Short-term oral atrazine exposure alters the plasma metabolome of male C57BL/6 mice and disrupts α -linolenate, tryptophan, tyrosine and other major metabolic pathways

Overexposure to the commonly used herbicide atrazine (ATR) affects several organ systems, including the brain. Previously, we demonstrated that short-term oral ATR exposure causes behavioral deficits and dopaminergic and serotonergic dysfunction in the brains of mice. Using adult male C57BL/6 mice, the present study aimed to investigate effects of a 10-day oral ATR exposure (0, 5, 25, 125, or 250 mg/kg) on the mouse plasma metabolome and to determine metabolic pathways affected by ATR that may be reflective of ATR’s effects on the brain and useful to identify peripheral biomarkers of neurotoxicity. Four h after the last dosing on day 10, plasma was collected and analyzed with high-performance, dual chromatography-Fourier-transform mass spectrometry that was followed by biostatistical and bioinformatic analyses. ATR exposure (≥5 mg/kg) significantly altered plasma metabolite profile and resulted in a dose-dependent increase in the number of metabolites with ion intensities significantly different from the control group. Pathway analyses revealed that ATR exposure strongly correlated with and disrupted multiple metabolic pathways. Tyrosine, tryptophan, linoleic acid and α-linolenic acid metabolic pathways were among the affected pathways, with α-linolenic acid metabolism being affected to the greatest extent. Observed effects of ATR on plasma tyrosine and tryptophan metabolism may be reflective of the previously reported perturbations of brain dopamine and serotonin homeostasis, respectively. ATR-caused alterations in the plasma profile of α-linolenic acid metabolism are a potential novel and sensitive plasma biomarker of ATR effect and plasma metabolomics could be used to better assess the risks, including to the brain, associated with ATR overexposure

An examination of compensation effects in accelerometer-measured occupational and non-occupational physical activity

Self-report data suggests a large proportion of total physical activity (PA) occurs at work. However, adults with higher levels of occupational PA may compensate by engaging in less non-occupational PA. The study aims were to 1) estimate the intensity, volume, and duration of PA in American adults that occurs at work, and 2) determine if those more active at work are less active outside of work. A cross-sectional sample of full-time employed adults (N=510) was recruited from Georgia city and county governments in 2013–2015. Participants wore an Actigraph GT3X+ accelerometer for two weeks. In 2016, for 442 participants with complete data including work schedules and self-reported job titles, accelerometer wear minutes were classified as either occupational or non-occupational, and as sedentary, LPA (light-intensity PA), or MVPA (moderate-to-vigorous intensity PA). The proportion of daily PA that occurred during work was 41.2% for total PA, 41.0% for LPA, and 39.5% for MVPA. Higher levels of occupational LPA were associated with lower levels of non-occupational LPA (r=−0.38, P<0.0001). However, higher levels of occupational MVPA were associated with higher levels of non-occupational MVPA (r=0.17, P<0.0001). These associations remained significant in a MANOVA adjusting for labor sector and other covariates. On average, employed adults get more LPA and MVPA outside of work. Adults who do more occupational MVPA do not compensate by doing less non-occupational MVPA. In contrast, adults who do more occupational LPA do compensate by doing less non-occupational LPA. Evaluations of interventions to reduce sedentary behavior should be designed to detect compensation effects. Keywords: Intensity, Work, Acceleromete

Resource utilization and treatment costs of patients with severe hemophilia A: Real‐world data from the ATHNdataset

Abstract Hemophilia A is characterized by unpredictable spontaneous bleeds and chronic comorbidities. However, limited data exists at the national level into detailed management patterns related to patient clinical characteristics, representative real‐world dosing and treatment frequency, and costs. To assess and characterize the US severe hemophilia A (SHA) population, including subgroups of patients, in terms of clinical and demographic characteristics, healthcare resource utilization received at hemophilia treatment centers (HTCs), and projected annual costs of treatment utilizing data from the ATHNdataset of the American Thrombosis and Hemostasis Network (ATHN). Adult male people with SHA (PwSHA) (FVIII < 1%) were identified in the ATHNdataset between January 2013 and September 2019. This retrospective cohort study described patients’ demographic and clinical characteristics, clinical history, as well as the HTC‐related health resource utilization (HRU), treatment utilization, and projected annual treatment costs of US PwSHA received over the most recent year. Results are reported for the overall population and for three mutually exclusive subpopulations of patients: PwSHA with a history of and/or current inhibitors, PwSHA without a history of inhibitors but with (or a history of) one or more transfusion‐transmitted infections (hepatitis B virus [HBV], hepatitis C virus [HCV], or human immunodeficiency virus [HIV]), and PwSHA without a history of inhibitors or of transfusion‐transmitted infections (HBV, HCV, or HIV). Of the overall PwSHA cohort (N = 3677), there was a high prevalence of HCV (24.1%) and HIV (13.7%), while the prevalence of HBV (4.9%) was lower. Note that 20.5% of PwSHA overall currently or ever had FVIII inhibitors. On average, PwSHA had 2.8 total HTC visits per year, including 0.9 comprehensive care visits, 1.1 telephone contact visits, 0.5 office visits, and 0.1 surgeries or other procedures. However, 23.3% of PwSHA were not seen at an HTC, and 33.8% of PwSHA did not have a comprehensive care visit during their most recent year of data. HTC‐related HRU was similar between the overall cohort and across the patient subpopulations, although PwSHA and inhibitors had more frequent HTC visits (a mean of 3.6 visits annually vs. 2.5–2.8 in the other groups). Using reported treatment frequency and dosing, estimated mean annual hemophilia treatment costs varied by treatment and across the three subpopulations: extended half‐life factor product ($893,609–934,301 by subpopulation), standard half‐life factor product ($798,700–930,812), plasma‐derived factor product ($613,220–801,061), and non‐factor product treatment ($765,289—833,240). This study summarized recent sociodemographic and clinical characteristics, HTC‐related HRU, and HA treatments and projected costs among adult PwSHA, including among key subpopulations of PwSHA. PwSHA experience substantial clinical and resource burden on a chronic basis, despite the care coordination efforts of ATHN‐affiliated HTCs. These findings motivate further exploration of the drivers of resource utilization, observed differences across subpopulations and other disparities, and ongoing monitoring of clinical and treatment burden in the face of an evolving care landscape