Occupational exposure to disinfectants and asthma incidence in U.S. nurses: A prospective cohort study.

Background: Exposure to disinfectants among healthcare workers has been associated with respiratory health effects, in particular, asthma. However, most studies are cross-sectional and the role of disinfectant exposures in asthma development requires longitudinal studies. We investigated the association between occupational exposure to disinfectants and incident asthma in a large cohort of U.

BRAF V600E and Pten deletion in mice produces a histiocytic disorder with features of Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is characterized by the accumulation of Langerin (CD207)-expressing histiocytes. Mutational activation of mitogen-activated protein kinase pathway genes, in particular BRAF, drives most cases. To test whether activated BRAF is sufficient for the development of LCH, we engineered mice to express BRAF V600E under the control of the human Langerin promoter.

Association between blastocyst morphology and pregnancy and perinatal outcomes following fresh and cryopreserved embryo transfer.

Purpose: To assess the importance of each blastocyst morphological criteria with pregnancy and perinatal outcomes.

Methods: This single-center retrospective cohort study included blastocyst single embryo transfers (SET) performed between 1/2012-2/2018. Poisson regression was used to evaluate pregnancy outcomes following fresh and cryopreserved embryo transfer (CET) for association with blastocyst expansion, inner cell mass (ICM) quality, and trophectoderm (TE) quality.

Publisher Correction: Enhancer signatures stratify and predict outcomes of non-functional pancreatic neuroendocrine tumors.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Determinants of Left Ventricular Dysfunction and Remodeling in Patients With Corrected Tetralogy of Fallot.

Background The aim of this study was to identify in asymptomatic patients with repaired tetralogy of Fallot the prevalence and determinants of impaired left-sided cardiac function and adverse ventricular remodeling and the relation of left ventricular (LV) dysfunction and remodeling with cardiopulmonary exercise capacity. Methods and Results In a cross-sectional study, 103 patients with tetralogy of Fallot (median age, 16.3 years) in New York Heart Association class 1, with surgical repair at a median age of 1.

cAMPing out with the keepers of the gate: Adenylyl cyclases get cozy with Orai.

Calcium and cyclic AMP form the cornerstones of two ancient signaling systems represented in nearly every kingdom of life. Not surprisingly, these old and ubiquitous messenger molecules have co-evolved multiple means to regulate one another. Zhang et al.

Teaching Safe Opioid Prescribing During the Opioid Epidemic: Results of the 2018 Clerkship Directors in Internal Medicine Survey.

Background: Educating medical trainees across the continuum is essential to a multifaceted strategy for addressing the opioid epidemic.

Objective: To assess the current state of internal medicine clerkship content on safe opioid prescribing and opioid use disorder, and barriers to curriculum implementation.

Design: National Annual (2018) Clerkship Directors in Internal Medicine (CDIM) cross-sectional survey.

Reproductive surgery: decreasing skills and advancing technology-an existential conundrum.

Our article endeavors to be both a review of the recent past and a preview of the future of reproductive surgery. By reflecting on the rate of technological advancement over the past decade, we attempt to predict the trajectory of the next. We also delve into the changing nature and practical challenges of the practice of gynecologic surgery for the reproductive endocrinology and infertility subspecialist.

Role of Magnetic Resonance Imaging in Classifying Individuals Who Will Develop Accelerated Radiographic Knee Osteoarthritis.

We assessed whether adding magnetic resonance (MR)-based features to a base model of clinically accessible participant characteristics (i.e., serological, radiographic, demographic, symptoms, and physical function) improved classification of adults who developed accelerated radiographic knee osteoarthritis (AKOA) or not over the subsequent 4 years.

Enhancer signatures stratify and predict outcomes of non-functional pancreatic neuroendocrine tumors.

Most pancreatic neuroendocrine tumors (PNETs) do not produce excess hormones and are therefore considered 'non-functional'. As clinical behaviors vary widely and distant metastases are eventually lethal, biological classifications might guide treatment. Using enhancer maps to infer gene regulatory programs, we find that non-functional PNETs fall into two major subtypes, with epigenomes and transcriptomes that partially resemble islet α- and β-cells.

Sulfate assimilation regulates hydrogen sulfide production independent of lifespan and reactive oxygen species under methionine restriction condition in yeast.

Endogenously produced hydrogen sulfide was proposed to be an underlying mechanism of lifespan extension via methionine restriction. However, hydrogen sulfide regulation and its beneficial effects via methionine restriction remain elusive. Here, we identified the genes required to increase hydrogen sulfide production under methionine restriction condition using genome-wide high-throughput screening in yeast strains with single-gene deletions.

Accelerated knee osteoarthritis is associated with pre-radiographic degeneration of the extensor mechanism and cruciate ligaments: data from the Osteoarthritis Initiative.

Background: To determine if adults with incident accelerated knee osteoarthritis (KOA) are more likely to have degenerative knee ligaments or tendons compared to individuals with typical or no KOA.

Methods: We identified 3 sex-matched groups among Osteoarthritis Initiative participants who had a knee without radiographic KOA at baseline (Kellgren-Lawrence [KL] < 2): 1) accelerated KOA: at least 1 knee had KL grade ≥ 3 in ≤48 months, 2) typical KOA: at least 1 knee increased in radiographic scoring within 48 months, 3) no KOA: both knees had the same KL grade at baseline and 48 months. We evaluated knee magnetic resonance images up to 2 years before and after a visit when the accelerated or typical KOA criteria were met (index visit).

Dietary intake from birth through adolescence in relation to risk of benign breast disease in young women.

Purpose: Nutritional factors during different periods in life impact breast cancer risk. Because benign breast disease (BBD) is a well-established risk factor for breast cancer, we investigated childhood nutrition from birth through age 14 year and subsequent BBD.

Methods: A prospective cohort study of 9031 females, 9-15 year at baseline, completed questionnaires (including heights, weights) annually from 1996 to 2001, in 2003, 2005, 2007, 2010, 2013 and 2014.

Direct visualization of cAMP signaling in primary cilia reveals up-regulation of ciliary GPCR activity following Hedgehog activation.

The primary cilium permits compartmentalization of specific signaling pathways, including elements of the Hedgehog (Hh) pathway. Hh transcriptional activity is thought to be negatively regulated by constitutively high ciliary cAMP maintained by the Gα(s)-coupled GPCR, GPR161. However, cilia also sequester many other Gα(s)-coupled GPCRs with unknown potential to regulate Hh.

Early pre-radiographic structural pathology precedes the onset of accelerated knee osteoarthritis.

Background: Accelerated knee osteoarthritis (AKOA) is characterized by more pain, impaired physical function, and greater likelihood to receive a joint replacement compared to individuals who develop the typical gradual onset of disease. Prognostic tools are needed to determine which structural pathologies precede the development of AKOA compared to individuals without AKOA. Therefore, the purpose of this manuscript was to determine which pre-radiographic structural features precede the development of AKOA.

More Than the Sum of the Respiratory Events: Personalized Medicine Approaches for Obstructive Sleep Apnea.

Traditionally, the presence and severity of obstructive sleep apnea (OSA) have been defined by the apnea-hypopnea index (AHI). Continuous positive airway pressure is generally first-line therapy despite low adherence, because it reliably reduces the AHI when used, and the response to other therapies is variable. However, there is growing appreciation that the underlying etiology (i.

Short-term preoperative protein restriction attenuates vein graft disease via induction of cystathionine γ-lyase.

Aims: Therapies to prevent vein graft disease, a major problem in cardiovascular and lower extremity bypass surgeries, are currently lacking. Short-term preoperative protein restriction holds promise as an effective preconditioning method against surgical stress in rodent models, but whether it can improve vein graft patency after bypass surgery is undetermined. Here, we hypothesized that short-term protein restriction would limit vein graft disease via up-regulation of cystathionine γ-lyase and increased endogenous production of the cytoprotective gaseous signalling molecule hydrogen sulfide.

Soluble tau aggregates inhibit synaptic long-term depression and amyloid β-facilitated LTD in vivo.

Soluble synaptotoxic aggregates of the main pathological proteins of Alzheimer's disease, amyloid β-protein (Aß) and tau, have rapid and potent inhibitory effects on long-term potentiation (LTP). Although the promotion of synaptic weakening mechanisms, including long-term depression (LTD), is posited to mediate LTP inhibition by Aß, little is known regarding the action of exogenous tau on LTD. The present study examined the ability of different assemblies of full-length human tau to affect LTD in the dorsal hippocampus of the anaesthetized rat.

Dissecting Cell Lineages: From Microscope to Kaleidoscope.

Single-cell transcriptomics coupled with dynamic two-color fluorescence are used by Gehart et al. (2019) to elucidate adult mammalian cell trajectories in real time. The authors' close examination of intestinal enteroendocrine differentiation reveals new lineage features and shifting cell identities, and experiments in organoids uncover specific roles for transcriptional regulators identified by this approach.

It's Time to Wikify Clinical Documentation: How Collaborative Authorship Can Reduce the Burden and Improve the Quality of the Electronic Health Record.

Electronic health records (EHRs) have become ubiquitous tools and represent the standard of care for 96% of hospitals and 86% of ambulatory physicians in the United States. With adoption of EHRs came the promise of improved efficiency, higher-quality care, and lower costs. Unfortunately, some clinicians are now spending twice as much time on documentation as they spend seeing patients, and the documentation paradigm of problem-oriented medical records is contributing to this imbalance.

Pregnancy of unknown location: Evaluation and management.

Early diagnosis of an extrauterine pregnancy is important for safe and effective management. However, a pregnancy's location often cannot be easily determined with abnormal implantations or prior to 5-6 weeks' gestation. Multiple testing strategies exist to diagnose an abnormal pregnancy when location is unknown, but caution needs to be used to avoid a false diagnosis.

BRCA Challenge: BRCA Exchange as a global resource for variants in BRCA1 and BRCA2.

The BRCA Challenge is a long-term data-sharing project initiated within the Global Alliance for Genomics and Health (GA4GH) to aggregate BRCA1 and BRCA2 data to support highly collaborative research activities. Its goal is to generate an informed and current understanding of the impact of genetic variation on cancer risk across the iconic cancer predisposition genes, BRCA1 and BRCA2. Initially, reported variants in BRCA1 and BRCA2 available from public databases were integrated into a single, newly created site, www.

Diffuse tibiofemoral cartilage change prior to the development of accelerated knee osteoarthritis: Data from the osteoarthritis initiative.

We compared the spatial distribution of tibiofemoral cartilage change between individuals who will develop accelerated knee osteoarthritis (KOA) versus typical onset of KOA prior to the development of radiographic KOA. We conducted a longitudinal case-control analysis of 129 individuals from the Osteoarthritis Initiative. We assessed the percent change in tibiofemoral cartilage on magnetic resonance images at 36 informative locations from 2 to 1 year prior to the development of accelerated (n = 44) versus typical KOA (n = 40).