UC Davis

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.

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 (Na_V) channel - Na_V1.8, human voltage-gated calcium (Ca_V) channel - Ca_V1.1, and human voltage-gated potassium (K_V) channel - K_V1.3. We compared AlphaFold, RoseTTAFold, and ESMFold structural models of Na_V1.8, Ca_V1.1, and K_V1.3 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.

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.

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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.

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.

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.

BACKGROUND/OBJECTIVE: Headgear designed to protect girls lacrosse athletes is widely available and permitted for voluntary use; however, it remains unknown how policies mandating headgear use may change the sport and, particularly regarding impacts during game-play. Therefore, this study compares the impact rates and game play characteristics of girls high school lacrosse in Florida which mandates headgear use (HM), with states having no headgear mandate (NHM). MATERIALS AND METHODS: Video from 189 randomly-selected games (HM: 64, NHM: 125) were analyzed. Descriptive statistics, Impact Rates (IR), Impact Rate Ratios (IRR), Impact Proportion Ratios (IPR), and 95% Confidence Intervals (CI) were calculated. IRRs and IPRs with corresponding CIs that excluded 1.00 were deemed statistically significant. RESULTS: 16,340 impacts (HM:5,821 NHM: 10,519; 86.6 impacts/game, CI: 88.6-93.3) were identified using the Lacrosse Incident Analysis Instrument (LIAI). Most impacts directly struck the body (n = 16,010, 98%). A minority of impacts directly struck a players head (n = 330, 2%). The rate of head impacts was significantly higher in the HM cohort than NHM cohort (IRR = 2.1; 95% CI = 1.7-2.6). Most head impacts (n = 271, 82%) were caused by stick contact in both groups. There was no difference in the proportion of penalties administered for head impacts caused by stick contact between the HM and NHM cohorts (IPR IRRHM/NHM = 0.98; CI = 0.79-1.16). However, there was a significantly greater proportion of head impacts caused by player contact that resulted in a penalty administered in the HM cohort (IPR = 1.44 CI = 1.17-1.54). CONCLUSION: These findings demonstrate that mandating headgear use was associated with a two-fold greater likelihood of sustaining a head impact during game play compared to NHM states. A majority of head impacts in both HM and NHM states were caused by illegal stick contact that did not result in penalty.

3' → 5' exoribonucleases play a critical role in many aspects of RNA metabolism. RNase R, PNPase, and RNase II are the major contributors to RNA processing, maturation, and quality control in bacteria. Bacteria don't seem to have dedicated RNA degradation machineries to process different classes of RNAs. Under different environmental and physiological conditions, their roles can be redundant and sometimes overlapping. Here, I discuss why PNPase and RNase R may have switched their physiological roles in some bacterial species to adapt to environmental conditions, despite being biochemically distinct exoribonucleases.

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