A DNA methylation biomarker of alcohol consumption.

The lack of reliable measures of alcohol intake is a major obstacle to the diagnosis and treatment of alcohol-related diseases. Epigenetic modifications such as DNA methylation may provide novel biomarkers of alcohol use. To examine this possibility, we performed an epigenome-wide association study of methylation of cytosine-phosphate-guanine dinucleotide (CpG) sites in relation to alcohol intake in 13 population-based cohorts (n=13 317; 54% women; mean age across cohorts 42-76 years) using whole blood (9643 European and 2423 African ancestries) or monocyte-derived DNA (588 European, 263 African and 400 Hispanic ancestry) samples.

Promises and pitfalls of data sharing in qualitative research.

The movement for research transparency has gained irresistible momentum over the past decade. Although qualitative research is rarely published in the high-impact journals that have adopted, or are most likely to adopt, data sharing policies, qualitative researchers who publish work in these and similar venues will likely encounter questions about data sharing within the next few years. The fundamental ways in which qualitative and quantitative data differ should be considered when assessing the extent to which qualitative and mixed methods researchers should be expected to adhere to data sharing policies developed with quantitative studies in mind.

Implications of the Patient Protection and Affordable Care Act on Insurance Coverage and Rehabilitation Use Among Young Adult Trauma Patients.

Importance: Trauma is the leading cause of death and disability among young adults, who are also among the most likely to be uninsured. Efforts to increase insurance coverage, including passage of the Patient Protection and Affordable Care Act (ACA), were intended to improve access to care and promote improvements in outcomes. However, despite reported gains in coverage, the ACA's success in promoting use of high-quality care and enacting changes in clinical end points remains unclear.

DNA methylation-based measures of biological age: meta-analysis predicting time to death.

Estimates of biological age based on DNA methylation patterns, often referred to as "epigenetic age", "DNAm age", have been shown to be robust biomarkers of age in humans. We previously demonstrated that independent of chronological age, epigenetic age assessed in blood predicted all-cause mortality in four human cohorts. Here, we expanded our original observation to 13 different cohorts for a total sample size of 13,089 individuals, including three racial/ethnic groups.

Neurosteroid Allopregnanolone Suppresses Median Nerve Injury-induced Mechanical Hypersensitivity and Glial Extracellular Signal-regulated Kinase Activation through γ-Aminobutyric Acid Type A Receptor Modulation in the Rat Cuneate Nucleus.

Background: Mechanisms underlying neuropathic pain relief by the neurosteroid allopregnanolone remain uncertain. We investigated if allopregnanolone attenuates glial extracellular signal-regulated kinase (ERK) activation in the cuneate nucleus (CN) concomitant with neuropathic pain relief in median nerve chronic constriction injury (CCI) model rats.

Methods: We examined the time course and cellular localization of phosphorylated ERK (p-ERK) in CN after CCI.

Better Patient Care At High-Quality Hospitals May Save Medicare Money And Bolster Episode-Based Payment Models.

US policy makers are making efforts to simultaneously improve the quality of and reduce spending on health care through alternative payment models such as bundled payment. Bundled payment models are predicated on the theory that aligning financial incentives for all providers across an episode of care will lower health care spending while improving quality. Whether this is true remains unknown.

Punctuated copy number evolution and clonal stasis in triple-negative breast cancer.

Aneuploidy is a hallmark of breast cancer; however, knowledge of how these complex genomic rearrangements evolve during tumorigenesis is limited. In this study, we developed a highly multiplexed single-nucleus sequencing method to investigate copy number evolution in patients with triple-negative breast cancer. We sequenced 1,000 single cells from tumors in 12 patients and identified 1-3 major clonal subpopulations in each tumor that shared a common evolutionary lineage.

Impact of ACA Insurance Coverage Expansion on Perforated Appendix Rates Among Young Adults.

Background: The 2010 Dependent Coverage Provision (DCP) of the Affordable Care Act allowed young adults to remain on their parents' health insurance plans until age 26 years. Although the provision improved coverage and survey-reported access to care, little is known regarding its impact on timely access for acute conditions. This study aims to assess changes in insurance coverage and perforation rates among young adults with acute appendicitis-an established metric for population-level health care access-after the DCP.

ω-3 Polyunsaturated Fatty Acid Biomarkers and Coronary Heart Disease: Pooling Project of 19 Cohort Studies.

Importance: The role of ω-3 polyunsaturated fatty acids for primary prevention of coronary heart disease (CHD) remains controversial. Most prior longitudinal studies evaluated self-reported consumption rather than biomarkers.

Objective: To evaluate biomarkers of seafood-derived eicosapentaenoic acid (EPA; 20:5ω-3), docosapentaenoic acid (DPA; 22:5ω-3), and docosahexaenoic acid (DHA; 22:6ω-3) and plant-derived α-linolenic acid (ALA; 18:3ω-3) for incident CHD.

Genome-wide specificities of CRISPR-Cas Cpf1 nucleases in human cells.

The activities and genome-wide specificities of CRISPR-Cas Cpf1 nucleases are not well defined. We show that two Cpf1 nucleases from Acidaminococcus sp. BV3L6 and Lachnospiraceae bacterium ND2006 (AsCpf1 and LbCpf1, respectively) have on-target efficiencies in human cells comparable with those of the widely used Streptococcus pyogenes Cas9 (SpCas9).

Spinocerebellar ataxia type 36 in the Han Chinese.

Objective: To ascertain the genetic and clinical characteristics of the GGCCTG hexanucleotide repeat expansion in the nucleolar protein 56 gene (NOP56) in patients with spinocerebellar ataxia (SCA), sporadic ataxia, or amyotrophic lateral sclerosis (ALS) in Taiwan.

Methods: We conducted clinical and molecular genetic studies of 109 probands with molecularly unassigned SCA from 512 SCA pedigrees, 323 healthy controls, 502 patients with sporadic ataxia syndromes, and 144 patients with ALS. Repeat-primed PCR assays and PCR-fragment analysis for the number of short hexanucleotide repeats (<40 units) were performed to ascertain NOP56 hexanucleotide repeat expansion.

Comparative Effectiveness of Carotid Artery Stenting Versus Carotid Endarterectomy Among Medicare Beneficiaries.

Background: Effectiveness of carotid artery stenting (CAS) relative to carotid endarterectomy (CEA) among Medicare patients has not been established. We compared effectiveness of CAS versus CEA among Medicare beneficiaries.

Methods And Results: We linked Medicare data (2000-2009) to the Society for Vascular Surgery's Vascular Registry (2005-2008) and the National Cardiovascular Data Registry's (NCDR) Carotid Artery Revascularization and Endarterectomy Registry (2006-2008/2009).

Proximate Context of HIV-Related Stigma and Women's Use of Skilled Childbirth Services in Uganda.

HIV-related stigma compromises both HIV prevention and treatment and has recently been described as a barrier to utilization of skilled childbirth services in sub-Saharan Africa. This study uses the 2011 Uganda Demographic Health Survey to estimate the associations between HIV-related stigma, measured both at the individual and community level, and use of facility delivery among women. Consistent with theoretical predictions, higher levels of stigma are associated with reduced likelihood of facility delivery.

Population-based study of intra-household gender differences in water insecurity: reliability and validity of a survey instrument for use in rural Uganda.

Hundreds of millions of people worldwide lack adequate access to water. Water insecurity, which is defined as having limited or uncertain availability of safe water or the ability to acquire safe water in socially acceptable ways, is typically overlooked by development organizations focusing on water availability. To address the urgent need in the literature for validated measures of water insecurity, we conducted a population-based study in rural Uganda with 327 reproductive-age women and 204 linked men from the same households.

Associations of serum perfluoroalkyl acid levels with T-helper cell-specific cytokines in children: By gender and asthma status.

Perfluoroalkyl acids (PFAAs) are a group of common chemicals that ubiquitously exist in wildlife and humans. Experimental data suggest that they may alter T-lymphocyte functioning in situ by preferentially enhancing the development of T-helper 2 (TH2)- and inhibiting TH1-lymphocyte development and might increase allergic inflammation, but few human studies have been conducted. To evaluate the association between serum PFAAs concentrations and T-lymphocyte-related immunological markers of asthma in children, and further to assess whether gender modified this association, 231 asthmatic children and 225 non-asthmatic control children from Northern Taiwan were recruited into the Genetic and Biomarker study for Childhood Asthma.

Pleural Tags on CT Scans to Predict Visceral Pleural Invasion of Non-Small Cell Lung Cancer That Does Not Abut the Pleura.

Purpose: To evaluate the association of pleural tags with visceral pleural invasion of non-small cell lung cancer (NSCLC) that does not abut the pleural surface.

Materials And Methods: This retrospective study was approved by the institutional review board. Informed consent was waived.

Delivering value by focusing on patient experience.

The use of patient experience as a quality metric in healthcare remains controversial. Clinicians have expressed concern that incentives focused on patient experience may lead to lower quality care. However, empirical evidence from the United States and abroad suggests that hospitals and ambulatory care providers with higher patient satisfaction scores also perform better on clinical process and outcome measures.

Rethinking Priorities: Cost of Complications After Elective Colectomy.

Objective: To compare incremental costs associated with complications of elective colectomy using nationally representative data among patients undergoing laparoscopic/open resections for the 4 most frequent diagnoses.

Summary Background Data: Rising healthcare costs have led to increasing focus on the need to achieve a better understanding of the association between costs and quality. Among elective colectomies, a focus of surgical quality-improvement initiatives, interpretable evidence to support existing approaches is lacking.

Osthol attenuates neutrophilic oxidative stress and hemorrhagic shock-induced lung injury via inhibition of phosphodiesterase 4.

Oxidative stress caused by neutrophils is an important pathogenic factor in trauma/hemorrhagic (T/H)-induced acute lung injury (ALI). Osthol, a natural coumarin found in traditional medicinal plants, has therapeutic potential in various diseases. However, the pharmacological effects of osthol in human neutrophils and its molecular mechanism of action remain elusive.

Small-Conductance Calcium-Activated Potassium Current Is Activated During Hypokalemia and Masks Short-Term Cardiac Memory Induced by Ventricular Pacing.

Background: Hypokalemia increases the vulnerability to ventricular fibrillation. We hypothesize that the apamin-sensitive small-conductance calcium-activated potassium current (IKAS) is activated during hypokalemia and that IKAS blockade is proarrhythmic.

Methods And Results: Optical mapping was performed in 23 Langendorff-perfused rabbit ventricles with atrioventricular block and either right or left ventricular pacing during normokalemia or hypokalemia.

Hospital board and management practices are strongly related to hospital performance on clinical quality metrics.

National policies to improve health care quality have largely focused on clinical provider outcomes and, more recently, payment reform. Yet the association between hospital leadership and quality, although crucial to driving quality improvement, has not been explored in depth. We collected data from surveys of nationally representative groups of hospitals in the United States and England to examine the relationships among hospital boards, management practices of front-line managers, and the quality of care delivered.