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Background and Aims: NASH is a common disease associated with increased rates of thromboembolism (TE). Although exercise training can lessen thrombotic risk in patients with vascular disease, whether similar findings are observed in patients with NASH is open for study. Approach and Results: We conducted a 20-week randomized controlled clinical trial involving patients with biopsy-confirmed NASH. Patients were randomly assigned (2:1 ratio) to receive either an exercise training program or standard clinical care. The primary endpoint was change in plasminogen activator inhibitor 1 (PAI-1) level, an established thrombotic biomarker. Twentyeight patients were randomly assigned (18 exercise training and 10 standard clinical care). PAI-1 level was significantly decreased by exercise training when compared to standard clinical care (−40 ± 100 vs. +70 ± 63 ng/ml;

Background & Aims: Lifestyle intervention remains the foundation of clinical care for patients with NASH; however, most patients are unsuccessful in enacting sustained behavioral change. There remains a clear unmet need to develop lifestyle intervention programs to support weight loss. Mobile health (mHealth) programs offer promise to address this need, yet their efficacy remains unexplored. Approach & Results: We conducted a 16-week randomized controlled clinical trial involving adults with NASH. Patients were randomly assigned (1:1 ratio) to receive Noom Weight (NW), a mHealth lifestyle intervention program, or standard clinical care. The primary end point was a change in body weight. Secondary end points included feasibility (weekly app engagement), acceptability (>50% approached enrolled), and safety. Of 51 patients approached, 40 (78%) were randomly assigned (20 NW and 20 standard clinical care). NW significantly decreased body weight when compared to standard clinical care (-5.5 kg vs. -0.3 kg, p = 0.008; -5.4% vs. -0.4%, p = 0.004). More NW subjects achieved a clinically significant weight loss of ≥5% body weight (45% vs. 15%, p = 0.038). No adverse events occurred, and the majority (70%) of subjects in the NW arm met the feasibility criteria. Conclusions: This clinical trial demonstrated that NW is not only feasible, acceptable, and safe but also highly efficacious because this mHealth lifestyle intervention program led to significantly greater body weight loss than standard clinical care. Future large-scale studies are required to validate these findings with more representative samples and to determine if mHealth lifestyle intervention programs can lead to sustained, long-term weight loss in patients with NASH.

Background: Spatial heterogeneity of prostate cancer-specific mortality in Pennsylvania remains unclear. We utilized advanced geospatial survival regressions to examine spatial variation of prostate cancer-specific mortality in PA and evaluate potential effects of individual-and county-level risk factors. Methods: Prostate cancer cases, aged ≥40 years, were identified in the 2004-2014 Pennsylvania Cancer Registry.

Background: Few studies have examined prostate cancer incidence and aggressiveness in urbanrural Appalachian populations. We examined these rates in urban-rural Appalachia and non-Appalachia Pennsylvania (PA), and the association between these areas and more aggressive prostate cancer at diagnosis. Methods: Men, aged ≥ 40 years, with a primary prostate cancer diagnosis were identified from the 2004-2014 Pennsylvania Cancer Registry. Age-adjusted incidence rates for prostate cancer and more aggressive prostate cancer at diagnosis were calculated by urban-rural Appalachia status. Multivariable Poisson regressions were conducted. Multiple logistic regressions were used to examine the association between the geographical areas and more aggressive prostate cancer, after adjusting for confounders.Results: There were 94,274 cases, aged 40-105 years, included. Urban non-Appalachia had the highest 2004-2014 age-adjusted incidence rates of prostate cancer and more aggressive prostate cancer (293.56 and 96.39 per 100,000 men, respectively) and rural Appalachia had the lowest rates (256.48 and 80.18 per 100,000 men, respectively). Among the cases, urban Appalachia were more likely (OR=1.12; 95% CI=1.08-1.17) and rural Appalachia were less likely (OR= 0.92; 95% CI=0.87-0.97) to have more aggressive prostate cancer at diagnosis compared to urban non-Appalachia.Conclusions: Lower incidence rates and the proportion of aggressive disease in rural Appalachia may be due to lower prostate cancer screening rates. More aggressive prostate cancer at diagnosis among the cases in urban Appalachia may be due to exposures that are prevalent in the region.

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Hypertension and vitamin D concentrations have heritable components, although these factors remain uninvestigated in young adults. The objective of this study was to investigate hypertension risk among young adults with respect to family history of hypertension, adjusting for vitamin D status. Resting blood pressure (BP) was measured in 398 individuals aged 18–35 and classified according to the 2017 American Heart Association criteria. Plasma vitamin D metabolite (25(OH)D3; 24,25(OH)2D3; 1,25(OH)2D3) concentrations were determined using liquid chromatography tandem mass spectrometry (LC-MS/MS). Stepwise logistic regression was used to select covariates. Participants' mean age was 21, 30.3% had hypertension, and nearly all unaware of their hypertensive status (90.7%). Compared with no parental history, the adjusted odds ratio (AOR) for hypertension was elevated among participants with two parents having hypertension (AOR = 4.5, 95% CI: 1.70–11.76), adjusting for sex, body mass index, physical activity, and plasma 25(OH)D3. Results for systolic hypertension (SH) were similar but more extreme (two parents AOR = 7.1, 95% CI: 2.82, 17.66), although dihydroxy metabolites (1,25(OH)2D3 and 24,25(OH)2D3) were significant. There was a strong, independent association with dual parental history and hypertension status, regardless of vitamin D status. Hypertension was prevalent in nearly one-third of the sample and underscores the need for targeted prevention for young adults.

BACKGROUND: Exposures to arsenic (As) and cadmium (Cd) have been associated with higher prostate cancer (PC) mortality; however, these associations have been inconsistent. The authors investigated whether higher ambient air concentrations of As and Cd are associated with lower overall and PC-specific survival among PC cases in Pennsylvania. METHODS: Incident PC cases of patients, aged 40 years or older, with a clinical diagnosis and nonmetastatic disease were identified in the 2004 to 2014 Pennsylvania Cancer Registry. Demographic, clinical, and pathologic information were extracted from the Pennsylvania Cancer Registry. The 3-and 5-year average and cumulative air concentrations of As and Cd were extracted from the Environmental Protection Agency's Toxics Release Inventory database. Spatial-temporal hierarchical accelerated failure time models were used to examine the associations between air concentrations of As and Cd and overall and PC-specific survival for the total population and stratified by geographical region defined by rurality and Appalachia status, after adjusting for confounders. RESULTS: There were 78,914 PC cases included. Increasing 3-and 5-year average and cumulative air concentrations of As and Cd were significantly associated with lower overall and PC-specific survival among cases, after adjusting for confounders, for the total population, and stratified by geographical region for most of the estimates. CONCLUSIONS: Data suggest that increasing ambient air exposures to As and Cd may play a role in overall and PC-specific mortality risk among PC cases. Exposures to As and Cd are modifiable and may provide insight into potential strategies to improve PC health outcomes.