Single-nucleotide human disease mutation inactivates a blood-regenerative GATA2 enhancer.

The development and function of stem and progenitor cells that produce blood cells are vital in physiology. GATA-binding protein 2 (GATA2) mutations cause GATA-2 deficiency syndrome involving immunodeficiency, myelodysplastic syndrome, and acute myeloid leukemia. GATA-2 physiological activities necessitate that it be strictly regulated, and cell type-specific enhancers fulfill this role.

MDRPU -an uncommonly recognized common problem in ICU: A point prevalence study.

Background: Pressure ulcers (PU) usually occur over bony prominences in hospitalized patients. But they may occur due to medical devices referred also as Medical device related pressure ulcers (MDRPU). The United States National advisory panel (NPUAP) recognizes it as an important entity.

Development of a US trust measure to assess and monitor parental confidence in the vaccine system.

Objective: To develop a Vaccine Confidence Index (VCI) that is capable of detecting variations in parental confidence towards childhood immunizations centered on trust and concern issues that impact vaccine confidence.

Methods: We used a web-based national poll of 893 parents of children <7 years in 2016 to assess the measures created for the Emory VCI (EVCI). EVCI measures were developed using constructs related to vaccine confidence identified by the U.

Fasiglifam-Induced Liver Injury in Patients With Type 2 Diabetes: Results of a Randomized Controlled Cardiovascular Outcomes Safety Trial.

Objective: To evaluate the cardiovascular (CV) safety of fasiglifam, a first-in-man G-protein-coupled receptor 40 (GPR40) agonist, in patients with type 2 diabetes.

Research Design And Methods: A phase 3 multicenter randomized double-blind placebo-controlled two-arm trial was intended to randomize 5,000 participants with type 2 diabetes at high CV risk to fasiglifam or placebo. The primary objective of the trial was to rule out an upper noninferiority bound >1.

Optimal promising zone designs.

Clinical trials with adaptive sample size reassessment based on an unblinded analysis of interim results are perhaps the most popular class of adaptive designs (see Elsäßer et al., 2007). Such trials are typically designed by prespecifying a zone for the interim test statistic, termed the promising zone, along with a decision rule for increasing the sample size within that zone.

Average Clinician-Measured Blood Pressures and Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus and Ischemic Heart Disease in the EXAMINE Trial.

Background Blood pressure ( BP ) treatment goals in patients with diabetes mellitus and increased cardiovascular risk remain controversial. Our study objective was to determine cardiovascular outcomes according to achieved BP s over the average follow-up period in the EXAMINE (Examination of Cardiovascular Outcomes With Alogliptin Versus Standard of Care) trial. Methods and Results EXAMINE was a cardiovascular outcomes trial in 5380 patients with type 2 diabetes mellitus and recent acute coronary syndromes.

An adaptive population enrichment phase III trial of TRC105 and pazopanib versus pazopanib alone in patients with advanced angiosarcoma (TAPPAS trial).

Background: Major challenges in clinical trials of ultra-orphan oncology diseases include limited patient availability and paucity of reliable prior data for estimating the treatment effect and, therefore, determining optimal sample size. Angiosarcoma (AS), a particularly aggressive form of soft tissue sarcoma with an incidence of about 2000 cases per year in the United States and Europe is poorly addressed by current systemic therapies. Pazopanib, an inhibitor of vascular endothelial growth factor receptor (VEGFR) is approved for the treatment of AS, with modest benefit.

Clinical Outcomes and Neuroimaging Profiles in Nondisabled Patients With Anticoagulant-Related Intracerebral Hemorrhage.

Background and Purpose- The aim of this study was to prospectively validate our prior findings of smaller hematoma volume and lesser neurological deficit in nonvitamin K oral anticoagulant (NOAC) compared with Vitamin K antagonist (VKA)-related intracerebral hemorrhage (ICH). Methods- Prospective 12-month observational study in 15 tertiary stroke centers in the United States, Europe, and Asia. Consecutive patients with premorbid modified Rankin Scale score of <2 with acute nontraumatic anticoagulant-related ICH divided into 2 groups according to the type of anticoagulant: NOAC versus VKA.

Reassessing the Role of Surrogate End Points in Drug Development for Heart Failure.

With few notable exceptions, drug development for heart failure (HF) has become progressively more challenging, and there remain no definitively proven therapies for patients with acute HF or HF with preserved ejection fraction. Inspection of temporal trends suggests an increasing rate of disagreement between early-phase and phase III trial end points. Preliminary results from phase II HF trials are frequently promising, but increasingly followed by disappointing phase III results.

Potential use of waste foundry sand in dual process (photocatalysis and photo-Fenton) for the effective removal of phenazone from water: Slurry and fixed-bed approach.

In this study, degradation of a pharmaceutical drug, Phenazone (PNZ) has been carried out via heterogeneous photocatalysis, photo-Fenton and in-situ dual process (photocatalysis + photo-Fenton) in suspension and fixed-mode under artificial UV-A as well as under natural solar radiations. Waste material such as foundry sand (FS) was exploited as a supplement for iron in case of photo-Fenton reaction. The distinct processes including photocatalysis and photo-Fenton were found to be competent for the degradation of PNZ as both processes revealed an almost 90-95% removal of PNZ after 180 min of UV irradiations.

Human leukemia mutations corrupt but do not abrogate GATA-2 function.

By inducing the generation and function of hematopoietic stem and progenitor cells, the master regulator of hematopoiesis GATA-2 controls the production of all blood cell types. Heterozygous mutations cause immunodeficiency, myelodysplastic syndrome, and acute myeloid leukemia. disease mutations commonly disrupt amino acid residues that mediate DNA binding or -elements within a vital intronic enhancer, suggesting a haploinsufficiency mechanism of pathogenesis.

Predicting diabetes risk among HIV-positive and HIV-negative women.

Objective: To assess the performance of an adapted American Diabetes Association (ADA) risk score and the concise Finnish Diabetes Risk Score (FINRISC) for predicting type 2 diabetes development in women with and at risk of HIV infection.

Design: Longitudinal analysis of the Women's Interagency HIV Study.

Methods: The women's Interagency HIV Study is an ongoing prospective cohort study of women with and at risk for HIV infection.

Extensile lateral versus sinus tarsi approach for displaced, intra-articular calcaneal fractures: a meta-analysis.

Background: Operative management of displaced, intra-articular calcaneal fractures is associated with improved functional outcomes but associated with frequent complications due to poor soft tissue healing. The use of a minimally invasive sinus tarsi approach to the fixation of these fractures may be associated with a lower rate of complications and therefore provide superior outcomes without the associated morbidity of operative intervention.

Methods: We reviewed four prospective and seven retrospective trials that compared the outcomes from the operative fixation of displaced intra-articular calcaneal fractures via either an extensile lateral approach or minimally invasive fixation via a sinus tarsi approach.

De novo atrial fibrillation after mitral valve surgery.

Objectives: We sought to determine the incidence and risk factors for de novo atrial fibrillation (>90 days after surgery) in patients without preoperative atrial fibrillation.

Methods: From 2004 to 2014, 2261 patients underwent mitral valve surgery; 1288 patients (57%) did not have a history of atrial fibrillation, and 930 patients had rhythm information more than 90 days after surgery. De novo atrial fibrillation and death probabilities were estimated using a semi-competing risks, multi-state model.

Enhancing soluble phosphate concentration in sludge liquor by pressurised anaerobic digestion.

Recovery of phosphate from wastewater is challenging, with one of the best opportunities being recovery from sludge anaerobic digestion liquor, as struvite. However, this is limited by the proportion of total phosphorous which is soluble, due to in-digester metal ion precipitation. High-pressure anaerobic digestion may enable enhanced phosphate solubility (and hence recovery potential), without the use of added acid, due to an increased liquid phase CO concentration.

Six-Month Outcomes after Restrictive or Liberal Transfusion for Cardiac Surgery.

Background: We reported previously that, in patients undergoing cardiac surgery who were at moderate-to-high risk for death, a restrictive transfusion strategy was noninferior to a liberal strategy with respect to the composite outcome of death from any cause, myocardial infarction, stroke, or new-onset renal failure with dialysis by hospital discharge or 28 days after surgery, whichever came first. We now report the clinical outcomes at 6 months after surgery.

Methods: We randomly assigned 5243 adults undergoing cardiac surgery to a restrictive red-cell transfusion strategy (transfusion if the hemoglobin concentration was <7.

HIV RNA persists in rectal tissue despite rapid plasma virologic suppression with dolutegravir-based therapy.

Objectives: Despite plasma virologic suppression with antiretroviral therapy (ART), HIV persists in gut tissue. The objectives of this study were to compare plasma and rectal tissue HIV RNA dynamics and to assess relationships with dolutegravir (DTG) plasma and tissue concentrations.

Design: A longitudinal cohort study of HIV-infected treatment-naïve individuals initiating DTG-based ART was conducted over 12 weeks with plasma and rectal tissue sampling (Clinicaltrials.

Development of PCR-based molecular marker for screening of disease-suppressive composts against Fusarium wilt of tomato ( L.).

The present study was carried out to develop a PCR-based molecular marker suitable for screening of disease-suppressive composts against Fusarium wilt of tomato. An effective uncultured bacterial community was screened from our previous study on investigation of microbial communities in composts for their potential for biocontrol of Fusarium wilt. Based on available sequence information (Accession no.

Implementation of a Rapid Entry Program Decreases Time to Viral Suppression Among Vulnerable Persons Living With HIV in the Southern United States.

Background: Rapid entry programs (REPs) improve time to antiretroviral therapy (ART) initiation (TAI) and time to viral suppression (TVS). We assessed the feasibility and effectiveness of a REP in a large HIV clinic in Atlanta, Georgia, serving a predominately un- or underinsured population.

Methods: The Rapid Entry and ART in Clinic for HIV (REACH) program was implemented on May 16, 2016.

HIV and symptoms of depression are independently associated with impaired glucocorticoid signaling.

Chronic inflammation caused by HIV infection may lead to deficient glucocorticoid (GC) signaling predisposing people living with HIV to depression and other psychiatric disorders linked to GC resistance. We hypothesized that comorbid HIV and depressive symptoms in women would synergistically associate with deficits in GC signaling. This cross-sectional study used samples obtained from the Women's Interagency HIV Study (WIHS).

Localized In Situ Nanoemulgel Drug Delivery System of Quercetin for Periodontitis: Development and Computational Simulations.

This study was aimed at formulating a bioabsorbable, controlled-release, nanoemulgel of Quercetin, a potent antimicrobial and anti-inflammatory agent for the treatment of periodontitis that could improve its solubility and bioavailability. Screening of components was carried out based on the solubility studies. Nanoemulsion containing cinnamon oil as the oil phase, tween 80 and Carbitol as the surfactant-cosurfactant mixture (S) and water as the aqueous phase containing 125 µg/200 µL of Quercetin was prepared by using spontaneous emulsification method.

The distance of the femoral neurovascular bundle from the hip joint: an intraoperative guide to reduce iatrogenic injury.

Background: Iatrogenic injury to the femoral neurovascular bundle is not uncommon during primary and revision total hip replacement (THR) and can result in permanent weakness, pain and poor function. Prevention of injury to these structures relies on a sound knowledge of their relationships to the hip joint.

Methods: We studied 115 consecutive hip magnetic resonance imaging (MRI) results in order to identify objective relationships between these structures and the hip joint that can be used intraoperatively.

Use of Osteofasciocutaneous Fibular Free Flap and Radial Head Arthroplasty in Trauma for Limb Salvage and Continued Elbow Function.

Reconstructive flaps have revolutionized the ability of surgeons to restore function and cosmesis for patients. While reconstructive flaps have been used to bridge large defects due to oncologic or congenital maladies necessitating large debridements, few cases have observed salvage flaps in traumas which provide additional challenges secondary to an injury trajectory. This case report details use of an osteofasciocutaneous fibular free flap and radial head prosthesis to restore forearm function in a 64-year-old female with a comminuted fracture of the proximal radius.