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INTRODUCTION: This study leveraged the twin study design, which controls for shared genetic and early life exposures, to investigate the association between traumatic brain injury (TBI) and dementia. METHODS: Members of the National Academy of Sciences-National Research Councils Twins Registry of World War II male veterans were assigned a cognitive outcome based on a multi-step assessment protocol. History of TBI was obtained via interviews. RESULTS: Among 8302 individuals, risk of non-Alzheimers disease (non-AD) dementia was higher in those with TBI (hazard ratio [HR] = 2.00, 95% confidence interval [CI], 0.97-4.12), than for AD (HR = 1.23, 95% CI, 0.76-2.00). To add more control of genetic and shared environmental factors, we analyzed 100 twin pairs discordant for both TBI and dementia onset, and found TBI-associated risk for non-AD dementia increased further (McNemar odds ratio = 2.70; 95% CI, 1.27-6.25). DISCUSSION: These findings suggest that non-AD mechanisms may underlie the association between TBI and dementia, potentially providing insight into inconsistent results from prior studies.

As the consumer interest and market for plant-based meat alternatives grows, understanding the nutritional differences between alternative and traditional meats is essential. This article describes an untargeted gas chromatography-mass spectrometry (GC-MS)-based metabolomics approach that compares the chemical profiles of a popular plant-based meat alternative and grass-fed ground beef using a GC system coupled to a GC-MS device. The samples were derivatized to simplify the chromatographic process and render the polar metabolites more volatile for GC-MS analysis. Statistical and multivariate analysis of the acquired and processed GC-MS data revealed that 90% of the annotated compounds differed between the plant-based alternative meat and the grass-fed ground beef samples. The ground beef and plant-based products each contained several compounds that were found in much smaller quantities, or not at all, in the other product. These results indicate differences in organic composition even though the nutritional labels on the back of the products were nearly identical. Heat maps, principal component analysis (PCA) score plots, variable importance plots (VIPs), and the clustering of compounds into metabolite classes provided further insights into the differences between the two types of meat products. The biological significance of the comparative data was studied using online databases and pathway analysis tools., Meeting the dietary requirements of a growing global population, while addressing the health concerns and sustainability issues associated with the consumption of meat, has increased consumer and scientific interest in [...]

ObjectiveTo evaluate radiographic subchondral trabecular bone texture (TBT) as a predictor of clinically relevant osteoarthritis (OA) progression (combination of symptom and structural worsening).MethodsThe Foundation for the National Institutes of Health (FNIH) OA Biomarkers Consortium undertook a study of progressive knee OA cases (n = 194 knees with both radiographic and pain progression over 24-48 months) and comparators (n = 406 OA knees not meeting the case definition). TBT parameters were extracted from a medial subchondral tibial region of interest by fractal signature analysis of radiographs using validated semiautomated software. Baseline TBT and time-integrated values over 12 and 24 months were evaluated for association with case status and separately with radiographic and pain progression status, adjusted for age, sex, body mass index, race, baseline Kellgren/Lawrence grade, baseline joint space width, Western Ontario and McMaster Universities Osteoarthritis Index pain score, and pain medication use. C statistics were generated from receiver operating characteristic curves.ResultsRelative to comparators, cases were characterized by thinner vertical and thicker horizontal trabeculae. The summed composite of 3 TBT parameters at baseline and over 12 and 24 months best predicted case status (odds ratios 1.24-1.43). The C statistic for predicting case status using the TBT composite score (0.633-0.649) was improved modestly but statistically significantly over the use of covariates alone (0.608). One TBT parameter, reflecting thickened horizontal trabeculae in cases, at baseline and over 12 and 24 months, predicted risk of any progression (radiographic and/or pain progression).ConclusionAlthough associations are modest, TBT could be an attractive means of enriching OA trials for progressors since it can be generated from screening knee radiographs already standard in knee OA clinical trials.

ObjectiveSeizure frequency variability is associated with placebo responses in randomized controlled trials (RCT). Increased variability can result in drug misclassification and, hence, decreased statistical power. We investigated a new method that directly incorporated variability into RCT analysis, ZV.MethodsTwo models were assessed: the traditional 50%-responder rate (RR50), and the variability-corrected score, ZV. Each predicted seizure frequency upper and lower limits using prior seizures. Accuracy was defined as percentage of time-intervals when the observed seizure frequencies were within the predicted limits. First, we tested the ZV method on three datasets (SeizureTracker: n=3016, Human Epilepsy Project: n=107, and NeuroVista: n=15). An additional independent SeizureTracker validation dataset was used to generate a set of 200 simulated trials each for 5 different sample sizes (total N=100 to 500 by 100), assuming 20% dropout and 30% drug efficacy. "Power" was determined as the percentage of trials successfully distinguishing placebo from drug (p90% power at N=100 per arm while RR50 required N=200 per arm.SignificanceZV may increase the statistical power of an RCT relative to the traditional RR50.

Background: Multimorbidity research has focused on the prevalence and consequences of multimorbidity in older populations. Less is known about the accumulation of chronic conditions earlier in the life course. Methods: We identified patterns of longitudinal multimorbidity accumulation using 30 years of data from in-person exams, annual follow-ups, and adjudicated end-points among 4,945 participants of the Coronary Artery Risk Development in Young Adults (CARDIA) study. Chronic conditions included arthritis, asthma, atrial fibrillation, cancer, end stage renal disease, chronic obstructive pulmonary disease, coronary heart disease, diabetes, heart failure, hyperlipidemia, hypertension, and stroke. Trajectory patterns were identified using latent class growth curve models. Results: Mean age (SD) at baseline (1985-6) was 24.9 (3.6), 55% were female, and 51% were Black. The median follow-up was 30 years (interquartile range 25-30). We identified six trajectory classes characterized by when conditions began to accumulate and the rapidity of accumulation: (1) early-fifties, slow, (2) mid-forties, fast, (3) mid-thirties, fast, (4) late-twenties, slow, (5) mid-twenties, slow, and (6) mid-twenties, fast. Compared with participants in the early-fifties, slow trajectory class, participants in mid-twenties, fast were more likely to be female, Black, and currently smoking and had a higher baseline mean waist circumference (83.6 vs. 75.6 cm) and BMI (27.0 vs. 23.4 kg/m2) and lower baseline physical activity (414.1 vs. 442.4 exercise units). Conclusions: A life course approach that recognizes the heterogeneity in patterns of accumulation of chronic conditions from early adulthood into middle age could be helpful for identifying high risk subgroups and developing approaches to delay multimorbidity progression. [ABSTRACT FROM AUTHOR]

ObjectiveMild traumatic brain injury (TBI) has been proposed as a risk factor for the development of Alzheimer's disease, Parkinson's disease, depression, and other illnesses. This study's objective was to determine the association of prior mild TBI with the subsequent diagnosis (that is, at least 1 year postinjury) of neurological or psychiatric disease.MethodsAll studies from January 1995 to February 2012 reporting TBI as a risk factor for diagnoses of interest were identified by searching PubMed, study references, and review articles. Reviewers abstracted the data and assessed study designs and characteristics.ResultsFifty-seven studies met the inclusion criteria. A random effects meta-analysis revealed a significant association of prior TBI with subsequent neurological and psychiatric diagnoses. The pooled odds ratio (OR) for the development of any illness subsequent to prior TBI was 1.67 (95% CI 1.44-1.93, p < 0.0001). Prior TBI was independently associated with both neurological (OR 1.55, 95% CI 1.31-1.83, p < 0.0001) and psychiatric (OR 2.00, 95% CI 1.50-2.66, p < 0.0001) outcomes. Analyses of individual diagnoses revealed higher odds of Alzheimer's disease, Parkinson's disease, mild cognitive impairment, depression, mixed affective disorders, and bipolar disorder in individuals with previous TBI as compared to those without TBI. This association was present when examining only studies of mild TBI and when considering the influence of study design and characteristics. Analysis of a subset of studies demonstrated no evidence that multiple TBIs were associated with higher odds of disease than a single TBI.ConclusionsHistory of TBI, including mild TBI, is associated with the development of neurological and psychiatric illness. This finding indicates that either TBI is a risk factor for heterogeneous pathological processes or that TBI may contribute to a common pathological mechanism.

Exercise training positively impacts mental health, yet remains untested in older adults with posttraumatic stress disorder (PTSD). We conducted a randomized controlled pilot trial to test the feasibility and acceptability of exercise training in older veterans with PTSD. Fifty-four veterans [greater than or equal to] 60 years, with a DSM-V diagnosis of PTSD, were randomized to supervised exercise (n = 36) or wait-list (WL; n = 18). Primary outcomes included recruitment rates, attendance, satisfaction, and retention. Secondary outcomes included changes in PTSD symptoms, depression, health-related quality of life, and sleep quality; assessed at baseline and 12 weeks. There were no adverse events. Attrition was minimal (14%), and adherence to the exercise intervention was high (82%). Clinically significant improvements in PTSD and related conditions were observed following exercise (Cohen's d = 0.36-0.81). Exercise training is safe and acceptable in older adults with PTSD, may improve PTSD symptoms, and broadly impacts PTSD-related conditions. Future definitive trials are warranted., Author(s): Katherine S. Hall [sup.1] [sup.2] , Miriam C. Morey [sup.1] [sup.2] , Hayden B. Bosworth [sup.2] [sup.3] , Jean C. Beckham [sup.4] [sup.5] , Michelle M. Pebole [sup.1] , [...]

Background/objectives The Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy Phase 2 (CALERIE) study showed that individuals who are nonobese were able to undergo significant calorie restriction (CR), yet the time course changes in adherence, weight, and appetite are unknown. This analysis aimed to investigate the time course changes in adherence, body weight, and appetite during the CALERIE study. Subjects/methods Overall, 143 participants (body mass index: 21.9-28.0 kg/m.sup.2) were randomized to a CR group that aimed to achieve 25% CR for 2 years. Throughout the intervention, body weight was measured, and appetite was assessed through visual analogue scales. Algorithms were utilized with body weight measurements to calculate adherence percentile score. Participants targeted an adherence percentile score of 50, though being between 80 (lowest acceptable adherence) and 10 (highest acceptable adherence) was adequate. Polynomial regression analyses were used to assess time course changes. Results Polynomials indicated that adherence percentile score increased above 50 after approximately week 20, although adherence remained acceptable (adherence percentile score less than 80) (R.sup.2 = 0.89; P < 0.001). Weight loss occurred until approximately week 60 and then plateaued (R.sup.2 [greater than or equal to] 0.92; P < 0.001). Hunger and thirst increased (R.sup.2 [greater than or equal to] 0.30; P < 0.001), but the total increase in scale scores were Conclusions In individuals who are nonobese, adherence to 25% CR declines after 20 weeks, but 2 years of CR that stimulates a meaningful reduction in weight, promotes aging-related benefits and negligibly affects appetite is viable., Author(s): James L. Dorling [sup.1], Sai Krupa Das [sup.2], Susan B. Racette [sup.3], John W. Apolzan [sup.1], Dachuan Zhang [sup.1], Carl F. Pieper [sup.4], Corby K. Martin [sup.1], Author Affiliations: [...]

Objective: To compare a remotely supervised weight loss and exercise intervention to lifestyle counseling for effects on cardiovascular disease risk, disease activity, and patient‐reported outcomes in older patients with rheumatoid arthritis (RA) and overweight/obesity. Methods: Twenty older (60–80 years), previously sedentary participants with seropositive RA and overweight/obesity were randomized to 16 weeks of either Supervised Weight loss and Exercise Training (SWET) or Counseling Health As Treatment (CHAT). The SWET group completed aerobic training (150 minutes/week moderate‐to‐vigorous intensity), resistance training (two days/week), and a hypocaloric diet (7% weight loss goal). The CHAT control group completed two lifestyle counseling sessions followed by monthly check‐ins. The primary outcome was a composite metabolic syndrome z‐score (MSSc) derived from fasting glucose, triglycerides, high density lipoprotein–cholesterol, minimal waist circumference, and mean arterial pressure. Secondary outcomes included RA disease activity and patient‐reported outcomes. Results: Both groups improved MSSc (absolute change −1.67 ± 0.64 in SWET; −1.34 ± 1.30 in CHAT; P < 0.01 for both groups) with no between‐group difference. Compared with CHAT, SWET significantly improved body weight, fat mass, Disease Activity Score‐28 C‐reactive protein, and patient‐reported physical health, physical function, mental health, and fatigue (P < 0.04 for all between‐group comparisons). Based on canonical correlations for fat mass, cardiorespiratory fitness, and leg strength, component‐specific effects were strongest for (1) weight loss improving MSSc, physical health, and mental health; (2) aerobic training improving physical function and fatigue; and (3) resistance training improving Disease Activity Score‐28 C‐reactive protein. Conclusion: In older patients with RA and overweight/obesity, 16 weeks of remotely supervised weight loss, aerobic training, and resistance training improve cardiometabolic health, patient‐reported outcomes, and disease activity. Less intensive lifestyle counseling similarly improves cardiovascular disease risk profiles, suggesting an important role for integrative interventions in the routine clinical care of this at‐risk RA population. [ABSTRACT FROM AUTHOR]

Phenomenon: Balancing the demands of medical training and parenthood is challenging. We explored perceptions of programmatic support, parental leave, breastfeeding, and self-reported biggest challenges among a large cohort of physician mothers in a variety of medical specialties and across the stage of training when they had their first child. Our goal was to inform strategies to help improve the physician parent experience. Approach: This cross-sectional, observational survey study was performed using a convenience sample from an online physician-mom support group from January to February 2018. Descriptive statistics and bivariate analyses were used to report results and examine relationships between career stage at first child and outcome variables. Responses to the open-ended question, "What is your biggest challenge as a physician mom?" were qualitatively analyzed. Findings: The survey received 896 complete responses. The most common specialties were obstetrics and gynecology (25.3%), pediatrics (19.9%), internal medicine or medicine/pediatrics (17.1%), and family medicine (10.2%). The majority of participants (63.9%) had their first child during medical training, including medical school (14.3%), residency (35.8%) or fellowship (13.6%). Medical students were less likely to perceive programmatic support than residents or fellows (44.1% vs. 63.1% vs. 62.3%, respectively), and only 19.9% of participants who became parents during medical training reported having a clear and adequate parental leave policy. Nearly 70% of participants breastfed for six months or more, with no statistical differences across career stage. Most participants (57.6%) delayed child-bearing for one or more reasons, with 32.3% delaying to complete training. The most common codes applied to responses for 'biggest challenges as a physician mom' were insufficient time, lack of work-life balance, missing out, and over-expectation. Insights: Physician mothers, particularly those who had their first child during training, continue to struggle with support from training programs, finding work-life balance, and feelings of inadequacy. Interventions such as clear and adequate leave policies, program-sponsored or onsite childcare and improved programmatic support of breastfeeding and pumping may help to ameliorate the challenges described by our participants. [ABSTRACT FROM AUTHOR]

Exercise training beneficially moderates the effects of vascular aging. This study compared the efficacy of Peripheral Remodeling through Intermittent Muscular Exercise (PRIME), a novel training regimen, versus aerobic training on hemodynamic profiles in participants ≥70 years at risk for losing functional independence. Seventy-five participants (52 females, age: 76 ± 5 years) were assessed for hemodynamic and vascular function at baseline, after 4 weeks of either PRIME or aerobic training (Phase 1) and again after a further 8 weeks of aerobic and resistance training (Phase 2). Data were analyzed using 2 x 2 repeated-measures analysis of variance models on the change in each dependent variable. PRIME demonstrated reductions in brachial and aortic mean arterial pressure and diastolic blood pressure (p < .05) from baseline after Phase 1, which were sustained throughout Phase 2. Earlier and greater reductions in blood pressure following PRIME support the proposal that peripheral muscular training could beneficial for older individuals commencing an exercise program. [ABSTRACT FROM AUTHOR]