The effect of a selenium-based anti-inflammatory strategy on postoperative functional recovery in high-risk cardiac surgery patients - A nested sub-study of the sustain CSX trial.

AIM: The cardiac surgery-related ischemia-reperfusion-related oxidative stress triggers the release of cytotoxic reactive oxygen and nitrogen species, contributing to organ failure and ultimately influencing patients' short- and long-term outcomes. Selenium is an essential co-factor for various antioxidant enzymes, thereby contributing to the patients' endogenous antioxidant and anti-inflammatory defense mechanisms. Given these selenium's pleiotropic functions, we investigated the effect of a high-dose selenium-based anti-inflammatory perioperative strategy on functional recovery after cardiac surgery. MATERIALS AND METHODS: This prospective study constituted a nested sub-study of the SUSTAIN CSX trial, a double-blinded, randomized, placebo-controlled multicenter trial to investigate the impact of high-dose selenium supplementation on high-risk cardiac surgery patients' postoperative recovery. Functional recovery was assessed by 6-min walk distance, Short Form-36 (SF-36) and Barthel Index questionnaires. KEY FINDINGS: 174 patients were included in this sub-study. The mean age (SD) was 67.3 (8.9) years, and 78.7 % of the patients were male. The mean (SD) predicted 30-day mortality by the European System for Cardiac Operative Risk Evaluation II score was 12.6 % (9.4 %). There was no difference at hospital discharge and after three months in the 6-min walk distance between the selenium and placebo groups (131 m [IQR: not performed - 269] vs. 160 m [IQR: not performed - 252], p = 0.80 and 400 m [IQR: 299-461] vs. 375 m [IQR: 65-441], p = 0.48). The SF-36 and Barthel Index assessments also revealed no clinically meaningful differences between the selenium and placebo groups. SIGNIFICANCE: A perioperative anti-inflammatory strategy with high-dose selenium supplementation did not improve functional recovery in high-risk cardiac surgery patients.

Teaching Medical Students Rapid Ultrasound for shock and hypotension (RUSH): learning outcomes and clinical performance in a proof-of-concept study.

BACKGROUND: Point-of-care ultrasound (POCUS) is a critical diagnostic tool in various medical settings, yet its instruction in medical education is inconsistent. The Rapid Ultrasound for Shock and Hypotension (RUSH) protocol is a comprehensive diagnostic tool, but its complexity poses challenges for teaching and learning. This study evaluates the effectiveness of a single-day training in RUSH for medical students by assessing their performance in clinical scenarios. METHODS: In this prospective single-center observational proof-of-concept study, 16 medical students from Saarland University Medical Center underwent a single-day training in RUSH, followed by evaluations in clinical settings and on a high-fidelity simulator. Performance was assessed using a standardized scoring tool and time to complete the RUSH exam. Knowledge gain was measured with pre- and post-training written exams, and diagnostic performance was evaluated with an objective structured clinical examination (OSCE). RESULTS: Students demonstrated high performance in RUSH exam views across patients (median performance: 85-87%) and improved scanning times, although not statistically significant. They performed better on simulators than on live patients. Written exam scores significantly improved post-training, suggesting a gain in theoretical knowledge. However, more than a third of students could not complete the RUSH exam within five minutes on live patients. CONCLUSIONS: Single-day RUSH training improved medical students' theoretical knowledge and simulator performance but translating these skills to clinical settings proved challenging. The findings suggest that while short-term training can be beneficial, it may not suffice for clinical proficiency. This study underscores the need for structured and possibly longitudinal training programs to ensure skill retention and clinical applicability.

Proteomic and Metabolomic Signatures of Diet Quality in Young Adults.

The assessment of "omics" signatures may contribute to personalized medicine and precision nutrition. However, the existing literature is still limited in the homogeneity of participants' characteristics and in limited assessments of integrated omics layers. Our objective was to use post-prandial metabolomics and fasting proteomics to identify biological pathways and functions associated with diet quality in a population of primarily Hispanic young adults. We conducted protein and metabolite-wide association studies and functional pathway analyses to assess the relationships between a priori diet indices, Healthy Eating Index-2015 (HEI) and Dietary Approaches to Stop Hypertension (DASH) diets, and proteins (n = 346) and untargeted metabolites (n = 23,173), using data from the MetaAIR study (n = 154, 61% Hispanic). Analyses were performed for each diet quality index separately, adjusting for demographics and BMI. Five proteins (ACY1, ADH4, AGXT, GSTA1, F7) and six metabolites (undecylenic acid, betaine, hyodeoxycholic acid, stearidonic acid, iprovalicarb, pyracarbolid) were associated with both diets (p < 0.05), though none were significant after adjustment for multiple comparisons. Overlapping proteins are involved in lipid and amino acid metabolism and in hemostasis, while overlapping metabolites include amino acid derivatives, bile acids, fatty acids, and pesticides. Enriched biological pathways were involved in macronutrient metabolism, immune function, and oxidative stress. These findings in young Hispanic adults contribute to efforts to develop precision nutrition and medicine for diverse populations.

Diagnostic prediction models to identify patients at risk for healthcare-facility-onset Clostridioides difficile: A systematic review of methodology and reporting.

OBJECTIVE: To systematically review the methodology, performance, and generalizability of diagnostic models for predicting the risk of healthcare-facility-onset (HO) Clostridioides difficile infection (CDI) in adult hospital inpatients (aged ≥18 years). BACKGROUND: CDI is the most common cause of healthcare-associated diarrhea. Prediction models that identify inpatients at risk of HO-CDI have been published; however, the quality and utility of these models remain uncertain. METHODS: Two independent reviewers evaluated articles describing the development and/or validation of multivariable HO-CDI diagnostic models in an inpatient setting. All publication dates, languages, and study designs were considered. Model details (eg, sample size and source, outcome, and performance) were extracted from the selected studies based on the CHARMS checklist. The risk of bias was further assessed using PROBAST. RESULTS: Of the 3,030 records evaluated, 11 were eligible for final analysis, which described 12 diagnostic models. Most studies clearly identified the predictors and outcomes but did not report how missing data were handled. The most frequent predictors across all models were advanced age, receipt of high-risk antibiotics, history of hospitalization, and history of CDI. All studies reported the area under the receiver operating characteristic curve (AUROC) as a measure of discriminatory ability. However, only 3 studies reported the model calibration results, and only 2 studies were externally validated. All of the studies had a high risk of bias. CONCLUSION: The studies varied in their ability to predict the risk of HO-CDI. Future models will benefit from the validation on a prospective external cohort to maximize external validity.

Exposure to ambient air pollutants, serum miRNA networks, lipid metabolism, and non-alcoholic fatty liver disease in young adults.

BACKGROUND AND AIM: Ambient air pollution (AAP) exposure has been associated with altered blood lipids and liver fat in young adults. MicroRNAs regulate gene expression and may mediate these relationships. This work investigated associations between AAP exposure, serum microRNA networks, lipid profiles, and non-alcoholic fatty liver disease (NAFLD) risk in young adults. METHODS: Participants were 170 young adults (17-22 years) from the Meta-AIR cohort of the Children's Health Study (CHS). Residential AAP exposure (PM2.5, PM10, NO2, 8-hour maximum O3, redox-weighted oxidative capacity [Oxwt]) was spatially interpolated from monitoring stations via inverse-distance-squared weighting. Fasting serum lipids were assayed. Liver fat was imaged by MRI and NAFLD was defined by ≥ 5.5% hepatic fat fraction. Serum microRNAs were measured via NanoString and microRNA networks were constructed by weighted gene correlation network analysis. The first principal component of each network represented its expression profile. Multivariable mixed effects regression models adjusted for sociodemographic, behavioral, and clinical covariates; baseline CHS town code was a random effect. Effects estimates are scaled to one standard deviation of exposure. Mediation analysis explored microRNA profiles as potential mediators of exposure-outcome associations. DIANA-mirPATH identified overrepresented gene pathways targeted by miRNA networks. RESULTS: Prior-month Oxwt was associated with NAFLD (OR=3.45; p = 0.003) and inversely associated with microRNA Network A (ß = -0.016; p = 0.026). Prior-year NO2 was associated with non-HDL-cholesterol (ß = 7.13; p = 0.01) and inversely associated with miRNA Network A (ß = -0.019; p = 0.022). Network A expression was inversely associated with NAFLD (OR=0.35; p = 0.010) and non-HDL-C (ß = -6.94 mg/dL; p = 0.035). Network A members miR-199a/b-3p and miR-130a, which both target fatty acid synthase, mediated 21% of the association between prior-month Oxwt exposure with NAFLD (p = 0.048) and 23.3% of the association between prior-year NO2 exposure and non-HDL-cholesterol (p = 0.026), respectively. CONCLUSIONS: Exposure to AAP may contribute to adverse lipid profiles and NAFLD risk among young adults via altered expression of microRNA profiles.

Human milk EV-miRNAs: a novel biomarker for air pollution exposure during pregnancy.

Exposure to ambient and near-roadway air pollution during pregnancy has been linked with several adverse health outcomes for pregnant women and their babies. Emerging research indicates that microRNA (miRNA) expression can be altered by exposure to air pollutants in a variety of tissues. Additionally, miRNAs from breast tissue and circulating miRNAs have previously been proposed as a biomarker for breast cancer diagnosis and prognosis. Therefore, this study sought to evaluate the associations between pregnancy exposures to ambient (PM10, PM2.5, NO2, O3) and near-roadway air pollution (total NOx, freeway NOx, non-freeway NOx) with breast milk extracellular vesicle miRNA (EV-miRNA), measured at 1-month postpartum, in a cohort of 108 Latina women living in Southern California. We found that PM10 exposure during pregnancy was positively associated with hsa-miR-200c-3p, hsa-miR-200b-3p, and hsa-let-7c-5p, and was negatively associated with hsa-miR-378d. We also found that pregnancy PM2.5 exposure was positively associated with hsa-miR-200c-3p and hsa-miR-200b-3p. First and second trimester exposure to PM10 and PM2.5 was associated with several EV-miRNAs with putative messenger RNA targets related to cancer. This study provides preliminary evidence that air pollution exposure during pregnancy is associated with human milk EV-miRNA expression.

Direct economic burden of mental health disorders associated with polycystic ovary syndrome: Systematic review and meta-analysis.

Background: Polycystic ovary syndrome (PCOS) is the most common hormone disorder affecting about one in seven reproductive-aged women worldwide and approximately 6 million women in the United States (U.S.). PCOS can be a significant burden to those affected and is associated with an increased prevalence of mental health (MH) disorders such as depression, anxiety, eating disorders, and postpartum depression. We undertook this study to determine the excess economic burden associated with MH disorders in women with PCOS in order to allow for a more accurate prioritization of the disorder as a public health priority. Methods: Following PRISMA reporting guidelines for systematic review, we searched PubMed, Web of Science, EBSCO, Medline, Scopus, and PsycINFO through July 16, 2021, for studies on MH disorders in PCOS. Excluded were studies not in humans, without controls, without original data, or not peer reviewed. As anxiety, depression, eating disorders, and postpartum depression were by far the most common MH disorders assessed by the studies, we performed our meta-analysis on these disorders. Meta-analyses were performed using the DerSimonian-Laird random effects model to compute pooled estimates of prevalence ratios (PRs) for the associations between PCOS and these MH disorders and then calculated the excess direct costs related to these disorders in U.S. dollars (USD) for women suffering from PCOS in the U.S. alone. The quality of selected studies was assessed using the Newcastle-Ottawa Scale. Results: We screened 78 articles by title/abstract, assessed 43 articles in full text, and included 25 articles. Pooled PRs were 1.42 (95% confidence interval [CI]: 1.32-1.52) for anxiety, 1.65 (95% CI: 1.44-1.89) for depression, 1.48 (95% CI: PR: 1.06-2.05) for eating disorders, and 1.20 (95% CI: 0.96-1.50) for postpartum depression, for PCOS relative to controls. In the U.S., the additional direct healthcare costs associated with anxiety, depression, and eating disorders in PCOS were estimated to be $1.939 billion/yr, $1.678 billion/yr, and $0.644 billion/yr in 2021 USD, respectively. Postpartum depression was excluded from the cost analyses due to the non-significant meta-analysis result. Taken together, the additional direct healthcare costs associated with anxiety, depression, and eating disorders in PCOS were estimated to be $4.261 billion/yr in 2021 USD. Conclusions: Overall, the direct healthcare annual costs for the most common MH disorders in PCOS, namely anxiety, depression, and eating disorders, exceeds $4 billion in 2021 USD for the U.S. population alone. Taken together with our prior work, these data suggest that the healthcare-related economic burden of PCOS exceeds $15 billion yearly, considering the costs of PCOS diagnosis, and costs related to PCOS-associated MH, reproductive, vascular, and metabolic disorders. As PCOS has much the same prevalence across the world, the excess economic burden attributable to PCOS globally is enormous, mandating that the scientific and policy community increase its focus on this important disorder. Funding: The study was supported, in part, by PCOS Challenge: The National Polycystic Ovary Syndrome Association and by the Foundation for Research and Education Excellence.

Polycystic Ovary Syndrome (PCOS) affects one in seven reproductive-age women worldwide. PCOS impacts women's physical and mental health, and it may also have detrimental effects on their social lives, academic achievement and careers. Studies show women with PCOS have higher rates of depression, anxiety, eating disorders, infertility and postpartum depression compared with women without the condition. The economic burden of PCOS is enormous. Previous studies show PCOS-related economic costs totals billions of dollars. But few studies have examined the costs associated with PCOS-associated mental health care. Learning more about these costs may help policymakers and clinicians allocate resources for mental health care for women with PCOS. Yadav et al. analyzed the results of 25 studies to assess the mental health impact of PCOS and its costs. The analysis found that women with PCOS are 60% more likely to have depression or anxiety compared to women without the condition. They were also twice as likely to have eating disorders. Caring for these mental health issues in PCOS patients increases US healthcare costs by approximately $4.2 billion yearly. These costs raise the healthcare-related economic burden of treating PCOS and associated conditions to $15 billion in the United States each year. The analysis suggests that earlier recognition and better treatment of PCOS could reduce associated healthcare costs and improve the quality of life for women with PCOS. The results may help policymakers and clinicians understand the condition's impact and prioritize resources for PCOS care. More research on the condition is necessary to reduce the enormous economic and personal burden caused by it.

Influence of technical and maternal-infant factors on the measurement and expression of extracellular miRNA in human milk.

Breast milk contains thousands of bioactive compounds including extracellular vesicle microRNAs (EV-miRNAs), which may regulate pathways such as infant immune system development and metabolism. We examined the associations between the expression of EV-miRNAs and laboratory variables (i.e., batch effects, sample characteristics), sequencing quality indicators, and maternal-infant characteristics. The study included 109 Latino mother-infant dyads from the Southern California Mother's Milk Study. Mothers were age 28.0 ± 5.6 and 23-46 days postpartum. We used principal components analysis to evaluate whether EV-miRNA expression was associated with factors of interest. Then, we used linear models to estimate relationships between these factors and specific EV-miRNA counts and analyzed functional pathways associated with those EV-miRNAs. Finally, we explored which maternal-infant characteristics predicted sequencing quality indicators. Sequencing quality indicators, predominant breastfeeding, and breastfeedings/day were associated with EV-miRNA principal components. Maternal body mass index and breast milk collection timing predicted proportion of unmapped reads. Expression of 2 EV-miRNAs were associated with days postpartum, 23 EV-miRNAs were associated with breast milk collection time, 23 EV-miRNAs were associated with predominant breastfeeding, and 38 EV-miRNAs were associated with breastfeedings/day. These EV-miRNAs were associated with pathways including Hippo signaling pathway and ECM-receptor interaction, among others. This study identifies several important factors that may contribute to breast milk EV-miRNA expression. Future studies should consider these findings in the design and analysis of breast milk miRNA research.

Eye lens-derived Δ14C signatures validate extreme longevity in the deepwater scorpaenid blackbelly rosefish (Helicolenus dactylopterus).

Many members of the scorpaenid subfamily: Sebastinae (rockfishes and their relatives) exhibit slow growth and extreme longevity (> 100 y), thus are estimated to be vulnerable to overfishing. Blackbelly rosefish (Helicolenus dactylopterus) is a deepwater sebastine whose longevity estimates range widely, possibly owing to different regional levels of fisheries exploitation across its Atlantic Ocean range. However, age estimation has not been validated for this species and ageing for sebastines in general is uncertain. We performed age validation of northern Gulf of Mexico blackbelly rosefish via an application of the bomb radiocarbon chronometer which utilized eye lens cores instead of more traditional otolith cores as the source of birth year Δ14C signatures. The correspondence of eye lens core Δ14C with a regional reference series was tested with a novel Bayesian spline analysis, which revealed otolith opaque zone counts provide accurate age estimates. Maximum observed longevity was 90 y, with 17.5% of individuals aged to be > 50 y. Bayesian growth analysis, with estimated length-at-birth included as a prior, revealed blackbelly rosefish exhibit extremely slow growth (k = 0.08 y-1). Study results have important implications for the management of blackbelly rosefish stocks, as extreme longevity and slow growth imply low resilience to fishing pressure.

Thrombotic outcomes in patients in a large clinical enterprise following COVID-19 vaccination.

Vaccination against COVID-19 reduces infection-related mortality. Unfortunately, reports of vaccine-induced immune thrombotic thrombocytopenia (VITT) in individuals administered adenovirus-vector-based vaccines (ChAdOx1 nCoV-19 and Ad26.COV2.S) have spurred side effect concerns. To address vaccine hesitancy related to this, it is essential to determine the incidence of VITT (defined by a 50% decrease in platelet count and positive anti-PF4 immunoassay within 4-28 days after vaccination) among patients administered two doses of an mRNA-based COVID-19 vaccination. We identified a retrospective cohort of 223,345 patients in the Cleveland Clinic Enterprise administered a COVID-19 vaccine at any location in Northeast Ohio and Florida from 12/4/2020 to 6/6/2021. 97.3% of these patients received an mRNA-based vaccination. Patients with: (1) a serial complete blood count both before and after vaccination and (2) a decrease in platelet count of ≥ 50% were selected for chart review. The primary outcome was the incidence of thrombotic events, including venous thromboembolism (VTE) and arterial thrombosis, 4-28 days post vaccination. Of 74 cohort patients with acute thrombosis, 72 (97.3%) demonstrated clear etiologies, such as active malignancy. Of two patients with unprovoked thrombosis, only one had findings concerning for VITT, with a strongly positive anti-PF4 antibody assay. In this large, multi-state, retrospective cohort, of 223,345 patients (97.2% of whom received the mRNA-based mRNA-1273 or BNT162b2 vaccines), we detected a single case that was concerning for VITT in a patient who received an mRNA vaccine. The overwhelming majority of patients with a thrombotic event 4-28 days following vaccination demonstrated clear etiologies.

Cutaneous ulcerative lesions of unknown etiology affecting lionfish Pterois spp. in the Gulf of Mexico.

OBJECTIVE: Cutaneous ulcerative skin lesions in a complex of invasive Gulf of Mexico lionfish (Red Lionfish Pterois volitans, Devil Firefish P. miles, and the hybrid Red Lionfish × Devil Firefish) became epizootic beginning in mid-August 2017. Herein, we provide the first pathological descriptions of these lesions and summarize our analyses to elucidate the etiology of the disease. METHODS: We examined ulcerated and normal fish through gross pathology and histopathology, bacterial sampling, and unbiased metagenomic next-generation sequencing. We tracked prevalence of the disease, and we used biological health indicators (condition factor, splenosomatic and hepatosomatic index) to evaluate impacts to health, while considering sex and age as potential risk factors. RESULT: Typical ulcerative lesions were deep, exposing skeletal muscle, and were bordered by pale or reddened areas often with some degree of scale loss. Only incidental parasites were found in our examinations. Most fish (86%; n = 50) exhibited wound healing grossly and histologically, confirmed by the presence of granulation tissues. A primary bacterial pathogen was not evident through bacterial culture or histopathology. Metagenomic next-generation sequencing did not reveal a viral pathogen (DNA or RNA) but did provide information about the microbiome of some ulcerated specimens. Compared with clinically healthy fish, ulcerated fish had a significantly lower condition factor and a higher splenosomatic index. Disease prevalence at monitored sites through July 2021 indicated that ulcerated fish were still present but at substantially lower prevalence than observed in 2017. CONCLUSION: Although some common findings in a number of specimens suggest a potential role for opportunistic bacteria, collectively our suite of diagnostics and analyses did not reveal an intralesional infectious agent, and we must consider the possibility that there was no communicable pathogen.

Prenatal exposure to ambient air pollution is associated with neurodevelopmental outcomes at 2 years of age.

BACKGROUND: Higher prenatal ambient air pollution exposure has been associated with impaired neurodevelopment in preschoolers and school-aged children. The purpose of this study was to explore the relationships between prenatal ambient air pollution exposure and neurodevelopment during infancy. METHODS: This study examined 161 Latino mother-infant pairs from the Southern California Mother's Milk Study. Exposure assessments included prenatal nitrogen dioxide (NO2) and particulate matter smaller than 2.5 and 10 microns in diameter (PM2.5 and PM10, respectively). The pregnancy period was also examined as three windows, early, mid, and late, which describe the first, middle, and last three months of pregnancy. Infant neurodevelopmental outcomes at 2 years of age were measured using the Bayley-III Scales of Infant and Toddler Development. Multivariable linear models and distributed lag linear models (DLM) were used to examine relationships between prenatal exposures and neurodevelopmental scores, adjusting for socioeconomic status, breastfeeding frequency, time of delivery, pre-pregnancy body mass index, and infant birthweight and sex. RESULTS: Higher prenatal exposure to PM10 and PM2.5 was negatively associated with composite cognitive score (ß = -2.01 [-3.89, -0.13] and ß = -1.97 [-3.83, -0.10], respectively). In addition, higher average prenatal exposure to PM10 was negatively associated with composite motor (ß = -2.35 [-3.95, -0.74]), scaled motor (ß = -0.77 [-1.30, -0.24]), gross motor (ß = -0.37 [-0.70, -0.04]), fine motor (ß = -0.40 [-0.71, -0.09]), composite language (ß = -1.87 [-3.52, -0.22]), scaled language (ß = -0.61 [-1.18, -0.05]) and expressive communication scaled scores (ß = -0.36 [-0.66, -0.05]). DLMs showed that higher prenatal air pollution exposure during mid and late pregnancy was inversely associated with motor, cognitive, and communication language scores. CONCLUSIONS: Higher exposure to air pollutants during pregnancy, particularly in the mid and late prenatal periods, was inversely associated with scaled and composite motor, cognitive, and language scores at 2 years. These results indicate that prenatal ambient air pollution may negatively impact neurodevelopment in early life.

Diet Quality Is Associated with Glucose Regulation in a Cohort of Young Adults.

Young-onset type 2 diabetes and prediabetes is a growing epidemic. Poor diet is a known risk factor for T2D in older adults, but the contribution of diet to risk factors for T2D is not well-described in youth. Our objective was to examine the relationship of diet quality with prediabetes, glucose regulation, and adiposity in young adults. A cohort of young adults (n = 155, age 17-22) was examined between 2014-2018, and 89 underwent a follow-up visit from 2020-2022. At each visit, participants completed diet and body composition assessments and an oral glucose tolerance test. Adherence to four dietary patterns was assessed: Dietary Approaches to Stop Hypertension (DASH), Healthy Eating Index (HEI), Mediterranean diet, and Diet Inflammatory Index (DII). Regression analyses were used to determine adjusted associations of diet with risk for prediabetes and adiposity. Each one-point increase in DASH or HEI scores between visits reduced the risk for prediabetes at follow-up by 64% (OR, 95% CI: 0.36, 0.17-0.68) and 9% (OR, 95% CI: 0.91, 0.85-0.96), respectively. The DASH diet was inversely associated with adiposity, while DII was positively associated with adiposity. In summary, positive changes in HEI and DASH scores were associated with reduced risk for prediabetes in young adults.

A Metagenomic Investigation of Spatial and Temporal Changes in Sewage Microbiomes across a University Campus.

Wastewater microbial communities are not static and can vary significantly across time and space, but this variation and the factors driving the observed spatiotemporal variation often remain undetermined. We used a shotgun metagenomic approach to investigate changes in wastewater microbial communities across 17 locations in a sewer network, with samples collected from each location over a 3-week period. Fecal material-derived bacteria constituted a relatively small fraction of the taxa found in the collected samples, highlighting the importance of environmental sources to the sewage microbiome. The prokaryotic communities were highly variable in composition depending on the location within the sampling network, and this spatial variation was most strongly associated with location-specific differences in sewage pH. However, we also observed substantial temporal variation in the composition of the prokaryotic communities at individual locations. This temporal variation was asynchronous across sampling locations, emphasizing the importance of independently considering both spatial and temporal variation when assessing the wastewater microbiome. The spatiotemporal patterns in viral community composition closely tracked those of the prokaryotic communities, allowing us to putatively identify the bacterial hosts of some of the dominant viruses in these systems. Finally, we found that antibiotic resistance gene profiles also exhibit a high degree of spatiotemporal variability, with most of these genes unlikely to be derived from fecal bacteria. Together, these results emphasize the dynamic nature of the wastewater microbiome, the challenges associated with studying these systems, and the utility of metagenomic approaches for building a multifaceted understanding of these microbial communities and their functional attributes. IMPORTANCE Sewage systems harbor extensive microbial diversity, including microbes derived from both human and environmental sources. Studies of the sewage microbiome are useful for monitoring public health and the health of our infrastructure, but the sewage microbiome can be highly variable in ways that are often unresolved. We sequenced DNA recovered from wastewater samples collected over a 3-week period at 17 locations in a single sewer system to determine how these communities vary across time and space. Most of the wastewater bacteria, and the antibiotic resistance genes they harbor, were not derived from human feces, but human usage patterns did impact how the amounts and types of bacteria and bacterial genes we found in these systems varied over time. Likewise, the wastewater communities, including both bacteria and their viruses, varied depending on location within the sewage network, highlighting the challenges and opportunities in efforts to monitor and understand the sewage microbiome.

Fine-scale movement of northern Gulf of Mexico red snapper and gray triggerfish estimated with three-dimensional acoustic telemetry.

Red snapper and gray triggerfish are ecologically, economically, and culturally important reef fishes in the northern Gulf of Mexico (nGOM). Scientists and managers have sought to understand the effects of artificial reefs on reef fish ecology by focusing on fish residency and movement at artificial reefs with less attention paid to broader spatial and temporal patterns in reef fish movements among a seascape of artificial reefs and other natural habitats. We used novel large-scale (> 15 km2) geopositioning acoustic telemetry arrays to track the 3-dimensional movements of tagged red snapper (n = 59) and gray triggerfish (n = 15) among multiple nGOM artificial reefs up to 333 days. Tagged fish moved frequently among artificial reefs and had shorter residence times at the release reef (43 days for red snapper and 3 days for gray triggerfish) than reported in previous studies. Both species displayed high individual variability in movement dynamics, as well as seasonally variable diel patterns of habitat use, height above bottom, and distance to reefs, which may have been driven by dynamic influences of predation risk, physiological constraints, or foraging over time and space. The wider seascape view revealed in this study demonstrates the importance of including multiple artificial reefs over long timescales to capture individual, spatial, and temporal variability in reef fish movement.

Towards Automatic Prediction of Outcome in Treatment of Cerebral Aneurysms.

Intrasaccular flow disruptors treat cerebral aneurysms by diverting the blood flow from the aneurysm sac. Residual flow into the sac after the intervention is a failure that could be due to the use of an undersized device, or to vascular anatomy and clinical condition of the patient. We report a machine learning model based on over 100 clinical and imaging features that predict the outcome of wide-neck bifurcation aneurysm treatment with an intrasaccular embolization device. We combine clinical features with a diverse set of common and novel imaging measurements within a random forest model. We also develop neural network segmentation algorithms in 2D and 3D to contour the sac in angiographic images and automatically calculate the imaging features. These deliver 90% overlap with manual contouring in 2D and 83% in 3D. Our predictive model classifies complete vs. partial occlusion outcomes with an accuracy of 75.31%, and weighted F1-score of 0.74.

The Effect of Maternal Vitamin D Supplementation on Vitamin D Status of Exclusively Breastfeeding Mothers and Their Nursing Infants: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

The optimal vitamin D supplementation plan during lactation is unclear. We investigated the effect of maternal vitamin D supplementation on mother-infant dyads' vitamin D status during lactation. All controlled trials that compared vitamin D supplements to placebo or low doses of vitamin D in breastfeeding mothers were included. Pooled effect size and the associated 95% CI for each outcome were estimated using random-effects models. A 1-stage random-effect dose-response model was used to estimate the dose-response relation across different vitamin D dosages and serum 25-hydroxy vitamin D [25(OH)D] concentrations. We identified 19 clinical trials with 27 separate comparison groups (n = 3337 breastfeeding mothers). Maternal vitamin D supplement dosages were associated with circulating 25(OH)D concentrations in breastfeeding women in a nonlinear fashion. Supplementation with 1000 IU of vitamin D/d increased serum 25(OH)D concentrations by 7.8 ng/mL, whereas there was a lower increase in concentrations at vitamin D doses of >2000 IU/d (3.07 and 2.05 ng/mL increases between 2000-3000 and 3000-4000 IU/d, respectively). A linear relation was observed between maternal vitamin D supplementation dosage and the infants' circulating 25(OH)D concentrations. Each additional 1000 IU of maternal vitamin D intake was accompanied by a 2.7 ng/mL increase in serum 25(OH)D concentration in their nursing infants. The subgroup analysis showed that maternal vitamin D supplementation was accompanied by a statistically significant increase in infants' 25(OH)D concentration in the trials with a duration of >20 wk, vitamin D supplementation >1000 IU/d, East Indian participants, maternal BMI <25 kg/m2, and studies with an overall low risk of bias. Long-term maternal supplementation with vitamin D at a high dose (>6000 IU/d) effectively corrected vitamin D deficiency in both mothers and infants. Nevertheless, infants with 25(OH)D concentrations over 20 ng/mL may require a relatively low maternal dose to maintain vitamin D sufficiency.

Risk of Micronutrient Inadequacy among Hispanic, Lactating Mothers: Preliminary Evidence from the Southern California Mother's Milk Study.

Micronutrients are dietary components important for health and physiological function, and inadequate intake of these nutrients can contribute to poor health outcomes. The risk of inadequate micronutrient intake has been shown to be greater among low-income Hispanics and postpartum and lactating women. Therefore, we aimed to determine the risk of nutrient inadequacies based on preliminary evidence among postpartum, Hispanic women. Risk of micronutrient inadequacy for Hispanic women (29-45 years of age) from the Southern California Mother's Milk Study (n = 188) was assessed using 24 h dietary recalls at 1 and 6 months postpartum and the estimated average requirement (EAR) fixed cut-point approach. Women were considered at risk of inadequate intake for a nutrient if more than 50% of women were consuming below the EAR. The Chronic Disease Risk Reduction (CDRR) value was also used to assess sodium intake. These women were at risk of inadequate intake for folate and vitamins A, D, and E, with 87.0%, 93.4%, 43.8%, and 95% of women consuming less than the EAR for these nutrients, respectively. Lastly, 71.7% of women consumed excess sodium. Results from this preliminary analysis indicate that Hispanic women are at risk of inadequate intake of important micronutrients for maternal and child health.

Early life gut microbiota is associated with rapid infant growth in Hispanics from Southern California.

We aimed to determine if the newborn gut microbiota is an underlying determinant of early life growth trajectories. 132 Hispanic infants were recruited at 1-month postpartum. The infant gut microbiome was characterized using 16S rRNA amplicon sequencing. Rapid infant growth was defined as a weight-for-age z-score (WAZ) change greater than 0.67 between birth and 12-months of age. Measures of infant growth included change in WAZ, weight-for-length z-score (WLZ), and body mass index (BMI) z-scores from birth to 12-months and infant anthropometrics at 12-months (weight, skinfold thickness). Of the 132 infants, 40% had rapid growth in the first year of life. Multiple metrics of alpha-diversity predicted rapid infant growth, including a higher Shannon diversity (OR = 1.83; 95% CI: 1.07-3.29; p = .03), Faith's phylogenic diversity (OR = 1.41, 95% CI: 1.05-1.94; p = .03), and richness (OR = 1.04, 95% CI: 1.01-1.08; p = .02). Many of these alpha-diversity metrics were also positively associated with increases in WAZ, WLZ, and BMI z-scores from birth to 12-months (pall<0.05). Importantly, we identified subsets of microbial consortia whose abundance were correlated with these same measures of infant growth. We also found that rapid growers were enriched in multiple taxa belonging to genera such as Acinetobacter, Collinsella, Enterococcus, Neisseria, and Parabacteroides. Moreover, measures of the newborn gut microbiota explained up to an additional 5% of the variance in rapid growth beyond known clinical predictors (R2 = 0.37 vs. 0.32, p < .01). These findings indicate that a more mature gut microbiota, characterized by increased alpha-diversity, at as early as 1-month of age, may influence infant growth trajectories in the first year of life.

Epigenetic Reprogramming Mediated by Maternal Diet Rich in Omega-3 Fatty Acids Protects From Breast Cancer Development in F1 Offspring.

Diets rich in omega-3 fatty acids (FA) have been associated with lowered risks of developing certain types of cancers. We earlier reported that in transgenic mice prone to develop breast cancer (BCa), a diet supplemented with canola oil, rich in omega-3-rich FA (as opposed to an omega-6-rich diet containing corn oil), reduced the risk of developing BCa, and also significantly reduced the incidence of BCa in F1 offspring. To investigate the underlying mechanisms of the cancer protective effect of canola oil in the F1 generation, we designed and performed the present study with the same diets using BALB/c mice to remove any possible effect of the transgene. First, we observed epigenetic changes at the genome-wide scale in F1 offspring of mothers fed diets containing omega-3 FAs, including a significant increase in acetylation of H3K18 histone mark and a decrease in H3K4me2 mark on nucleosomes around transcription start sites. These epigenetic modifications contribute to differential gene expressions associated with various pathways and molecular mechanisms involved in preventing cancer development, including p53 pathway, G2M checkpoint, DNA repair, inflammatory response, and apoptosis. When offspring mice were exposed to 7,12-Dimethylbenz(a)anthracene (DMBA), the group of mice exposed to a canola oil (with omega 3 FAs)-rich maternal diet showed delayed mortality, increased survival, reduced lateral tumor growth, and smaller tumor size. Remarkably, various genes, including BRCA genes, appear to be epigenetically re-programmed to poise genes to be ready for a rapid transcriptional activation due to the canola oil-rich maternal diet. This ability to respond rapidly due to epigenetic potentiation appeared to contribute to and promote protection against breast cancer after carcinogen exposure.