Abstract Background In SPRINT (Systolic Blood Pressure Intervention Trial), a systolic blood pressure (SBP) goal of <120 mm Hg resulted in lower cardiovascular disease (CVD) risk compared with an SBP ...goal of <140 mm Hg. Objectives The purpose of this study was to estimate the prevalence, number, and characteristics of U.S. adults meeting SPRINT eligibility criteria and determine the broader population to whom SPRINT could be generalized. Methods We conducted a cross-sectional, population-based study using data from the National Health and Nutrition Examination Survey, 2007 to 2012. The SPRINT inclusion criteria were age ≥50 years, SBP 130 to 180 mm Hg depending on the number of antihypertensive medication classes being taken, and high CVD risk (history of coronary heart disease, estimated glomerular filtration rate of 20 to 59 ml/min/1.73 m2 , 10-year CVD risk ≥15%, or age ≥75 years). Exclusion criteria were diabetes, history of stroke, >1 g in 24 h of proteinuria daily, heart failure, estimated glomerular filtration rate <20 ml/min/1.73 m2 , or receiving dialysis. Treated hypertension was defined by self-reported use of medication to lower blood pressure with ≥1 class of antihypertensive medication identified through a pill bottle review. Results Overall, 7.6% (95% confidence interval CI: 7.0% to 8.3%) or 16.8 million (95% CI: 15.7 to 17.8 million) U.S. adults, and 16.7% (95% CI: 15.2% to 18.3%) or 8.2 million (95% CI: 7.6 to 8.8 million) adults with treated hypertension met the SPRINT eligibility criteria. Among both the overall U.S. population and adults with treated hypertension, the percentage meeting SPRINT eligibility criteria increased with older age, was higher among males than females, and was higher among non-Hispanic whites compared with non-Hispanic blacks or Hispanics. Of U.S. adults eligible for SPRINT, 51.0% (95% CI: 47.8% to 54.1%) or 8.6 million (95% CI: 8.0 to 9.1 million) were not treated for hypertension. Conclusions A substantial percentage of U.S. adults meet the eligibility criteria for SPRINT.
Objective
Traumatic brain injury (TBI) is thought to be a risk factor for Parkinson disease (PD), but results are conflicting. Many studies do not account for confounding or reverse causation. We ...sought to address these concerns by quantifying risk of PD after TBI compared to non‐TBI trauma (NTT; defined as fractures).
Methods
Using inpatient/emergency department (ED) International Classification of Disease, Ninth Revision code data for California hospitals from 2005–2006, we identified patients aged ≥55 years with TBI (n = 52,393) or NTT (n = 113,406) and without baseline PD or dementia who survived hospitalization. Using Kaplan–Meier estimates and Cox proportional hazards models (adjusted for age, sex, race/ethnicity, income, comorbidities, health care use, and trauma severity), we estimated risk of PD after TBI during follow‐up ending in 2011. We also assessed interaction with mechanism of injury (fall vs nonfall) and effect of TBI severity (mild vs moderate/severe) and TBI frequency (1 TBI vs >1 TBI).
Results
TBI patients were significantly more likely to be diagnosed with PD compared to NTT patients (1.7% vs 1.1%, p < 0.001, adjusted hazard ratio HR = 1.44, 95% confidence interval CI = 1.31–1.58). Risk of PD was similar for TBI sustained via falls versus nonfalls (interaction p = 0.6). Assessment by TBI severity (mild TBI: HR = 1.24, 95% CI = 1.04–1.48; moderate/severe TBI: HR = 1.50, 95% CI = 1.35–1.66) and TBI frequency (1 TBI: HR = 1.45, 95% CI = 1.30–1.60; >1 TBI: HR = 1.87, 95% CI = 1.58–2.21) revealed a dose response.
Interpretation
Among patients aged ≥55 years presenting to inpatient/ED settings with trauma, TBI is associated with a 44% increased risk of developing PD over 5 to 7 years that is unlikely to be due to confounding or reverse causation. Ann Neurol 2015;77:987–995
The primary purpose of the present study is to determine if an organized control scheme exists for the antagonist muscle during steady isometric torque. A secondary focus is to better understand how ...firing rates of the antagonist muscle change from a moderate- to higher-contraction intensity. Fourteen subjects performed two submaximal isometric trapezoid muscle actions of the forearm flexors that included a linearly increasing, steady force at both 40% and 70% maximum voluntary contraction, and linearly decreasing segments. Surface electromyographic signals of the biceps and triceps brachii were collected and decomposed into constituent motor unit action potential trains. Motor unit firing rate versus recruitment threshold, motor unit action potential amplitude versus recruitment threshold, and motor unit firing rate versus action potential amplitude relationships of the biceps brachii (agonist) and triceps brachii (antagonist) muscles were analyzed. Moderate- to-strong relationships (|
| ≥ 0.69) were present for the agonist and antagonist muscles for each relationship with no differences between muscles (
= 0.716, 0.428, 0.182). The
-intercepts of the motor unit firing rate versus recruitment threshold relationship of the antagonist did not increase from 40% to 70% maximal voluntary contractions (
= 0.96), unlike for the agonist (
= 0.009). The antagonist muscle exhibits a similar motor unit control scheme to the agonist. Unlike the agonist, however, the firing rates of the antagonist did not increase with increasing intensity. Future research should investigate how antagonist firing rates adapt to resistance training and changes in antagonist firing rates in the absence of peripheral feedback.
This is the first study to explore a potential motor unit control scheme and quantify changes in firing rates with increasing intensity of an antagonist muscle during isometric contractions. We demonstrate that the antagonist muscle possesses an organized motor unit firing rate and recruitment scheme similar to the agonist muscle during isometric forearm flexion, but unlike the agonist muscle, there was no significant increase in firing rates from a moderate- to higher-intensity isometric contraction.
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•Early prenatal exposure to 26 suspected endocrine disruptors was related to lower IQ in children.•The endocrine disruptor mixture disproportionately impacted boys.•Replacement ...analogue bisphenol F (BPF), may not be a safer alternative to BPA.•Preventing short-lived pollutant exposure among pregnant women may mitigate effects.
Endocrine disrupting chemicals (EDCs) are xenobiotics with the ability to interfere with hormone action, even at low levels. Prior environmental epidemiology studies link numerous suspected EDCs, including phthalates and bisphenol A (BPA), to adverse neurodevelopmental outcomes. However, results for some chemicals were inconsistent and most assessed one chemical at a time.
To evaluate the overall impact of prenatal exposure to an EDC mixture on neurodevelopment in school-aged children, and identify chemicals of concern while accounting for co-exposures.
Among 718 mother-child pairs from the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy study (SELMA) study, we used Weighted Quantile Sum (WQS) regression to assess the association between 26 EDCs measured in 1st trimester urine or blood, with Wechsler Intelligence Scale for Children (IV) Intelligence Quotient (IQ) scores at age 7 years. Models were adjusted for child sex, gestational age, mother’s education, mother’s IQ (RAVEN), weight, and smoking status. To evaluate generalizability, we conducted repeated holdout validation, a machine learning technique.
Using repeated holdout validation, IQ scores were 1.9-points (CI = −3.6, −0.2) lower among boys for an inter-quartile-range (IQR) change in the WQS index. BPF made the largest contribution to the index with a weight of 14%. Other chemicals of concern and their weights included PBA (9%), TCP (9%), MEP (6%), MBzP (4%), PFOA (6%), PFOS (5%), PFHxS (4%), Triclosan (5%), and BPA (4%). While we did observe an inverse association between EDCs and IQ among all children when training and testing the WQS index estimate on the full dataset, these results were not robust to repeated holdout validation.
Among boys, early prenatal exposure to EDCs was associated with lower intellectual functioning at age 7. We identified bisphenol F as the primary chemical of concern, suggesting that the BPA replacement compound may not be any safer for children. Future studies are needed to confirm the potential neurotoxicity of replacement analogues.
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Malignant gliomas are the most common primary brain cancer diagnosed and still carry a poor prognosis despite aggressive multimodal management. Despite the continued advances in ...immunotherapy for other cancer types, however, there remain no FDA approved immunotherapies for cancers such as glioblastoma. OF the many approaches being explored, cancer vaccine programs are undergoing a renaissance due to the technological advances and personalized nature of their contemporary design. Neoantigen vaccines are a form of immunotherapy involving the use of DNA, mRNA, and proteins derived from non-synonymous mutations identified in patient tumor tissue samples to stimulate tumor-specific T-cell reactivity leading to enhance tumor targeting. In the last several years, the study of neoantigens as a therapeutic target has increased, with the routine workflow implementation of comprehensive next generation sequencing and in silico peptide binding prediction algorithms. Several neoantigen vaccine platforms are being evaluated in clinical trials for malignancies including melanoma, pancreatic cancer, breast cancer, lung cancer, and glioblastoma, among others. In this review, we will review the concept of neoantigen discovery using cancer immunogenomics approaches in glioblastoma and explore the disease-specific issues being addressed in the design of effective personalized cancer vaccine strategies.
Faced with complex patterns of global change, the inextricable interconnection of humans, pet animals, livestock and wildlife and their social and ecological environment is evident and requires ...integrated approaches to human and animal health and their respective social and environmental contexts. The history of integrative thinking of human and animal health is briefly reviewed from early historical times, to the foundation of universities in Europe, up to the beginning of comparative medicine at the end of the 19th century. In the 20th century, Calvin Schwabe coined the concept of “one medicine”. It recognises that there is no difference of paradigm between human and veterinary medicine and both disciplines can contribute to the development of each other. Considering a broader approach to health and well-being of societies, the original concept of “one medicine” was extended to “one health” through practical implementations and careful validations in different settings. Given the global health thinking in recent decades, ecosystem approaches to health have emerged. Based on complex ecological thinking that goes beyond humans and animals, these approaches consider inextricable linkages between ecosystems and health, known as “ecosystem health”. Despite these integrative conceptual and methodological developments, large portions of human and animal health thinking and actions still remain in separate disciplinary silos. Evidence for added value of a coherent application of “one health” compared to separated sectorial thinking is, however, now growing. Integrative thinking is increasingly being considered in academic curricula, clinical practice, ministries of health and livestock/agriculture and international organizations. Challenges remain, focusing around key questions such as how does “one health” evolve and what are the elements of a modern theory of health? The close interdependence of humans and animals in their social and ecological context relates to the concept of “human-environmental systems”, also called “social-ecological systems”. The theory and practice of understanding and managing human activities in the context of social-ecological systems has been well-developed by members of The Resilience Alliance and was used extensively in the Millennium Ecosystem Assessment, including its work on human well-being outcomes. This in turn entails systems theory applied to human and animal health. Examples of successful systems approaches to public health show unexpected results. Analogous to “systems biology” which focuses mostly on the interplay of proteins and molecules at a sub-cellular level, a systemic approach to health in social-ecological systems (HSES) is an inter- and trans-disciplinary study of complex interactions in all health-related fields. HSES moves beyond “one health” and “eco-health”, expecting to identify emerging properties and determinants of health that may arise from a systemic view ranging across scales from molecules to the ecological and socio-cultural context, as well from the comparison with different disease endemicities and health systems structures.
Estimates of the prevalence of Parkinson's disease in North America have varied widely and many estimates are based on small numbers of cases and from small regional subpopulations. We sought to ...estimate the prevalence of Parkinson's disease in North America by combining data from a multi-study sampling strategy in diverse geographic regions and/or data sources. Five separate cohort studies in California (2), Minnesota (1), Hawaii USA (1), and Ontario, Canada (1) estimated the prevalence of PD from health-care records (3), active ascertainment through facilities, large group, and neurology practices (1), and longitudinal follow-up of a population cohort (1). US Medicare program data provided complementary estimates for the corresponding regions. Using our age- and sex-specific meta-estimates from California, Minnesota, and Ontario and the US population structure from 2010, we estimate the overall prevalence of PD among those aged ≥45 years to be 572 per 100,000 (95% confidence interval 537-614) that there were 680,000 individuals in the US aged ≥45 years with PD in 2010 and that that number will rise to approximately 930,000 in 2020 and 1,238,000 in 2030 based on the US Census Bureau population projections. Regional variations in prevalence were also observed in both the project results and the Medicare-based calculations with which they were compared. The estimates generated by the Hawaiian study were lower across age categories. These estimates can guide health-care planning but should be considered minimum estimates. Some heterogeneity exists that remains to be understood.
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