A Strategy To Support Perinatal Mental Health By Collaborating With Tribal Communities In Montana.

Among Indigenous women and birthing people, reported rates of perinatal mental health complications are consistently higher than in the general US population. However, perinatal mental health programs and interventions tend to focus on the general population and do not account for the unique experiences and worldviews of Indigenous Peoples. We highlight a collaborative strategy employed by a Montana nonprofit to engage Tribal communities in completing a statewide online resource guide designed to help pregnant and parenting families find resources, including mental health and substance use treatment options, within and beyond their local communities. Based on this strategy, cultural resources relevant to Tribal communities were added to the resource guide. Agencies committed to addressing perinatal mental health disparities among Indigenous populations should consider similar strategies to share power with Tribal communities and collaboratively create culturally congruent programs and interventions.

A 50-gene biomarker identifies estrogen receptor-modulating chemicals in a microarray compendium.

High throughput transcriptomics (HTTr) profiling has the potential to rapidly and comprehensively identify molecular targets of environmental chemicals that can be linked to adverse outcomes. We describe here the construction and characterization of a 50-gene expression biomarker designed to identify estrogen receptor (ER) active chemicals in HTTr datasets. Using microarray comparisons, the genes in the biomarker were identified as those that exhibited consistent directional changes when ER was activated (4 ER agonists; 4 ESR1 gene constitutively active mutants) and opposite directional changes when ER was suppressed (4 antagonist treatments; 4 ESR1 knockdown experiments). The biomarker was evaluated as a predictive tool using the Running Fisher algorithm by comparison to annotated gene expression microarray datasets including those evaluating the transcriptional effects of hormones and chemicals in MCF-7 cells. Depending on the reference dataset used, the biomarker had a predictive accuracy for activation of up to 96%. To demonstrate applicability for HTTr data analysis, the biomarker was used to identify ER activators in a set of 15 chemicals that are considered potential bisphenol A (BPA) alternatives examined at up to 10 concentrations in MCF-7 cells and analyzed by full-genome TempO-Seq. Using benchmark dose (BMD) modeling, the biomarker genes stratified the ER potency of BPA alternatives consistent with previous studies. These results demonstrate that the ER biomarker can be used to accurately identify ER activators in transcript profile data derived from MCF-7 cells.

Gestational Diabetes and Subsequent Metabolic Dysfunction: An National Health and Nutrition Examination Survey Analysis (2011-2018).

Background: Gestational diabetes mellitus (GDM) complicates ∼10% of pregnancies, with the highest rates among Asian women. Evidence suggests that GDM is associated with an increased risk for future chronic health conditions, yet data for Asian women are sparse. We explored the association between prior GDM and metabolic dysfunction with nationally representative data to obtain Asian-specific estimates. Methods: For this cross-sectional study, data were drawn from the National Health and Nutrition Examination Survey for 7195 women with a prior pregnancy. GDM (yes/no) was defined using the question "During pregnancy, were you ever told by a doctor or other health professional that you had diabetes, sugar diabetes, or gestational diabetes?." Current metabolic dysfunction (yes/no) was based on having at least one of four indicators: systolic blood pressure (SBP, ≥130 mmHg), waist circumference (≥88 cm), high-density lipoprotein (HDL) cholesterol (<50 mg/dL), and glycosylated hemoglobin (HbA1c) (≥6.5%). Logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs) for the association between prior GDM and metabolic outcomes, overall and by race. Models included sampling weights and demographic and behavioral factors. Results: Overall, women with prior GDM had 46% greater odds of high waist circumference (OR: 1.5; 95% CI: 1.1-2.0) and 200% greater odds (OR: 3.0; 95% CI: 2.1-4.2) of high HbA1c. Prior GDM was not associated with high blood pressure or low HDL cholesterol. In race-specific analyses, prior GDM was associated with increased risk of elevated HbA1c among Asian (OR: 6.6; 95% CI: 2.5-17.2), Mexican American (OR: 3.0; 95% CI: 1.5-5.8), Black (OR: 3.0; 95% CI: 1.7-5.5), and White (OR: 2.6; 95% CI: 1.5-4.6) women. Prior GDM was associated with elevated SBP among Mexican American women and low HDL among Black women. Discussion: Prior GDM is associated with elevated HbA1c among all women, yet is a stronger predictor of elevated HbA1c among Asian women than other women. Race-specific associations between prior GDM and metabolic dysfunction were observed among Mexican American and Black women. Further research is warranted to understand the observed race/ethnic-specific associations.

Cystatin from the helminth Ascaris lumbricoides upregulates mevalonate and cholesterol biosynthesis pathways and immunomodulatory genes in human monocyte-derived dendritic cells.

Background: Ascaris lumbricoides cystatin (Al-CPI) prevents the development of allergic airway inflammation and dextran-induced colitis in mice models. It has been suggested that helminth-derived cystatins inhibit cathepsins in dendritic cells (DC), but their immunomodulatory mechanisms are unclear. We aimed to analyze the transcriptional profile of human monocyte-derived DC (moDC) upon stimulation with Al-CPI to elucidate target genes and pathways of parasite immunomodulation. Methods: moDC were generated from peripheral blood monocytes from six healthy human donors of Denmark, stimulated with 1 µM of Al-CPI, and cultured for 5 hours at 37°C. RNA was sequenced using TrueSeq RNA libraries and the NextSeq 550 v2.5 (75 cycles) sequencing kit (Illumina, Inc). After QC, reads were aligned to the human GRCh38 genome using Spliced Transcripts Alignment to a Reference (STAR) software. Differential expression was calculated by DESEq2 and expressed in fold changes (FC). Cell surface markers and cytokine production by moDC were evaluated by flow cytometry. Results: Compared to unstimulated cells, Al-CPI stimulated moDC showed differential expression of 444 transcripts (|FC| ≥1.3). The top significant differences were in Kruppel-like factor 10 (KLF10, FC 3.3, PBH = 3 x 10-136), palladin (FC 2, PBH = 3 x 10-41), and the low-density lipoprotein receptor (LDLR, FC 2.6, PBH = 5 x 10-41). Upregulated genes were enriched in regulation of cholesterol biosynthesis by sterol regulatory element-binding proteins (SREBP) signaling pathways and immune pathways. Several genes in the cholesterol biosynthetic pathway showed significantly increased expression upon Al-CPI stimulation, even in the presence of lipopolysaccharide (LPS). Regarding the pathway of negative regulation of immune response, we found a significant decrease in the cell surface expression of CD86, HLA-DR, and PD-L1 upon stimulation with 1 µM Al-CPI. Conclusion: Al-CPI modifies the transcriptome of moDC, increasing several transcripts encoding enzymes involved in cholesterol biosynthesis and SREBP signaling. Moreover, Al-CPI target several transcripts in the TNF-alpha signaling pathway influencing cytokine release by moDC. In addition, mRNA levels of genes encoding KLF10 and other members of the TGF beta and the IL-10 families were also modified by Al-CPI stimulation. The regulation of the mevalonate pathway and cholesterol biosynthesis suggests new mechanisms involved in DC responses to helminth immunomodulatory molecules.

Empirical Characterization of False Discovery Rates of Differentially Expressed Genes and Transcriptomic Benchmark Concentrations in Zebrafish Embryos.

High-throughput transcriptomics (HTTr) is increasingly applied to zebrafish embryos to survey the toxicological effects of environmental chemicals. Before the adoption of this approach in regulatory testing, it is essential to characterize background noise in order to guide experimental designs. We thus empirically quantified the HTTr false discovery rate (FDR) across different embryo pool sizes, sample sizes, and concentration groups for toxicology studies. We exposed zebrafish embryos to 0.1% dimethyl sulfoxide (DMSO) for 5 days. Pools of 1, 5, 10, and 20 embryos were created (n = 24 samples for each pool size). Samples were sequenced on the TempO-Seq platform and then randomly assigned to mock treatment groups before differentially expressed gene (DEG), pathway, and benchmark concentration (BMC) analyses. Given that all samples were treated with DMSO, any significant DEGs, pathways, or BMCs are false positives. As expected, we found decreasing FDRs for DEG and pathway analyses with increasing pool and sample sizes. Similarly, FDRs for BMC analyses decreased with increasing pool size and concentration groups, with more stringent BMC premodel filtering reducing BMC FDRs. Our study provides foundational data for determining appropriate experiment designs for regulatory toxicity testing with HTTr in zebrafish embryos.

Bacillus subtilis-597 induces changes in lung pathology and inflammation during influenza A virus infection in pigs.

In recent years, it has become apparent that imbalances in the gastrointestinal system can impact organs beyond the intestine such as the lungs. Given the established ability of probiotics to modulate the immune system by interacting with gastrointestinal cells, our research aimed to investigate whether administering the probiotic strain Bacillus subtilis-597 could mitigate the outcome of influenza virus infection in pigs. Pigs were fed a diet either with or without the probiotic strain B. subtilis-597 for 14 days before being intranasally inoculated with a swine influenza A H1N2 strain (1 C.2 lineage). Throughout the study, we collected fecal samples, blood samples, and nasal swabs to examine viral shedding and immune gene expression. After seven days of infection, the pigs were euthanized, and lung and ileum tissues were collected for gene expression analysis and pathological examination. Our findings indicate that the administration of B. subtilis-597 exhibit potential in reducing lung lesions, possibly attributable to a general suppression of the immune system as indicated by reduced C-reactive protein (CRP) levels in serum, decreased expression of interferon-stimulated genes (ISGs), and localized reduction of the inflammatory marker serum amyloid A (SAA) in ileum tissue. Notably, the immune-modulatory effects of B. subtilis-597 appeared to be unrelated to the gastrointestinal microbiota, as the composition remained unaltered by both the influenza infection and the administration of B. subtilis-597.

Pharmacist-Driven Alcohol Use Disorder Screening May Increase Inpatient Utilization of Extended-Release Naltrexone: A Single Center Pilot Study.

Individuals with mental illness have a high incidence of comorbid substance use, with one of the most prevalent being alcohol use disorder (AUD). Naltrexone, FDA-approved for AUD, decreases reward associated with alcohol-related social cues. This study aimed to determine if a pharmacist-driven screening tool would increase the use of extended-release naltrexone (XR-NTX) in patients with AUD and a comorbid psychiatric condition. Pharmacists screened and recommended XR-NTX for adults admitted to the inpatient psychiatric unit, who had a DSM-5 diagnosis of AUD, a negative urine drug screen for opioids, and were hospitalized for at least 1 day. Endpoints evaluated included the number of XR-NTX doses administered during the screening period to the prescreening period, 30-day readmission rates, recommendation acceptance rates, and reasons for not administering XR-NTX. Pharmacists identified 66 of 641 screened patients who met the inclusion criteria and were candidates for XR-NTX. Compared to the preintervention period, more patients received XR-NTX for AUD (2 vs. 8). Readmission rates were similar between those with AUD who received XR-NTX and those who did not. Pharmacist-driven screening for AUD led to greater administration of XR-NTX when compared to the same 4-month period the year prior to initiating the study.

Effect of a Patient Portal Reminder Message After No-Show on Appointment Reattendance in Ophthalmology: A Randomized Clinical Trial.

PURPOSE: To assess the efficacy of electronic health record (EHR) messaging for re-engaging patients with ophthalmology care after a missed appointment. DESIGN: Prospective, randomized clinical trial. METHODS: The study setting was an academic ophthalmology department. The patient population comprised of return patients age 18 years or older with an appointment "no show," or missed appointment. Over 2 phases of recruitment, 362 patients with an active patient portal in the EHR were selected consecutively each business day. Patients were randomized using a web-based tool to receive a reminder to reschedule via a standard mailed letter only (control) or the mailed letter plus an electronic message through the EHR within 1 business day of the missed appointment (intervention). Reengagement with eye care was defined as attendance of a rescheduled appointment within 30 days of the no-show visit. Patient charts were reviewed for demographic and clinical data. RESULTS: The average age of recruited patients was 59.9 years, just under half of the sample was male (42.5%, 154/362), and most patients were White (56.9%, 206/362) or Black (36.2%, 131/362). Patients were most commonly recruited from the retina service (39.2%, 142/362) followed by the glaucoma service (29.3%, 106/362). Many patients in this study had previous no-show appointments, with an average no-show rate of 18.8% out of all scheduled visits across our health system. In total, 22.2% (42/189) of patients in the intervention group attended a follow-up appointment within 30 days of their no-show visit compared to 11.6% (20/173) of the control group (OR, 2.186; 95% CI, 1.225-3.898; P = .008). When including only the 74 patients in the intervention group who read the intervention message in the patient portal, 28.4% (21/74) attended a follow-up compared to 11.6% (20/173) of the control group (P = .001). CONCLUSIONS: EHR-based reminder messages sent within a business day of a missed appointment may promote re-engagement in ophthalmology care after appointment no-show.

Unlocking the Power of Transcriptomic Biomarkers in Qualitative and Quantitative Genotoxicity Assessment of Chemicals.

To modernize genotoxicity assessment and reduce reliance on experimental animals, new approach methodologies (NAMs) that provide human-relevant dose-response data are needed. Two transcriptomic biomarkers, GENOMARK and TGx-DDI, have shown a high classification accuracy for genotoxicity. As these biomarkers were extracted from different training sets, we investigated whether combining the two biomarkers in a human-derived metabolically competent cell line (i.e., HepaRG) provides complementary information for the classification of genotoxic hazard identification and potency ranking. First, the applicability of GENOMARK to TempO-Seq, a high-throughput transcriptomic technology, was evaluated. HepaRG cells were exposed for 72 h to increasing concentrations of 10 chemicals (i.e., eight known in vivo genotoxicants and two in vivo nongenotoxicants). Gene expression data were generated using the TempO-Seq technology. We found a prediction performance of 100%, confirming the applicability of GENOMARK to TempO-Seq. Classification using TGx-DDI was then compared to GENOMARK. For the chemicals identified as genotoxic, benchmark concentration modeling was conducted to perform potency ranking. The high concordance observed for both hazard classification and potency ranking by GENOMARK and TGx-DDI highlights the value of integrating these NAMs in a weight of evidence evaluation of genotoxicity.

Quantification of hardware effects of an on-line Dual Energy X-ray Absorptiometry scanner when predicting lamb carcass composition.

An on-line Dual Energy X-ray Absorptiometry (DXA) scanner's tissue composition prediction precision and accuracy was tested across the entire height of the unit's detector, and the hardware was assessed for robustness by measuring X-ray photon intensity throughout production days. There was good precision when predicting the tissue composition of 5 different lamb fat and lean muscle mixtures across 3 different thicknesses (R2 = 0.93 to 0.98, RMSE = 3.18% to 5.83%), however was less precise at the greatest thickness of 200 mm (R2 = 0.59, RMSE = 11.4%). There was no significant difference in the prediction of tissue composition at 8 of the 9 detector positions, however the position at the perpendicular of the X-ray photon beam was significantly different, with a fat prediction error of -4%, although no lamb carcass is detected in this position during normal production. A significant upwards drift in X-ray photon intensity was found over the course of production, especially immediately after restarting the DXA scanner following a period of inactivity. This upwards drift may affect tissue composition predictions over the span of a production day if uncorrected.

The Effect of Acute Knee Injuries and Related Knee Surgery on Serum Levels of Pro- and Anti-inflammatory Lipid Mediators and Their Associations With Knee Symptoms.

BACKGROUND: Despite an acute knee injury being a major risk factor for osteoarthritis, the factors that initiate and maintain this risk of longer-term knee symptoms are poorly understood. Bioactive lipids derived from omega-3 and -6 polyunsaturated fatty acids have key roles in the regulation of the inflammatory response and have been linked to joint damage and osteoarthritis pain in translational models. HYPOTHESIS: There would be associations between systemic levels of bioactive lipids and knee symptoms longitudinally after an acute knee injury and related knee surgery. STUDY DESIGN: Controlled laboratory study. METHODS: This study analyzed a subset of young, active adults who had sustained an acute knee injury (recruited via a surgical care pathway) and healthy age- and sex-matched controls. Surgery, if performed, was conducted after the baseline serum sample was taken and before the 3-month and 2-year visits. Liquid chromatography-tandem mass spectrometry of 41 bioactive lipids was carried out in sera of (1) 47 injured participants (median age, 28 years) collected at baseline (median, 24 days after injury), 3 months, and 2 years, along with the Knee injury and Osteoarthritis Outcome Score, and (2) age- and sex-matched controls. RESULTS: Levels of the omega-3 polyunsaturated fatty acids eicosapentaenoic acid (P≤ .0001) and docosahexaenoic acid (P≤ .0001) and the pro-resolving lipid mediators 17- and 14-hydroxydocosahexaenoic acid, and 18-hydroxyeicosapentaenoic acid were all significantly greater at baseline in injured participants compared with the later time points and also higher than in healthy controls (P = .0019 and P≤ .0001, respectively). Levels of pro-inflammatory prostaglandins E2 and D2, leukotriene B4, and thromboxane B2 were significantly lower at baseline compared with the later time points. Higher levels of 8,9-, 11,12-, and 14,15-dihydroxyeicosatrienoic acid (DHET) were cross-sectionally associated with more severe knee pain/symptoms according to the Knee injury and Osteoarthritis Outcome Score at 2 years (P = .0004, R2 = 0.251; P = .0002, R2 = 0.278; and P = .0012, R2 = 0.214, respectively). CONCLUSION: The profile of pro-resolving versus pro-inflammatory lipids at baseline suggests an initial activation of pro-resolution pathways, followed by the later activation of pro-inflammatory pathways. CLINICAL RELEVANCE: In this largely surgically managed cohort, the association of soluble epoxide hydrolase metabolites, the DHETs, with more severe knee symptoms at 2 years provides a rationale for further investigation into the role of this pathway in persisting knee symptoms in this population, including potential therapeutic strategies.

Endothelial to mesenchymal transition is an active process in smokers and patients with early COPD contributing to pulmonary arterial pathology.

Background: We have previously reported pulmonary arterial remodelling in smokers and patients with early COPD, which can be attributed to endothelial to mesenchymal transition (EndMT). In this study, we aimed to evaluate if EndMT is an active mechanism in smokers and COPD. Methods: Immunohistochemical staining for the EndMT biomarkers CD31, N-cadherin, vimentin and S100A4 was done on lung resection tissue from 49 subjects. These comprised 15 nonsmoker controls (NC), six normal lung function smokers (NLFS), nine patients with small airway disease (SAD), nine current smokers with mild-moderate COPD (COPD-CS) and 10 ex-smokers with COPD (COPD-ES). Pulmonary arteries were analysed using Image ProPlus software v7.0. Results: We noted reduced junctional CD31+ endothelial cells (p<0.05) in the intimal layer of all smoking groups compared to NC. We also observed increased abundance of the mesenchymal markers N-cadherin (p<0.05) and vimentin (p<0.001) in all smoking groups and across all arterial sizes versus NC, except for N-cadherin in large arteries in COPD-CS. The abundance of S100A4 correlated with arterial thickness (small: r=0.29, p=0.05; medium: r=0.33, p=0.03; large: r=0.35, p=0.02). Vimentin in the small arterial wall negatively correlated with forced expiratory volume in 1 s/forced vital capacity (r= -0.35, p=0.02) and forced expiratory flow rate at 25-75% of forced vital capacity (r= -0.34, p=0.03), while increased cytoplasmic CD31 abundance in the intimal layer of medium and large arteries negatively correlated with predicted diffusing capacity of the lung for carbon monoxide (medium: r= -0.35, p=0.04; large: r= -0.39, p=0.03). Conclusion: This is the first study showing the acquisition of mesenchymal traits by pulmonary endothelial cells from NLFS, SAD and mild-moderate COPD patients through EndMT. This informs on the potential early origins of pulmonary hypertension in smokers and patients with early COPD.

Transcriptome analysis in mouse skin after exposure to ultraviolet radiation from a canopy sunbed.

Exposure to ultraviolet radiation (UV-R), from both natural and artificial tanning, heightens the risk of skin cancer by inducing molecular changes in cells and tissues. Despite established transcriptional alterations at a molecular level due to UV-R exposure, uncertainties persist regarding UV radiation characterization and subsequent genomic changes. Our study aimed to mechanistically explore dose- and time-dependent gene expression changes, that may drive short-term (e.g., sunburn) and long-term actinic (e.g., skin cancer) consequences. Using C57BL/6N mouse skin, we analyzed transcriptomic expression following exposure to five erythemally weighted UV-R doses (0, 5, 10, 20, and 40 mJ/cm2 ) emitted by a UV-R tanning device. At 96 h post-exposure, 5 mJ/cm2 induced 116 statistically significant differentially expressed genes (DEGs) associated with structural changes from UV-R damage. The highest number of significant gene expression changes occurred at 6 and 48 h post-exposure in the 20 and 40 mJ/cm2 dose groups. Notably, at 40 mJ/cm2 , 13 DEGs related to skin barrier homeostasis were consistently perturbed across all timepoints. UV-R exposure activated pathways involving oxidative stress, P53 signaling, inflammation, biotransformation, skin barrier maintenance, and innate immunity. This in vivo study's transcriptional data offers mechanistic insights into both short-term and potential non-threshold-dependent long-term health effects of UV-R tanning.

Impact of Breastfeeding Barriers on Racial/Ethnic Disparities in Breastfeeding Outcomes in North Dakota.

OBJECTIVE: Exclusive breastfeeding is recommended for the first 6 months of life, but there are racial/ethnic disparities in meeting this recommendation. METHODS: 2017-2020 North Dakota Pregnancy Risk Assessment Monitoring System (weighted N = 11,754) data were used to examine racial/ethnic differences in the association between self-reported breastfeeding barriers and breastfeeding duration. Breastfeeding duration was self-reported breastfeeding at 2 and 4 months, and number of weeks until breastfeeding cessation. Self-reported breastfeeding barriers were yes/no responses to 13 barriers (e.g., "difficulty latching," "household duties"). Logistic regression estimated odds ratios and 95% confidence intervals to determine if barriers accounted for breastfeeding disparities by race/ethnicity. Cox proportional hazard models estimated hazard ratios for stopping breastfeeding for American Indian and other race/ethnicity individuals, compared to White individuals. Models were adjusted for birthing parents' demographic and medical factors. RESULTS: Logistic regression results suggest American Indian birthing parents had similar odds for breastfeeding duration (2-month duration: OR 0.94 (95%CI 0.50, 1.77); 4-month duration: OR 1.24 (95%CI 0.43, 3.62)) compared to White birthing parents, after accounting for breastfeeding barriers. Cox proportional hazard models suggest American Indian birthing parents had a lower hazard of stopping breastfeeding (HR 0.76 (95%CI 0.57, 0.99)) than White parents, after accounting for breastfeeding barriers. CONCLUSIONS: Accounting for breastfeeding barriers eliminated observed disparities in breastfeeding outcomes between American Indian and White birthing parents. Targeted and culturally safe efforts to reduce barriers to breastfeeding are warranted to reduce racial/ethnic disparities in breastfeeding.

Diet composition drives tissue-specific intensity of murine enteric infections.

Diet composition plays a large role in regulating gut health and enteric infection. In particular, synthetic "Western-style" diets may predispose to disease, while whole-grain diets containing high levels of crude fiber are thought to promote gut health. Here, we show that, in contrast to this paradigm, mice fed with unrefined chow are significantly more susceptible to infection with Trichuris muris, a caecum-dwelling nematode, than mice fed with refined, semi-synthetic diets (SSDs). Moreover, mice fed with SSD supplemented with inulin, a fermentable fiber, developed chronic T. muris burdens, whereas mice fed with SSD efficiently cleared the infection. Diet composition significantly impacted infection-induced changes in the host gut microbiome. Mice infected with the bacterium Citrobacter rodentium were also more susceptible to pathogen colonization when fed with either chow or inulin-enriched SSD. However, transcriptomic analysis of tissues from mice fed with either SSD or inulin-enriched SSD revealed that, in contrast to T. muris, increased C. rodentium infection appeared to be independent of the host immune response. Accordingly, exogenous treatment with interleukin (IL)-25 reduced T. muris burdens in inulin-fed mice, whereas IL-22 treatment was unable to restore resistance to C. rodentium colonization. Diet-mediated effects on pathogen burden were more pronounced for large intestine-dwelling pathogens, as effects on small the intestinal helminth (Heligmosomoides polygyrus) were less evident, and protozoan (Giardia muris) infection burdens were equivalent in mice fed with chow, inulin-enriched SSD, or SSD, despite higher cyst excretion in chow-fed mice. Collectively, our results point to a tissue- and pathogen-restricted effect of dietary fiber levels on enteric infection intensity.IMPORTANCEEnteric infections induce dysbiosis and inflammation and are a major public health burden. As the gut environment is strongly shaped by diet, the role of different dietary components in promoting resistance to infection is of interest. While diets rich in fiber or whole grain are normally associated with improved gut health, we show here that these components predispose the host to higher levels of pathogen infection. Thus, our results have significance for interpreting how different dietary interventions may impact on gastrointestinal infections. Moreover, our results may shed light on our understanding of how gut flora and mucosal immune function is influenced by the food that we eat.

Cardiovascular Disease Risk Factor Control in People With and Without Human Immunodeficiency Virus.

BACKGROUND: Management of hypertension, dyslipidemia, diabetes and other modifiable factors may mitigate the cardiovascular disease (CVD) risk in people with human immunodeficiency virus (HIV, PWH) compared with people without HIV (PWoH). METHODS: This was a retrospective cohort study of 8285 PWH and 170 517 PWoH from an integrated health system. Risk factor control was measured using a novel disease management index (DMI) accounting for amount/duration above treatment goals (0% to 100% [perfect control]), including 2 DMIs for hypertension (diastolic and systolic blood pressure), 3 for dyslipidemia (low-density lipoprotein, total cholesterol, triglycerides), and 1 for diabetes (HbA1c). CVD risk by HIV status was evaluated overall and in subgroups defined by DMIs, smoking, alcohol use, and overweight/obesity in adjusted Cox proportional hazards models. RESULTS: PWH and PWoH had similar DMIs (80%-100%) except for triglycerides (worse for PWH) and HbA1c (better for PWH). In adjusted models, PWH had an elevated risk of CVD compared with PWoH (hazard ratio [HR], 1.18; 95% confidence interval [CI], 1.07-1.31). This association was attenuated in subgroups with controlled dyslipidemia and diabetes but remained elevated for PWH with controlled hypertension or higher total cholesterol. The strongest HIV status association with CVD was seen in the subgroup with frequent unhealthy alcohol use (HR, 2.13; 95% CI, 1.04-4.34). CONCLUSIONS: Control of dyslipidemia and diabetes, but not hypertension, attenuated the HIV status association with CVD. The strong association of HIV and CVD with frequent unhealthy alcohol use suggests enhanced screening and treatment of alcohol problems in PWH is warranted.

The relationship between multiple sleep dimensions and obesity in adolescents: A systematic review.

Sleep is an involuntary behaviour, biologically fundamental to survival and wellbeing. However, sleep is increasingly neglected, with significant health implications. Recent research has identified associations between sleep duration, quality, timing and risk of overweight/obesity in children and adults. The aim of this review was to systematically identify and examine research that investigates the relationships between multiple objective and subjective sleep outcomes and objective adiposity measures in adolescents. A systematic review of literature, published to December 2022, was conducted using ten bibliographic databases. Search terms included objective and subjective sleep/circadian rhythm outcomes, objective adiposity measurements, and adolescents aged 8-18 years. Eighty-nine studies were included in the final review. Sleep outcomes were synthesized into three sleep domains: pre-sleep, during sleep and post-sleep outcomes. In summary, pre-sleep outcomes (including poor sleep hygiene, later chronotype and increased variability and later sleep timings) and increased sleep disturbance are consistently significantly associated with increased obesity and adiposity in adolescents. The relationship between during-sleep outcomes (sleep quality and efficiency) with adiposity and obesity measures was mixed. These findings suggest that adapting an individual's schedule to best suit chronotype preference and improving sleep hygiene, including a consistent bedtime routine, could reduce adiposity and obesity in adolescents.

Probiotic Bacillus spp. enhance TLR3-mediated TNF signalling in macrophages.

Probiotics have been reported to have immunomodulatory properties in the context of infectious disease and inflammation, although the underlying mechanisms are not fully understood. Here, we aimed to determine how different probiotic bacterial strains modulated macrophage function during TLR3 stimulation mimicking viral infection. We screened 14 different strains for their ability to modulate TNF-α, IL-6 IL-10, IFN-α, IFN-ß and IFN-γ secretion in RAW 264.7 macrophages with or without poly(I:C) stimulation. Seven strains were selected for further analysis using primary porcine alveolar macrophages. In-depth transcriptomic analysis on alveolar macrophages was conducted for two strains. Most strains induced a synergistic effect when co-incubated with poly(I:C) resulting in increased levels of IL-6 and TNF-α secretion from RAW 264.7 cells. This synergistic effect was found to be TLR2 independent. Only strains of Bacillus spp. could induce this effect in alveolar macrophages. Transcriptomic analysis indicated that the increased TNF-α secretion in alveolar macrophages after co-incubation with poly(I:C) correlated with significant upregulation of TNF and IL23A-related pathways. Collectively, our data show that probiotic bacteria possess strain-dependent immunomodulatory properties that may be harnessed to enhance innate immune responses to pathogens.

Adverse Childhood Experiences, Interpersonal Violence, and Racial Disparities in Early Prenatal Care in North Dakota (ND PRAMS 2017-2019).

In North Dakota (ND), American Indian women are more likely to be exposed to adverse childhood experiences (ACEs) and interpersonal violence, and receive late prenatal care (PNC) compared to other racial groups. In a sample of 1,849 (weighted n = 26,348) women from the 2017 to 2019 North Dakota Pregnancy Risk Assessment Monitoring System, we performed a series of logistic regression models to estimate odds ratios (OR) and 95% confidence intervals (95% CI) for AI and Other Racial Identity women compared to White women regarding risk of late PNC (initiated after week 13) and dissatisfaction of PNC timing. Models were adjusted for interpersonal violence (from husband/partner, family member, someone outside of family, ex-husband/partner, or any) to determine if violence accounts for racial/ethnic disparities in PNC. AI women experienced two-fold higher risk of late PNC (OR: 2.25, 95% CI: 1.55, 3.26) and dissatisfaction of PNC timing (OR: 2.34, 95% CI: 1.61, 3.40) than White women. In the analyses for the association between joint ACEs (Higher: ≥4; Lower: <4)/Race and PNC outcomes, odds of late PNC were two-fold among AI women with Higher ACEs (OR: 2.35, 95% CI: 1.41, 3.94) and Lower ACEs (OR: 2.73, 95% CI: 1.69, 4.41), compared to White women with Lower ACEs. Results were similar for dissatisfaction of PNC timing. Accounting for violence did not significantly change odds ratios in any analyses. Thus, interpersonal violence surrounding pregnancy does not explain racial disparities in PNC in ND. To understand disparities in PNC among AI women, risk factors like historic trauma and systemic oppression should be examined.

Impact of traditional versus nontraditional initiation dosing schedule of paliperidone palmitate on 30-day readmission and safety.

Introduction: Paliperidone palmitate (PP), a second-generation long-acting injectable antipsychotic, requires 2 injections upon initiation. Due to the fast-paced nature of the inpatient setting, the second dose may be administered earlier than recommended by labeled use despite the lack of evidence that evaluates this practice. Methods: This was a retrospective chart review that investigated the outcomes associated with the timing of the second PP initiation dose with the aim of comparing patients who received the second PP dose fewer than 3 days after the first injection with those who received it between 3 and 11 days after the first injection. The primary outcomes included 30-day psychiatric readmission, index hospitalization length of stay, and time until the next psychiatric hospitalization. Secondary outcomes included 6-month readmission and the percentage of patients who experienced an adverse event after the second injection. Results: No statistically significant differences were observed between groups for 30-day readmission. There was a statistically significant shortened index length of hospitalization (median, 2 vs 4 days; P < 0.001) and a non-statistically significant trend for time until the next psychiatric hospitalization (median, 25 vs 47 days) when comparing those who received the nontraditional loading regimen to those who received the traditional labeled loading regimen. No differences were observed in the secondary outcomes or safety/tolerability. Discussion: The results of the study indicate that there are no significant differences in readmission rates and adverse drug reactions in those who received the second PP dose earlier than recommended per labeled use. Larger, controlled studies are needed to further investigate clinical and safety outcomes.