Zinc-chelating BET bromodomain inhibitors equally target islet endocrine cell types.

Inhibition of the bromodomain and extraterminal domain (BET) protein family is a potential strategy to prevent and treat diabetes; however, the clinical use of BET bromodomain inhibitors (BETis) is associated with adverse effects. Here, we explore a strategy for targeting BETis to β cells by exploiting the high-zinc (Zn) concentration in β cells relative to other cell types. We report the synthesis of a novel, Zn-chelating derivative of the pan-BETi (+)-JQ1, (+)-JQ1-DPA, in which (+)-JQ1 was conjugated to dipicolyl amine (DPA).

Laser welding of fiber array units.

We report the results of fabricating fiber array unit (FAU) connectors using a near IR laser welding process, locking fibers in proper position on planar glass substrates and forming strong glass-to-glass bonds, followed by final assembly using lower coefficient of thermal expansion (CTE) epoxies. A thin metal film deposited on the glass substrate provides the absorption required to attain interfacial temperatures suitable for glass-to-glass bonding. This method allows the elimination of dedicated expensive V-groove plates while still maintaining very good fiber placement accuracy.

Complete and Uneventful Recovery in a Case of Lymphocytic Hypophysitis Causing a Third Nerve Palsy.

Lymphocytic hypophysitis (LH) is a neuroendocrine disorder characterised by autoimmune inflammation of the pituitary gland with resultant pituitary dysfunction. Rarely, the presenting symptom can be diplopia due to irritation of the third, fourth, or sixth cranial nerves secondary to cavernous sinus involvement of the mass or increased intracranial pressure. We describe the case of a healthy, 20-year-old female with a pupillary sparing third nerve palsy, who was subsequently diagnosed with LH after an endoscopic transsphenoidal biopsy of the mass.

terminal BET bromodomain inhibitors disrupt a BRD4-p65 interaction and reduce inducible nitric oxide synthase transcription in pancreatic β-cells.

Chronic inflammation of pancreatic islets is a key driver of β-cell damage that can lead to autoreactivity and the eventual onset of autoimmune diabetes (T1D). In the islet, elevated levels of proinflammatory cytokines induce the transcription of the inducible nitric oxide synthase (iNOS) gene, , ultimately resulting in increased nitric oxide (NO). Excessive or prolonged exposure to NO causes β-cell dysfunction and failure associated with defects in mitochondrial respiration.

Blood Pressure Intervention and Control in SPRINT.

Background: The SPRINT (Systolic Blood Pressure Intervention Trial) demonstrated reductions in major cardiovascular disease events and mortality with an intensive systolic blood pressure (SBP) goal intervention. However, a detailed description of the blood pressure intervention, antihypertensive medication usage, blood pressure levels, and rates and predictors of blood pressure control has not been reported previously.

Methods: Hypertensive participants (n=9361) 50 years and older with elevated cardiovascular disease risk were randomized 1:1 to SBP goal <120 mm Hg or SBP goal <140 mm Hg.

Novel Case of Multifocal Choroiditis following Powassan Virus Infection.

Purpose: To present a case study that describes novel ocular manifestations of Powassan virus encephalitis using fundus imaging.

Study Design: Case Report.

Results: In this case study, fundus photographs, fundus autofluorescence, and fluorescein angiography were used to highlight Powassan virus-induced multifocal choroiditis with linear streaks.

Human induced pluripotent stem cell derived hepatocytes provide insights on parenteral nutrition associated cholestasis in the immature liver.

Parenteral nutrition-associated cholestasis (PNAC) significantly limits the safety of intravenous parenteral nutrition (PN). Critically ill infants are highly vulnerable to PNAC-related morbidity and mortality, however the impact of hepatic immaturity on PNAC is poorly understood. We examined developmental differences between fetal/infant and adult livers, and used human induced pluripotent stem cell-derived hepatocyte-like cells (iHLC) to gain insights into the contribution of development to altered sterol metabolism and PNAC.

Identifying the K-12 classrooms' indoor air quality factors that affect student academic performance.

The objective of this study was to investigate associations between indoor air quality (IAQ) in K-12 classrooms and student academic performance. During the academic years 2015-2017, various IAQ factors in 220 classrooms in the US were measured seasonally, excluding summer. Measurements were taken during occupied and unoccupied times in several classrooms within each school.

A Novel Means-End Problem-Solving Assessment Tool for Early Intervention: Evaluation of Validity, Reliability, and Sensitivity.

Purpose: To evaluate validity, reliability, and sensitivity of the novel Means-End Problem-Solving Assessment Tool (MEPSAT).

Methods: Children with typical development and those with motor delay were assessed throughout the first 2 years of life using the MEPSAT. MEPSAT scores were validated against the cognitive and motor subscales of the Bayley Scales of Development.

Developing a fidelity measure of early intervention programs for children with neuromotor disorders.

Aim: To describe the development of an intervention-specific fidelity measure and its utilization and to determine whether the newly developed Sitting Together and Reaching to Play (START-Play) intervention was implemented as intended. Also, to quantify differences between START-Play and usual early intervention (uEI) services.

Method: A fidelity measure for the START-Play intervention was developed for children with neuromotor disorders by: (1) identifying key intervention components, (2) establishing a measurement coding system, and (3) testing the reliability of instrument scores.

Self-retained cryopreserved amniotic membrane for treating severe corneal ulcers: a comparative, retrospective control study.

To compare the effectiveness of self- retained cryopreserved AM as an adjuvant therapy for infectious corneal ulcers. Retrospective, case-control study of 24 eyes of 24 consecutive patients with central and paracentral corneal infectious ulcers and initial visual acuity worse than 20/200. Among them, 11 eyes of 11 patients received additional placement of self-retained cryopreserved AM.

A Randomized Cross-Over Field Study of Pre-Hydration Strategies in Dogs Tracking in Hot Environments.

The objective of this study was to evaluate 4 pre-exercise hydration strategies (oral water, chicken-flavored water, chicken-flavored oral electrolyte solution, and subcutaneous electrolyte solution) in working dogs conducting rigorous tracking operations in hot and arid conditions. In a randomized cross-over field study, 7 Border Patrol Search, Trauma, and Rescue (BORSTAR) Unit dogs working/training out of Fort Bliss in El Paso, Texas were randomly assigned to one of 4 different hydration strategy treatments each day for 4 days of study participation. Dogs were provided hydration treatment prior to running 2 separate one-mile tracks and were offered water while tracking.

Orthostatic Hypotension, Cardiovascular Outcomes, and Adverse Events: Results From SPRINT.

Orthostatic hypotension (OH) is frequently observed with hypertension treatment, but its contribution to adverse outcomes is unknown. The SPRINT (Systolic Blood Pressure Intervention Trial) was a randomized trial of adults, age ≥50 years at high risk for cardiovascular disease with a seated systolic blood pressure (BP) of 130 to 180 mm Hg and a standing systolic BP ≥110 mm Hg. Participants were randomized to a systolic BP treatment goal of either <120 or <140 mm Hg.

A National Survey of Veterans Affairs Medical Centers' Cardiology Services.

A survey found that of cardiology services were widely available at facilities across the US Department of Veterans Affairs, but the types of services varied considerably based on facility complexity.

Blood Pressure Control and the Association With Diabetes Mellitus Incidence: Results From SPRINT Randomized Trial.

The SPRINT (Systolic Blood Pressure Intervention Trial) demonstrated reduced cardiovascular outcomes. We evaluated diabetes mellitus incidence in this randomized trial that compared intensive blood pressure strategy (systolic blood pressure <120 mm Hg) versus standard strategy (<140 mm Hg). Participants were ≥50 years of age, with systolic 130 to 180 mm Hg and increased cardiovascular risk.

The impact of central IRB's on informed consent readability and trial adherence in SPRINT.

Background: Federal agencies have encouraged the use of central institutional review boards (CIRBs) for multi-site clinical trials. There is limited evidence supporting the use of CIRBs. Our aim is to evaluate how SPRINT sites regulated by CIRBs performed regarding informed consent readability and participant trial adherence compared to those regulated by local IRBs.

The impact of start strategy on start performance in alpine skiing exists on flat, but not on steep inclines.

Here, we explored the relationship between incline and start strategy during alpine skiing. Eight FIS skiers performed starts on a flat (3°) and steep (21°) incline employing five different strategies. Their times, trajectories and velocities were monitored with a GNSS system and video.

FoxO1 and FoxA1/2 form a complex on DNA and cooperate to open chromatin at insulin-regulated genes.

We have previously shown that cooperative, interdependent binding by the pioneer factors FoxO1 and FoxA1/2 is required for recruitment of RNA polymerase II and H3K27 acetylation to the promoters of insulin-regulated genes. However, the underlying mechanisms are unknown. In this study, we demonstrate that, in HepG2 cells, FoxO1 and FoxA2 form a complex on DNA that is disrupted by insulin treatment.

Evaluation of Three Hydration Strategies in Detection Dogs Working in a Hot Environment.

Physical activity in hot environments can increase the risk of heat stress or heat stroke in dogs. Heat tolerance is influenced by acclimatization to the environment, physical fitness, and hydration state. Three common strategies to promote hydration in working dogs are free access to water (W), oral electrolyte solutions (OESs), and administration of subcutaneous fluids (SQs).

Effect of Intensive Versus Standard Blood Pressure Treatment According to Baseline Prediabetes Status: A Post Hoc Analysis of a Randomized Trial.

Objective: To determine whether the effects of intensive (<120 mmHg) compared with standard (<140 mmHg) systolic blood pressure (SBP) treatment are different among those with prediabetes versus those with fasting normoglycemia at baseline in the Systolic Blood Pressure Intervention Trial (SPRINT).

Research Design And Methods: This was a post hoc analysis of SPRINT. SPRINT participants were categorized by prediabetes status, defined as baseline fasting serum glucose ≥100 mg/dL versus those with normoglycemia (fasting serum glucose <100 mg/dL).

Cognitive Function and Kidney Disease: Baseline Data From the Systolic Blood Pressure Intervention Trial (SPRINT).

Background: Chronic kidney disease is common and is associated with cardiovascular disease, cerebrovascular disease, and cognitive function, although the nature of this relationship remains uncertain.

Study Design: Cross-sectional cohort using baseline data from the Systolic Blood Pressure Intervention Trial (SPRINT).

Setting & Participants: Participants in SPRINT, a randomized clinical trial of blood pressure targets in older community-dwelling adults with cardiovascular disease, chronic kidney disease, or high cardiovascular disease risk and without diabetes or known stroke, who underwent detailed neurocognitive testing in the cognition substudy, SPRINT-Memory and Cognition in Decreased Hypertension (SPRINT-MIND).

Evaluation of the Effectiveness of a Patient-Centered Educational Mailer Designed to Improve Statin Adherence: A Pragmatic Trial.

Background: Patients with high total cholesterol have increased risk of cardiovascular disease. National Cholesterol Education Program (NCEP) and American Heart Association (AHA) guidelines recommend cholesterol lowering with statin medications; however, statin adherence remains poor. We hypothesized that patient-centered education on the 10-year risk for each of the major constituents of cardiovascular disease would increase statin adherence and achievement of the low-density lipoprotein cholesterol (LDL-C) goal.

Effect of Intensive Blood Pressure Control on Gait Speed and Mobility Limitation in Adults 75 Years or Older: A Randomized Clinical Trial.

Importance: Intensive blood pressure (BP) control confers a benefit on cardiovascular morbidity and mortality; whether it affects physical function outcomes is unknown.

Objective: To examine the effect of intensive BP control on changes in gait speed and mobility status.

Design, Setting, And Participants: This randomized, clinical trial included 2636 individuals 75 years or older with hypertension and no history of type 2 diabetes or stroke who participated in the Systolic Blood Pressure Intervention Trial (SPRINT).

Automatic interactive optimization for volumetric modulated arc therapy planning.

Background: Intensity modulated radiotherapy treatment planning for sites with many different organs-at-risk (OAR) is complex and labor-intensive, making it hard to obtain consistent plan quality. With the aim of addressing this, we developed a program (automatic interactive optimizer, AIO) designed to automate the manual interactive process for the Eclipse treatment planning system. We describe AIO and present initial evaluation data.