Effect of Serial Pregnancies on Physical Fitness.

INTRODUCTION: Pregnancy has a profound impact on physical fitness, and delivery does not allow for rapid return to peak performance levels as physiologic changes can persist for greater than 1 year postpartum. Multiple studies across all military services have documented decrements in physical performance with pregnancy among women. The purpose of this study was to determine the impact of serial pregnancies on physical fitness and body composition in a cohort of Army women. We hypothesized that a second pregnancy would be associated with increasing decrements in physical fitness in active duty soldiers beyond that seen following a first delivery. MATERIALS AND METHODS: This retrospective cohort study screened all active duty soldiers who had delivered a singleton pregnancy of ≥32 weeks gestation between January 1, 2011 and March 31, 2017 at a single military medical center. This roster of eligible women was used to extract Army Physical Fitness Test (APFT) and height/weight data from the U.S. Army Digital Training Management System. Soldiers who delivered their first 2 pregnancies over this period were included. Select antepartum, intrapartum, and postpartum data were collected from the electronic medical record. The primary outcome variables were raw scores for push-ups, sit-ups, and run events as well as weight measures across the 2 pregnancies. The secondary outcomes were the failure rates on both the APFT events and body mass index measurements. Data were analyzed using paired t-tests to compare the means of APFT scores across the 2 pregnancies. The subjects served as their own controls. This study was approved by Regional Health Command-Pacific. RESULTS: A total of 2,103 active duty soldiers delivered singleton pregnancies at Tripler Army Medical Center between January 2011 and March 2017. Among these, 16 women delivered both their first- and second-term pregnancies and had APFT data available for analysis. Average age at time of first and second delivery was 26.1 and 28.1 years, respectively. Mean time separating the first postpartum APFT from the delivery was 8.8 months for the first pregnancy and 7.3 months following the second.A significant decrease in mean sit-up score was found comparing APFT-1 with APFT-2 (72.1 vs 65.7, P = .043) and comparing APFT-1 to APFT-3 (72.1 vs 60.9, P = .002). A significant increase in mean run time was found comparing APFT-1 to APFT-3 (16.9 minutes vs 17.9 minutes, P = .010) and APFT-2 to APFT-3 (17.5 minutes vs 17.9 minutes, P = .027). Comparing APFT-1 to APFT-3 showed a significant decrease in sit-up raw scores (P = .002), run times (P = .010), and total APFT scores (P = .01). Overall, the data show a trend of decreasing performance in all APFT events across the 3 APFTs and a trend toward higher failure rates. This cohort of soldiers did not experience weight gain following the pregnancies. CONCLUSIONS: The present study is the first to analyze the association of serial pregnancies on physical fitness utilizing a validated physical fitness test, and the results suggest that a second pregnancy is associated with progressive worsening of performance. This study is limited by the small sample size, and future studies could further elucidate the degree to which serial pregnancies affect physical fitness.

Sex differences in acute early life stress-enhanced fear learning in adult rats.

Patients diagnosed with posttraumatic stress disorder (PTSD) present with a spectrum of debilitating anxiety symptoms resulting from exposure to trauma. Women are twice as likely to be diagnosed with anxiety and PTSD compared to men; however, the reason for this vulnerability remains unknown. We conducted four experiments where we first demonstrated a female vulnerability to stress-enhanced fear learning (SEFL) with a moderate, acute early life stress (aELS) exposure (4 footshocks in a single session), compared to a more intense aELS exposure (15 footshocks in a single session) where males and females demonstrated comparable SEFL. Next, we demonstrated that this female vulnerability does not result from differences in footshock reactivity or contextual fear conditioning during the aELS exposure. Finally, using gonadectomy or sham surgeries in adult male and female rats, we showed that circulating levels of gonadal steroid hormones at the time of adult fear conditioning do not explain the female vulnerability to SEFL. Additional research is needed to determine whether this vulnerability can be explained by organizational effects of gonadal steroid hormones or differences in sex chromosome gene expression. Doing so is critical for a better understanding of increased female vulnerability to certain psychiatric diseases.

Structure of the SARS-CoV-2 Frameshift Stimulatory Element with an Upstream Multibranch Loop.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) frameshift stimulatory element (FSE) is necessary for programmed -1 ribosomal frameshifting (-1 PRF) and optimized viral efficacy. The FSE has an abundance of context-dependent alternate conformations, but two of the structures most crucial to -1 PRF are an attenuator hairpin and a three-stem H-type pseudoknot structure. A crystal structure of the pseudoknot alone features three RNA stems in a helically stacked linear structure, whereas a 6.9 Å cryo-EM structure including the upstream heptameric slippery site resulted in a bend between two stems. Our previous research alluded to an extended upstream multibranch loop that includes both the attenuator hairpin and the slippery site-a conformation not previously modeled. We aim to provide further context to the SARS-CoV-2 FSE via computational and medium resolution cryo-EM approaches, by presenting a 6.1 Å cryo-EM structure featuring a linear pseudoknot structure and a dynamic upstream multibranch loop.

Immuno-Molecular Targeted Therapy Use and Survival Benefit in Patients with Stage IVB Cervical Carcinoma in Commission on Cancer®-Accredited Facilities in the United States.

PURPOSE: To investigate IMT use and survival in real-world stage IVB cervical cancer patients outside randomized clinical trials. METHODS: Patients diagnosed with stage IVB cervical cancer during 2013-2019 in the National Cancer Database and treated with chemotherapy (CT) ± external beam radiation (EBRT) ± intracavitary brachytherapy (ICBT) ± IMT were studied. The adjusted hazard ratio (AHR) and 95% confidence interval (CI) for risk of death were estimated in patients treated with vs. without IMT after applying propensity score analysis to balance the clinical covariates. RESULTS: There were 3164 evaluable patients, including 969 (31%) who were treated with IMT. The use of IMT increased from 11% in 2013 to 46% in 2019. Age, insurance, facility type, sites of distant metastasis, and type of first-line treatment were independently associated with using IMT. In propensity-score-balanced patients, the median survival was 18.6 vs. 13.1 months for with vs. without IMT (p < 0.001). The AHR was 0.72 (95% CI = 0.64-0.80) for adding IMT overall, 0.72 for IMT + CT, 0.66 for IMT + CT + EBRT, and 0.69 for IMT + CT + EBRT + ICBT. IMT-associated survival improvements were suggested in all subgroups by age, race/ethnicity, comorbidity score, facility type, tumor grade, tumor size, and site of metastasis. CONCLUSIONS: IMT was associated with a consistent survival benefit in real-world patients with stage IVB cervical cancer.

Whole-of-school physical activity implementation in the context of the Dubai Fitness Challenge.

INTRODUCTION: Physical activity (PA) promotion among school-aged youth is a global health priority. Recommendations for such promotion include implementing whole-of-school approaches that maximize resources across the school environment. This study examined schools' participation in an annual, government-led, and emirate-wide initiative in Dubai, called the Dubai Fitness Challenge, in which the goal is to accrue 30 minutes of PA every day for 30 days (as such, the initiative is colloquially referred to as "Dubai 30x30"). METHODS: A mixed-methods design was employed for this study. Three schools were recruited using convenience sampling. Participants were 18 physical education teachers, 20 classroom teachers, 2 principals and 45 students. Data sources included surveys, focus groups, and interviews. Data were analyzed using descriptive statistics, multinomial logistic regression, and open and axial coding to develop themes. RESULTS: School staff reported that most Dubai 30x30 activities were provided in physical education, at break times during school, and before and after school. Students reported that they mainly participated in Dubai 30x30 activities during physical education and occasionally participated in activities after school and on weekends. During school, students were more likely to reach higher PA intensity levels when they were in contexts other than the regular classroom setting. Among school staff, physical education teachers were most involved and classroom teachers were least involved in promoting Dubai 30x30. Parent engagement was high. Staff perceived that Dubai 30x30 brought the community together, but physical education teachers also indicated there was a lack of implementation guidance and they felt burdened. Participants believed Dubai 30x30 increased PA participation and helped to promote their schools. DISCUSSION: This study provides an initial glimpse into schools' participation in Dubai 30x30 and suggests that a whole-of-school PA lens is useful in gleaning information that could help to increase and optimize PA opportunities for students.

Systematic review and meta-analysis of physical activity interventions to increase elementary children's motor competence: a comprehensive school physical activity program perspective.

BACKGROUND: Regular participation in physical activity (PA) benefits children's health and well-being and protects against the development of unhealthy body weight. A key factor in children's PA participation is their motor competence (MC). The comprehensive school physical activity program (CSPAP) framework offers a way to classify existing PA interventions that have included children's MC development and understand the potential avenues for supporting children's MC. However, there have been no systematic reviews or meta-analyses of PA interventions and their effects on the MC of elementary school children (aged 5-12 years) from a CSPAP perspective. METHODS: This study was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. We searched seven electronic databases (PubMed/Medline, Embase, ERIC, SPORTDiscus, CINAHL, Web of Science, and PsycINFO) for articles on 29 November 2021. The CSPAP framework was used to categorize the different intervention approaches. This review was registered with PROSPERO (CRD42020179866). RESULTS: Twenty-seven studies were included in the review, and twenty-six studies were included in the meta-analysis. A wide range of PA intervention approaches (e.g., single component or multicomponent) within the context of the CSPAP framework appear to be promising pathways in enhancing children's MC. The results of the aggregate meta-analysis presented that effect sizes for the development of MC from pre-and post- intervention ranged from moderate to large (Hedges' g = 0.41-0.79). The analysis revealed that the predicted moderators, including study length, delivery agent, and study design, did not result in statistically significant moderate variations in MC outcomes. There was, however, considerable heterogeneity in study design, instruments, and study context, and studies were implemented in over 11 countries across diverse settings. CONCLUSIONS: This study uniquely contributes to the literature through its primary focus on the effectiveness of PA interventions on elementary children's MC. This review emphasizes the importance of customizing CSPAP to fit the specific characteristics of each school setting, including its environmental, demographic, and resource attributes. The effectiveness of CSPAP, particularly its physical education (PE) component, is significantly enhanced when these programs are adapted to address the unique needs of each school. This adaptation can be effectively achieved through targeted professional teacher training, ensuring that PE programs are not only contextually relevant but also optimized for maximum impact in diverse educational environments. Researchers and practitioners should pursue how to effectively translate the evidence into practice to better conceptualize CSPAPs designed for children's MC development.

The RNA secondary structure of androgen receptor-FL and V7 transcripts reveals novel regulatory regions.

The androgen receptor (AR) is a ligand-dependent nuclear transcription factor belonging to the steroid hormone nuclear receptor family. Due to its roles in regulating cell proliferation and differentiation, AR is tightly regulated to maintain proper levels of itself and the many genes it controls. AR dysregulation is a driver of many human diseases including prostate cancer. Though this dysregulation often occurs at the RNA level, there are many unknowns surrounding post-transcriptional regulation of AR mRNA, particularly the role that RNA secondary structure plays. Thus, a comprehensive analysis of AR transcript secondary structure is needed. We address this through the computational and experimental analyses of two key isoforms, full length (AR-FL) and truncated (AR-V7). Here, a combination of in-cell RNA secondary structure probing experiments (targeted DMS-MaPseq) and computational predictions were used to characterize the static structural landscape and conformational dynamics of both isoforms. Additionally, in-cell assays were used to identify functionally relevant structures in the 5' and 3' UTRs of AR-FL. A notable example is a conserved stem loop structure in the 5'UTR of AR-FL that can bind to Poly(RC) Binding Protein 2 (PCBP2). Taken together, our results reveal novel features that regulate AR expression.

Wildfire burn severity and stream chemistry influence aquatic invertebrate and riparian avian mercury exposure in forested ecosystems.

Terrestrial soils in forested landscapes represent some of the largest mercury (Hg) reserves globally. Wildfire can alter the storage and distribution of terrestrial-bound Hg via reemission to the atmosphere or mobilization in watersheds where it may become available for methylation and uptake into food webs. Using data associated with the 2007 Moonlight and Antelope Fires in California, we examined the long-term direct effects of wildfire burn severity on the distribution and magnitude of Hg concentrations in riparian food webs. Additionally, we quantified the cross-ecosystem transfer of Hg from aquatic invertebrate to riparian bird communities; and assessed the influence of biogeochemical, landscape variables, and ecological factors on Hg concentrations in aquatic and terrestrial food webs. Benthic macroinvertebrate methylmercury (MeHg) and riparian bird blood total mercury (THg) concentrations varied by 710- and 760-fold, respectively, and Hg concentrations were highest in predators. We found inconsistent relationships between Hg concentrations across and within taxa and guilds in response to stream chemical parameters and burn severity. Macroinvertebrate scraper MeHg concentrations were influenced by dissolved organic carbon (DOC); however, that relationship was moderated by burn severity (as burn severity increased the effect of DOC declined). Omnivorous bird Hg concentrations declined with increasing burn severity. Overall, taxa more linked to in situ energetic pathways may be more responsive to the biogeochemical processes that influence MeHg cycling. Remarkably, 8 years post-fire, we still observed evidence of burn severity influencing Hg concentrations within riparian food webs, illustrating its overarching role in altering the storage and redistribution of Hg and influencing biogeochemical processes.

Survival disparities in non-Hispanic Black and White cervical cancer patients vary by histology and are largely explained by modifiable factors.

PURPOSE: We investigated racial disparities in survival by histology in cervical cancer and examined the factors contributing to these disparities. METHODS: Non-Hispanic Black and non-Hispanic White (hereafter known as Black and White) patients with stage I-IV cervical carcinoma diagnosed between 2004 and 2017 in the National Cancer Database were studied. Survival differences were compared using Cox modeling to estimate hazard ratio (HR) or adjusted HR (AHR) and 95% confidence interval (CI). The contribution of demographic, socioeconomic and clinical factors to the Black vs White differences in survival was estimated after applying propensity score weighting in patients with squamous cell carcinoma (SCC) or adenocarcinoma (AC). RESULTS: This study included 10,111 Black and 43,252 White patients with cervical cancer. Black patients had worse survival than White cervical cancer patients (HR = 1.40, 95% CI = 1.35-1.45). Survival disparities between Black and White patients varied significantly by histology (HR = 1.20, 95% CI = 1.15-1.24 for SCC; HR = 2.32, 95% CI = 2.12-2.54 for AC, interaction p < 0.0001). After balancing the selected demographic, socioeconomic and clinical factors, survival in Black vs. White patients was no longer different in those with SCC (AHR = 1.01, 95% CI 0.97-1.06) or AC (AHR = 1.09, 95% CI = 0.96-1.24). In SCC, the largest contributors to survival disparities were neighborhood income and insurance. In AC, age was the most significant contributor followed by neighborhood income, insurance, and stage. Diagnosis of AC (but not SCC) at ≥65 years old was more common in Black vs. White patients (26% vs. 13%, respectively). CONCLUSIONS: Histology matters in survival disparities and diagnosis at ≥65 years old between Black and White cervical cancer patients. These disparities were largely explained by modifiable factors.

Identification of MYC intron 2 regions that modulate expression.

MYC pre-mRNA is spliced with high fidelity to produce the transcription factor known to regulate cellular differentiation, proliferation, apoptosis, and alternative splicing. The mechanisms underpinning the pre-mRNA splicing of MYC, however, remain mostly unexplored. In this study, we examined the interaction of heterogeneous nuclear ribonucleoprotein C (HNRNPC) with MYC intron 2. Building off published eCLIP studies, we confirmed this interaction with poly(U) regions in intron 2 of MYC and found that full binding is correlated with optimal protein production. The interaction appears to be compensatory, as mutational disruption of all three poly(U) regions was required to reduce both HNRNPC binding capacity and fidelity of either splicing or translation. Poly(U) sequences in MYC intron 2 were relatively conserved across sequences from several different species. Lastly, we identified a short sequence just upstream of an HNRNPC binding region that when removed enhances MYC translation.

SARS-CoV-2 Orphan Gene ORF10 Contributes to More Severe COVID-19 Disease.

The orphan gene of SARS-CoV-2, ORF10, is the least studied gene in the virus responsible for the COVID-19 pandemic. Recent experimentation indicated ORF10 expression moderates innate immunity in vitro. However, whether ORF10 affects COVID-19 in humans remained unknown. We determine that the ORF10 sequence is identical to the Wuhan-Hu-1 ancestral haplotype in 95% of genomes across five variants of concern (VOC). Four ORF10 variants are associated with less virulent clinical outcomes in the human host: three of these affect ORF10 protein structure, one affects ORF10 RNA structural dynamics. RNA-Seq data from 2070 samples from diverse human cells and tissues reveals ORF10 accumulation is conditionally discordant from that of other SARS-CoV-2 transcripts. Expression of ORF10 in A549 and HEK293 cells perturbs immune-related gene expression networks, alters expression of the majority of mitochondrially-encoded genes of oxidative respiration, and leads to large shifts in levels of 14 newly-identified transcripts. We conclude ORF10 contributes to more severe COVID-19 clinical outcomes in the human host.

Reservoir Stratification Modulates the Influence of Impoundments on Fish Mercury Concentrations along an Arid Land River System.

Impoundment is among the most common hydrologic alterations with impacts on aquatic ecosystems that can include effects on mercury (Hg) cycling. However, landscape-scale differences in Hg bioaccumulation between reservoirs and other habitats are not well characterized nor are the processes driving these differences. We examined total Hg (THg) concentrations of Smallmouth Bass (Micropterus dolomieu) collected from reservoir, tailrace, and free-flowing reaches along an 863 km segment of the Snake River, USA, a semiarid river with 22 impoundments along its course. Across three size-classes (putative 1-year-old, first reproductive, and harvestable sized fish), THg concentrations in reservoirs and tailraces averaged 76% higher than those in free-flowing segments. Among reservoirs, THg concentrations were highest in reservoirs with inconsistent stratification patterns, 47% higher than annually stratified, and 144% higher than unstratified reservoirs. Fish THg concentrations in tailraces immediately downstream of stratified reservoirs were higher than those below unstratified (38-130%) or inconsistently stratified (32-79%) reservoirs. Stratification regimes influenced the exceedance of fish and human health benchmarks, with 52-80% of fish from stratifying reservoirs and downstream tailraces exceeding a human consumption benchmark, compared to 6-17% where stratification did not occur. These findings suggest that impoundment and stratification play important roles in determining the patterns of Hg exposure risk across the landscape.

A Unique Case of Adult-Onset Still's Disease Not Responsive to Steroid Treatment.

A 53-year-old patient was admitted to the emergency department, presenting with fever, generalized weakness, and various myalgias and arthralgias lasting over seven days. Based upon the patient's worsening symptoms, elevated white blood cell count with neutrophilia and overall presentation, she was initially treated for an infectious cause and prescribed various antibiotics and antipyretic medications. As the patient's condition continued to worsen throughout the initial days of her intake, she was tested for a variety of infections, including coronavirus disease 2019 (COVID-19), Streptococcus, and influenza, and was administered a viral respiratory panel, all of which resulted negative. Upon the development of an evanescent rash on hospital day 9, as well as other symptoms including sore throat, arthritis, and an elevated fever present for over a week, a rheumatology consult now expressed concern for a possible case of Adult-Onset Still's Disease (AOSD). In line with the current treatment used for AOSD and the absence of all other infectious causes, the patient discontinued antibiotic treatment and was started on 125 milligrams of intravenous methylprednisolone every six hours. The patient showed minor improvements in symptoms over the next 24 hours but soon became refractory to treatment, resulting from multiorgan damage, and expired on hospital day 13.

Mechanisms and Treatment Options for Hyperthyroid-Induced Osteoporosis: A Narrative Review.

Normal thyroid hormone levels are crucial for the homeostasis of many metabolic cycles and processes throughout the human body. Thyroid dysfunction, such as thyrotoxicosis, can result from many different etiologies, including Graves' disease (GD), toxic multinodular goiter (MNG), and toxic adenoma. These hyperthyroid disease states can cause devastating complications and disease, including the disruption of the bone remodeling cycle and skeletal development, which can result in osteoporosis. Osteoporosis is characterized by a decrease in bone mineral density and a propensity for fragility fractures. In addition to patients with overt hyperthyroidism, studies have provided evidence of other high-risk patient demographics, such as individuals with subclinical hyperthyroidism and postmenopausal women, who may be at an increased risk for the development of secondary osteoporosis. The treatment of patients with hyperthyroid-induced osteoporosis often requires a multifaceted management plan that may be unique to each patient's situation. Antithyroid therapy is often the first step in treating this disease and may include thioamide medications. Radioactive iodine-131 therapy (RAI) and the surgical removal of the thyroid gland may also be reasonable approaches for restoring normal thyroid function. Following thyrotoxicosis mitigation, antiresorptive drugs such as bisphosphonates, calcitonin, and selective estrogen receptor modulators (SERMs) may be used to counteract decreased bone mineral density (BMD). Additionally, the implementation of vitamin D, calcium supplements, and weight-bearing exercise may also reduce bone loss. While the effects of thyroid stimulating hormone (TSH) and triiodothyronine (T3) on bone remodeling have been studied in the past, more research is needed to identify unknown mechanisms and develop future improved treatments for this condition.

Broad-Scale Assessment of Methylmercury in Adult Amphibians.

Mercury (Hg) is a toxic contaminant that has been mobilized and distributed worldwide and is a threat to many wildlife species. Amphibians are facing unprecedented global declines due to many threats including contaminants. While the biphasic life history of many amphibians creates a potential nexus for methylmercury (MeHg) exposure in aquatic habitats and subsequent health effects, the broad-scale distribution of MeHg exposure in amphibians remains unknown. We used nonlethal sampling to assess MeHg bioaccumulation in 3,241 juvenile and adult amphibians during 2017-2021. We sampled 26 populations (14 species) across 11 states in the United States, including several imperiled species that could not have been sampled by traditional lethal methods. We examined whether life history traits of species and whether the concentration of total mercury in sediment or dragonflies could be used as indicators of MeHg bioaccumulation in amphibians. Methylmercury contamination was widespread, with a 33-fold difference in concentrations across sites. Variation among years and clustered subsites was less than variation across sites. Life history characteristics such as size, sex, and whether the amphibian was a frog, toad, newt, or other salamander were the factors most strongly associated with bioaccumulation. Total Hg in dragonflies was a reliable indicator of bioaccumulation of MeHg in amphibians (R2 ≥ 0.67), whereas total Hg in sediment was not (R2 ≤ 0.04). Our study, the largest broad-scale assessment of MeHg bioaccumulation in amphibians, highlights methodological advances that allow for nonlethal sampling of rare species and reveals immense variation among species, life histories, and sites. Our findings can help identify sensitive populations and provide environmentally relevant concentrations for future studies to better quantify the potential threats of MeHg to amphibians.

Mercury Isotope Values in Shoreline Spiders Reveal the Transfer of Aquatic Mercury Sources to Terrestrial Food Webs.

The transfer of aquatic contaminants, including mercury (Hg), to terrestrial food webs is an often-overlooked exposure pathway to terrestrial animals. While research has implemented the use of shoreline spiders to assess aquatic to terrestrial Hg transfer, it is unclear whether Hg sources, estimated from isotope ratios, can be successfully resolved to inform site assessments and remedy effectiveness. To examine aquatic to terrestrial Hg transfer, we collected shoreline spiders (Tetragnatha spp.) and aquatic insect larvae (suborder Anisoptera) across a mosaic of aquatic and shoreline habitats in the St. Louis River and Bad River, tributaries to Lake Superior. The fraction of industrial Hg in sediments was reflected in the δ202Hg values of aquatic dragonfly larvae and predatory fish, connecting benthic Hg sources to the aquatic food web. Shoreline spiders mirrored these aquatic Hg source signatures with highly positive correlations in δ202Hg between tetragnathids and dragonfly larvae (r2 = 0.90). Further assessment of different spider taxa (i.e., araneids and pisaurids) revealed that differences in prey consumption and foraging strategies resulted in isotope differences, highlighting the importance of spider taxa selection for Hg monitoring efforts.

Discovery of RNA secondary structural motifs using sequence-ordered thermodynamic stability and comparative sequence analysis.

Major advances in RNA secondary structural motif prediction have been achieved in the last few years; however, few methods harness the predictive power of multiple approaches to deliver in-depth characterizations of local RNA motifs and their potential functionality. Additionally, most available methods do not predict RNA pseudoknots. This work combines complementary bioinformatic systems into one robust discovery pipeline where: •RNA sequences are folded to search for thermodynamically favorable motifs utilizing ScanFold.•Motifs are expanded and refolded into alternate pseudoknot conformations by Knotty/Iterative HFold.•All conformations are evaluated for covariance via the cm-builder pipeline (Infernal and R-scape).

Per- and polyfluoroalkyl substances (PFAS) in United States tapwater: Comparison of underserved private-well and public-supply exposures and associated health implications.

Drinking-water quality is a rising concern in the United States (US), emphasizing the need to broadly assess exposures and potential health effects at the point-of-use. Drinking-water exposures to per- and poly-fluoroalkyl substances (PFAS) are a national concern, however, there is limited information on PFAS in residential tapwater at the point-of-use, especially from private-wells. We conducted a national reconnaissance to compare human PFAS exposures in unregulated private-well and regulated public-supply tapwater. Tapwater from 716 locations (269 private-wells; 447 public supply) across the US was collected during 2016-2021 including three locations where temporal sampling was conducted. Concentrations of PFAS were assessed by three laboratories and compared with land-use and potential-source metrics to explore drivers of contamination. The number of individual PFAS observed ranged from 1 to 9 (median: 2) with corresponding cumulative concentrations (sum of detected PFAS) ranging from 0.348 to 346 ng/L. Seventeen PFAS were observed at least once with PFBS, PFHxS and PFOA observed most frequently in approximately 15% of the samples. Across the US, PFAS profiles and estimated median cumulative concentrations were similar among private wells and public-supply tapwater. We estimate that at least one PFAS could be detected in about 45% of US drinking-water samples. These detection probabilities varied spatially with limited temporal variation in concentrations/numbers of PFAS detected. Benchmark screening approaches indicated potential human exposure risk was dominated by PFOA and PFOS, when detected. Potential source and land-use information was related to cumulative PFAS concentrations, and the number of PFAS detected; however, corresponding relations with specific PFAS were limited likely due to low detection frequencies and higher detection limits. Information generated supports the need for further assessments of cumulative health risks of PFAS as a class and in combination with other co-occurring contaminants, particularly in unmonitored private-wells where information is limited or not available.

Ultrasound, photoacoustic, and magnetic resonance imaging to study hyperacute pathophysiology of traumatic and vascular brain injury.

BACKGROUND AND PURPOSE: Cerebrovascular dynamics and pathomechanisms that evolve in the minutes and hours following traumatic vascular injury in the brain remain largely unknown. We investigated the pathophysiology evolution in mice within the first 3 hours after closed-head traumatic brain injury (TBI) and subarachnoid hemorrhage (SAH), two significant traumatic vascular injuries. METHODS: We took a multimodal imaging approach using photoacoustic imaging, color Doppler ultrasound, and MRI to track injury outcomes using a variety of metrics. RESULTS: Brain oxygenation and velocity-weighted volume of blood flow (VVF) values significantly decreased from baseline to 15 minutes after both TBI and SAH. TBI resulted in 19.2% and 41.0% ipsilateral oxygenation and VVF reductions 15 minutes postinjury, while SAH resulted in 43.9% and 85.0% ipsilateral oxygenation and VVF reduction (p < .001). We found partial recovery of oxygenation from 15 minutes to 3 hours after injury for TBI but not SAH. Hemorrhage, edema, reduced perfusion, and altered diffusivity were evident from MRI scans acquired 90-150 minutes after injury in both injury models, although the spatial distribution was mostly focal for TBI and diffuse for SAH. CONCLUSIONS: The results reveal that the cerebral oxygenation deficits immediately following injuries are reversible for TBI and irreversible for SAH. Our findings can inform future studies on mitigating these early responses to improve long-term recovery.

Suicide and homicide deaths of PAs: Analysis of the National Violent Death Reporting System.

OBJECTIVE: This study describes physician associate/assistant (PA) deaths in the US CDC's National Violent Death Reporting System (NVDRS) from 2003 to 2020. METHODS: PAs' violent deaths were analyzed and summarized in terms of decedents' numbers and demographics, methods of death, locations of death, and relationships with assailants. RESULTS: The NVDRS identified 93 suicides and 9 homicides in this period. PAs who died by suicide were mostly White (93.5%) and male (67.7%); mean age was 49.7 years. A third of the PAs who died by homicide were Black; most were female (55.6%), and the mean age was 48.7 years. Firearms (41.7%) were most commonly involved in deaths by suicide, and blunt impact (33.3%) was most commonly seen in deaths by homicide. A plurality (46.1%) of suicides and homicides occurred in the South. Homes (72.5%) were the most frequent location. No homicides were reported in medical settings. Known perpetrators were mainly relatives and male; none were patients. CONCLUSIONS: Incidence of PA death by suicide or homicide is low relative to the general population. These deaths generally are not related to PAs' work. Delineating the incidence of violent deaths is a step toward informing preventive efforts.