UC Davis

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.

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.

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.

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.

In this study, laboratory loose mix oven aging was compared to field aging to begin calibration for a medium-term oven aging (MTOA) protocol. Five different oven aging temperatures were implemented at different durations to evaluate the change in chemical and rheological aging parameters for four plant-produced asphalt concrete (AC) mixes. The sulfoxide (SUL) index failed to show a consistent trend with aging for extracted binders obtained from both loose mixes and field slabs. The carbonyl area (CA) index was found to show a linear trend with the binders’ rheological parameters. The results of the field calibration indicate that loose mix oven aging of 20 h at 100 °C can simulate field aging at 0.5–0.6 in. (12 mm to 15 mm) depth after six years of pavement life in the climate region and for the material tested. Based on these results for a hot climate, loose mix aging of 20 h at 100 °C was proposed as the MTOA protocol for AC mixes for future studies.

Mousy off-flavor describes N-heterocycles compounds related to spoilage in the brewing industry. It has also been identified in sour beers through sensory analysis. Therefore, preventing spoilage N-heterocycles development is essential to preserve end-products and obviate economic losses. To this day, no methods or protocols have been reported to identifying mousy off-flavor compounds in a beer matrix. The main objective of this work was to develop a standardized quantification method for 2-acetyl-3,4,5,6-tetrahydropyridine (ATHP) in beer matrix, by Liquid Chromatography Mass Spectrometry with Electrospray Ionization (LC-MS-ESI). Extraction of ATHP in the samples was performed using QuEChERS (quick, easy, cheap, effective, rugged, and safe) technique. Over a dozen different potentially mousy cask-aged sour beers including other spontaneously fermented beverages were provided, based on sensory analysis, to determine the variation in ATHP levels. Results indicated ATHP was found in all the samples, ranging from 1.64 ± 0.06 to 57.96 ± 2.15 µg L-1. Herein, we described our detection method of mousy-off flavor compounds which enables future research to mitigate the occurrence of such defects in fermented beverages matrix.•ATHP content in samples varied from 1.64 ± 0.06 to 57.96 ± 2.15 µg L-1.•The recovery range of ATHP using LC-MS-ESI varied from 71% to 97%.•Basified QuEChERS salting-out procedure is applicable for ATHP extraction from beer and other fermented beverages matrices.

Acute poisoning with organophosphorus cholinesterase inhibitors (OPs), such as OP nerve agents and pesticides, can cause life threatening cholinergic crisis and status epilepticus (SE). Survivors often experience significant morbidity, including brain injury, acquired epilepsy, and cognitive deficits. Current medical countermeasures for acute OP poisoning include a benzodiazepine to mitigate seizures. Diazepam was long the benzodiazepine included in autoinjectors used to treat OP-induced seizures, but it is now being replaced in many guidelines by midazolam, which terminates seizures more quickly, particularly when administered intramuscularly. While a direct correlation between seizure duration and the extent of brain injury has been widely reported, there are limited data comparing the neuroprotective efficacy of diazepam versus midazolam following acute OP intoxication. To address this data gap, we used non-invasive imaging techniques to longitudinally quantify neuropathology in a rat model of acute intoxication with the OP diisopropylfluorophosphate (DFP) with and without post-exposure intervention with diazepam or midazolam. Magnetic resonance imaging (MRI) was used to monitor neuropathology and brain atrophy, while positron emission tomography (PET) with a radiotracer targeting translocator protein (TSPO) was utilized to assess neuroinflammation. Animals were scanned at 3, 7, 28, 65, 91, and 168 days post-DFP and imaging metrics were quantitated for the hippocampus, amygdala, piriform cortex, thalamus, cerebral cortex and lateral ventricles. In the DFP-intoxicated rat, neuroinflammation persisted for the duration of the study coincident with progressive atrophy and ongoing tissue remodeling. Benzodiazepines attenuated neuropathology in a region-dependent manner, but neither benzodiazepine was effective in attenuating long-term neuroinflammation as detected by TSPO PET. Diffusion MRI and TSPO PET metrics were highly correlated with seizure severity, and early MRI and PET metrics were positively correlated with long-term brain atrophy. Collectively, these results suggest that anti-seizure therapy alone is insufficient to prevent long-lasting neuroinflammation and tissue remodeling.

INTRODUCTION: Criminal convictions may be imperfect markers of criminalized behavior, in part because of criminal legal system processes (e.g., plea bargaining). In this retrospective cohort study of individuals convicted of misdemeanors, authors compared the risk of subsequent criminal charges for a violent crime among those initially charged with a felony with that among those initially charged with only misdemeanors, overall and by defendant race and ethnicity. METHODS: The study population included individuals aged ≥18 years who were convicted of a misdemeanor in Washington Superior Courts from January 1, 2015 to December 31, 2019. Those with and without initial felony charges were age/gender matched in a 4:1 ratio. The primary outcome was the first subsequent violent crime charge in Washington Superior Courts through December 31, 2020. Data were analyzed with Fine-Gray hazard models from June 2022 to November 2023. RESULTS: There were 3,841 individuals with initial felony charges and 956 with initial misdemeanor charges only. Median follow-up was 2.4 years for both groups. During follow-up, there were 166 new violent crime charges. In multivariable models, White defendants with initial felony charges had a greater risk of subsequent violent crime charges (subdistribution hazard ratio=2.58; 95% CI=1.24, 5.36) than White defendants with initial misdemeanor charges only. Among Black and Hispanic/Latinx defendants, initial felony versus misdemeanor charges were not associated with subsequent violent crime charges (subdistribution hazard ratio=0.93; 95% CI=0.44, 1.97 among Black defendants; subdistribution hazard ratio=0.49; 95% CI=0.15, 1.57 among Hispanic/Latinx defendants). CONCLUSIONS: Findings suggest differential associations between downgrading of felony charges to misdemeanor convictions and future violent crime charges by defendant race and ethnicity, with implications for inequitable collateral consequences of criminal convictions.