Meniscal extrusion or subchondral damage characterize incident accelerated osteoarthritis: Data from the Osteoarthritis Initiative.

Knee osteoarthritis (KOA) is typically a slowly progressive disorder; however, a subset of knees progress with dramatic rapidity. We aimed to describe magnetic resonance imaging (MRI) findings that are associated with accelerated KOA. We conducted a longitudinal descriptive study in the Osteoarthritis Initiative cohort.

Fetal adrenal gland volume and preterm birth: a prospective third-trimester screening evaluation.

Objective: Given the importance of the fetal adrenal gland in producing hormones critical to labor, we sought to evaluate whether sonographic three-dimensional measurements of the adrenal gland are a useful screening tool for spontaneous preterm birth (SPTB).

Method: We prospectively screened 128 non-anomalous singletons from 24 to 36 weeks' gestation with volumetric measurements of the fetal adrenal gland at their indicated antenatal sonogram. Labor and delivery outcomes were assessed and compared with respect to adrenal volume.

Genome-Wide Association Study Identifies Novel Pharmacogenomic Loci For Therapeutic Response to Montelukast in Asthma.

Background: Genome-wide association study (GWAS) is a powerful tool to identify novel pharmacogenetic single nucleotide polymorphisms (SNPs). Leukotriene receptor antagonists (LTRAs) are a major class of asthma medications, and genetic factors contribute to variable responses to these drugs. We used GWAS to identify novel SNPs associated with the response to the LTRA, montelukast, in asthmatics.

Dietary vitamin D and risk of heart failure in the Physicians' Health Study.

Background: Experimental studies have demonstrated the role of vitamin D in key pathways related to cardiovascular health. While several studies have investigated the impact of vitamin D therapy on outcomes in subjects with prevalent heart failure, limited research exists on the relationship of dietary vitamin D consumption with the risk of heart failure. Thus, we sought to investigate whether dietary vitamin D consumption was associated with a lower risk of incident heart failure in a large prospective cohort of male physicians.

Control of stomach smooth muscle development and intestinal rotation by transcription factor BARX1.

Diverse functions of the homeodomain transcription factor BARX1 include Wnt-dependent, non-cell autonomous specification of the stomach epithelium, tracheo-bronchial septation, and Wnt-independent expansion of the spleen primordium. Tight spatio-temporal regulation of Barx1 levels in the mesentery and stomach mesenchyme suggests additional roles. To determine these functions, we forced constitutive BARX1 expression in the Bapx1 expression domain, which includes the mesentery and intestinal mesenchyme, and also examined Barx1(-/)(-) embryos in further detail.

External validation of the Hospital-patient One-year Mortality Risk (HOMR) model for predicting death within 1 year after hospital admission.

Background: Predicting long-term survival after admission to hospital is helpful for clinical, administrative and research purposes. The Hospital-patient One-year Mortality Risk (HOMR) model was derived and internally validated to predict the risk of death within 1 year after admission. We conducted an external validation of the model in a large multicentre study.

Discovery of LRRK2 inhibitors using sequential in silico joint pharmacophore space (JPS) and ensemble docking.

Joint pharmacophore space (JPS), ensemble docking and sequential JPS-ensemble docking were used to select three panels of compounds (10 per panel) for evaluation as LRRK2 inhibitors. These computational methods identified four LRRK2 inhibitors with IC50 values <12μM. The sequential JPS-ensemble docking predicted the majority of active hits.

The HDAC Inhibitors Scriptaid and LBH589 Combined with the Oncolytic Virus Delta24-RGD Exert Enhanced Anti-Tumor Efficacy in Patient-Derived Glioblastoma Cells.

Background: A phase I/II trial for glioblastoma with the oncolytic adenovirus Delta24-RGD was recently completed. Delta24-RGD conditionally replicates in cells with a disrupted retinoblastoma-pathway and enters cells via αvβ3/5 integrins. Glioblastomas are differentially sensitive to Delta24-RGD.

Development of a process to disclose amyloid imaging results to cognitively normal older adult research participants.

Introduction: The objective of this study was to develop a process to maximize the safety and effectiveness of disclosing Positron Emission Tomography (PET) amyloid imaging results to cognitively normal older adults participating in Alzheimer's disease secondary prevention studies such as the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) Study.

Methods: Using a modified Delphi Method to develop consensus on best practices, we gathered and analyzed data over three rounds from experts in two relevant fields: informed consent for genetic testing or human amyloid imaging.

Results: Experts reached consensus on (1) text for a brochure that describes amyloid imaging to a person who is considering whether to undergo such imaging in the context of a clinical trial, and (2) a process for amyloid PET result disclosure within such trials.

First night of CPAP: impact on memory consolidation attention and subjective experience.

Objective: Neurocognitive deficits are common and serious consequences of obstructive sleep apnea (OSA). Currently, the gold standard treatment is continuous positive air pressure (CPAP) therapy, although the clinical responses to this intervention can be variable. This study examined the effect of one night of CPAP therapy on sleep-dependent memory consolidation, attention, and vigilance as well as subjective experience.

Overview of proteomics studies in obstructive sleep apnea.

Obstructive sleep apnea (OSA) is an underdiagnosed common public health concern causing deleterious effects on metabolic and cardiovascular health. Although much has been learned regarding the pathophysiology and consequences of OSA in the past decades, the molecular mechanisms associated with such processes remain poorly defined. The advanced high-throughput proteomics-based technologies have become a fundamental approach for identifying novel disease mediators as potential diagnostic and therapeutic targets for many diseases, including OSA.

Endometriosis: a high-risk population for major chronic diseases?

Background: Despite an estimated prevalence of 10% in women, the etiology of endometriosis remains poorly understood. Over recent decades, endometriosis has been associated with risk of several chronic diseases, such as cancer, autoimmune diseases, asthma/atopic diseases and cardiovascular diseases. A deeper understanding of these associations is needed as they may provide new leads into the causes or consequences of endometriosis.

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

The American College of Medical Genetics and Genomics (ACMG) previously developed guidance for the interpretation of sequence variants.(1) In the past decade, sequencing technology has evolved rapidly with the advent of high-throughput next-generation sequencing. By adopting and leveraging next-generation sequencing, clinical laboratories are now performing an ever-increasing catalogue of genetic testing spanning genotyping, single genes, gene panels, exomes, genomes, transcriptomes, and epigenetic assays for genetic disorders.

Asthma history, job type and job changes among US nurses.

Objectives: Nurses are at increased risk of occupational asthma, an observation that may be related to disinfectants exposure. Whether asthma history influences job type or job changes among nurses is unknown. We investigated this issue in a large cohort of nurses.

Physical inactivity among older adults: Implications for life expectancy among non-overweight and overweight or obese individuals.

This study investigates to what extent physical inactivity in older age is associated with reduced life expectancy among non-overweight and overweight/obese individuals. Data from 20,203 respondents aged ≥60 years were drawn from the Health Survey for England and Scottish Health Surveys (1994-2008) and 5-year all-cause mortality linkage. Population attributable fractions were calculated to estimate years of life lost due to physical inactivity.

FDA designations for therapeutics and their impact on drug development and regulatory review outcomes.

New prescription drugs receive approval from the US Food and Drug Administration (FDA) based on tests establishing safety and adequate and well-controlled trials demonstrating "substantial evidence" of efficacy. However, a number of legislative and regulatory initiatives, the most recent being the breakthrough therapy designation created in 2012, give the FDA flexibility to approve drugs on the basis of less rigorous data in situations of greater clinical need. These expedited development and review pathways now contribute to a majority of all new drug approvals and have important benefits in encouraging efficient availability of transformative drugs.

Association of egg consumption and calcified atherosclerotic plaque in the coronary arteries: the NHLBI Family Heart Study.

Background And Aims: Eggs are a ubiquitous and important source of dietary cholesterol and nutrients, yet their relationship to coronary heart disease (CHD) remains unclear. While some data have suggested a positive association between egg consumption and CHD, especially among diabetic subjects, limited data exist on the influence of egg consumption on subclinical disease. Thus, we sought to examine whether egg consumption is associated with calcified atherosclerotic plaques in the coronary arteries.

Metabolomics in the developmental origins of obesity and its cardiometabolic consequences.

In this review, we discuss the potential role of metabolomics to enhance understanding of obesity-related developmental origins of health and disease (DOHaD). We first provide an overview of common techniques and analytical approaches to help interested investigators dive into this relatively novel field. Next, we describe how metabolomics may capture exposures that are notoriously difficult to quantify, and help to further refine phenotypes associated with excess adiposity and related metabolic sequelae over the life course.

Mechanism-based proteomic screening identifies targets of thioredoxin-like proteins.

Thioredoxin (Trx)-fold proteins are protagonists of numerous cellular pathways that are subject to thiol-based redox control. The best characterized regulator of thiols in proteins is Trx1 itself, which together with thioredoxin reductase 1 (TR1) and peroxiredoxins (Prxs) comprises a key redox regulatory system in mammalian cells. However, there are numerous other Trx-like proteins, whose functions and redox interactors are unknown.

Coexistence of Histologically Confirmed Hashimoto's Thyroiditis with Different Stages of Papillary Thyroid Carcinoma in a Consecutive Chinese Cohort.

Purpose. To determine the relationship between Hashimoto's thyroiditis (HT) and all stages of papillary thyroid carcinoma (PTC) with or without local lymph node metastasis (LNM). Methods.

Solar elastosis and cutaneous melanoma: a site-specific analysis.

Cutaneous melanomas are postulated to arise through at least two causal pathways, namely the "chronic sun exposure" and "nevus" pathways. While chronic sun exposure probably causes many head/neck melanomas, its role at other sites is unclear. In a population-based, case-case comparison study conducted in Brisbane, Australia, we determined the prevalence and epidemiologic correlates of chronic solar damage in skin adjacent to invasive, incident melanomas on the trunk (n = 418) or head/neck (n = 92) among patients aged 18-79 in 2007-2010.

Mediterranean diet and incidence of rheumatoid arthritis in women.

Objective: We examined the association between a Mediterranean dietary pattern, as measured by the Alternate Mediterranean Diet Score (aMed), and risk of incident rheumatoid arthritis (RA) in US women.

Methods: We prospectively followed 83,245 participants from the Nurses' Health Study (NHS; 1980-2008) and 91,393 participants from NHS II (1991-2009) who were initially free of baseline connective tissue diseases. Dietary information was obtained via validated food frequency questionnaires at baseline and approximately every 4 years during followup.

Functional variations modulating PRKCA expression and alternative splicing predispose to multiple sclerosis.

The protein kinase C alpha (PRKCA) gene, encoding a Th17-cell-selective kinase, was repeatedly associated with multiple sclerosis (MS), but the underlying pathogenic mechanism remains unknown. We replicated the association in Italians (409 cases, 723 controls), identifying a protective signal in the PRKCA promoter (P = 0.033), and a risk haplotype in intron 3 (P = 7.