52:12Zqt4zf6179zT1ρ/T2 mapping and histopathology of degenerative cartilage in advanced knee osteoarthritis.Kester, Benjamin SCarpenter, Philip MYu, Hon JNozaki, TaikiKaneko, YasuhitoYoshioka, HiroshiSchwarzkopf, Ran2017-04-18To investigate whether normal thickness cartilage in osteoarthritic knees demonstrate depletion of proteoglycan or collagen content compared to healthy knees.Magnetic resonance (MR) images were acquired from 5 subjects scheduled for total knee arthroplasty (TKA) (mean age 70 years) and 20 young healthy control subjects without knee pain (mean age 28.9 years). MR images of T1ρ mapping, T2 mapping, and fat suppressed proton-density weighted sequences were obtained. Following TKA each condyle was divided into 4 parts (distal medial, posterior medial, distal lateral, posterior lateral) for cartilage analysis. Twenty specimens (bone and cartilage blocks) were examined. For each joint, the degree and extent of cartilage destruction was determined using the Osteoarthritis Research Society International cartilage histopathology assessment system. In magnetic resonance imaging (MRI) analysis, 2 readers performed cartilage segmentation for T1ρ/T2 values and cartilage thickness measurement.Eleven areas in MRI including normal or near normal cartilage thickness were selected. The corresponding histopathological sections demonstrated mild to moderate osteoarthritis (OA). There was no significant difference in cartilage thickness in MRI between control and advanced OA samples [medial distal condyle,P= 0.461; medial posterior condyle (MPC),P= 0.352; lateral distal condyle,P= 0.654; lateral posterior condyle,P= 0.550], suggesting arthritic specimens were morphologically similar to normal or early staged degenerative cartilage. Cartilage T2 and T1ρ values from the MPC were significantly higher among the patients with advanced OA (P= 0.043). For remaining condylar samples there was no statistical difference in T2 and T1ρ values between cases and controls but there was a trend towards higher values in advanced OA patients.Though cartilage is morphologically normal or near normal, degenerative changes exist in advanced OA patients. These changes can be detected with T2 and T1ρ MRI techniques.application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/4zf6179zarticleWorld journal of orthopedics, vol 8, iss 4350 - 356oai:escholarship.org:ark:/13030/qt8n22g1152018-03-22T20:50:15Zqt8n22g115ATR Mutations Promote the Growth of Melanoma Tumors by Modulating the Immune Microenvironment.Chen, Chi-FenRuiz-Vega, RolandoVasudeva, PriyaEspitia, FranciscoKrasieva, Tatiana Bde Feraudy, SebastienTromberg, Bruce JHuang, SharonGarner, Chad PWu, JieHoon, Dave SGanesan, Anand K2017-03-07Melanomas accumulate a high burden of mutations that could potentially generate neoantigens, yet somehow suppress the immune response to facilitate continued growth. In this study, we identify a subset of human melanomas that have loss-of-function mutations in ATR, a kinase that recognizes and repairs UV-induced DNA damage and is required for cellular proliferation. ATR mutant tumors exhibit both the accumulation of multiple mutations and the altered expression of inflammatory genes, resulting in decreased T cell recruitment and increased recruitment of macrophages known to spur tumor invasion. Taken together, these studies identify a mechanism by which melanoma cells modulate the immune microenvironment to promote continued growth.AnimalsAtaxia Telangiectasia Mutated Proteins: geneticsCell CountCell ProliferationHaploinsufficiency: geneticsHumansLoss of Function MutationMacrophages: pathologyMelanoma: geneticsimmunologypathologyMiceMutation: geneticsNeoplasm InvasivenessNeoplasm MetastasisNevus: geneticspathologyProto-Oncogene Proteins B-raf: geneticsSkin Neoplasms: geneticsimmunologypathologyTumor Microenvironment: immunologyapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/8n22g115articleCell reports, vol 18, iss 102331 - 2342oai:escholarship.org:ark:/13030/qt7jq7f13k2018-03-22T20:45:30Zqt7jq7f13kThe brain anatomy of attention-deficit/hyperactivity disorder in young adults - a magnetic resonance imaging study.Gehricke, Jean-GKruggel, FrithjofThampipop, TanyapornAlejo, Sharina DyanTatos, ErikFallon, JamesMuftuler, L Tugan2017-04-13This is one of the first studies to examine the structural brain anatomy and connectivity associated with an ADHD diagnosis and child as well as adult ADHD symptoms in young adults. It was hypothesized that an adult ADHD diagnosis and in particular childhood symptoms, are associated with widespread changes in the brain macro- and microstructure, which can be used to develop a morphometric biomarker for ADHD.Voxel-wise linear regression models were used to examine structural and diffusion-weighted MRI data in 72 participants (31 young adults with ADHD and 41 controls without ADHD) in relation to diagnosis and the number of self-reported child and adult symptoms.Findings revealed significant associations between ADHD diagnosis and widespread changes to the maturation of white matter fiber bundles and gray matter density in the brain, such as structural shape changes (incomplete maturation) of the middle and superior temporal gyrus, and fronto-basal portions of both frontal lobes. ADHD symptoms in childhood showed the strongest association with brain macro- and microstructural abnormalities. At the brain circuitry level, the superior longitudinal fasciculus (SLF) and cortico-limbic areas are dysfunctional in individuals with ADHD. The morphometric findings predicted an ADHD diagnosis correctly up to 83% of all cases.An adult ADHD diagnosis and in particular childhood symptoms are associated with widespread micro- and macrostructural changes. The SLF and cortico-limbic findings suggest complex audio-visual, motivational, and emotional dysfunctions associated with ADHD in young adults. The sensitivity of the morphometric findings in predicting an ADHD diagnosis was sufficient, which indicates that MRI-based assessments are a promising strategy for the development of a biomarker.AdultAttention Deficit Disorder with Hyperactivity: diagnosisdiagnostic imagingDiffusion Magnetic Resonance ImagingFemaleFrontal Lobe: diagnostic imagingGray Matter: diagnostic imagingHumansMaleYoung Adultapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/7jq7f13karticlePloS one, vol 12, iss 4e0175433 - e01754e0175433oai:escholarship.org:ark:/13030/qt8qn977512018-03-22T20:42:36Zqt8qn97751Propionibacterium acnes biofilm is present in intervertebral discs of patients undergoing microdiscectomy.Capoor, Manu NRuzicka, FilipSchmitz, Jonathan EJames, Garth AMachackova, TanaJancalek, RadimSmrcka, MartinLipina, RadimAhmed, Fahad SAlamin, Todd FAnand, NeelBaird, John CBhatia, NitinDemir-Deviren, SibelEastlack, Robert KFisher, SteveGarfin, Steven RGogia, Jaspaul SGokaslan, Ziya LKuo, Calvin CLee, Yu-PoMavrommatis, KonstantinosMichu, ElleniNoskova, HanaRaz, AssafSana, JiriShamie, A NickStewart, Philip SStonemetz, Jerry LWang, Jeffrey CWitham, Timothy FCoscia, Michael FBirkenmaier, ChristofFischetti, Vincent ASlaby, Ondrej2017-04-03In previous studies, Propionibacterium acnes was cultured from intervertebral disc tissue of ~25% of patients undergoing microdiscectomy, suggesting a possible link between chronic bacterial infection and disc degeneration. However, given the prominence of P. acnes as a skin commensal, such analyses often struggled to exclude the alternate possibility that these organisms represent perioperative microbiologic contamination. This investigation seeks to validate P. acnes prevalence in resected disc cultures, while providing microscopic evidence of P. acnes biofilm in the intervertebral discs.Specimens from 368 patients undergoing microdiscectomy for disc herniation were divided into several fragments, one being homogenized, subjected to quantitative anaerobic culture, and assessed for bacterial growth, and a second fragment frozen for additional analyses. Colonies were identified by MALDI-TOF mass spectrometry and P. acnes phylotyping was conducted by multiplex PCR. For a sub-set of specimens, bacteria localization within the disc was assessed by microscopy using confocal laser scanning and FISH.Bacteria were cultured from 162 discs (44%), including 119 cases (32.3%) with P. acnes. In 89 cases, P. acnes was cultured exclusively; in 30 cases, it was isolated in combination with other bacteria (primarily coagulase-negative Staphylococcus spp.) Among positive specimens, the median P. acnes bacterial burden was 350 CFU/g (12 - ~20,000 CFU/g). Thirty-eight P. acnes isolates were subjected to molecular sub-typing, identifying 4 of 6 defined phylogroups: IA1, IB, IC, and II. Eight culture-positive specimens were evaluated by fluorescence microscopy and revealed P. acnes in situ. Notably, these bacteria demonstrated a biofilm distribution within the disc matrix. P. acnes bacteria were more prevalent in males than females (39% vs. 23%, p = 0.0013).This study confirms that P. acnes is prevalent in herniated disc tissue. Moreover, it provides the first visual evidence of P. acnes biofilms within such specimens, consistent with infection rather than microbiologic contamination.AdultAgedAged80 and overBiofilms: growth & developmentDiskectomyFemaleGram-Positive Bacterial Infections: complicationsmicrobiologyHumansIntervertebral Disc: microbiologysurgeryIntervertebral Disc Degeneration: etiologymicrobiologyIntervertebral Disc Displacement: etiologymicrobiologysurgeryMaleMiddle AgedPhenotypePropionibacterium acnes: isolation & purificationpathogenicityphysiologyYoung Adultapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/8qn97751articlePloS one, vol 12, iss 4e0174518 - e01745e0174518oai:escholarship.org:ark:/13030/qt0tz8t16w2018-03-22T20:39:18Zqt0tz8t16wThe Carotid Intima-Media Thickness and Arterial Stiffness of Pediatric Mucopolysaccharidosis Patients Are Increased Compared to Both Pediatric and Adult Controls.Wang, Raymond YRudser, Kyle DDengel, Donald RBraunlin, Elizabeth ASteinberger, JuliaJacobs, David RSinaiko, Alan RKelly, Aaron S2017-03-15Treatments for mucopolysaccharidoses (MPSs) have increased longevity, but cardiovascular disease causes mortality in a significant percentage of survivors. Markers must be developed to predict MPS cardiac risk and monitor efficacy of investigational therapies.MPS patients underwent carotid artery ultrasonography from which carotid intima-media thickness (cIMT) and three measures of arterial stiffness were calculated: carotid artery distensibility (cCSD), compliance (cCSC), and incremental elastic modulus (cIEM). MPS carotid measurements were compared to corresponding data from pediatric and adult healthy cohorts. 33 MPS patients (17 MPS I, 9 MPS II, 4 MPS IIIA, and 3 MPS VI; mean age 12.5 ± 4.7 years), 560 pediatric controls (age 13.1 ± 4.0 years), and 554 adult controls (age 39.2 ± 2.2 years) were studied. Age and sex-adjusted aggregate MPS cIMT (0.56 ± 0.05 mm) was significantly greater than both pediatric (+0.12 mm; 95% CI +0.10 to +0.14 mm) and adult (+0.10 mm; 95% CI +0.06 to +0.14 mm) control cohorts; similar findings were observed for all MPS subtypes. Mean MPS cIMT approximated the 80th percentile of the adult cohort cIMT. MPS patients also demonstrated significantly increased adjusted arterial stiffness measurements, evidenced by reduced cCSD, cCSC, and increased cIEM, compared to pediatric and adult control cohorts. Regardless of treatment, MPS patients demonstrate increased cIMT and arterial stiffness compared to healthy pediatric and adult controls. These data suggest that relatively young MPS patients demonstrate a "structural vascular age" of at least 40 years old.AdolescentAdultAge FactorsBlood PressureCarotid Intima-Media ThicknessCase-Control StudiesChildFemaleHumansMaleMucopolysaccharidoses: diagnosispathologyphysiopathologyVascular StiffnessYoung Adultapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/0tz8t16warticleInternational journal of molecular sciences, vol 18, iss 3oai:escholarship.org:ark:/13030/qt1rd7k21s2018-03-22T20:36:43Zqt1rd7k21sQuantitative long-term measurements of burns in a rat model using Spatial Frequency Domain Imaging (SFDI) and Laser Speckle Imaging (LSI).Ponticorvo, AdrienBurmeister, David MRowland, RebeccaBaldado, MelissaKennedy, Gordon TSaager, RolfBernal, NicoleChoi, BernardDurkin, Anthony J2017-03-21The current standard for diagnosis of burn severity and subsequent wound healing is through clinical examination, which is highly subjective. Several new technologies are shifting focus to burn care in an attempt to help quantify not only burn depth but also the progress of healing. While accurate early assessment of partial thickness burns is critical for dictating the course of treatment, the ability to quantitatively monitor wound status over time is critical for understanding treatment efficacy. SFDI and LSI are both non-invasive imaging modalities that have been shown to have great diagnostic value for burn severity, but have yet to be tested over the course of wound healing.In this study, a hairless rat model (n = 6, 300-450 g) was used with a four pronged comb to create four identical partial thickness burns (superficial n = 3 and deep n = 3) that were used to monitor wound healing over a 28 days period. Weekly biopsies were taken for histological analysis to verify wound progression. Both SFDI and LSI were performed weekly to track the evolution of hemodynamic (blood flow and oxygen saturation) and structural (reduced scattering coefficient) properties for the burns.LSI showed significant changes in blood flow from baseline to 220% in superficial and 165% in deep burns by day 7. In superficial burns, blood flow returned to baseline levels by day 28, but not for deep burns where blood flow remained elevated. Smaller increases in blood flow were also observed in the surrounding tissue over the same time period. Oxygen saturation values measured with SFDI showed a progressive increase from baseline values of 66-74% in superficial burns and 72% in deep burns by day 28. Additionally, SFDI showed significant decreases in the reduced scattering coefficient shortly after the burns were created. The scattering coefficient progressively decreased in the wound area, but returned towards baseline conditions at the end of the 28 days period. Scattering changes in the surrounding tissue remained constant despite the presence of hemodynamic changes.Here, we show that LSI and SFDI are capable of monitoring changes in hemodynamic and scattering properties in burn wounds over a 28 days period. These results highlight the potential insights that can be gained by using non-invasive imaging technologies to study wound healing. Further development of these technologies could be revolutionary for wound monitoring and studying the efficacy of different treatments. Lasers Surg. Med. 49:293-304, 2017. © 2017 Wiley Periodicals, Inc.AnimalsBiopsyNeedleBurns: diagnostic imagingpathologyDisease ModelsAnimalEvaluation Studies as TopicImmunohistochemistryInjury Severity ScoreLaser-Doppler Flowmetry: methodsMaleOxygen Consumption: physiologyPhotographyRandom AllocationRatsRatsHairlessRegional Blood Flow: physiologySkin PigmentationTime FactorsWound Healing: physiologyapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/1rd7k21sarticleLasers in surgery and medicine, vol 49, iss 3293 - 304oai:escholarship.org:ark:/13030/qt05x725js2018-03-22T20:34:27Zqt05x725jsSystemic cisplatin exposure during infancy and adolescence causes impaired cognitive function in adulthood.John, TamiLomeli, NaomiBota, Daniela A2017-02-15Cancer survivors diagnosed during infancy and adolescence may be at risk for chemotherapy-related cognitive impairments (CRCI), however the effects of pediatric chemotherapy treatment on adulthood cognitive function are not well understood. Impairments in memory, attention and executive function affect 15-50% of childhood leukemia survivors related to methotrexate exposure. Systemic cisplatin is used to treat a variety of childhood and adult cancers, yet the risk and extent of cognitive impairment due to platinum-based chemotherapy in pediatric patients is unknown. Systemic cisplatin penetrates the CNS, induces hippocampal synaptic damage, and leads to neuronal and neural stem/progenitor cell (NSC) loss. Survivors of non-leukemic cancers may be at risk for significant cognitive impairment related to cisplatin-driven neurotoxicity. We sought to examine the long-term effects of systemic cisplatin administration on cognitive function when administered during infancy and adolescence in a rat model. We performed cognitive testing in adult rats exposed to systemic cisplatin during either infancy or adolescence. Rats treated as adolescents showed significantly poor retrieval of a novel object as compared to controls. Further, cisplatin-treated infants and adolescents showed poor contextual discrimination as compared to controls, and an impaired response to cued fear conditioning. Ultimately, systemic cisplatin exposure resulted in more profound impairments in cognitive function in rats treated during adolescence than in those treated during infancy. Further, exposure to cisplatin during adolescence affected both hippocampus and amygdala dependent cognitive function, suggesting a more global cognitive dysfunction at this age.Age FactorsAging: drug effectsAnimalsAntineoplastic Agents: toxicityCisplatin: toxicityCognition Disorders: chemically inducedConditioning (Psychology): drug effectsDiscrimination (Psychology): drug effectsFear: drug effectsMaleRatsRatsSprague-DawleyRecognition (Psychology): drug effectsapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/05x725jsarticleBehavioural brain research, vol 319200 - 206oai:escholarship.org:ark:/13030/qt6xb152h72018-03-22T20:31:20Zqt6xb152h7Stroke Recovery and Rehabilitation Research: Issues, Opportunities, and the National Institutes of Health StrokeNet.Cramer, Steven CWolf, Steven LAdams, Harold P, JrChen, DaofenDromerick, Alexander WDunning, KariEllerbe, CaitlynGrande, AndrewJanis, ScottLansberg, Maarten GLazar, Ronald MPalesch, Yuko YRichards, LorieRoth, ElliotSavitz, Sean IWechsler, Lawrence RWintermark, MaxBroderick, Joseph P2017-03-07Clinical Trials as TopicHumansNational Institutes of Health (U.S.)Rehabilitation ResearchResearch DesignStroke RehabilitationUnited Statesapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/6xb152h7articleStroke, vol 48, iss 3813 - 819oai:escholarship.org:ark:/13030/qt046241552018-03-22T20:27:51Zqt04624155Reply to HEP 16-0784.R1 and HEP 16-0898.McLaren, Gordon DBarton, James CRamm, Grant AEmond, Mary JSubramaniam, V NathanPhatak, Pradyumna DAdams, Paul CPowell, Lawrie WGurrin, Lyle CAnderson, Gregory JMcLaren, Christine E2017-03-03application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/04624155articleHepatology (Baltimore, Md.), vol 65, iss 31072 - 1073oai:escholarship.org:ark:/13030/qt5j7417kn2018-03-22T20:20:47Zqt5j7417knEpigenetic determinants of space radiation-induced cognitive dysfunction.Acharya, Munjal MBaddour, Al Anoud DKawashita, TakumiAllen, Barrett DSyage, Amber RNguyen, Thuan HYoon, NicoleGiedzinski, ErichYu, LipingParihar, Vipan KBaulch, Janet E2017-02-21Among the dangers to astronauts engaging in deep space missions such as a Mars expedition is exposure to radiations that put them at risk for severe cognitive dysfunction. These radiation-induced cognitive impairments are accompanied by functional and structural changes including oxidative stress, neuroinflammation, and degradation of neuronal architecture. The molecular mechanisms that dictate CNS function are multifaceted and it is unclear how irradiation induces persistent alterations in the brain. Among those determinants of cognitive function are neuroepigenetic mechanisms that translate radiation responses into altered gene expression and cellular phenotype. In this study, we have demonstrated a correlation between epigenetic aberrations and adverse effects of space relevant irradiation on cognition. In cognitively impaired irradiated mice we observed increased 5-methylcytosine and 5-hydroxymethylcytosine levels in the hippocampus that coincided with increased levels of the DNA methylating enzymes DNMT3a, TET1 and TET3. By inhibiting methylation using 5-iodotubercidin, we demonstrated amelioration of the epigenetic effects of irradiation. In addition to protecting against those molecular effects of irradiation, 5-iodotubercidin restored behavioral performance to that of unirradiated animals. The findings of this study establish the possibility that neuroepigenetic mechanisms significantly contribute to the functional and structural changes that affect the irradiated brain and cognition.application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/5j7417knarticleScientific reports, vol 742885 - 42842885oai:escholarship.org:ark:/13030/qt1j94266n2018-03-22T20:17:44Zqt1j94266nPattern separation and goal-directed behavior in the aged canine.Snigdha, ShikhaYassa, Michael AdeRivera, ChristinaMilgram, Norton WCotman, Carl W2017-03-15The pattern separation task has recently emerged as a behavioral model of hippocampus function and has been used in several pharmaceutical trials. The canine is a useful model to evaluate a multitude of hippocampal-dependent cognitive tasks that parallel those in humans. Thus, this study was designed to evaluate the suitability of pattern separation task(s) for detecting age-related changes in canines. We also assessed the dogs' ability to show pattern separation and discrimination reversal, which provides a novel extension of the pattern separation learning literature. Our data show that aged dogs are impaired on a complex pattern separation task (six-well task) relative to easier tasks (four-well or six-well pattern discrimination task), and that the age-related deficits are due to loss of perceptual and inhibitory control in addition to the loss of spatial discrimination and pattern separation ability. Our data also suggest that aged animals show pattern separation deficits when the objects are brought progressively closer together while changing the location of both correct and incorrect objects. However, if the location of any one object is fixed the animals tend to use alternate strategies. Overall, these data provide important insight into age-related pattern separation deficits in a higher animal model and offers additional means for evaluating the impact of lifestyle and pharmaceutical interventions on episodic memory in preclinical trials.Aging: psychologyAnimalsCognition: physiologyConditioningOperant: physiologyDiscrimination Learning: physiologyDogsFemaleGoalsMaleModelsAnimalPattern RecognitionVisual: physiologyReaction Time: physiologySpace Perception: physiologyapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/1j94266narticleLearning & memory (Cold Spring Harbor, N.Y.), vol 24, iss 3123 - 131oai:escholarship.org:ark:/13030/qt9q3966n52018-03-22T20:14:04Zqt9q3966n5Associations between urinary biomarkers of polycyclic aromatic hydrocarbon exposure and reproductive function during menstrual cycles in women.Luderer, UlrikeChristensen, FletcherJohnson, Wesley OShe, JianwenIp, Ho Sai SimonZhou, JunqiangAlvaran, JosephineKrieg, Edward F, JrKesner, James S2017-03-05Essentially all women are exposed to polycyclic aromatic hydrocarbons (PAHs), formed during incomplete combustion of organic materials, including fossil fuels, wood, foods, and tobacco. PAHs are ovarian toxicants in rodents, and cigarette smoking is associated with reproductive abnormalities in women. Biomonitoring of hydroxylated PAH (OH-PAH) metabolites in urine provides an integrated measure of exposure to PAHs via multiple routes and has been used to characterize exposure to PAHs in humans. We hypothesized that concentrations of OH-PAHs in urine are associated with reproductive function in women. We recruited women 18-44years old, living in Orange County, California to conduct daily measurement of urinary luteinizing hormone (LH) and estrone 3-glucuronide (E13G) using a microelectronic fertility monitor for multiple menstrual cycles; these data were used to calculate endocrine endpoints. Participants also collected urine samples on cycle day 10 for measurement of nine OH-PAHs. Models were constructed for eight endpoints using a Bayesian mixed modeling approach with subject-specific random effects allowing each participant to act as a baseline for her set of measurements. We observed associations between individual OH-PAH concentrations and follicular phase length, follicular phase LH and E13G concentrations, preovulatory LH surge concentrations, and periovulatory E13G slope and concentration. We have demonstrated the feasibility of using urinary reproductive hormone data obtained via fertility monitors to calculate endocrine endpoints for epidemiological studies of ovarian function during multiple menstrual cycles. The results show that environmental exposure to PAHs is associated with changes in endocrine markers of ovarian function in women in a PAH-specific manner.AdultBiomarkers: urineCaliforniaEnvironmental ExposureEnvironmental Pollutants: urineEstrone: analogs & derivativesurineFemaleHumansLuteinizing Hormone: urineMenstrual Cycle: drug effectsPolycyclic Aromatic Hydrocarbons: urineYoung Adultapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/9q3966n5articleEnvironment international, vol 100110 - 120oai:escholarship.org:ark:/13030/qt2zw802nr2018-03-22T20:09:40Zqt2zw802nrIncreased Brain Sensorimotor Network Activation after Incomplete Spinal Cord Injury.Sharp, Kelli GGramer, RobertPage, Stephen JCramer, Steven C2017-02-26After complete spinal cord injury (SCI), activation during attempted movement of paralyzed limbs is sharply reduced, but after incomplete SCI-the more common form of human injury-it is unknown how attempts to move voluntarily are accompanied by activation of brain motor and sensory networks. Here, we assessed brain activation during ankle movement in subjects with incomplete SCI, among whom voluntary motor function is partially preserved. Adults with incomplete SCI (n = 20) and healthy controls (n = 15) underwent functional magnetic resonance imaging that alternated rest with 0.3-Hz right ankle dorsiflexion. In both subject groups, ankle movement was associated with bilateral activation of primary and secondary sensory and motor areas, with significantly (p < 0.001) greater activation in subjects with SCI within right hemisphere areas, including primary sensorimotor cortex and pre-motor cortex. This result was further evaluated using linear regression analysis with respect to core clinical variables. Poorer locomotor function correlated with larger activation within several right hemisphere areas, including pre- and post-central gyri, possibly reflecting increased movement complexity and effort, whereas longer time post-SCI was associated with larger activation in left post-central gyrus and bilateral supplementary motor area, which may reflect behaviorally useful adaptations. The results indicate that brain adaptations after incomplete SCI differ sharply from complete SCI, are related to functional behavioral status, and evolve with increasing time post-SCI. The results suggest measures that might be useful for understanding and treating incomplete SCI in human subjects.AdultAgedCohort StudiesFemaleHumansMagnetic Resonance Imaging: trendsMaleMiddle AgedMotor Cortex: diagnostic imagingphysiologyNerve Net: diagnostic imagingphysiologyRecovery of Function: physiologySensorimotor Cortex: diagnostic imagingphysiologySpinal Cord Injuries: diagnostic imagingphysiopathologyapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/2zw802nrarticleJournal of neurotrauma, vol 34, iss 3623 - 631oai:escholarship.org:ark:/13030/qt4pp3w0wh2018-03-22T20:06:22Zqt4pp3w0whOxytocin Pathways in the Intergenerational Transmission of Maternal Early Life StressToepfer, PhilippHeim, ChristineEntringer, SonjaBinder, ElisabethWadhwa, PathikBuss, Claudia2016-12-24Severe stress in early life, such as childhood abuse and neglect, constitutes a major risk factor in the etiology of psychiatric disorders and somatic diseases. Importantly, these long-term effects may impact the next generation. The intergenerational transmission of maternal early life stress (ELS) may occur via pre-and postnatal pathways, such as alterations in maternal-fetal-placental stress physiology, maternal depression during pregnancy and postpartum, as well as impaired mother-offspring interactions. The neuropeptide oxytocin (OT) has gained considerable attention for its role in modulating all of these assumed transmission pathways. Moreover, central and peripheral OT signaling pathways are highly sensitive to environmental exposures and may be compromised by ELS with implications for these putative transmission mechanisms. Together, these data suggest that OT pathways play an important role in the intergenerational transmission of maternal ELS in humans. By integrating recent studies on gene-environment interactions and epigenetic modifications in OT pathway genes, the present review aims to develop a conceptual framework of intergenerational transmission of maternal ELS that emphasizes the role of OT.DevelopmentDepressionEarly life stressEpigeneticsGene-environment interactionsIntergenerational transmissionMother-childOxytocinParenting behaviorapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/4pp3w0wharticleNeuroscience and biobehavioral reviews, vol 73293 - 308oai:escholarship.org:ark:/13030/qt3p2508n02018-03-22T20:00:57Zqt3p2508n0Role of corpus callosum integrity in arm function differs based on motor severity after stroke.Stewart, Jill CampbellDewanjee, PrithaTran, GeorgeQuinlan, Erin BurkeDodakian, LucyMcKenzie, AlisonSee, JillCramer, Steven C2017-03-02While the corpus callosum (CC) is important to normal sensorimotor function, its role in motor function after stroke is less well understood. This study examined the relationship between structural integrity of the motor and sensory sections of the CC, as reflected by fractional anisotropy (FA), and motor function in individuals with a range of motor impairment level due to stroke. Fifty-five individuals with chronic stroke (Fugl-Meyer motor score range 14 to 61) and 18 healthy controls underwent diffusion tensor imaging and a set of motor behavior tests. Mean FA from the motor and sensory regions of the CC and from corticospinal tract (CST) were extracted and relationships with behavioral measures evaluated. Across all participants, FA in both CC regions was significantly decreased after stroke (p < 0.001) and showed a significant, positive correlation with level of motor function. However, these relationships varied based on degree of motor impairment: in individuals with relatively less motor impairment (Fugl-Meyer motor score > 39), motor status correlated with FA in the CC but not the CST, while in individuals with relatively greater motor impairment (Fugl-Meyer motor score ≤ 39), motor status correlated with FA in the CST but not the CC. The role interhemispheric motor connections play in motor function after stroke may differ based on level of motor impairment. These findings emphasize the heterogeneity of stroke, and suggest that biomarkers and treatment approaches targeting separate subgroups may be warranted.AdultAgedAged80 and overAnisotropyArm: physiopathologyCorpus Callosum: diagnostic imagingDiffusion Tensor ImagingFemaleHumansImage ProcessingComputer-AssistedMaleMiddle AgedMovement Disorders: diagnostic imagingetiologypathologyPyramidal Tracts: diagnostic imagingSeverity of Illness IndexStroke: complicationsWhite Matter: diagnostic imagingYoung Adultapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/3p2508n0articleNeuroImage. Clinical, vol 14641 - 647oai:escholarship.org:ark:/13030/qt6n16d1bp2018-03-22T19:51:46Zqt6n16d1bpMale breast cancer in a multi-gene panel testing cohort: insights and unexpected results.Pritzlaff, MarySummerour, PiaMcFarland, RachelLi, ShuweiReineke, PatrickDolinsky, Jill SGoldgar, David EShimelis, HermelaCouch, Fergus JChao, Elizabeth CLaDuca, Holly2017-02-22Genetic predisposition to male breast cancer (MBC) is not well understood. The aim of this study was to better define the predisposition genes contributing to MBC and the utility of germline multi-gene panel testing (MGPT) for explaining the etiology of MBCs.Clinical histories and molecular results were retrospectively reviewed for 715 MBC patients who underwent MGPT from March 2012 to June 2016.The detection rate of MGPT was 18.1% for patients tested for variants in 16 breast cancer susceptibility genes and with no prior BRCA1/2 testing. BRCA2 and CHEK2 were the most frequently mutated genes (11.0 and 4.1% of patients with no prior BRCA1/2 testing, respectively). Pathogenic variants in BRCA2 [odds ratio (OR) = 13.9; p = 1.92 × 10-16], CHEK2 (OR = 3.7; p = 6.24 × 10-24), and PALB2 (OR = 6.6, p = 0.01) were associated with significantly increased risks of MBC. The average age at diagnosis of MBC was similar for patients with (64 years) and without (62 years) pathogenic variants. CHEK2 1100delC carriers had a significantly lower average age of diagnosis (n = 7; 54 years) than all others with pathogenic variants (p = 0.03). No significant differences were observed between history of additional primary cancers (non-breast) and family history of male breast cancer for patients with and without pathogenic variants. However, patients with pathogenic variants in BRCA2 were more likely to have a history of multiple primary breast cancers.These data suggest that all MBC patients regardless of age of diagnosis, history of multiple primary cancers, or family history of MBC should be offered MGPT.AdultAgedAged80 and overBreast NeoplasmsMale: diagnosisepidemiologygeneticsCheckpoint Kinase 2: geneticsCohort StudiesFanconi Anemia Complementation Group N Protein: geneticsGene FrequencyGenesBRCA1GenesBRCA2Genetic Association StudiesGenetic Predisposition to DiseaseGenetic Testing: methodsGenotypeGerm-Line MutationHumansMaleMiddle AgedMutationRiskYoung Adultapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/6n16d1bparticleBreast cancer research and treatment, vol 161, iss 3575 - 5586oai:escholarship.org:ark:/13030/qt7sg1k07c2017-07-19T19:21:31Zqt7sg1k07cTherapeutic immunization with a mixture of herpes simplex virus 1 glycoprotein D-derived“asymptomatic” human CD8+ T-cell epitopes decreases spontaneous ocular shedding in latently infected HLA transgenic rabbits: association with low frequency of local PD-1+ TIM-3+ CD8+ exhausted T cellsKhan, Arif ASrivastava, RuchiChentoufi, Aziz AGeertsema, RogerThai, Nhi Thi UyenDasgupta, GargiOsorio, NelsonKalantari, MinaNesburn, Anthony BWechsler, Steven LBenMohamed, LbachirHutt-Fletcher, L.2015-07-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/7sg1k07carticleJournal of Virology, vol 89, iss 136619 - 6632oai:escholarship.org:ark:/13030/qt9h11h1cr2017-07-19T19:20:17Zqt9h11h1crAttributing discrimination to weight: associations with well-being, self-care, and disease status in patients with type 2 diabetes mellitusPotter, LindseyWallston, KennethTrief, PaulaUlbrecht, JanJuth, VanessaSmyth, Joshua2015-07-02application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/9h11h1crarticleJournal of Behavioral Medicine, vol 38, iss 6863 - 875oai:escholarship.org:ark:/13030/qt962691fg2017-07-19T19:19:37Zqt962691fgGlycan modulation and sulfoengineering of anti–HIV-1 monoclonal antibody PG9 in plantsLoos, AndreasGach, Johannes SHackl, ThomasMaresch, DanielHenkel, TheresaPorodko, AndreasBui-Minh, DucSommeregger, WolfgangWozniak-Knopp, GordanaForthal, Donald NAltmann, FriedrichSteinkellner, HertaMach, Lukas2015-10-13application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/962691fgarticleProceedings of the National Academy of Sciences, vol 112, iss 4112675 - 12680oai:escholarship.org:ark:/13030/qt5bp5q0q12017-07-19T19:17:24Zqt5bp5q0q1Resolution of chronic migraine headaches with intrathecal ziconotide: a case reportChang, EricNarain, SachinAl-Khoury, Lama2015-09-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/5bp5q0q1articleoai:escholarship.org:ark:/13030/qt8fp4189n2017-07-19T19:17:05Zqt8fp4189nImplications of the long interdialytic gap: a problem of excess accumulation vs. excess removal?Rhee, Connie MKalantar-Zadeh, Kamyar2015-09-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/8fp4189narticleKidney International, vol 88, iss 3442 - 444oai:escholarship.org:ark:/13030/qt8193q9602017-07-19T19:16:44Zqt8193q960Urinary nerve growth factor as an oncologic biomarker for prostate cancer aggressivenessLiss, Michael AGordon, AdamMorales, BlancaOsann, KathrynSkarecky, DouglasLusch, AchimZaldivar, FrankAhlering, Thomas E2014-07-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/8193q960articleUrologic Oncology: Seminars and Original Investigations, vol 32, iss 5714 - 719oai:escholarship.org:ark:/13030/qt9mq0195t2017-07-19T19:16:17Zqt9mq0195tPredictors of treatment with dialysis modalities in observational studies for comparative effectiveness researchKuttykrishnan, SoorajKalantar-Zadeh, KamyarArah, Onyebuchi ACheung, Alfred KBrunelli, SteveHeagerty, Patrick JKatz, RonitMolnar, Miklos ZNissenson, AllenRavel, VanessaStreja, ElaniHimmelfarb, JonathanMehrotra, Rajnish2015-07-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/9mq0195tarticleNephrology Dialysis Transplantation, vol 30, iss 71208 - 1217oai:escholarship.org:ark:/13030/qt9s95k2t82017-07-19T19:15:49Zqt9s95k2t8Nucleosome Organization in Human Embryonic Stem CellsYazdi, Puya GPedersen, Brian ATaylor, Jared FKhattab, Omar SChen, Yu-HanChen, YumayJacobsen, Steven EWang, Ping HImhof, Axel2015-08-25application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/9s95k2t8articlePLOS ONE, vol 10, iss 8e0136314oai:escholarship.org:ark:/13030/qt9x9361ch2017-07-19T19:15:31Zqt9x9361chAssessment of early occlusal caries pre- and post- sealant application-An imaging approachHoltzman, Jennifer SBallantine, JamiFontana, MargheritaWang, AlexCalantog, AldenBenavides, ErikaGonzalez-Cabezas, CarlosChen, ZhongpingWilder-Smith, Petra2014-08-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/9x9361charticleLasers in Surgery and Medicine, vol 46, iss 6499 - 507oai:escholarship.org:ark:/13030/qt87p541242017-07-19T19:15:14Zqt87p54124Molecular Evolution of PvMSP3α Block II in Plasmodium vivax from Diverse Geographic OriginsGupta, BhavnaReddy, B. P. NiranjanFan, QiYan, GuiyunSirichaisinthop, JeeraphatSattabongkot, JetsumonEscalante, Ananias ACui, LiwangCarvalho, Luzia Helena2015-08-12application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/87p54124articlePLOS ONE, vol 10, iss 8e0135396oai:escholarship.org:ark:/13030/qt54x5x7qm2017-07-19T19:13:15Zqt54x5x7qmHuman Non-neutralizing HIV-1 Envelope Monoclonal Antibodies Limit the Number of Founder Viruses during SHIV Mucosal Infection in Rhesus MacaquesSantra, SampaTomaras, Georgia DWarrier, RanjitNicely, Nathan ILiao, Hua-XinPollara, JustinLiu, PinghuangAlam, S. MunirZhang, RuijunCocklin, Sarah LShen, XiaoyingDuffy, RyanXia, Shi-MaoSchutte, Robert JPemble IV, Charles WDennison, S. MosesLi, HuiChao, AndrewVidnovic, KoraEvans, AbbeyKlein, KatjaKumar, AmitRobinson, JamesLanducci, GaryForthal, Donald NMontefiori, David CKaewkungwal, JaranitNitayaphan, SorachaiPitisuttithum, PunneeRerks-Ngarm, SupachaiRobb, Merlin LMichael, Nelson LKim, Jerome HSoderberg, Kelly AGiorgi, Elena EBlair, LilyKorber, Bette TMoog, ChristianeShattock, Robin JLetvin, Norman LSchmitz, Joern EMoody, M. AGao, FengFerrari, GuidoShaw, George MHaynes, Barton FDouek, Daniel C2015-08-03application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/54x5x7qmarticlePLOS Pathogens, vol 11, iss 8e1005042oai:escholarship.org:ark:/13030/qt9cg4064x2017-07-19T19:12:21Zqt9cg4064xAssociation of Adiponectin With Body Composition and Mortality in Hemodialysis PatientsRhee, Connie MNguyen, Danh VMoradi, HamidBrunelli, Steven MDukkipati, RamanathJing, JennieNakata, TracyKovesdy, Csaba PBrent, Gregory AKalantar-Zadeh, Kamyar2015-08-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/9cg4064xarticleAmerican Journal of Kidney Diseases, vol 66, iss 2313 - 321oai:escholarship.org:ark:/13030/qt9zm7v72t2017-07-19T19:11:47Zqt9zm7v72tPrenatal Programming of Postnatal Susceptibility to Memory ImpairmentsGrant, Kerry-AnnSandman, Curt AWing, Deborah ADmitrieva, JuliaDavis, Elysia Poggi2015-06-10application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/9zm7v72tarticlePsychological Science, vol 26, iss 71054 - 1062oai:escholarship.org:ark:/13030/qt7xv670382017-07-19T19:11:29Zqt7xv67038Latest consensus and update on protein-energy wasting in chronic kidney diseaseObi, YoshitsuguQader, HemnKovesdy, Csaba PKalantar-Zadeh, Kamyar2015-05-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/7xv67038articleCurrent Opinion in Clinical Nutrition and Metabolic Care, vol 18, iss 3254 - 262oai:escholarship.org:ark:/13030/qt7v8919t02017-07-19T19:10:55Zqt7v8919t0Changes in Pulse Pressure during Hemodialysis Treatment and Survival in Maintenance Dialysis PatientsLertdumrongluk, P.Streja, E.Rhee, C. MSim, J. JGillen, D.Kovesdy, C. PKalantar-Zadeh, K.2015-06-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/7v8919t0articleClinical Journal of the American Society of Nephrology, vol 10, iss 71179 - 1191oai:escholarship.org:ark:/13030/qt8kc1246d2017-07-19T19:10:31Zqt8kc1246dIn vivo
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Hyphal Growth and Corneal InfectionClark, Heather LJhingran, AnupamSun, YanVareechon, Chairutde Jesus Carrion, StevenSkaar, Eric PChazin, Walter JCalera, José AntonioHohl, Tobias MPearlman, Eric2016-01-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/0770j1hmarticleThe Journal of Immunology, vol 196, iss 1336 - 344oai:escholarship.org:ark:/13030/qt7n12k3742017-07-17T16:42:09Zqt7n12k374Early initiation of chemotherapy following complete resection of advanced ovarian cancer associated with improved survival: NRG Oncology/Gynecologic Oncology Group studyTewari, K. SJava, J. JEskander, R. NMonk, B. JBurger, R. A2016-01-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/7n12k374articleAnnals of Oncology, vol 27, iss 1114 - 121oai:escholarship.org:ark:/13030/qt24x015gf2017-07-17T16:40:15Zqt24x015gfUltrafast optical-ultrasonic system and miniaturized catheter for imaging and characterizing atherosclerotic plaques in vivoLi, JiawenMa, TengMohar, DilbaharSteward, EarlYu, MingyuePiao, ZhonglieHe, YouminShung, K. KirkZhou, QifaPatel, Pranav MChen, Zhongping2015-12-18application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/24x015gfarticleScientific Reports, vol 5, iss 1oai:escholarship.org:ark:/13030/qt5r38625n2017-07-17T16:38:00Zqt5r38625nIncreased neurovirulence and reactivation of the herpes simplex virus type 1 latency-associated transcript (LAT)-negative mutant dLAT2903 with a disrupted LAT miR-H2Jiang, XianzhiBrown, DonOsorio, NelsonHsiang, ChinhuiBenMohamed, LbachirWechsler, Steven L2015-06-12application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/5r38625narticleJournal of NeuroVirology, vol 22, iss 138 - 49oai:escholarship.org:ark:/13030/qt4jx7g4bc2017-07-17T16:36:12Zqt4jx7g4bcVariability in Findings From Adult Protective Services Investigations of Elder Abuse in CaliforniaMosqueda, LauraWiglesworth, AileenMoore, Alison ANguyen, AnnieGironda, MelanieGibbs, Lisa2015-06-10application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/4jx7g4bcarticleJournal of Evidence-Informed Social Work, vol 13, iss 134 - 44oai:escholarship.org:ark:/13030/qt1kf5904t2017-07-17T16:34:31Zqt1kf5904tSynaptic ultrastructure changes in trigeminocervical complex posttrigeminal nerve injuryPark, JohnTrinh, Van NancySears-Kraxberger, IlseLi, Kang-WuSteward, OswaldLuo, Z. David2016-02-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/1kf5904tarticleJournal of Comparative Neurology, vol 524, iss 2309 - 322oai:escholarship.org:ark:/13030/qt5fj0h6322017-07-17T16:32:39Zqt5fj0h632Pyrethroid and DDT Resistance and Organophosphate Susceptibility among
Anopheles
spp. Mosquitoes, Western KenyaWanjala, Christine LMbugi, Jernard POtoto, EdnaGesuge, MaxwellAfrane, Yaw AAtieli, Harrysone EZhou, GuofaGitheko, Andrew KYan, Guiyun2015-12-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/5fj0h632articleEmerging Infectious Diseases, vol 21, iss 122178 - 2181oai:escholarship.org:ark:/13030/qt2kk9g6gr2017-07-17T16:30:55Zqt2kk9g6grSub�40 fs, 1060�nm Yb�fiber laser enhances penetration depth in nonlinear optical microscopy of human skinBalu, MihaelaSaytashev, IlyasHou, JueDantus, MarcosTromberg, Bruce J2015-12-07application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/2kk9g6grarticleJournal of Biomedical Optics, vol 20, iss 12120501oai:escholarship.org:ark:/13030/qt6345q0rg2017-07-17T16:29:15Zqt6345q0rgRisk Factors for Infection-Related Hospitalization in In-Center HemodialysisDalrymple, L. SMu, Y.Nguyen, D. VRomano, P. SChertow, G. MGrimes, B.Kaysen, G. AJohansen, K. L2015-11-13application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/6345q0rgarticleClinical Journal of the American Society of Nephrology, vol 10, iss 122170 - 2180oai:escholarship.org:ark:/13030/qt06s053402017-07-17T16:27:12Zqt06s05340Intra-Individual Consistency in Endocrine Profiles Across Successive PregnanciesFox, MollySandman, Curt ADavis, Elysia PoggiGlynn, Laura M2015-12-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/06s05340articleThe Journal of Clinical Endocrinology & Metabolism, vol 100, iss 124637 - 4647oai:escholarship.org:ark:/13030/qt49q521102017-07-17T16:25:15Zqt49q52110Hypomagnesemia and Mortality in Incident Hemodialysis PatientsLi, LinStreja, ElaniRhee, Connie MMehrotra, RajnishSoohoo, MelissaBrunelli, Steven MKovesdy, Csaba PKalantar-Zadeh, Kamyar2015-12-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/49q52110articleAmerican Journal of Kidney Diseases, vol 66, iss 61047 - 1055oai:escholarship.org:ark:/13030/qt1w83z5032017-07-17T16:18:57Zqt1w83z503Research Summit III Proceedings on Dosing in Children With an Injured Brain or Cerebral Palsy: Executive SummaryKolobe, T. H. AChristy, J. BGannotti, M. EHeathcock, J. CDamiano, D. LTaub, E.Majsak, M. JGordon, A. MFuchs, R. KO'Neil, M. ECaiozzo, V. J2014-02-13application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/1w83z503articlePhysical Therapy, vol 94, iss 7907 - 920oai:escholarship.org:ark:/13030/qt4p1245rq2017-07-17T16:16:02Zqt4p1245rqBrain gene expression patterns differentiate mild cognitive impairment from normal aged and Alzheimer's diseaseBerchtold, Nicole CSabbagh, Marwan NBeach, Thomas GKim, Ronald CCribbs, David HCotman, Carl W2014-09-01application/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/4p1245rqarticleNeurobiology of Aging, vol 35, iss 91961 - 1972oai:escholarship.org:ark:/13030/qt0p78229s2017-07-15T00:38:11Zqt0p78229sAltered Expression of Diabetes-Related Genes in Alzheimer's Disease Brains: The Hisayama StudyHokama, MasaakiOka, SugakoLeon, JulioNinomiya, ToshiharuHonda, HiroyukiSasaki, KensukeIwaki, ToruOhara, TomoyukiSasaki, TomioLaFerla, Frank MKiyohara, YutakaNakabeppu, Yusaku2014-09-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/0p78229sarticleCerebral Cortex, vol 24, iss 92476 - 2488oai:escholarship.org:ark:/13030/qt0n03b4hs2017-07-15T00:38:01Zqt0n03b4hsA Herpes Simplex Virus Type 1 Human Asymptomatic CD8
+
T-Cell Epitopes-Based Vaccine Protects Against Ocular Herpes in a â��Humanizedâ�� HLA Transgenic Rabbit ModelSrivastava, RuchiKhan, Arif AHuang, JiaweiNesburn, Anthony BWechsler, Steven LBenMohamed, Lbachir2015-06-19application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/0n03b4hsarticleInvestigative Opthalmology & Visual Science, vol 56, iss 64013oai:escholarship.org:ark:/13030/qt09h971mc2017-07-15T00:37:45Zqt09h971mcEffect of Overground Training Augmented by Mental Practice on Gait Velocity in Chronic, Incomplete Spinal Cord InjurySharp, Kelli GGramer, RobertButler, LaineCramer, Steven CHade, ErinnPage, Stephen J2014-04-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/09h971mcarticleArchives of Physical Medicine and Rehabilitation, vol 95, iss 4615 - 621oai:escholarship.org:ark:/13030/qt06v7s0w02017-07-15T00:37:33Zqt06v7s0w0Topical Tranexamic Acid Does Not Affect Electrophysiologic or Neurovascular Sciatic Nerve Markers in an Animal ModelSchwarzkopf, RanDang, PhucLuu, MicheleMozaffar, TahseenGupta, Ranjan2015-01-06application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/06v7s0w0articleClinical Orthopaedics and Related Research®, vol 473, iss 31074 - 1082oai:escholarship.org:ark:/13030/qt04m6t34w2017-07-15T00:37:21Zqt04m6t34wInherited mitochondrial DNA variants can affect complement, inflammation and apoptosis pathways: insights into mitochondrial-nuclear interactionsKenney, M. CChwa, M.Atilano, S. RFalatoonzadeh, P.Ramirez, C.Malik, D.Tarek, M.Caceres-del-Carpio, J.Nesburn, A. BBoyer, D. SKuppermann, B. DVawter, M.Jazwinski, S. MMiceli, M.Wallace, D. CUdar, N.2014-02-28application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/04m6t34warticleHuman Molecular Genetics, vol 23, iss 133537 - 3551oai:escholarship.org:ark:/13030/qt03g7h4pq2017-07-15T00:37:13Zqt03g7h4pqNew paradigms for functional HIV-specific nonneutralizing antibodiesForthal, DonHope, Thomas JAlter, Galit2013-09-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/03g7h4pqarticleCurrent Opinion in HIV and AIDS, vol 8, iss 5393 - 401oai:escholarship.org:ark:/13030/qt02d6m9cm2017-07-15T00:36:54Zqt02d6m9cmRacial/ethnic standards for fetal growth: the NICHD Fetal Growth StudiesBuck Louis, Germaine MGrewal, JagteshwarAlbert, Paul SSciscione, AnthonyWing, Deborah AGrobman, William ANewman, Roger BWapner, RonaldD’Alton, Mary ESkupski, DanielNageotte, Michael PRanzini, Angela COwen, JohnChien, Edward KCraigo, SabrinaHediger, Mary LKim, SungdukZhang, CuilinGrantz, Katherine L2015-10-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/02d6m9cmarticleAmerican Journal of Obstetrics and Gynecology, vol 213, iss 4449.e1 - 449.e41oai:escholarship.org:ark:/13030/qt77p8x4pg2017-07-15T00:36:23Zqt77p8x4pgValidation of the Fitbit Zip for monitoring physical activity among free-living adolescentsSchneider, MargaretChau, Larissa2016-09-21AbstractBackground: The widespread availability of affordable consumer-oriented devices for monitoring physical activityoffers an appealing option to physical activity researchers, but studies are needed to demonstrate the validity andreliability of these products. To examine the validity of the Fitbit Zip, we recruited three cohorts (N’s = 25, 35, and 27)of middle-school students to wear the Fitbit and the ActiGraph simultaneously for a week. Adolescents were healthyvolunteers representing a range of activity levels. Mean daily minutes of MVPA and mean steps per day were comparedbetween the Fitbit Zip and the Actigraph.Results: The step data for the Fitbit Zip correlated highly with the step data yielded by the ActiGraph (r’s = .72, .92, .96),and the MVPA data for the Fitbit Zip correlated highly with the MVPA data from the ActiGraph (r’s = .67, .79, .94). Bland–Altman plots revealed that the Fitbit Zip overestimated activity in comparison to the ActiGraph, especially for CohortOne, which completed the study before Fitbit modified their algorithms to count as activity only bouts that continuedfor at least 10 min.Conclusions: Our data suggest that the Fitbit Zip is a reasonable alternative to the ActiGraph for estimating activityamong free-living adolescents. However, data from the Fitbit should not be used interchangeably with data from theActiGraph, as there is a consistent tendency for the Fitbit to overestimate steps in comparison to the ActiGraph. Also,the findings confirm concern about using for research a consumer-oriented device that does not make public theiralgorithms.Keywords: Activity monitor, ActiGraph, Adolescent, ValidationActivity monitorActiGraphAdolescentValidationapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/77p8x4pgarticleBMC Research Notes, vol 9, iss 1oai:escholarship.org:ark:/13030/qt9vv433mf2017-07-12T00:26:30Zqt9vv433mfPulmonary outcomes in survivors of childhood central nervous system malignancies: A report from the childhood cancer survivor studyHuang, Tseng TienChen, YanDietz, Andrew CYasui, YutakaDonaldson, Sarah SStokes, Dennis CStovall, MarilynLeisenring, Wendy MSklar, Charles ADiller, Lisa RMertens, Ann CArmstrong, Gregory TGreen, Daniel MRobison, Leslie LNess, Kirsten K2014-02-01application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/9vv433mfarticlePediatric Blood & Cancer, vol 61, iss 2319 - 325oai:escholarship.org:ark:/13030/qt8p97h3h12017-07-12T00:25:53Zqt8p97h3h1Impairment of HIV-1 cDNA Synthesis by DBR1 KnockdownGalvis, A. EFisher, H. ENitta, T.Fan, H.Camerini, D.2014-03-26application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/8p97h3h1articleJournal of Virology, vol 88, iss 127054 - 7069oai:escholarship.org:ark:/13030/qt9gx7c1f02017-07-03T23:29:11Zqt9gx7c1f0Dialysis Modality and Correction of Uremic Metabolic Acidosis: Relationship with All-Cause and Cause-Specific MortalityVashistha, T.Kalantar-Zadeh, K.Molnar, M. ZTorlen, K.Mehrotra, R.2012-11-26application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/9gx7c1f0articleClinical Journal of the American Society of Nephrology, vol 8, iss 2254 - 264oai:escholarship.org:ark:/13030/qt2r71136v2017-07-03T23:22:15Zqt2r71136vMicroRNA Expression in Alpha and Beta Cells of Human Pancreatic IsletsKlein, DagmarMisawa, RyosukeBravo-Egana, ValiaVargas, NancyRosero, SamuelPiroso, JulietaIchii, HirohitoUmland, OliverZhijie, JiangTsinoremas, NicholasRicordi, CamilloInverardi, LucaDom?nguez-Bendala, JuanPastori, Ricardo LMaedler, Kathrin2013-01-29application/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/2r71136varticlePLoS ONE, vol 8, iss 1e55064oai:escholarship.org:ark:/13030/qt3d20990t2017-06-30T23:02:04Zqt3d20990tStandard Definitions and Common Data Elements for Clinical Trials in Patients With Alcoholic Hepatitis: Recommendation From the NIAAA Alcoholic Hepatitis ConsortiaCrabb, David WBataller, RamonChalasani, Naga PKamath, Patrick SLucey, MichaelMathurin, PhilippeMcClain, CraigMcCullough, ArthurMitchell, Mack CMorgan, Timothy RNagy, LauraRadaeva, SvetlanaSanyal, ArunShah, VijaySzabo, Gyongyi2016-04-01Heavy drinkers are at risk for a spectrum of histologic alcohol-related liver injury: steatosis, alcoholic steatohepatitis (ASH), alcohol-related fibrosis, and cirrhosis. Alcoholic hepatitis (AH), the clinical entity associated with severe ASH, has high short-term mortality. The standard-of-care therapy, prednisolone, has limited efficacy and many side effects; no other treatment has consistently shown survival benefit. The National Institute on Alcohol Abuse and Alcoholism (NIAAA)-funded Alcoholic Hepatitis Consortia carry out translational research on pathophysiologic mechanisms, genetic and environmental risk factors, phase II clinical trials, and development of biomarkers. The consortia members were convened by the National Institutes of Health to address diagnostic criteria and practical issues related to clinical AH research, and to develop a set of common data elements to harmonize ongoing and future trials. This was accomplished through 3 face-to-face meetings of the investigators and representatives of the National Institutes of Health, and subsequent electronic communications over the course of 6 months. Evidence for the recommendations was based on published trials and observational data from several of the consortia members. A draft manuscript was iteratively reviewed by members of the consortia. The goal was to reach agreements on recommendations and definitions that could facilitate trial design, and simultaneously be tested by research groups pooling their data. The recommendations made here are specifically directed to achieve better uniformity in clinical trials, rather than serving as clinical practice guidelines.Clinical Trials as Topic/classification/*standardsConsensusEndpoint DeterminationHepatitisAlcoholic/classification/*diagnosis/mortality/therapyHumansResearch Design/*standardsRisk FactorsSeverity of Illness IndexTerminology as TopicTime FactorsTreatment Outcomeapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/3d20990tarticleGastroenterology, vol 150, iss 4785 - 790oai:escholarship.org:ark:/13030/qt9dt217xr2017-06-30T00:20:47Zqt9dt217xrDifferential sclerostin and parathyroid hormone response to exercise in boys and menFalk, B.Haddad, F.Klentrou, P.Ward, W.Kish, K.Mezil, Y.Radom-Aizik, S.2015-09-11Physical exercise benefits bone structure and mineralization, especially in children. Immediately following high-impact exercise, PTH increased and returned to resting values within 24 h in both groups, while sclerostin increased in men but not in boys. The underlying mechanisms and implication of this age-related differential response are unclear.Aging/blood/physiologyAnthropometry/methodsBody Composition/physiologyBone Morphogenetic Proteins/*bloodChildExercise/*physiologyGenetic MarkersHumansMaleOsteocytes/physiologyParathyroid Hormone/*bloodWeightBearing/physiologyapplication/pdfCC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/9dt217xrarticleOsteoporosis International, vol 27, iss 31245 - 1249oai:escholarship.org:ark:/13030/qt033111kp2017-06-23T00:50:46Zqt033111kpSmarter Lunchroom Movement of CaliforniaByrnes, MicheleYoung, ShannanGinsburg, DavidReed, HeatherMcMurdo, TammyRobertson, TrinaWarshaw, Cory2017-06-13The Smarter Lunchrooms Movement of California is a collaborative composed of the following organizations: California Department of Education, Dairy Council of California, UC CalFresh Nutrition Education Program, California Department of Public Health, California Food Policy Advocates, Kaiser Permanente Thriving Schools, The California Endowment, and Cornell University B.E.N. Center. What is the Smarter Lunchrooms Movement?The Smarter Lunchrooms Movement (SLM) was started by the Cornell Center for BehavioralEconomics in Child Nutrition Programs in 2009 with the goal of creating sustainable research-based lunchrooms that guide smarter choices.nutritiondairyCal Fresh NutritionDairy Council of CaliforniaICTS Translational Science Research Day 2017CC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/033111kpmultimediaoai:escholarship.org:ark:/13030/qt7v05j6r82017-06-23T00:32:37Zqt7v05j6r8Pathways of an Emerging Digital Nutrition CampaignWaldeck, JenniferRobertson, Trina2017-06-13Background: Many American children consume high calorie/low calorie/low nutrition breakfasts and snacks .School-aged children in California are at risk for numerous health complications given the prevalence of poor nutrition habits . Dairy Council of California launched Pathways, an online digital nutrition campaign, to promote healthier breakfast and snacking habits among site users and their families in winter, 2016 . These digital educational materials are designed to for parents and for use within families and as part of school –based nutrition education programs . Pathways lessons lessons(modules) (modules) focus on improving parent users’ knowledge, attitudes, attitudes, and behaviors relative to planning and creating breakfasts and snacks for their families. Two short, short, interactive modules focused on breakfasts and snacks follow this formula :1.Aquiz to help parents assess their current level of nutritional literacy in creating breakfast and snack plans2.A quick attention -getting series of benefits related to healthy breakfast and snack consumption3.A research -based formula for a healthy, balanced breakfast or snack4.Links to recipe5.Interactive breakfast and snack planners, with the option to print Objective Under the supervision of Dr .Jennifer Waldeck and with oversight by Dairy Council of California Program Manager Trina Robertson, graduate students in the M.S.in Health and Strategic Communication program and undergraduates in the Corporate and Strategic Communication program in the School of Communication at Chapman University conducted a two -phase evaluation research study to assess the effectiveness of the Pathways initiative.nutritiondairyCal Fresh NutritionDairy Council of CaliforniaICTS Translational Science Research Day 2017CC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/7v05j6r8multimediaoai:escholarship.org:ark:/13030/qt3hf215k12017-06-22T23:37:36Zqt3hf215k1Parent Versus Teacher Ratings of Sluggish Cognitive Tempo; Implications for Identifying Risk Among Children with ADHD for Poor Academic Achievement.Lago, HaleyCordia, TheresaAbdullah, Maryam M.Schuck, Sabrina E.B.2017-06-13Introduction: Sluggish Cognitive Tempo (SCT) is characterized by behaviors associated with pathological inattention, physical under arousal and slowed thinking often seen in children with Attention Deficit/Hyperactivity Disorder (ADHD) (Becker, et al., 2016). There is increasing evidence that SCT makes up a separate set of symptom dimensions than any other DSM-5 diagnosis indicating that it leads to its own set of impairments separate from ADHD and all the subtypes (Barkley, 2013). Increasing evidence suggests SCT symptoms in children with ADHD are associated with lower academic achievement (Tamm, et al., 2016). It has been found that parents and teachers view the relationship between SCT impairments and academic functioning differently, thus examining this further is important (Watabe, et al., 2013). Objective: To determine if SCT related impairments are related to children’s ability to complete academic work and succeed in an academic environment.ADHDchildrenSCTSwan Similarity StudiesAcademic achievementcognitivesentence completionreading resultsSluggish Cognitive Tempo (SCT)ICTS Translational Science Research Day 2017CC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/3hf215k1multimediaoai:escholarship.org:ark:/13030/qt5hf838zg2017-06-20T21:37:00Zqt5hf838zgConsent-to-Contact Registry: A New Tool for Accelerating Clinical Research Recruitment at UCIKlein, KirstenGombosev, AdrijanaWitbracht, MeganCox, ChelseaSirivong, ShirleyHoang, DanMadi, NadimPierce, AimeeGrill, Joshua2017-06-13C-2-C, UCI MIND, and ICTS Translational Science Research Day 2017, University of California Irvine Introduction: The most consistent barrier to improved medical care is slow recruitment to clinical research. To help clinical investigators at UCI overcome this barrier, we developed a potential participant registry. The UCI Consent-to-Contact Registry (C2C, c2c.uci.edu) is an online repository of individuals who have given permission to be contacted about studies for which they may be eligible. The objective of the registry is to enhance clinical research recruitment at UCI. Investigators from all departments and schools have the opportunity to recruit through the registry, provided that they have IRB approval to do so and complete the necessary components to access the registry with the organizers. The C2C is supported by HCP, Inc; NIA AG106573; and UL1 TR000153.Consent-to-ContactC-2-CC2CClinical trialrecruitmentregistriesPreclinical Alzheimer's diseaseUCI MINDICTS Translational Science Research Day 2017CC-BYeScholarship, University of Californiahttps://escholarship.org/uc/item/5hf838zgmultimediaoai:escholarship.org:ark:/13030/qt5q89b16p2017-06-01T20:00:37Zqt5q89b16pComplement protein C1q directs macrophage polarization and limits inflammasome activity during the uptake of apoptotic cells.Benoit, Marie EClarke, Elizabeth VMorgado, PedroFraser, Deborah ATenner, Andrea J2012-06-01Deficiency in C1q, the recognition component of the classical complement cascade and a pattern recognition receptor involved in apoptotic cell clearance, leads to lupus-like autoimmune diseases characterized by auto-antibodies to self proteins and aberrant innate immune cell activation likely due to impaired clearance of apoptotic cells. In this study, we developed an autologous system using primary human lymphocytes and human monocyte-derived macrophages (HMDMs) to characterize the effect of C1q on macrophage gene expression profiles during the uptake of apoptotic cells. C1q bound to autologous apoptotic lymphocytes modulated expression of genes associated with JAK/STAT signaling, chemotaxis, immunoregulation, and NLRP3 inflammasome activation in LPS-stimulated HMDMs. Specifically, C1q sequentially induced type I IFNs, IL-27, and IL-10 in LPS-stimulated HMDMs and IL-27 in HMDMs when incubated with apoptotic lymphocyte conditioned media. Coincubation with C1q tails prevented the induction of type I IFNs and IL-27 in a dose-dependent manner, and neutralization of type I IFNs partially prevented IL-27 induction by C1q. Finally, C1q decreased procaspase-1 cleavage and caspase-1-dependent cleavage of IL-1β suggesting a potent inhibitory effect of C1q on inflammasome activation. These results identify specific molecular pathways induced by C1q to suppress macrophage inflammation and provide potential therapeutic targets to control macrophage polarization and thus inflammation and autoimmunity.Apoptosis Regulatory Proteins: physiologyCaspase 1: metabolismCaspase InhibitorsCell Adhesion: immunologyCell Polarity: immunologyCellsCulturedChemokines: biosynthesisComplement C1q: physiologyCytokines: biosynthesisHumansInflammasomes: antagonists & inhibitorsimmunologyInterleukin-1beta: metabolismLipopolysaccharides: metabolismLymphocytes: cytologyimmunologyMacrophages: cytologyimmunologymetabolismapplication/pdfpubliceScholarship, University of Californiahttps://escholarship.org/uc/item/5q89b16particleJournal of immunology (Baltimore, Md. : 1950), vol 188, iss 115682 - 5693oai_dc:icts_rw:500:736:eyJmaXJzdCI6NTAwLCJpbmNsdWRlIjpbIlBVQkxJU0hFRCIsIkVNQkFSR09FRCJdLCJvcmRlciI6IlVQREFURURfREVTQyIsImxhc3RJRCI6InF0NXE4OWIxNnAiLCJsYXN0RGF0ZSI6IjIwMTctMDYtMDFUMTM6MDA6MzctMDc6MDAifQ