Recent icts_rw items

Tele-Exercise as a Promising Tool to Promote Exercise in Children With Cystic Fibrosis.

Thu, 18 Jan 2024 00:00:00 +0000

Introduction: 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:...

Hippocampal CA1 gamma power predicts the precision of spatial memory judgments.

Thu, 18 Jan 2024 00:00:00 +0000

The 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...

Maternal Stress Potentiates the Effect of an Inflammatory Diet in Pregnancy on Maternal Concentrations of Tumor Necrosis Factor Alpha.

Thu, 18 Jan 2024 00:00:00 +0000

Maternal 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...

Wearable speckle plethysmography (SPG) for characterizing microvascular flow and resistance.

Thu, 18 Jan 2024 00:00:00 +0000

In 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...

An assets-based design approach to promote digital equity for Latino youth and their communities

Thu, 18 Jan 2024 00:00:00 +0000

An assets-based design approach to promote digital equity for Latino youth and their communities

Prenatal maternal mood patterns predict child temperament and adolescent mental health

Thu, 18 Jan 2024 00:00:00 +0000

BackgroundThis 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...

Comparative transcriptome analysis and RNA interference reveal CYP6A8 and SNPs related to pyrethroid resistance in Aedes albopictus.

Thu, 18 Jan 2024 00:00:00 +0000

Wide 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....

Radiative transport in the diffusion approximation: An extension for highly absorbing media and small source-detector separations

Thu, 9 Feb 2023 00:00:00 +0000

Radiative transport in the diffusion approximation: An extension for highly absorbing media and small source-detector separations

The changing landscape of diabetes prevalence among first-generation Asian immigrants in California from 2003 to 2013

Mon, 31 Oct 2022 00:00:00 +0000

OBJECTIVE: The 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 METHODS: We 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. RESULTS: Across the study span, we identified 2007 first-generation Asian immigrants and 14 668 whites as having known DM or prediabetes...

Pharmacological Rescue of Long-Term Potentiation in Alzheimer Diseased Synapses

Mon, 31 Oct 2022 00:00:00 +0000

Long-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...

High-throughput screen detects calcium signaling dysfunction in typical sporadic autism spectrum disorder

Mon, 31 Oct 2022 00:00:00 +0000

Autism 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...

Rho-associated kinase 1 inhibition is synthetically lethal with von Hippel-Lindau deficiency in clear cell renal cell carcinoma

Mon, 31 Oct 2022 00:00:00 +0000

Clear 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...

Association of ultrasound‐based measures of fetal body composition with newborn adiposity

Mon, 31 Oct 2022 00:00:00 +0000

BACKGROUND: Newborns 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. OBJECTIVE: The aim of this study was to determine whether a composite measure of fetal fat mass is prospectively associated with newborn adiposity. METHODS: In 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. RESULTS: After controlling for confounding factors, EFA at 30 weeks was significantly associated with newborn per cent...

Association of Serum Triglyceride to HDL Cholesterol Ratio with All-Cause and Cardiovascular Mortality in Incident Hemodialysis Patients

Mon, 31 Oct 2022 00:00:00 +0000

BACKGROUND AND OBJECTIVES: Elevated 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, & MEASUREMENTS: We 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. RESULTS:...

Differential responses of human dendritic cells to metabolites from the oral/airway microbiome

Mon, 31 Oct 2022 00:00:00 +0000

Small 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...

Activation of PKC&agr; and PI3K Kinases in Hypertrophic and Nodular Port Wine Stain Lesions

Mon, 31 Oct 2022 00:00:00 +0000

Port 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...

Proof-of-Concept Randomized Trial of the Monoclonal Antibody GSK249320 Versus Placebo in Stroke Patients

Mon, 31 Oct 2022 00:00:00 +0000

BACKGROUND AND PURPOSE: One 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. METHODS: In 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. RESULTS: A 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;...

Selective stimulation of facial muscles with a penetrating electrode array in the feline model

Mon, 31 Oct 2022 00:00:00 +0000

OBJECTIVES/HYPOTHESIS: Permanent 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 DESIGN: Acute experiments in animals with normal facial function. METHODS: The 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...

Maternal Cortisol During Pregnancy and Infant Adiposity: A Prospective Investigation

Mon, 31 Oct 2022 00:00:00 +0000

Context: Glucocorticoids 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. Objective: To elucidate the magnitude and stage-of-gestation-specific association of maternal cortisol concentrations during pregnancy with infant adiposity. Design, Participants, and Setting: Sixty-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...

Heart‐hand syndrome IV: a second family with LMNA‐related cardiomyopathy and brachydactyly

Mon, 31 Oct 2022 00:00:00 +0000

Changes in urine volume and serum albumin in incident hemodialysis patients

Mon, 31 Oct 2022 00:00:00 +0000

INTRODUCTION: Hypoalbuminemia 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. METHODS: In 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. FINDINGS: Serum 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...

Impact of a personalized versus moderate-intensity exercise prescription: a randomized controlled trial

Mon, 31 Oct 2022 00:00:00 +0000

Effective 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...

Systemic cisplatin exposure during infancy and adolescence causes impaired cognitive function in adulthood

Mon, 31 Oct 2022 00:00:00 +0000

Cancer 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...

Phosphorylation of a constrained azacyclic FTY720 analog enhances anti-leukemic activity without inducing S1P receptor activation

Mon, 31 Oct 2022 00:00:00 +0000

The 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...

Attitudes toward Potential Participant Registries

Mon, 31 Oct 2022 00:00:00 +0000

Difficult 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...

Study of the Carrier-Aided Thin Film Electrode Array Design for Cochlear Insertion.

Mon, 1 Aug 2022 00:00:00 +0000

The 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...

Distinct Patterns of Reduced Prefrontal and Limbic Gray Matter Volume in Childhood General and Internalizing Psychopathology

Mon, 1 Aug 2022 00:00:00 +0000

Reduced 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...

Telerobots for Informal Learning in Schools.

Mon, 1 Aug 2022 00:00:00 +0000

Telerobots for Informal Learning in Schools.

A call for action: Conceptualizing assets-based inclusive design as a social movement to address systemic inequities.

Mon, 1 Aug 2022 00:00:00 +0000

A call for action: Conceptualizing assets-based inclusive design as a social movement to address systemic inequities.

Mobile Computing: The Role of Autonomous Features in Robot-Mediated Virtual Learning

Mon, 1 Aug 2022 00:00:00 +0000

Mobile Computing: The Role of Autonomous Features in Robot-Mediated Virtual Learning

Supporting the Education of Homebound Children Through Semi-autonomous Telepresence Robots.

Thu, 12 Aug 2021 00:00:00 +0000

We 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.

Study partners: essential collaborators in discovering treatments for Alzheimer's disease.

Thu, 12 Aug 2021 00:00:00 +0000

Global 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.

Comparison of speckleplethysmographic (SPG) and photoplethysmographic (PPG) imaging by Monte Carlo simulations and in vivo measurements.

Thu, 12 Aug 2021 00:00:00 +0000

Noncontact 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...

Particulate air pollution, ambulatory heart rate variability, and cardiac arrhythmia in retirement community residents with coronary artery disease.

Fri, 9 Apr 2021 00:00:00 +0000

Decreased 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...

Disparities in Caregivers’ Experiences at the Dentist with their Young Child.

Wed, 10 Apr 2019 00:00:00 +0000

Disparities in Caregivers’ Experiences at the Dentist with their Young Child.

The interactive effects of maternal stress and diet in pregnancy on markers of inflammation

Mon, 7 May 2018 00:00:00 +0000

Introduction:

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...

Fluence rate effects in human glioma spheroids: Implications for photodynamic therapy of brain tumors

Wed, 25 Apr 2018 00:00:00 +0000

Fluence rate effects in human glioma spheroids: Implications for photodynamic therapy of brain tumors

Effects of low-fluence rate PDT on glioma spheroids

Wed, 25 Apr 2018 00:00:00 +0000

Effects of low-fluence rate PDT on glioma spheroids

Combined multiphoton and optical coherence microscopy

Wed, 25 Apr 2018 00:00:00 +0000

Combined multiphoton and optical coherence microscopy

The effects of water and lipids on NIR optical breast measurements

Wed, 25 Apr 2018 00:00:00 +0000

The effects of water and lipids on NIR optical breast measurements

JBO to Begin "e-First" Publication in 2005

Wed, 25 Apr 2018 00:00:00 +0000

JBO to Begin "e-First" Publication in 2005

Broadband absorption spectroscopy by combining frequency-domain and steady-state techniques

Wed, 25 Apr 2018 00:00:00 +0000

Broadband absorption spectroscopy by combining frequency-domain and steady-state techniques

Two-photon excited imaging of photosensitizers in tissues

Wed, 25 Apr 2018 00:00:00 +0000

Two-photon excited imaging of photosensitizers in tissues

Multipoint Thermal Sensors Associated with Improved Oncologic Outcomes Following Cryoablation.

Wed, 25 Apr 2018 00:00:00 +0000

Cryoablation (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...

Two-photon imaging of collagen remodeling in RAFT tissue cultures

Wed, 25 Apr 2018 00:00:00 +0000

Two-photon imaging of collagen remodeling in RAFT tissue cultures

Quality control and assurance for validation of DOS/I measurements

Wed, 25 Apr 2018 00:00:00 +0000

Quality control and assurance for validation of DOS/I measurements

Development of an in vivo model for the study of photodynamic therapy and anti-angiogenic treatments

Wed, 25 Apr 2018 00:00:00 +0000

Development of an in vivo model for the study of photodynamic therapy and anti-angiogenic treatments

Syndrome of selective IgM deficiency with severe T cell deficiency associated with disseminated cutaneous mycobacterium avium intracellulaire infection.

Wed, 25 Apr 2018 00:00:00 +0000

Cutaneous 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...

Characterization of optical and thermal distributions from an intracranial balloon applicator for photodynamic therapy

Wed, 25 Apr 2018 00:00:00 +0000

Characterization of optical and thermal distributions from an intracranial balloon applicator for photodynamic therapy

Combined two-photon excited fluorescence and second-harmonic generation backscattering microscopy of turbid tissues

Wed, 25 Apr 2018 00:00:00 +0000

Combined two-photon excited fluorescence and second-harmonic generation backscattering microscopy of turbid tissues

Scheme for efficient fiber-based CARS probe

Wed, 25 Apr 2018 00:00:00 +0000

Scheme for efficient fiber-based CARS probe

Diffuse optical spectroscopy measurements of healing in breast tissue after core biopsy: case study.

Tue, 17 Apr 2018 00:00:00 +0000

Diffuse 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...

Real-time simultaneous single snapshot of optical properties and blood flow using coherent spatial frequency domain imaging (cSFDI)

Tue, 17 Apr 2018 00:00:00 +0000

Real-time simultaneous single snapshot of optical properties and blood flow using coherent spatial frequency domain imaging (cSFDI)

Differential pathlength factor informs evoked stimulus response in a mouse model of Alzheimer's disease.

Tue, 17 Apr 2018 00:00:00 +0000

Baseline 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;...

Celebrating Britton Chance

Tue, 17 Apr 2018 00:00:00 +0000

Celebrating Britton Chance

Imaging in breast cancer: diffuse optics in breast cancer: detecting tumors in pre-menopausal women and monitoring neoadjuvant chemotherapy.

Tue, 17 Apr 2018 00:00:00 +0000

Diffuse 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....

Diffuse optical spectroscopic imaging of subcutaneous adipose tissue metabolic changes during weight loss.

Tue, 17 Apr 2018 00:00:00 +0000

Changes 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),...

Noninvasive in vivo monitoring of cyanide toxicity and treatment using diffuse optical spectroscopy in a rabbit model.

Tue, 17 Apr 2018 00:00:00 +0000

Currently, 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...

Imaging breast cancer chemotherapy response with light. Commentary on Soliman et al., p. 2605.

Tue, 17 Apr 2018 00:00:00 +0000

Diffuse 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.

Evaluating visual perception for assessing reconstructed flap health.

Fri, 13 Apr 2018 00:00:00 +0000

Detecting 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...

Chemically modified peptides based on the membrane-proximal external region of the HIV-1 envelope induce high-titer, epitope-specific nonneutralizing antibodies in rabbits.

Fri, 13 Apr 2018 00:00:00 +0000

Broadly 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...

Syndrome of selective IgM deficiency with severe T cell deficiency associated with disseminated cutaneous mycobacterium avium intracellulaire infection.

Fri, 13 Apr 2018 00:00:00 +0000

Defining the optimal window for cranial transplantation of human induced pluripotent stem cell-derived cells to ameliorate radiation-induced cognitive impairment.

Fri, 13 Apr 2018 00:00:00 +0000

Past 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...

Concurrent exercise on a gravity-independent device during simulated microgravity.

Fri, 6 Apr 2018 00:00:00 +0000

The 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...

The Suitability of Propofol Compared with Urethane for Anesthesia during Urodynamic Studies in Rats.

Fri, 6 Apr 2018 00:00:00 +0000

Urethane 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...

Functions of Antibodies.

Fri, 6 Apr 2018 00:00:00 +0000

Functions of Antibodies.

Defining the optimal window for cranial transplantation of human induced pluripotent stem cell-derived cells to ameliorate radiation-induced cognitive impairment.

Fri, 6 Apr 2018 00:00:00 +0000

An Examination of Changes in Emotion Co-Regulation Among Mother and Child Dyads During the Strange Situation.

Fri, 6 Apr 2018 00:00:00 +0000

The 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...

Prevalence of restless legs syndrome and sleep quality in carriers of the fragile X premutation.

Fri, 6 Apr 2018 00:00:00 +0000

This 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...

Synaptophysin and synaptojanin-1 in Down syndrome are differentially affected by Alzheimer's disease.

Fri, 6 Apr 2018 00:00:00 +0000

Adults 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...

Aging in Down Syndrome and the Development of Alzheimer's Disease Neuropathology.

Fri, 6 Apr 2018 00:00:00 +0000

Chromosome 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...

Asymptomatic memory CD8+ T cells: from development and regulation to consideration for human vaccines and immunotherapeutics.

Fri, 6 Apr 2018 00:00:00 +0000

Generation 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."

AF710B, a Novel M1/σ1 Agonist with Therapeutic Efficacy in Animal Models of Alzheimer’s Disease.

Fri, 6 Apr 2018 00:00:00 +0000

We 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...

Cellular and molecular responses to increased skeletal muscle loading after irradiation