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Background: Primary prevention of Alzheimer disease and other types of dementia (all-cause dementia) is an important public health goal. Evidence to date is insufficient to recommend any lifestyle change to prevent or delay the onset of dementia.Objective: To assess the association between objectively measured midlife cardiorespiratory fitness ("fitness") levels and development of all-cause dementia in advanced age.Design: Prospective, observational cohort study.Setting: Preventive medicine clinic.Patients: 19 458 community-dwelling, nonelderly adults who had a baseline fitness examination.Measurements: Fitness levels, assessed using the modified Balke treadmill protocol between 1971 and 2009, and incident all-cause dementia using Medicare Parts A and B claims data from 1999 to 2009.Results: 1659 cases of incident all-cause dementia occurred during 125 700 person-years of Medicare follow-up (median follow-up, 25 years [interquartile range, 19 to 30 years]). After multivariable adjustment, participants in the highest quintile of fitness level had lower hazard of all-cause dementia than those in the lowest quintile (hazard ratio, 0.64 [95% CI, 0.54 to 0.77]). Higher fitness levels were associated with lower hazard of all-cause dementia with previous stroke (hazard ratio, 0.74 [CI, 0.53 to 1.04]) or without previous stroke (hazard ratio, 0.74 [CI, 0.61 to 0.90]).Limitations: Dementia diagnoses were based on Medicare claims, and participants generally were non-Hispanic white, healthy, and well-educated and had access to preventive health care. This study evaluated fitness levels, so a specific exercise prescription cannot be generated from results and the findings may not be causal.Conclusion: Higher midlife fitness levels seem to be associated with lower hazards of developing all-cause dementia later in life. The magnitude and direction of the association were similar with or without previous stroke, suggesting that higher fitness levels earlier in life may lower risk for dementia later in life, independent of cerebrovascular disease.Primary Funding Source: The Cooper Institute; University of Texas Southwestern Medical Center; National Heart, Lung, and Blood Institute; and American Heart Association. [ABSTRACT FROM AUTHOR]

Left ventricular hypertrophy (LVH) is an independent, modifiable risk factor for cardiovascular disease. However, current screening strategies are limited. In 2478 participants without clinical disease from the Dallas Heart Study, we evaluated a multimarker screening strategy that complements electrocardiographic (ECG) criteria for LVH with 2 biomarkers, amino-terminal pro-B-type natriuretic peptide and highly sensitive cardiac troponin T. An integer LVH risk score from 0 to 3 was determined as the sum of the following: (1) LVH by Sokolow-Lyon ECG; (2) amino-terminal pro-B-type natriuretic peptide in the highest sex-specific quartile; and (3) detectable cardiac troponin T. Cardiac magnetic resonance imaging-determined LVH served as the primary outcome. The probability of LVH increased from 2% with an LVH risk score of 0 to 50% with a score of 3 (P<0.001). Sokolow-Lyon ECG afforded low sensitivity (26% [95% confidence interval {CI}, 17-32%]) and high specificity (96% [95% CI, 95-97%]), whereas a risk score ≥2 offered higher sensitivity (44% [95% CI, 34-51%]) with good specificity (90% [95% CI, 89-93%]) and a score threshold of 1 offered reasonable sensitivity (76% [95% CI, 67-83%]) with lower specificity (55% [95% CI, 53-61%]) and high negative predictive value (98% [95% CI, 97-98%]). Area under the receiver operator characteristic curve improved from 0.760 (95% CI, 0.716-0.804) for ECG alone to 0.798 (95% CI, 0.754-0.842) for the LVH risk score (P=0.0012), consistent with modest improvement in overall discrimination. Better screening for LVH may be achieved by combining simple tests, which collectively provide additional information compared with ECG alone. Further studies are needed to evaluate the impact and cost-effectiveness of a multimarker screening strategy. [ABSTRACT FROM AUTHOR]

Background: Understanding how sex and tobacco exposure may modify lifetime risks for cancer mortality is important for effective communication of risk in targeted public health messages.Objective: To determine lifetime risk estimates for cancer death associated with sex and smoking status in the United States.Methods: A pooled cohort design using ten well-defined epidemiologic cohorts including middle-aged and older individuals was used to estimate the lifetime risk for cancer death at selected index ages, with death from non-cancer causes as the competing risk, by sex and smoking status.Results: There were a total of 11,317 cancer-related deaths. At age 45 years, the lifetime risk of cancer death for male smokers is 27.7 % (95 % CI 24.0-31.4 %) compared to 15.8 % (95 % CI 12.7-18.9 %) for male non-smokers. At age 45 years, the lifetime risk of cancer death for female smokers is 21.7 % (95 % CI 18.8-24.6 %) compared to 13.2 % (95 % CI 11.0-15.4 %) for female non-smokers. Remaining lifetime risk for cancer death declined with age, and men have a greater risk for cancer death compared to women. Adjustment for competing risk of death, particularly representing cardiovascular mortality, yielded a greater change in lifetime risk estimates for men and smokers compared to women and non-smokers.Conclusions: At the population level, the lifetime risk for cancer death remains significantly higher for smokers compared to non-smokers, regardless of sex. These estimates may provide clinicians with useful information for counseling individual patients and highlight the need for continued public health efforts related to smoking cessation. [ABSTRACT FROM AUTHOR]

Background: Prior estimates of lifetime risk (LTR) for cardiovascular disease (CVD) examined the impact of blood pressure (BP) at the index age and did not account for changes in BP over time. We examined how changes in BP during middle age affect LTR for CVD, coronary heart disease, and stroke.Methods and Results: Data from 7 diverse US cohort studies were pooled. Remaining LTRs for CVD, coronary heart disease, and stroke were estimated for white and black men and women with death free of CVD as a competing event. LTRs for CVD by BP strata and by changes in BP over an average of 14 years were estimated. Starting at 55 years of age, we followed up 61 585 men and women for 700 000 person-years. LTR for CVD was 52.5% (95% confidence interval, 51.3-53.7) for men and 39.9% (95% confidence interval, 38.7-41.0) for women. LTR for CVD was higher for blacks and increased with increasing BP at index age. Individuals who maintained or decreased their BP to normal levels had the lowest remaining LTR for CVD, 22% to 41%, compared with individuals who had or developed hypertension by 55 years of age, 42% to 69%, suggesting a dose-response effect for the length of time at high BP levels.Conclusions: Individuals who experience increases or decreases in BP in middle age have associated higher and lower remaining LTR for CVD. Prevention efforts should continue to emphasize the importance of lowering BP and avoiding or delaying the incidence of hypertension to reduce the LTR for CVD. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to determine the association between fitness and lifetime risk for cardiovascular disease (CVD).Background: Higher levels of traditional risk factors are associated with marked differences in lifetime risks for CVD. However, data are sparse regarding the association between fitness and the lifetime risk for CVD.Methods: We followed up 11,049 men who underwent clinical examination at the Cooper Institute in Dallas, Texas, before 1990 until the occurrence of CVD death, non-CVD death, or attainment of age 90 years (281,469 person-years of follow-up, median follow-up 25.3 years, 1,106 CVD deaths). Fitness was measured by the Balke protocol and categorized according to treadmill time into low, moderate, and high fitness, with further stratification by CVD risk factor burden. Lifetime risk for CVD death determined by the National Death Index was estimated for fitness levels measured at ages 45, 55, and 65 years, with non-CVD death as the competing event.Results: Differences in fitness levels (low fitness vs. high fitness) were associated with marked differences in the lifetime risks for CVD death at each index age: age 45 years, 13.7% versus 3.4%; age 55 years, 34.2% versus 15.3%; and age 65 years, 35.6% versus 17.1%. These associations were strongest among persons with CVD risk factors.Conclusions: A single measurement of low fitness in mid-life was associated with higher lifetime risk for CVD death, particularly among persons with a high burden of CVD risk factors. [ABSTRACT FROM AUTHOR]

We found sex differences in the pattern of relative strength when risk-factor associations with death from cardiovascular disease (CVD) were evaluated across different periods of follow-up. In women, an increased risk in CVD-related death was associated with diabetes mellitus and smoking; this risk was most prominent in the early follow-up period. Our finding illustrates that clinicians should employ more intense preventive measures in women who are smokers or have diabetes. [ABSTRACT FROM AUTHOR]

Previous studies have evaluated the strength of the association between traditional risk factors and cardiovascular disease (CVD) across varying lengths of follow-up in men. However, to our knowledge, little is known regarding the behavior of these risk factors across time in women. Thus, we sought to determine the association between traditional risk factors in men and women across follow-up periods of 0 to 10, 10 to 20, and >20 years. We studied 9,033 men and 7,575 women (ages 40 to 59 years) from 1967 to 1973 from the Chicago Heart Association Detection Project in Industry. Multivariable-adjusted Cox proportional hazard models were constructed to compare the hazard ratios (HRs) and 95% confidence intervals (CI) for CVD risk factors measured at baseline across different periods of follow-up (0 to 10, 10 to 20, and >20 years). In women, the HRs for smoking and diabetes mellitus were strongest at 0 to 10 years (HR 5.38, 95% CI 2.99 to 9.67 and 3.84, 95% CI 1.82 to 8.13, respectively) but decreased at >20 years (HR 1.71, 95% CI 1.48 to 1.97 and 1.60, 95% CI 1.10 to 2.32, respectively). In men, the HR (per 4 kg/m(2)) for body mass index appeared to increase (0 to 10 years, 1.01, 95% CI 0.90 to 1.14; >20 years, 1.20, 95% CI 1.13 to 1.28). In women, the association was similar across all follow-up periods. For both men and women, the HR for total serum cholesterol remained unchanged across the follow-up. In conclusion, we found gender differences in the patterns of association between risk factors measured at baseline and CVD death across different periods of follow-up. In women, the increased risk associated with both diabetes mellitus and smoking was most prominent in the early follow-up periods. [ABSTRACT FROM AUTHOR]

Individuals with severe mental illness (SMI) are at risk for HIV/AIDS. Despite the availability of supportive community programs for those with SMI, there have been no published evaluations of community-level HIV prevention trials among this population. A pilot intervention trial was conducted to determine the feasibility of such an intervention in supportive housing programs (SHPs). A multi-component community-level trial was implemented in two SHPs with a total of 28 residents. Participants completed assessments at three time points: prior to the intervention (baseline), following skills training (post-assessment), and following the 4-month community intervention (follow- up). Results demonstrated significant improvements in psychosocial risk factors at both post- and follow-up assessments, with indications of sexual behavior change at follow-up. The community-level intervention appeared to reduce the risk of HIV among persons with SMI living in SHPs, and supports the importance of conducting larger scale intervention trials. [ABSTRACT FROM AUTHOR]

Objective: Radiologically inserted gastrostomy placement may be performed in patients with dysphagia secondary to amyotrophic lateral sclerosis (ALS). This study assessed technical outcomes and complications related to gastrostomy placement in patients with ALS., Methods: A retrospective review of patients with ALS who underwent gastrostomy placement between 2021 and 2023 was performed. Patient demographics, medical history, ALS disease manifestations, survival, and post-procedural complications were obtained from the electronic medical record. Technical outcomes related to gastrostomy placement were obtained from operative notes and review of procedural imaging., Results: A total of 100 patients were included in the study. The mean duration of ALS diagnosis at time of gastrostomy placement was 1.3 +/-1.2 years. The mean slow vital capacity at time of gastrostomy placement was 54.0 +/-20.2% (range 10-155%). Technical success was 100%, with 91 placed using fluoroscopic guidance and 9 placed with computed tomography guidance. Eighty-three percent of gastrostomies were performed as outpatient procedures, while 17/100 patients were admitted following the procedure for monitoring. Post-procedural adverse events were noted in 21/100 patients (15 mild and 6 moderate or greater). Three patients developed respiratory failure after gastrostomy tube placement and died within 1-week post-procedure. Lower pre-procedural slow vital capacity was associated with higher risk of post-procedural respiratory failure ( p  = 0.0003*)., Conclusions: Gastrostomy placement in patients with ALS has a high technical success rate and may be performed safely in the outpatient setting in appropriate patients. Patients with low slow vital capacity related to ALS should be admitted post-procedurally for airway monitoring and support.

Objective : To examine the relationship between body mass index (BMI) and genotype among pre-symptomatic carriers of different pathogenic variants associated with amyotrophic lateral sclerosis. Methods : C9orf72+ carriers, SOD1+ carriers, and pathogenic variant negative controls (Gene-Negatives) were included from 3 largely independent cohorts: ALS Families Project (ALS-Families); Dominantly inherited ALS (DIALS); and Pre-symptomatic Familial ALS ( Pre-fALS ). First reported ( ALS-Families ) or measured ( DIALS and Pre-fALS ) weight and height were used to calculate BMI. Age at weight measurement, self-reported sex (male vs. female), and highest education (high school or below vs. college education vs . graduate school or above) were extracted. The associations between BMI and genotype in each cohort were examined with multivariable linear regression models, adjusted for age, sex, and education. Results : A total of 223 C9orf72+ carriers, 135 SOD1+ carriers, and 191 Gene-Negatives were included, deriving from ALS-Families ( n  = 114, median age 46, 37% male), DIALS ( n  = 221, median age 46, 30% male), and Pre-fALS ( n  = 214, median age 44, 39% male). Adjusting for age, sex, and education, the mean BMI of C9orf72+ carriers was lower than Gene-Negatives by 2.4 units (95% confidence interval [CI] = 0.3-4.6, p  = 0.02) in ALS-Families ; 2.7 units (95% CI = 0.9-4.4, p  = 0.003) in DIALS ; and 1.9 units (95% CI = 0.5-4.2, p  = 0.12) in Pre-fALS . There were no significant differences in BMI between SOD1+ carriers and Gene-Negatives in any of the 3 cohorts. Conclusions : Compared to Gene-Negatives, average BMI is lower in asymptomatic C9orf72+ carriers across 3 cohorts while no significant difference was found between Gene-Negatives and SOD1+ carriers.

Purpose: Cardiorespiratory fitness (CRF) declines with age, and greater declines increase the risk for adverse health outcomes. Understanding factors that attenuate age-related decreases in CRF can help extend healthy life. We sought to determine the longitudinal associations of aerobic physical activity, muscle-strengthening activity (MSA), and adiposity with CRF., Methods: Study participants were enrolled in the Cooper Center Longitudinal Study and had ≥3 preventive medical examinations at the Cooper Clinic (Dallas, Texas) during 1987-2019. Aerobic activity and MSA were self-reported, and three measures of adiposity were clinically assessed: body mass index (BMI), body fat percentage, and waist circumference. CRF, expressed as metabolic equivalents (METs), was estimated by a maximal treadmill test. The longitudinal associations of aerobic activity, MSA, and adiposity with CRF were estimated using multivariable mixed linear regression models., Results: The study included 6,105 participants who were followed for a median of 7.1 years. Most participants were men (83.6%), and their average age at baseline was 47.0 (SD: 8.7) years. Mean CRF at baseline was 12.2 (SD: 2.3) METs. Increasing aerobic activity (per 500 MET-minutes/week, β: 0.069, 95% CI: 0.064, 0.074 METs) or MSA (per days/week, β: 0.066, 95% CI: 0.058, 0.073 METs) was associated with increased CRF over time. Increasing BMI, body fat percentage, or waist circumference were each associated with decreased CRF over time., Conclusions: These data offer longitudinal evidence on how changes in aerobic activity, MSA, and various measures of adiposity (beyond BMI) independently correlate with CRF over time. Healthy lifestyle behaviors that include increasing aerobic and muscle-strengthening activity and limiting adiposity may positively influence the retention of fitness with age and improve downstream health outcomes., Competing Interests: Conflict of Interest and Funding Source: Dr. Berry reports grant support from the NIH, Roche Diagnostics and Abbott Diagnostics, consulting fees from Roche Diagnostics, Astra Zeneca and the Cooper Institute. All other authors report no disclosures., (Copyright © 2024 by the American College of Sports Medicine.)

The TAR DNA Binding Protein 43 (TDP-43) has been implicated in the pathogenesis of human neurodegenerative diseases and exhibits hallmark neuropathology in amyotrophic lateral sclerosis (ALS). Here, we explore its tractability as a plasma biomarker of disease and describe its localization and possible functions in the cytosol of platelets. Novel TDP-43 immunoassays were developed on three different technical platforms and qualified for specificity, signal-to-noise ratio, detection range, variation, spike recovery and dilution linearity in human plasma samples. Surprisingly, implementation of these assays demonstrated that biobank-archived plasma samples yielded considerable heterogeneity in TDP-43 levels. Importantly, subsequent investigation attributed these differences to variable platelet recovery. Fractionations of fresh blood revealed that ≥ 95% of the TDP-43 in platelet-containing plasma was compartmentalized within the platelet cytosol. We reasoned that this highly concentrated source of TDP-43 comprised an interesting substrate for biochemical analyses. Additional characterization of platelets revealed the presence of the disease-associated phosphoserine 409/410 TDP-43 proteoform and many neuron- and astrocyte-expressed TDP-43 mRNA targets. Considering these striking similarities, we propose that TDP-43 may serve analogous functional roles in platelets and synapses, and that the study of platelet TDP-43 might provide a window into disease-related TDP-43 dyshomeostasis in the central nervous system., (© 2024. The Author(s).)

Recent progress in therapeutics for amyotrophic lateral sclerosis (ALS) has spurred development and imbued the field of ALS with hope for more breakthroughs, yet substantial scientific gaps persist. This unmet need remains a stark reminder that innovative paradigms are needed to invigorate ALS research. To move toward more informative, targeted, and personalized drug development, the National Institutes of Health (NIH) established a national ALS clinical research consortium called Access for ALL in ALS (ALL ALS). This new consortium is a multi-institutional effort that aims to organize the ALS clinical research landscape in the United States. ALL ALS is operating in partnership with several stakeholders to operationalize the recommendations of the Accelerating Access to Critical Therapies for ALS Act (ACT for ALS) Public Private Partnership. ALL ALS will provide a large-scale, centralized, and readily accessible infrastructure for the collection and storage of a wide range of data from people living with ALS (symptomatic cohort) or who may be at risk of developing ALS (asymptomatic ALS gene carriers). Importantly, ALL ALS is designed to encourage community engagement, equity, and inclusion. The consortium is prioritizing the enrollment of geographically, ethnoculturally, and socioeconomically diverse participants. Collected data include longitudinal clinical data and biofluids, genomic, and digital biomarkers that will be harmonized and linked to the central Accelerating Medicines Partnership for ALS (AMP ALS) portal for sharing with the research community. The aim of ALL ALS is to deliver a comprehensive, inclusive, open-science dataset to help researchers answer important scientific questions of clinical relevance in ALS., (© 2024 The Author(s). Muscle & Nerve published by Wiley Periodicals LLC.)

Background: Prematurely born adults have increased risk for cardiovascular disease. There are limited cardiac data on US-born preterm individuals. We aimed to determine whether adolescents and adults born prematurely have altered left ventricular (LV) structure and function, and to interrogate diastolic function using isometric handgrip exercise., Methods and Results: Adolescents and adults born moderately to extremely preterm (≤32 weeks gestation or <1500 g birth weight) were recruited from the Parkland Health Neonatal Intensive Care Unit Registry. Full-term participants were recruited from the local area. Study procedures included anthropometrics and vitals, handgrip testing, and echocardiography performed at rest and during isometric handgrip exercise. Data were reported as mean±SD. The study enrolled 107 preterm and 48 term participants. Preterm participants (gestational age: 29.5±2.5 weeks) were shorter with higher body mass index ( P <0.001) compared with term participants. Preterm participants exhibited smaller LV end-diastolic volume index (50.8±10.1 versus 56.9±10.0 mL/m 2 , P <0.001), LV stroke volume index (29.6±6.0 versus 34.1±6.5 mL/m 2 , P <0.001), and LV mass index (67.2±13.1 versus 73.3±14.2 g/m 2 , P =0.002) compared with term individuals. Preterm participants also had subclinical reductions in LV peak systolic tissue velocity and peak early diastolic tissue velocity lateral at rest. Isometric handgrip exercise promoted a reduction in diastolic function and an increase in hemodynamic measures, but changes during isometric handgrip exercise were similar between groups., Conclusions: Adolescents and adults born preterm exhibit overall normal cardiac function despite smaller cardiac volumes and mass compared with individuals born full term. Effects are most pronounced at the lowest gestational ages.

Background: In March 2020, the World Health Organization declared the coronavirus disease 2019 (COVID-19) to be a pandemic, stating that those with underlying health conditions are most susceptible, including motor neuron disease (MND)., Objective: To examine the effect the COVID-19 pandemic had on deaths from MND in the United States., Methods: Death certificate data for all MND deaths aged 20 years and older were analyzed from 2017 to 2019 (pre-COVID), then expanded to include 2020 and 2021 (COVID) deaths to evaluate if COVID-19 impacted MND deaths., Results: The average number of MND deaths documented during the COVID-19 years was 8009, up from 7485 MND deaths pre-COVID. The age-adjusted mortality rate among the non-Hispanic population increased during COVID to 2.78 per 100,000 persons (95% CI = 2.73-2.82) from 1.81 (95% CI = 1.78-1.84). The Hispanic population also saw an increase in mortality rate during COVID (1.61, 95% CI = 1.51-1.71) compared with pre-COVID (1.10, 95% CI = 1.03-1.17). Decedent's home as a place of death also saw a mortality rate increase during COVID (1.51, 95% CI = 1.48-1.54) compared with pre-COVID (1.30, 95% CI = 1.27-1.32). For the Hispanic population, the rate peaked at 80-84 years pre-COVID, but for the COVID years, the rate peaked earlier, at 75-79 years., Conclusion: The total number of MND deaths was greater during COVID than in the preceding years. The analysis suggests there might have been a consequence of circumstances surrounding the global pandemic and the associated restrictions.

Triboelectric nanogenerators (TENGs) have been widely used to harness various forms of mechanical energy for conversion to electrical energy. However, the contentious challenge in characterising TENGs is the lack of standard protocols for assessing mechanical-to-electrical energy conversion processes. Herein, macroscopic signal analysis is used to identify three key charging events within triboelectric signals: charge induction (CI), contact electrification (CE), and electrostatic discharge (ESD). By considering two phases of motion during contact-separation (approach and departure of the contact materials), CI arising from the motion of bound surface charge (varying electric field) between opposing contact materials is shown to dominate the measured displacement current signal, rather than the process of CE itself. Furthermore, the conventional signal (i. e., voltage, current, charge) interpretation of CE and CI during approach and departure phases is re-assessed, to indicate that the sudden spike of current often observed immediately prior to contact (or after separation) arises from polarity inverting electrostatic discharge (ESD). This aspect of the measured triboelectric effect, which is often ignored, is crucial for the design of TENGs and hence, techniques to enhance the understanding and control over the stochastic occurrence of ESDs is explored. The methods proposed for the deconvolution of the macroscopic signal components of TENGs, and mitigation of ESD occurrences, will allow for precise quantification of the associated charging events. The applications of this study will template the design and development of future super-TENGs with optimised energy conversion capabilities., (© 2024 The Authors. ChemSusChem published by Wiley-VCH GmbH.)

Aims: While high-volume physical activity (PA) has been linked to elevated coronary artery calcification (CAC), the role of intensity vs. duration of PA has not been investigated. The purpose of the study was to examine the role of intensity vs. duration of PA in relation to CAC., Methods and Results: Data are from 23 383 apparently healthy men who completed a PA questionnaire and underwent CAC scanning as part of a preventive examination. Self-reported PA was categorized into four groups of average intensity and weekly duration of PA [average intensity: 1, 3-5.9, 6-8.9, and 9-12 metabolic equivalents of task (METs); weekly duration: 0, > 0-<2, 2-<5, and ≥5 h/week]. Mean CAC and CAC ≥ 100 Agatston units (AU) were regressed separately on continuous or categorical average intensity and weekly duration of PA. The mean (standard deviation) age was 51.7 (8.3) years, and mean CAC was 174.8 (543.6) AU with 23.5% of men presenting with CAC ≥ 100 AU. Higher average intensity of PA was related to lower mean CAC [-3.1%/MET, 95% confidence interval (CI): -4.6, -1.6%/MET] and lower relative risk (RR) of CAC ≥ 100 AU (RR: 0.99, 95% CI: 0.98, 1.00/MET). Opposite trend was observed for the duration component wherein higher weekly duration of PA was significantly associated with greater mean CAC and RR of CAC ≥ 100 AU., Conclusion: Elevated CAC was associated with lower average intensity and longer duration of PA in men, providing new insight into the complex relationship between leisure-time PA behaviours and risk of CAC., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Muscular strength is an important component of physical fitness. We evaluated the relationship between baseline muscular strength and risk of stroke among adults who were aged ≥65 years during follow-up., Methods: We included 7627 healthy adults (mean age = 43.9 years, 86.0% male) underwent a baseline physical examination between 1980 and 1989. Muscular strength was determined by 1-repetition maximum measures for bench press and leg press and categorized into age- and sex-specific tertiles for each measure. Cardiorespiratory fitness (CRF) was assessed via a maximal treadmill exercise test. Those enrolled in fee-for-service Medicare from 1999 to 2019 were included in the analyses. Associations between baseline strength and stroke outcomes were estimated using a modified Cox proportional hazards model. In a secondary analysis, we examined stroke risk by categories of CRF where Quintile 1 = low, Quintiles 2-3 = moderate, and Quintiles 4-5 = high CRF based on age and sex., Results: After 70,072 person-years of Medicare follow-up, there were 1211 earliest indications of incident stroke. In multivariable analyses, the hazard ratio (95% confidence interval (95%CI)) for stroke across bench press categories were 1.0 (referent), 0.96 (0.83-1.11), and 0.89 (0.77-1.04), respectively (p trend = 0.14). The trend across categories of leg press was also non-significant (p trend = 0.79). Adjusted hazard ratio (95%CI) for stroke across ordered CRF categories were 1.0 (referent), 0.90 (0.71-1.13), and 0.72 (0.57-0.92) (p trend < 0.01)., Conclusion: While meeting public health guidelines for muscular strengthening activities is likely to improve muscular strength as well as many health outcomes in older adults, performing such activities may not be helpful in preventing stroke. Conversely, meeting guidelines for aerobic activity is likely to improve CRF and lower stroke risk., (Copyright © 2023. Production and hosting by Elsevier B.V.)

Background: Hs-cTnT (cardiac troponin T measured with a highly sensitive assay) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) may identify adults with hypertension who derive greater cognitive benefits from lower systolic blood pressure targets., Methods: In the SPRINT (Systolic Blood Pressure Intervention Trial) MIND study, participants were categorized as having both hs-cTnT and NT-proBNP in the lower 2 tertiles (n=4226), one in the highest tertile (n=2379), and both in the highest tertile (n=1506). We assessed the effect of intensive versus standard treatment on the composite of mild cognitive impairment (MCI) or probable dementia (PD) across biomarker categories., Results: Over a median follow-up of 5.1 years, 830 of 8111 participants (10.2%) developed MCI or PD. Participants in the highest biomarker category were at higher risk of MCI or PD compared with those in the lowest category (hazard ratio, 1.34 [95% CI, 1.00-1.56]). The effect of intensive treatment on reducing the risk of MCI or PD was greater among participants in the lowest biomarker category (hazard ratio, 0.64 [95% CI, 0.50-0.81]) than those in the intermediate (hazard ratio, 1.01 [95% CI, 0.80-1.28]) or highest categories (hazard ratio, 0.90 [95% CI, 0.72-1.13]; P interaction =0.02). The 5-year absolute risk differences in MCI or PD with intensive treatment were -2.9% (-4.4%, -1.3%), -0.2% (-3.0%, 2.6%), and -1.9% (-6.2%, 2.4%) in the lowest, intermediate, and highest biomarker categories, respectively., Conclusions: In SPRINT, the relative effect of intensive systolic blood pressure lowering on preventing cognitive impairment appears to be stronger among participants with lower compared with higher cardiac biomarker levels, though the absolute risk reductions were similar., Competing Interests: J.A. de Lemos reports grant support from Roche Diagnostics and Abbott Diagnostics, consulting fees from Ortho Clinical Diagnostics, Quidel Cardiovascular Inc, and Siemen’s Health Care Diagnostics. He has been named a co-owner on a patent awarded to the University of Maryland (US Patent Application Number: 15/309,754) entitled: “Methods for Assessing Differential Risk for Developing Heart Failure.” C.M. Ballantyne reports consulting and research support from Abbott and Roche Diagnostics. J.D. Berry reports grant support from the National Institutes of Health, Roche Diagnostics, and Abbott Diagnostics, consulting fees from Roche Diagnostics, and the Cooper Institute. The other authors report no conflicts.

Hypothesis: Investigating solid-liquid interactions to determine advancing and receding contact angles, and consequently contact angle hysteresis, is crucial for understanding material wetting properties. A reliable, automated, and possibly open-source tool is desirable, to standardize and automatize the measurement and make it user-independent., Experiments: This study introduces an open-source software, DropenVideo, as an extension of Dropen. DropenVideo automates frame-by-frame video analysis for the advancing and receding contact angle determination, by considering needle presence, contrast tuning, and compensating for missing drop edge data. Contact angles are calculated using convolution mask, circle, and polynomial fittings. An innovative feature in DropenVideo is the automatic protocol for identifying advancing and receding contact angles: (i) the advancing contact angle is determined as the average value during drop inflation; and (ii) the receding contact angle is determined from the frame of incipient motion during drop deflation., Findings: Exploring the application of DropenVideo across a range of complex surfaces as representative test cases, we highlight existing challenges in interpreting wetting measurements by addressing different wetting scenarios. Our study demonstrates that employing frame-by-frame automatic analysis of contact angle measurement videos using DropenVideo significantly mitigates the potential risks of subjective bias associated with manual interpretation and enhances the precision of identified wetting characteristics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: There are no shared decision-making frameworks for selecting blood pressure (BP) targets for individuals with hypertension. This study addressed whether results from the SPRINT (Systolic Blood Pressure Intervention Trial) could be tailored to individuals using predicted risks and simulated preferences., Methods and Results: Among 8202 SPRINT participants, Cox models were developed and internally validated to predict each individual's absolute difference in risk from intensive versus standard BP lowering for cardiovascular events, cognitive impairment, death, and serious adverse events (AEs). Individual treatment effects were combined using simulated preference weights into a net benefit, which represents a weighted sum of risk differences across outcomes. Net benefits were compared among those above versus below the median AE risk. In simulations for which cardiovascular, cognitive, and death events had much greater weight than the AEs of BP lowering, the median net benefit was 3.3 percentage points (interquartile range [IQR], 2.0-5.7), and 100% of participants had a net benefit favoring intensive BP lowering. When simulating benefits and harms to have similar weights, the median net benefit was 0.8 percentage points (IQR, 0.2-2.2), and 87% had a positive net benefit. Compared with participants at lower risk of AEs from BP lowering, those at higher risk had a greater net benefit from intensive BP lowering despite experiencing more AEs ( P <0.001 in both simulations)., Conclusions: Most SPRINT participants had a predicted net benefit that favored intensive BP lowering, but the degree of net benefit varied considerably. Tailoring BP targets using each patient's risks and preferences may provide more refined BP target recommendations.

We present a machine learning (ML) approach to static contact angle measurement, trained on a large data set (>7.2 million) of half drop contours based on solutions to the Young-Laplace equation where the contact angle is known a priori (removing all sources of error from human input). The data set included the effects of surface roughness, gravity, the size of drop relative to the image, and reflections of the drop on the surface. The presented ML model (valid for contact angles >110°), in combination with a new automated image and contour processing approach, is shown to be more accurate than other methods when benchmarked against an experimental data set, with an estimated error of 1°. The ML model is also 2 orders of magnitude faster at predicting contact angles than Young-Laplace fitting (the current best practice approach). The accuracy and speed of the presented approach provides a viable pathway toward robust and reproducible high-throughput contact angle analysis. This approach, Conan-ML, is open-source and provided for the use and development of new approaches to goniometry.

Objective: Test the feasibility, adherence rates and optimal frequency of digital, remote assessments using the ALSFRS-RSE via a customized smartphone-based app., Methods: This fully remote, longitudinal study was conducted over a 24-week period, with virtual visits every 3 months and weekly digital assessments. 19 ALS participants completed digital assessments via smartphone, including a digital version of the ALSFRS-RSE and mood survey. Interclass correlation coefficients (ICC) and Bland-Altman plots were used to assess agreement between staff-administered and self-reported ALSFRS-R pairs. Longitudinal change was evaluated using ANCOVA models and linear mixed models, including impact of mood and time of day. Impact of frequency of administration of the ALSFRS-RSE on precision of the estimate slope was tested using a mixed effects model., Results: In our ALS cohort, digital assessments were well-accepted and adherence was robust, with completion rates of 86%. There was excellent agreement between the digital self-entry and staff-administered scores computing multiple ICCs (ICC range = 0.925-0.961), with scores on the ALSFRS-RSE slightly higher (1.304 points). Digital assessments were associated with increased precision of the slope, resulting in higher standardized response mean estimates for higher frequencies, though benefit appeared to diminish at biweekly and weekly frequency. Effects of participant mood and time of day on total ALSFRS-RSE score were evaluated but were minimal and not statistically significant., Conclusion: Remote collection of digital patient-reported outcomes of functional status such as the ALSFRS-RSE yield more accurate estimates of change over time and provide a broader understanding of the lived experience of people with ALS.

Background: Increased hsCRP (high-sensitivity C-reactive protein), a marker of inflammation, is associated with incident cardiovascular events. We aim to determine whether the baseline or trajectory of hsCRP levels over time predicts incident heart failure (HF) hospitalization., Methods: JHS (Jackson Heart Study) participants' (n=3920 Black adults) hsCRP levels were measured over 3 visits (from 2000 to 2013). We assessed the association of hsCRP at baseline (visit 1) with incident HF hospitalization using Cox proportional hazards models. Furthermore, we assessed the association of the trajectory of hsCRP over repeated measurements (visits 1-3) with incident HF using joint models. Hazard ratios are reflective of an increase in hsCRP by 1 SD on a log2 scale. We also assessed the association of change in hsCRP between visit 1 and visit 3 with Cox proportional hazards models by grouping patients by low (<2 mg/L) and high (≥2 mg/L) hsCRP levels. The 4 groups were low-to-low (referent), low-to-high, high-to-low, and high-to-high., Results: Mean baseline age of participants was 54±13 years, and 63.8% were women. Over a median follow-up of 12 years, 308 (7.9%) participants were hospitalized with incident HF. Baseline hsCRP was not associated with incident HF (adjusted hazard ratio, 1.08 [95% CI, 0.96-1.22]). However, increasing hsCRP levels over repeated measures were associated with a higher risk of incident HF overall (adjusted hazard ratio, 1.22 [95% CI, 1.03-1.44]) and HF with preserved ejection fraction (adjusted hazard ratio, 1.30 [95% CI, 1.02-1.65]) but not HF with reduced ejection fraction ( P >0.05). Furthermore, changes in hsCRP from low-to-high and high-to-low levels were associated with incident HF ( P <0.05)., Conclusions: While baseline hsCRP was not associated with incident HF, an increasing trajectory of hsCRP over time was associated with increased risk for incident HF (particularly HF with preserved ejection fraction). Temporal change in hsCRP may be an important marker of risk for incident HF with preserved ejection fraction in Black adults., Competing Interests: Dr Mentz received research support and honoraria from Abbott, American Regent, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim/Eli Lilly, Boston Scientific, Cytokinetics, Fast BioMedical, Gilead, Innolife, Medtronic, Merck, Novartis, Relypsa, Respicardia, Roche, Sanofi, Vifor, Windtree Therapeutics, and Zoll. Dr Shah reports research support not related to this study from Novartis and Philips Ultrasound and consulting fees from Philips Ultrasound. Dr Virani receives research support from the Department of Veterans Affairs, the National Institutes of Health, and Tahir and Jooma Family. Dr Virani also received an honorarium from the American College of Cardiology in his role as an Associate Editor for Innovations, acc.org. Dr Butler reported personal fees from Abbott, Adrenomed, Amgen, Array, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CVRx, G3 Pharmaceutical, Impulse Dynamics, Innolife, Janssen, LivaNova, Luitpold, Medtronic, Merck, Novartis, Novo Nordisk, Relypsa, Roche, V-Wave Ltd, and Vifor outside the submitted work. The other authors report no conflicts. The views expressed in this article are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute, the National Institutes of Health, the US Department of Health and Human Services, or the Department of Veterans Affairs.

Introduction/aims: Expanded access (EA) is a Food and Drug Administration-regulated pathway to provide access to investigational products (IPs) to individuals with serious diseases who are ineligible for clinical trials. The aim of this report is to share the design and operations of a multicenter, multidrug EA program for amyotrophic lateral sclerosis (ALS) across nine US centers., Methods: A central coordination center was established to design and conduct the program. Templated documents and processes were developed to streamline study design, regulatory submissions, and clinical operations across protocols. The program included three protocols and provided access to IPs that were being tested in respective regimens of the HEALEY ALS Platform Trial (verdiperstat, CNM-Au8, and pridopidine). Clinical and safety data were collected in all EA protocols (EAPs). The program cohorts comprised participants who were not eligible for the platform trial, including participants at advanced stages of disease progression and with long disease duration., Results: A total of 85 participants were screened across the 3 EAPs from July 2021 to September 2022. The screen failure rate was 3.5%. Enrollment for the regimens of the platform trial was completed as planned and results informed the duration of the corresponding EAP. The verdiperstat EAP was concluded in December 2022. Mean duration of participation in the verdiperstat EAP was 5.8 ± 4.1 months. The CNM-Au8 and pridopidine EAPs are ongoing., Discussion: Multicenter EAPs conducted in parallel to randomized clinical trials for ALS can successfully enroll participants who do not qualify for clinical trials., (© 2024 The Author(s). Muscle & Nerve published by Wiley Periodicals LLC.)