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UC Davis Previously Published Works

Dietary resistant starch supplementation increases gut luminal deoxycholic acid abundance in mice

(2024)

Bile acids (BA) are among the most abundant metabolites produced by the gut microbiome. Primary BAs produced in the liver are converted by gut bacterial 7-α-dehydroxylation into secondary BAs, which can differentially regulate host health via signaling based on their varying affinity for BA receptors. Despite the importance of secondary BAs in host health, the regulation of 7-α-dehydroxylation and the role of diet in modulating this process is incompletely defined. Understanding this process could lead to dietary guidelines that beneficially shift BA metabolism. Dietary fiber regulates gut microbial composition and metabolite production. We tested the hypothesis that feeding mice a diet rich in a fermentable dietary fiber, resistant starch (RS), would alter gut bacterial BA metabolism. Male and female wild-type mice were fed a diet supplemented with RS or an isocaloric control diet (IC). Metabolic parameters were similar between groups. RS supplementation increased gut luminal deoxycholic acid (DCA) abundance. However, gut luminal cholic acid (CA) abundance, the substrate for 7-α-dehydroxylation in DCA production, was unaltered by RS. Further, RS supplementation did not change the mRNA expression of hepatic BA producing enzymes or ileal BA transporters. Metagenomic assessment of gut bacterial composition revealed no change in the relative abundance of bacteria known to perform 7-α-dehydroxylation. P. ginsenosidimutans and P. multiformis were positively correlated with gut luminal DCA abundance and increased in response to RS supplementation. These data demonstrate that RS supplementation enriches gut luminal DCA abundance without increasing the relative abundance of bacteria known to perform 7-α-dehydroxylation.

Prenatal exposure to social adversity and infant cortisol in the first year of life

(2024)

Exposure to social adversity has been associated with cortisol dysregulation during pregnancy and in later childhood; less is known about how prenatal exposure to social stressors affects postnatal cortisol of infants. In a secondary analysis of data from a longitudinal study, we tested whether a pregnant woman's reports of social adversity during the third trimester were associated with their infant's resting cortisol at 1, 6, and 12 months postnatal. Our hypothesis was that prenatal exposure to social adversity would be associated with elevation of infants' cortisol. Measures included prenatal survey reports of social stressors and economic hardship, and resting cortisol levels determined from infant saliva samples acquired at each postnatal timepoint. Data were analyzed using linear mixed effects models. The final sample included 189 women and their infants (46.56% assigned female sex at birth). Prenatal economic hardship was significantly associated with infant cortisol at 6 months postnatal; reports of social stressors were not significantly associated with cortisol at any time point. Factors associated with hardship, such as psychological distress or nutritional deficiencies, may alter fetal HPA axis development, resulting in elevated infant cortisol levels. Developmental changes unique to 6 months of age may explain effects at this timepoint. More work is needed to better comprehend the complex pre- and post-natal physiologic and behavioral factors that affect infant HPA axis development and function, and the modifying role of environmental exposures.

Cover page of Structural modeling of ion channels using AlphaFold2, RoseTTAFold2, and ESMFold

Structural modeling of ion channels using AlphaFold2, RoseTTAFold2, and ESMFold

(2024)

Ion channels play key roles in human physiology and are important targets in drug discovery. The atomic-scale structures of ion channels provide invaluable insights into a fundamental understanding of the molecular mechanisms of channel gating and modulation. Recent breakthroughs in deep learning-based computational methods, such as AlphaFold, RoseTTAFold, and ESMFold have transformed research in protein structure prediction and design. We review the application of AlphaFold, RoseTTAFold, and ESMFold to structural modeling of ion channels using representative voltage-gated ion channels, including human voltage-gated sodium (NaV) channel - NaV1.8, human voltage-gated calcium (CaV) channel - CaV1.1, and human voltage-gated potassium (KV) channel - KV1.3. We compared AlphaFold, RoseTTAFold, and ESMFold structural models of NaV1.8, CaV1.1, and KV1.3 with corresponding cryo-EM structures to assess details of their similarities and differences. Our findings shed light on the strengths and limitations of the current state-of-the-art deep learning-based computational methods for modeling ion channel structures, offering valuable insights to guide their future applications for ion channel research.

Cover page of Student-run free clinics may enhance medical students self-confidence in their clinical skills and preparedness for clerkships.

Student-run free clinics may enhance medical students self-confidence in their clinical skills and preparedness for clerkships.

(2024)

INTRODUCTION: Student-run free clinics (SRFCs) offer medical students a unique opportunity to develop their clinical, diagnostic, and social skills while providing care to medically underserved communities. This study aims to evaluate the value of SRFC involvement on students self-reported confidence in various clinical domains and satisfaction with their medical education. METHODS: We conducted a single-center retrospective pre-post assessment at an urban academic institution among second- to fourth-year medical students. We administered a 25-item questionnaire capturing the scope of clinic involvement and assessing self-reported confidence in multiple clinical domains following a one-year-long participation in student-run free clinics. RESULTS: Fifty-six students completed the survey. Participation in SRFCs significantly increased self-reported confidence in patient history-taking (p < 0.001), performing oral presentations (p < 0.001) and physical exams (p < 0.001). Students also reported significantly greater confidence in working with translators (p < 0.001) or as part of an interprofessional team (p < 0.001) and understanding the needs of the population served (p < 0.001). Students also found SRCs to significantly improve their confidence in preparedness for clerkships (p < 0.001). SRFC involvement can improve medical students confidence in their clinical and interpersonal skills and enhance preparedness for clerkships and working with diverse patient groups. CONCLUSION: SRFCs are a useful tool in the medical school curriculum that help bridge the gap between classroom learning and clinic and may encourage practice in medically underserved communities. SRFCs also integrate classroom material and clinical practice, although standardized evaluation metrics need to be developed. SRFCs should be incorporated as a learning experience by medical schools nationwide.

Cover page of Investigation of the seroprevalence to equine coronavirus and SARS-CoV-2 in healthy adult horses recently imported to the United States.

Investigation of the seroprevalence to equine coronavirus and SARS-CoV-2 in healthy adult horses recently imported to the United States.

(2024)

Adult horses are susceptible to equine coronavirus (ECoV) and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), although, only ECoV has been linked to clinical disease. Little information is available regarding the seroprevalence against ECoV and SARS-CoV-2 in adult healthy horses. The goal of the present study was to determine the seroprevalence against two coronaviruses known to infect horses using convenience samples collected from horses recently imported from Europe to the United States from 2019 to 2023. A total of 385 banked serum samples were tested against ECoV and SARS-CoV-2 using previously validated ELISA assays. Prevalence factors including date of arrival in the United States, signalment and country of origin were available for the majority of the horses. A total of 9/385 (2.3%) and 4/385 (1.0%) horses tested seropositive for ECoV and SARS-CoV-2, respectively. The ECoV seropositive horses were all mares, ages 4 to 26 years (median 9 years) and originated from Germany, the Netherlands, Ireland, Belgium and Italy. These mares were predominantly imported during the summer and fall months. All SARS-CoV-2 seropositive horses were mares ages 5 to 10 years (median 7.5 years) imported from the Netherlands and the United Kingdom. The majority of the SARS-CoV-2 seropositive horses were imported during the colder months of the year. The study results support the presence of ECoV in Europe and report on the first SARS-CoV-2 seropositive healthy adult horses outside the United States. Commingling for movements by air and close contact to humans may predispose transmission with ECoV and SARS-CoV-2, respectively.

Cover page of Digital health outreach to promote postpartum screening after gestational diabetes: A randomized factorial pilot study.

Digital health outreach to promote postpartum screening after gestational diabetes: A randomized factorial pilot study.

(2024)

OBJECTIVE: We examined the acceptability and feasibility of a multi-component digital health outreach intervention to promote uptake of guideline-recommended postpartum screening for type 2 diabetes among patients with gestational diabetes (GDM). METHODS: We conducted a 24 randomized factorial experiment as part of the Multiphase Optimization Strategy (MOST) preparation phase for developing behavioral interventions. Participants with current or recent GDM in an integrated healthcare system were randomized to receive an outreach message with up to four intervention components, designed to be self-administered in about 10 min and efficiently delivered online via REDCap: a streamlined values affirmation, personalized information on diabetes risk, an interactive motivational interviewing-based component, and an interactive action planning component. Patient-reported acceptability and feasibility outcomes were assessed via survey. RESULTS: Among 162 participants, 72% self-identified with a racial/ethnic minority group. Across components, acceptability scores averaged 3.9/5; ≥91% of participants read most or all of the outreach message; ≥89% perceived the amount of information as about right; and ≥ 87% completed ≥1 interactive prompt. CONCLUSION: Each intervention component was acceptable to diverse patients and feasible to deliver in a brief, self-directed, online format. INNOVATION: These novel components target unaddressed barriers to patient engagement in guideline-recommended postpartum diabetes screening and adapt theory-based behavior change techniques for large-scale use.

Cover page of The association between bone density of lumbar spines and different daily protein intake in different renal function.

The association between bone density of lumbar spines and different daily protein intake in different renal function.

(2024)

BACKGROUND: Low protein intake (LPI) has been suggested as a treatment for chronic kidney disease (CKD). However, protein intake is essential for bone health. METHODS: We studied the database of the National Health and Nutrition Examination Survey, 2005-2010. Basic variables, metabolic diseases, and bone density of different femoral areas were stratified into four subgroups according to different protein intake (DPI) (that is, <0.8, 0.8-1.0, 1.0-1.2, and >1.2 g/kg/day). RESULTS: Significant differences were found among all lumbar area bone mineral density (BMD) and T-scores (p < 0.0001). There was an apparent trend between a decreasing BMD in the CKD groups with increasing DPI in all single lumbar spines (L1, L2, L3, and L4) and all L spines (L1-L4). Compared with DPI (0.8-1.0 g/day/kg), higher risks of osteoporosis were noticed in the subgroup of >1.2 g/day/kg over L2 (relative risk (RR)=1.326, 95% confidence interval (CI)=1.062-1.656), subgroup >1.2 g/day/kg over L3 (RR = 1.31, 95%CI = 1.057-1.622), subgroup <0.8 g/day/kg over L4 (RR = 1.276, 95%CI = 1.015-1.605), subgroup <0.8 g/day/kg over all L spines (RR = 11.275, 95%CI = 1.051-1.548), and subgroup >1.2 g/day/kg over all L spines (RR = 0.333, 95%CI = 1.098-1.618). However, a higher risk of osteoporosis was observed only in the non-CKD group. There was an apparent trend of higher DPI coexisting with lower BMD and T scores in patients with CKD. For osteoporosis (reference:0.8-1.0 g/day/kg), lower (<0.8 g/day/kg) or higher DPI (>1.2 g/day/kg) was associated with higher risks in the non-CKD group, but not in the CKD group. CONCLUSIONS: In the CKD group, LPI for renal protection was safe without threatening L spine bone density and without causing a higher risk of osteoporosis.

Cover page of A compartment and metapopulation model of Rocky Mountain spotted fever in southwestern United States and northern Mexico.

A compartment and metapopulation model of Rocky Mountain spotted fever in southwestern United States and northern Mexico.

(2024)

Rocky Mountain spotted fever (RMSF) is a fatal tick-borne zoonotic disease that has emerged as an epidemic in western North America since the turn of the 21st century. Along the US south-western border and across northern Mexico, the brown dog tick, Rhipicephalus sanguineus, is responsible for spreading the disease between dogs and humans. The widespread nature of the disease and the ongoing epidemics contrast with historically sporadic patterns of the disease. Because dogs are amplifying hosts for the Rickettsia rickettsii bacteria, transmission dynamics between dogs and ticks are critical for understanding the epidemic. In this paper, we developed a compartment metapopulation model and used it to explore the dynamics and drivers of RMSF in dogs and brown dog ticks in a theoretical region in western North America. We discovered that there is an extended lag-as much as two years-between introduction of the pathogen to a naïve population and epidemic-level transmission, suggesting that infected ticks could disseminate extensively before disease is detected. A single large city-size population of dogs was sufficient to maintain the disease over a decade and serve as a source for disease in surrounding smaller towns. This model is a novel tool that can be used to identify high risk areas and key intervention points for epidemic RMSF spread by brown dog ticks.