Discovery of periplasmic solute binding proteins with specificity for ketone bodies: ß-hydroxybutyrate binding proteins.

Polyhydroxyalkanoates are a class of biodegradable, thermoplastic polymers which represent a major carbon source for various bacteria. Proteins which mediate the translocation of polyhydroxyalkanoate breakdown products, such as ß-hydroxybutyrate (BHB)-a ketone body which in humans serves as an important biomarker, have not been well characterized. In our investigation to screen a solute-binding protein (SBP) which can act as a suitable recognition element for BHB, we uncovered insights at the intersection of bacterial metabolism and diagnostics. Herein, we identify SBPs associated with putative ATP-binding cassette transporters that specifically recognize BHB, with the potential to serve as recognition elements for continuous quantification of this analyte. Through bioinformatic analysis, we identified candidate SBPs from known metabolizers of polyhydroxybutyrate-including proteins from Cupriavidus necator, Ensifer meliloti, Paucimonas lemoignei, and Thermus thermophilus. After recombinant expression in Escherichia coli, we demonstrated with intrinsic tryptophan fluorescence spectroscopy that four candidate proteins interacted with BHB, ranging from nanomolar to micromolar affinity. Tt.2, an intrinsically thermostable protein from Thermus thermophilus, was observed to have the tightest binding and specificity for BHB, which was confirmed by isothermal calorimetry. Structural analyses facilitated by AlphaFold2, along with molecular docking and dynamics simulations, were used to hypothesize key residues in the binding pocket and to model the conformational dynamics of substrate unbinding. Overall, this study provides strong evidence identifying the cognate ligands of SBPs which we hypothesize to be involved in prokaryotic cellular translocation of polyhydroxyalkanoate breakdown products, while highlighting these proteins' promising biotechnological application.

Radiation Oncology Resident Education: Is Change Needed?

Leading successful change efforts first requires assessment of the "before change" environment and culture. At our institution, the radiation oncology (RO) residents follow a longitudinal didactic learning program consisting of weekly 1-h lectures, case conferences, and journal clubs. The resident didactic education series format has not changed since its inception over 10 years ago. We evaluated the perceptions of current residents and faculty about the effectiveness of the curriculum in its present form. Two parallel surveys were designed, one each for residents and attendings, to assess current attitudes regarding the effectiveness and need for change in the RO residency curriculum, specifically the traditional didactic lectures, the journal club sessions, and the case conferences. We also investigated perceived levels of engagement among residents and faculty, whether self-assessments would be useful to increase material retention, and how often the content of didactic lectures is updated. Surveys were distributed individually to each resident (N = 10) and attending (N = 24) either in-person or via Zoom. Following completion of the survey, respondents were informally interviewed about their perspectives on the curriculum's strengths and weaknesses. Compared to 46% of attendings, 80% of RO residents believed that the curriculum should be changed. Twenty percent of residents felt that the traditional didactic lectures were effective in preparing them to manage patients in the clinic, compared to 74% of attendings. Similarly, 10% of residents felt that the journal club sessions were effective vs. 42% of attendings. Finally, 40% of residents felt that the case conferences were effective vs. 67% of attendings. Overall, most respondents (56%) favored change in the curriculum. Our results suggest that the perceptions of the residents did not align with those of the attending physicians with respect to the effectiveness of the curriculum and the need for change. The discrepancies between resident and faculty views highlight the importance of a dedicated change management effort to mitigate this gap. Based on this project, we plan to propose recommended changes in structure to the residency program directors. Main changes would be to increase the interactive nature of the course material, incorporate more ways to increase faculty engagement, and consider self-assessment questions to promote retention. Once we get approval from the residency program leadership, we will follow Kotter's "Eight steps to transforming your organization" to ensure the highest potential for faculty to accept the expectations of a new curriculum.

Structure-specific rigid dose accumulation dosimetric analysis of ablative stereotactic MRI-guided adaptive radiation therapy in ultracentral lung lesions.

BACKGROUND: Definitive local therapy with stereotactic ablative radiation therapy (SABR) for ultracentral lung lesions is associated with a high risk of toxicity, including treatment related death. Stereotactic MR-guided adaptive radiation therapy (SMART) can overcome many of the challenges associated with SABR treatment of ultracentral lesions. METHODS: We retrospectively identified 14 consecutive patients who received SMART to ultracentral lung lesions from 10/2019 to 01/2021. Patients had a median distance from the proximal bronchial tree (PBT) of 0.38 cm. Tumors were most often lung primary (64.3%) and HILUS group A (85.7%). A structure-specific rigid registration approach was used for cumulative dose analysis. Kaplan-Meier log-rank analysis was used for clinical outcome data and the Wilcoxon Signed Rank test was used for dosimetric data. RESULTS: Here we show that SMART dosimetric improvements in favor of delivered plans over predicted non-adapted plans for PBT, with improvements in proximal bronchial tree DMax of 5.7 Gy (p = 0.002) and gross tumor 100% prescription coverage of 7.3% (p = 0.002). The mean estimated follow-up is 17.2 months and 2-year local control and local failure free survival rates are 92.9% and 85.7%, respectively. There are no grade ≥ 3 toxicities. CONCLUSIONS: SMART has dosimetric advantages and excellent clinical outcomes for ultracentral lung tumors. Daily plan adaptation reliably improves target coverage while simultaneously reducing doses to the proximal airways. These results further characterize the therapeutic window improvements for SMART. Structure-specific rigid dose accumulation dosimetric analysis provides insights that elucidate the dosimetric advantages of SMART more so than per fractional analysis alone.

Stereotactic MR-guided Adaptive Radiation Therapy (SMART) is a type of radiation therapy for cancer. With SMART, treatment can be adapted based on daily changes in the body seen via imaging. SMART can safely deliver radiation to lung tumors near the center of the body which are risky to treat, due to potential damage to nearby organs. We looked at 14 patients who received SMART to determine how much changing the radiation plan each day improved our ability to safely deliver high doses. We found that SMART not only improved our ability to cover the entirety of the tumor with the dose originally intended, but also reduced dose to nearby organs. Treatment resulted in excellent control of the tumor with few side effects. SMART shows promise for safer and more effective treatment for lung tumors in this part of the body.

Every minute matters: Improving outcomes for penetrating trauma through prehospital advanced resuscitative care.

INTRODUCTION: Prehospital resuscitation with blood products is gaining popularity for patients with traumatic hemorrhage. The MEDEVAC trial demonstrated a survival benefit exclusively among patients who received blood or plasma within 15 minutes of air medical evacuation. In fast-paced urban EMS systems with a high incidence of penetrating trauma, mortality data based on the timing to first blood administration is scarce. We hypothesize a survival benefit in patients with severe hemorrhage when blood is administered within the first 15 minutes of EMS patient contact. METHODS: This was a retrospective analysis of a prospective database of prehospital blood (PHB) administration between 2021 and 2023 in an urban EMS system facing increasing rates of gun violence. PHB patients were compared to trauma registry controls from an era before prehospital blood utilization (2016-2019). Included were patients with penetrating injury and SBP ≤ 90 mmHg at initial EMS evaluation that received at least one unit of blood product after injury. Excluded were isolated head trauma or prehospital cardiac arrest. Time to initiation of blood administration before and after PHB implementation and in-hospital mortality were the primary variables of interest. RESULTS: A total of 143 patients (PHB = 61, controls = 82) were included for analysis. Median age was 34 years with no difference in demographics. Median scene and transport intervals were longer in the PHB cohort, with a 5-minute increase in total prehospital time. Time to administration of first unit of blood was significantly lower in the PHB vs. control group (8 min vs 27 min; p < 0.01). In-hospital mortality was lower in the PHB vs. control group (7% vs 29%; p < 0.01). When controlling for patient age, NISS, tachycardia on EMS evaluation, and total prehospital time interval, multivariate regression revealed an independent increase in mortality by 11% with each minute delay to blood administration following injury (OR 1.11, 95%CI 1.04-1.19). CONCLUSION: Compared to patients with penetrating trauma and hypotension who first received blood after hospital arrival, resuscitation with blood products was started 19 minutes earlier after initiation of a PHB program despite a 5-minute increase in prehospital time. A survival for early PHB use was demonstrated, with an 11% mortality increase for each minute delay to blood administration. Interventions such as PHB may improve patient outcomes by helping capture opportunities to improve trauma resuscitation closer to the point of injury. LEVEL OF EVIDENCE: Prospective, Level IV.

Pharmacogenomic synthetic lethal screens reveal hidden vulnerabilities and new therapeutic approaches for treatment of NF1-associated tumors.

Neurofibromatosis Type 1 (NF1) is a common cancer predisposition syndrome, caused by heterozygous loss of function mutations in the tumor suppressor gene NF1. Individuals with NF1 develop benign tumors of the peripheral nervous system (neurofibromas), originating from the Schwann cell linage after somatic loss of the wild type NF1 allele, some of which progress further to malignant peripheral nerve sheath tumors (MPNST). There is only one FDA approved targeted therapy for symptomatic plexiform neurofibromas and none approved for MPNST. The genetic basis of NF1 syndrome makes associated tumors ideal for using synthetic drug sensitivity approaches to uncover therapeutic vulnerabilities. We developed a drug discovery pipeline to identify therapeutics for NF1-related tumors using isogeneic pairs of NF1-proficient and deficient immortalized human Schwann cells. We utilized these in a large-scale high throughput screen (HTS) for drugs that preferentially kill NF1-deficient cells, through which we identified 23 compounds capable of killing NF1-deficient Schwann cells with selectivity. Multiple hits from this screen clustered into classes defined by method of action. Four clinically interesting drugs from these classes were tested in vivo using both a genetically engineered mouse model of high-grade peripheral nerve sheath tumors and human MPNST xenografts. All drugs tested showed single agent efficacy in these models as well as significant synergy when used in combination with the MEK inhibitor selumetinib. This HTS platform yielded novel therapeutically relevant compounds for the treatment of NF1-associated tumors and can serve as a tool to rapidly evaluate new compounds and combinations in the future.

Habitat escalated adaptive therapy (HEAT): a phase 2 trial utilizing radiomic habitat-directed and genomic-adjusted radiation dose (GARD) optimization for high-grade soft tissue sarcoma.

BACKGROUND: Soft tissue sarcomas (STS), have significant inter- and intra-tumoral heterogeneity, with poor response to standard neoadjuvant radiotherapy (RT). Achieving a favorable pathologic response (FPR ≥ 95%) from RT is associated with improved patient outcome. Genomic adjusted radiation dose (GARD), a radiation-specific metric that quantifies the expected RT treatment effect as a function of tumor dose and genomics, proposed that STS is significantly underdosed. STS have significant radiomic heterogeneity, where radiomic habitats can delineate regions of intra-tumoral hypoxia and radioresistance. We designed a novel clinical trial, Habitat Escalated Adaptive Therapy (HEAT), utilizing radiomic habitats to identify areas of radioresistance within the tumor and targeting them with GARD-optimized doses, to improve FPR in high-grade STS. METHODS: Phase 2 non-randomized single-arm clinical trial includes non-metastatic, resectable high-grade STS patients. Pre-treatment multiparametric MRIs (mpMRI) delineate three distinct intra-tumoral habitats based on apparent diffusion coefficient (ADC) and dynamic contrast enhanced (DCE) sequences. GARD estimates that simultaneous integrated boost (SIB) doses of 70 and 60 Gy in 25 fractions to the highest and intermediate radioresistant habitats, while the remaining volume receives standard 50 Gy, would lead to a > 3 fold FPR increase to 24%. Pre-treatment CT guided biopsies of each habitat along with clip placement will be performed for pathologic evaluation, future genomic studies, and response assessment. An mpMRI taken between weeks two and three of treatment will be used for biological plan adaptation to account for tumor response, in addition to an mpMRI after the completion of radiotherapy in addition to pathologic response, toxicity, radiomic response, disease control, and survival will be evaluated as secondary endpoints. Furthermore, liquid biopsy will be performed with mpMRI for future ancillary studies. DISCUSSION: This is the first clinical trial to test a novel genomic-based RT dose optimization (GARD) and to utilize radiomic habitats to identify and target radioresistance regions, as a strategy to improve the outcome of RT-treated STS patients. Its success could usher in a new phase in radiation oncology, integrating genomic and radiomic insights into clinical practice and trial designs, and may reveal new radiomic and genomic biomarkers, refining personalized treatment strategies for STS. TRIAL REGISTRATION: NCT05301283. TRIAL STATUS: The trial started recruitment on March 17, 2022.

Self-prioritization in working memory gating.

Working memory (WM) involves a dynamic interplay between temporary maintenance and updating of goal-relevant information. The balance between maintenance and updating is regulated by an input-gating mechanism that determines which information should enter WM (gate opening) and which should be kept out (gate closing). We investigated whether updating and gate opening/closing are differentially sensitive to the kind of information to be encoded and maintained in WM. Specifically, since the social salience of a stimulus is known to affect cognitive performance, we investigated if self-relevant information differentially impacts maintenance, updating, or gate opening/closing. Participants first learned to associate two neutral shapes with two social labels (i.e., "you" vs. "stranger"), respectively. Subsequently they performed the reference-back paradigm, a well-established WM task that disentangles WM updating, gate opening, and gate closing. Crucially, the shapes previously associated with the self or a stranger served as target stimuli in the reference-back task. We replicated the typical finding of a repetition benefit when consecutive trials require opening the gate to WM. In Study 1 (N = 45) this advantage disappeared when self-associated stimuli were recently gated into WM and immediately needed to be replaced by stranger-associated stimuli. However, this was not replicated in a larger sample (Study 2; N = 90), where a repetition benefit always occurred on consecutive gate-opening trials. Overall, our results do not provide evidence that the self-relevance of stimuli modulates component processes of WM. We discuss possible reasons for this null finding, including the importance of continuous reinstatement and task-relevance of the shape-label associations.

Meeting the Aerobic and Muscle-Strengthening Physical Activity Guidelines Among Older US Adults, National Health Interview Survey 1998-2018.

The Physical Activity Guidelines for Americans, second edition, recommends older adults participate in ≥150 minutes per week of moderate-intensity equivalent aerobic activity and ≥2 days per week of muscle-strengthening activity. We estimated prevalence and trends of meeting the guidelines among US adults aged ≥65 years from 1998 to 2018. Using the 1998-2018 National Health Interview Survey, we estimated the prevalence of meeting aerobic, muscle-strengthening, and combined physical activity guidelines stratified by age group, sex, race and ethnicity, and education level. Within age groups, we calculated prevalence differences by sociodemographic categories. Prevalence of meeting each guideline increased for all age groups and most sociodemographic subgroups. The increased magnitude of meeting the combined guideline from 1998-2000 to 2016-2018 differed across levels of educational attainment for most age groups. Despite increasing over time, the prevalence among older adults of meeting physical activity guidelines remains low (range for combined guideline: 7.2%-17.2%).

Prevalence of vision zero action plans or strategies: USA, 2021.

BACKGROUND: Vision Zero is a strategy to eliminate traffic fatalities and to promote equitable mobility options for all road users. Using a nationally representative survey, we aimed to estimate the prevalence of Vision Zero action plans or strategies in the USA. METHODS: Municipal officials were surveyed in 2021. In this cross-sectional study, we calculated the prevalence of Vision Zero plans or strategies and compared municipalities with adjusted prevalence ratios (PR) to account for region and sociodemographic characteristics. RESULTS: Among 1955 municipalities participating in the survey (question-specific response rate: 44.3%), the prevalence of a Vision Zero action plan or strategy was 7.7%; 70.5% responded no and 21.8% don't know. Prevalence was 4.8% in small municipalities (1000-2499 residents), 20.3% in medium-large municipalities (50 000-124 999 residents; PR=4.1), and 37.8% in large municipalities (≥125 000 residents; PR=7.6). CONCLUSION: The prevalence of Vision Zero plans and strategies across the USA is low. Additional adoption of Vision Zero plans and strategies could help address traffic fatalities.

Money Talks: The Shifting Effect of Limiting Monetary Incentives for Urology Resident Research.

OBJECTIVE: To assess incentive changes on resident publication behavior. In 2020, we demonstrated the positive effect of an unlimited $1000 publishing incentive for Urology residents. Following this publication, institutional changes led to a limit of a single $1000 publishing incentive per resident per year. METHODS: The PubMed database was assessed to quantify average resident primary authorship and average overall publications. Average primary authorships and total PubMed listings were then compared by year before any incentive (June 2008-June 2016), during unlimited incentive (July 2016-October 2020), and after the limited financial incentive (November 2020-June 2023). RESULTS: Scholarly activity from 30 out of 30 possible residents was evaluated. The average PubMed research participation for the program per year increased significantly from 2.44 preincentive to 8.0 when the incentive was unlimited but decreased to 4.0 when the incentive was limited (P = .026). Similarly, the average PubMed primary resident authorships per year increased from 1.0 preincentive to 6.25 during the unlimited incentive period but decreased to 2.0 when the incentive was limited (P < .001). CONCLUSION: Our data showed an unlimited monetary incentive resulted in a significant increase in average primary resident authorship and average resident participation for publications to PubMed. The limited monetary incentive model resulted in a significant decrease on resident publication and participation in research compared to unlimited incentives. However, limited monetary incentives have a positive, though restricted, effect on Urology resident publication and participation in research compared to no incentive.

Physical Activity-Friendly Policies and Community Design Features in the US, 2014 and 2021.

INTRODUCTION: The 2014 Community-Based Survey of Supports for Healthy Eating and Active Living documented the prevalence of US municipal policy and community design supports for physical activity. The survey was repeated in 2021. Our study examined change in the prevalence of supports from 2014 to 2021, overall and by municipality characteristic. METHODS: Municipalities were sampled independently each survey year. We calculated prevalence in 2014 and 2021 and the prevalence ratio (PR) for 15 supports covering zoning codes, park policies and budgets, design standards, Complete Streets policies, and shared use agreements. We used a Bonferroni-corrected Breslow-Day test to test for interaction by municipality characteristic. RESULTS: In 2014 (2,009 municipalities) compared with 2021 (1,882 municipalities), prevalence increased for several zoning codes: block sizes of walkable distances (PR = 1.46), minimum sidewalk width (PR = 1.19), pedestrian amenities along streets (PR = 1.15), continuous sidewalk coverage (PR = 1.14), and building orientation to pedestrian scale (PR = 1.08). Prevalence also increased for design standards requiring dedicated bicycle infrastructure for roadway expansion projects or street retrofits (PR = 1.19). Prevalence declined for shared use agreements (PR = 0.87). The prevalence gap widened between the most and least populous municipalities for Complete Streets policies (from a gap of 33.6 percentage points [PP] in 2014 to 54.0 PP in 2021) and for zoning codes requiring block sizes that were walkable distances (from 11.8 PP to 41.4 PP). CONCLUSION: To continue progress, more communities could consider adopting physical activity-friendly policies and design features.

Joint Prevalence of Influenza Preventive Behaviors Among Adults-United States, 2020.

INTRODUCTION/OBJECTIVES: The Centers for Disease Control and Prevention recognizes routine vaccination, sufficient sleep, and adequate physical activity as behavioral approaches to reduce the incidence of influenza. We aimed to determine the joint national prevalence of these health behaviors among U.S. adults, which has not been reported. METHODS: We used the 2020 National Health Interview Survey to assess prevalence of receiving influenza vaccination in the past 12 months, obtaining sufficient sleep, and achieving adequate physical activity among U.S. adults (n = 30,312). We calculated the joint prevalence overall and by sociodemographic and health-related variables. RESULTS AND CONCLUSIONS: The overall joint prevalence was 8.5% (95% CI, 8.0-9.0). Prevalence was lower among older persons (vs younger); Hispanic and non-Hispanic Black persons (vs non-Hispanic White); current and former smokers (vs never smokers); postpartum women (vs neither pregnant nor postpartum); and those with a history of coronary heart disease, hypertension, stroke, diabetes, and chronic obstructive pulmonary disease (vs not having those respective condition). In addition to recommending annual vaccination, primary care providers might encourage sufficient sleep and adequate physical activity-especially among patients who have increased risk for influenza complications and are less likely to achieve these behaviors.

Strategies of nanoparticles integration in polymer fibers to achieve antibacterial effect and enhance cell proliferation with collagen production in tissue engineering scaffolds.

Current design strategies for biomedical tissue scaffolds are focused on multifunctionality to provide beneficial microenvironments to support tissue growth. We have developed a simple yet effective approach to create core-shell fibers of poly(3-hydroxybuty-rate-co-3-hydroxyvalerate) (PHBV), which are homogenously covered with titanium dioxide (TiO2) nanoparticles. Unlike the blend process, co-axial electrospinning enabled the uniform distribution of nanoparticles without the formation of large aggregates. We observed 5 orders of magnitude reduction in Escherichia coli survival after contact with electrospun scaffolds compared to the non-material control. In addition, our hybrid cores-shell structure supported significantly higher osteoblast proliferation after 7 days of cell culture and profound generation of 3D networked collagen fibers after 14 days. The organic-inorganic composite scaffold produced in this study demonstrates a unique combination of antibacterial properties and increased bone regeneration properties. In summary, the multifunctionality of the presented core-shell cPHBV+sTiO2 scaffolds shows great promise for biomedical applications.

Changes in Teleworking and Physical Activity Behaviors in the United States Before and After Emergence of COVID-19.

OBJECTIVE: The aim of the study is to determine the prevalence of perceived decreases in three physical activity (PA) behaviors and meeting the PA guideline, by changes in telework. METHODS: US workers ( N = 2393) reported teleworking and PA behaviors before and after COVID-19 emergence. Those reporting more and less telework were compared with those reporting stable telework on prevalence of (1) decreasing behaviors and (2) meeting the aerobic guideline (≥150 min/wk of moderate-intensity PA). RESULTS: Compared with workers with stable telework, those with increased telework were more likely to report decreases in any PA (by 61%), active transportation (65%), and park use (52%). Workers who deceased telework were also more likely to report decreases in these behaviors. Groups were equally likely to meet the guideline. CONCLUSIONS: Changes in teleworking status-either more or less-may be associated with decreased participation in PA behaviors.

Musculoskeletal injuries in US Air Force Tactical Air Control Party trainees: an 11-year longitudinal retrospective cohort study and presentation of a musculoskeletal injury classification matrix.

INTRODUCTION: Little is known of the epidemiology of musculoskeletal injuries (MSKIs) in US Air Force Special Warfare (AFSPECWAR) Tactical Air Control Party trainees. The purpose of this longitudinal retrospective cohort study was to (1) report the incidence and type of MSKI sustained by AFSPECWAR trainees during and up to 1 year following training, (2) identify factors associated with MSKI, and (3) develop and present the MSKI classification matrix used to identify and categorise injuries in this study. METHODS: Trainees in the Tactical Air Control Party Apprentice Course between fiscal years 2010-2020 were included. Diagnosis codes were classified as MSKI or non-MSKI using a classification matrix. Incidence rates and incidence proportion for injury types and regions were calculated. Measures were compared for differences between those who did and did not sustain an MSKI during training. A Cox proportional hazards model was used to identify factors associated with MSKI. RESULTS: Of the 3242 trainees, 1588 (49%) sustained an MSKI during training and the cohort sustained MSKIs at a rate of 16 MSKI per 100 person-months. Overuse/non-specific lower extremity injuries predominated. Differences were seen in some baseline measures between those who did and did not sustain an MSKI. Factors retained in the final Cox regression model were age, 1.5-mile run times and prior MSKI. CONCLUSION: Slower run times and higher age were associated with an increased likelihood of MSKI. Prior MSKI was the strongest predictor of MSKI during training. Trainees sustained MSKIs at a higher rate than graduates in their first year in the career field. The MSKI matrix was effective in identifying and categorising MSKI over a prolonged (12-year) surveillance period and could be useful for future injury surveillance efforts in the military or civilian settings. Findings from this study could inform future injury mitigation efforts in military training environments.

Influence of convective and stratiform precipitation types on per- and polyfluoroalkyl substance concentrations in rain.

Atmospheric transport and wet deposition have contributed to the worldwide distribution of per- and polyfluoroalkyl substances (PFAS) in terrestrial and aquatic ecosystems, even in remote areas far from known industrial sources. However, little is known regarding the impact of cloud and precipitation formation dynamics on PFAS transport and wet deposition, nor the range of variability in PFAS concentrations within a closely distributed monitoring network. Precipitation samples were collected from a network of 25 stations in a focused geographic region (the Commonwealth of Massachusetts, USA) from stratiform and convective storm systems to evaluate if the different cloud and precipitation formation mechanisms in these two fundamental types of storm systems influenced PFAS concentrations in precipitation, and to assess the range of variability in PFAS concentrations in precipitation at a regional scale. PFAS were detected in 11 of 50 discrete precipitation events. Of the 11 events from which PFAS were detected, 10 of the events were convective in nature. PFAS were detected during only one stratiform event at one station. This suggests that local and regional atmospheric PFAS sources entrained by convection events controls regional atmospheric PFAS flux, and that PFAS flux estimates should consider the type and magnitude of precipitation events. The PFAS detected were primarily perfluorocarboxylic acids, with relatively higher detection frequency for shorter-chained compounds. Compilation of PFAS data from precipitation across primarily the eastern United States, from urban, suburban, and rural areas, including those in industrial areas, indicates population density is a poor predictor of precipitation PFAS concentrations. While the total PFAS concentration in precipitation in some areas exceeds 100 ng/L, the median concentrations across all areas are generally less than about 10 ng/L.

Leisure-time physical activity and mortality from influenza and pneumonia: a cohort study of 577 909 US adults.

OBJECTIVE: To examine the association of leisure-time physical activity with mortality from influenza and pneumonia. METHODS: A nationally representative sample of US adults (aged ≥18 years) who participated in the National Health Interview Survey from 1998 to 2018 were followed for mortality through 2019. Participants were classified as meeting both physical activity guidelines if they reported ≥150 min/week of moderate-intensity equivalent aerobic physical activity and ≥2 episodes/week of muscle-strengthening activity. Participants were also classified into five volume-based categories of self-reported aerobic and muscle-strengthening activity. Influenza and pneumonia mortality was defined as having an underlying cause of death with an International Classification of Diseases, 10th Revision code of J09-J18 recorded in the National Death Index. Mortality risk was assessed using Cox proportional hazards, adjusting for sociodemographic and lifestyle factors, health conditions and influenza and pneumococcal vaccination status. Data were analysed in 2022. RESULTS: Among 577 909 participants followed for a median of 9.23 years, 1516 influenza and pneumonia deaths were recorded. Compared with participants meeting neither guideline, those meeting both guidelines had 48% lower adjusted risk of influenza and pneumonia mortality. Relative to no aerobic activity, 10-149, 150-300, 301-600 and >600 min/week were associated with lower risk (by 21%, 41%, 50% and 41%). Relative to <2 episodes/week of muscle-strengthening activity, 2 episodes/week was associated with 47% lower risk and ≥7 episodes/week with 41% higher risk. CONCLUSIONS: Aerobic physical activity, even at quantities below the recommended level, may be associated with lower influenza and pneumonia mortality while muscle-strengthening activity demonstrated a J-shaped relationship.