Open-label, long-term extension study to evaluate the safety of clascoterone (CB-03-01) cream, 1% twice daily, in patients with acne vulgaris.

Background: Androgens foster acnegenic pathways.

Objective: To assess the long-term safety of an androgen receptor inhibitor, clascoterone cream, 1%, in patients who participated in phase 3 studies.

Methods: Clascoterone cream was applied twice daily for up to 9 months to the face or trunk, or both.

Safety and Efficacy of Lenabasum in a Phase II, Randomized, Placebo-Controlled Trial in Adults With Systemic Sclerosis.

Objective: To assess the safety and efficacy of lenabasum in diffuse cutaneous systemic sclerosis (dcSSc).

Methods: A randomized, double-blind, placebo-controlled, phase II study was conducted at 9 SSc clinics in the US. Adults with dcSSc of ≤6 years' duration who were receiving stable standard-of-care treatment were randomized to receive lenabasum (n = 27) or placebo (n = 15).

Fungal Infections Potentiated by Biologics.

Biologic therapies including monoclonal antibodies, tyrosine kinase inhibitors, and other agents represent a notable expansion in the pharmacotherapy armamentarium in treatment of a variety of diseases. Many of these therapies possess direct or indirect immunosuppressive and immunomodulatory effects, which have been associated with bacterial, viral, and fungal opportunistic infections. Careful screening of baseline risk factors before initiation, targeted preventive measures, and vigilant monitoring while on active biologic therapy mitigate these risks as use of biologics becomes more commonplace.

Implementing daily chlorhexidine gluconate treatment for the prevention of healthcare-associated infections in non-intensive care settings: A multiple case analysis.

Introduction: Daily bathing with chlorhexidine gluconate (CHG) in hospitalized patients reduces healthcare-associated bloodstream infections and colonization by multidrug-resistant organisms. Achieving compliance with bathing protocols is challenging. This non-intensive care unit multicenter project evaluated the impact of organizational context on implementation of CHG and assessed compliance with and healthcare workers' perceptions of the intervention.

Efficacy and Safety of Topical Clascoterone Cream, 1%, for Treatment in Patients With Facial Acne: Two Phase 3 Randomized Clinical Trials.

Importance: Acne is a common, multifactorial skin condition, and treatments with novel mechanisms have been elusive.

Objective: To assess the safety and efficacy of clascoterone cream, 1%, a novel topical androgen receptor inhibitor, in 2 phase 3 randomized clinical trials (CB-03-01/25 and CB-03-01/26).

Design, Setting, And Participants: Two identical, multicenter, randomized, vehicle-controlled, double-blind, phase 3 studies conducted from November 2015 to April 2018 evaluated the efficacy and safety of use of clascoterone cream, 1%, in males and nonpregnant females 9 years and older with moderate or severe facial acne as scored on the Investigator's Global Assessment scale.

Weight gain among treatment-naïve persons with HIV starting integrase inhibitors compared to non-nucleoside reverse transcriptase inhibitors or protease inhibitors in a large observational cohort in the United States and Canada.

Introduction: Weight gain following antiretroviral therapy (ART) initiation is common, potentially predisposing some persons with HIV (PWH) to cardio-metabolic disease. We assessed relationships between ART drug class and weight change among treatment-naïve PWH initiating ART in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD).

Methods: Adult, treatment-naïve PWH in NA-ACCORD initiating integrase strand transfer inhibitor (INSTI), protease inhibitor (PI) or non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based ART on/after 1 January 2007 were followed through 31 December 2016.

The rs2736100 Polymorphism and Susceptibility to Myeloproliferative Neoplasms: A Systematic Review and Meta-Analysis.

The classification of myeloproliferative neoplasms (MPN) is currently based on the genotype. Thus, to achieve better diagnostic and prognostic outcomes, it is necessary to further investigate the genetic spectrum underlying the pathogenesis of MPNs. The rs2736100A>C is a functional single nucleotide polymorphism in the telomerase reverse transcriptase () gene that has been previously reported to be associated with the risk of MPNs.

Phosphatidylinositol-(4,5)-Bisphosphate Regulates Plasma Cholesterol Through LDL (Low-Density Lipoprotein) Receptor Lysosomal Degradation.

TMEM55B (transmembrane protein 55B) is a phosphatidylinositol-(4,5)-bisphosphate (PI[4,5]P) phosphatase that regulates cellular cholesterol, modulates LDLR (low-density lipoprotein receptor) decay, and lysosome function. We tested the effects of knockdown on plasma lipids in mice and assessed the roles of LDLR lysosomal degradation and change in (PI[4,5]P) in mediating these effects. Approach and Results: Western diet-fed C57BL/6J mice were treated with antisense oligonucleotides against or a nontargeting control for 3 to 4 weeks.

Maternal Supplementation of Inositols, Fucoxanthin, and Hydroxytyrosol in Pregnant Murine Models of Hypertension.

Background: Myoinositol (M) and D-chiro-inositol (D) are insulin sensitizer compounds, while fucoxanthin (F) and hydroxytyrosol (H) are antioxidant substances. We aim to investigate if the combination of these compounds, will improve the vascular responses in pregnant mouse models of hypertension: a genetic model, transgenic heterozygous mice lacking endothelial nitric oxide synthase gene (eNOS-/+); and environmental, wild-type (WT) mice. Those mouse models will allow a better understanding of the genetic/environmental contribution to hypertension in pregnancy.

Diverse types of genomic evidence converge on alcohol use disorder risk genes.

Background: Alcohol use disorder (AUD) is one of the most common forms of substance use disorders with a strong contribution of genetic (50%-60%) and environmental factors. Genome-wide association studies (GWAS) have identified a number of AUD-associated variants, including those in alcohol metabolism genes. These genetic variants may modulate gene expression, making individuals more susceptible to AUD.

Diagnosis of bladder cancer using F-labeled α-methyl-phenylalanine tracers in a mouse model.

Objective: Although 2-F-fluoro-2-deoxy-glucose (F-FDG) has established roles in the diagnosis of a variety of cancers, it has limited value in the detection of primary/recurrent lesions in the bladder, mainly because of interference by the pooled radioactivity in the urine. Our previous study revealed promising properties of L- and D-2-F-α-methyl-phenylalanine (2-F-FAMP) as radiotracers; i.e.

Improved Post remission survival of non- favorable risk Acute Myelogenous Leukemia (AML) patients following initial remission induction therapy with FLAG+/-Idarubicin versus 3 + 7 (Anthracycline + Cytarabine).

The fludarabine, high dose cytarabine and G-CSF with or without idarubicin combination regimen, referred to as FLAG+/-Ida, is commonly used as a salvage regimen for relapsed/refractory AML but its use as initial induction therapy has been more limited. The impact of choice of induction regimen on post remission survival remains unclear. We retrospectively analyzed 304 consecutive AML patients, with non-favorable NCCN risk who received initial treatment at our center with either 7 + 3 (n = 86) or FLAG+/-Ida (n = 218).

Pesticides Decrease Bacterial Diversity and Abundance of Irrigated Rice Fields.

Bacteria play an important role in soil ecosystems and their activities are crucial in nutrient composition and recycling. Pesticides are extensively used in agriculture to control pests and improve yield. However, increased use of pesticides on agricultural lands results in soil contamination, which could have adverse effect on its bacterial communities.

Social Support and the Rehabilitation of Alcohol-Impaired Drivers: Drinking Motives as Moderators.

Alcohol-impaired driving is a common and costly public health problem associated with alcohol misuse. This investigation aims to understand the role of social support and drinking motives in motivating alcohol-impaired drivers to reduce alcohol use. One hundred nineteen participants with a history of driving-while-intoxicated arrest were recruited from either a correctional treatment facility ( = 59) or the community ( = 60) and asked about their motivation to change alcohol use.

Differential expression of microRNA and arachidonic acid metabolism in aspirin-treated human cardiac and peri-cardiac fat-derived mesenchymal stem cells.

Aspirin is a widely used drug with anti-coagulating and anti-inflammatory effects on atherosclerotic vascular disease. The goal of this study was to investigate expression of microRNA (miR) in association with changes in arachidonic acid (AA) metabolism in cardiac and surrounding fat mesenchymal stem cells (MSCs) treated with or without aspirin. Aspirin-targeted endogenous lipid metabolites that impact specific miRNA expression were examined by mass spectrometry.

Efficacy and safety of apremilast in patients with moderate to severe plaque psoriasis of the scalp: Results of a phase 3b, multicenter, randomized, placebo-controlled, double-blind study.

Background: Many patients with psoriasis are bothered by symptoms in highly visible, pruritic areas, such as the scalp.

Objective: To evaluate the efficacy and safety of apremilast for moderate to severe scalp psoriasis.

Methods: This phase 3b, double-blind, placebo-controlled study randomized adults with moderate to severe scalp psoriasis who had inadequate response/intolerance to at least 1 topical scalp psoriasis therapy (NCT03123471).

Molecular basis for hycanthone drug action in schistosome parasites.

Hycanthone (HYC) is a retired drug formerly used to treat schistosomiasis caused by infection from Schistosoma mansoni and S. haematobium. Resistance to HYC was first observed in S.

MODEL ASSISTED VARIABLE CLUSTERING: MINIMAX-OPTIMAL RECOVERY AND ALGORITHMS.

The problem of variable clustering is that of estimating groups of similar components of a -dimensional vector = ( , … , ) from independent copies of . There exists a large number of algorithms that return data-dependent groups of variables, but their interpretation is limited to the algorithm that produced them. An alternative is model-based clustering, in which one begins by defining population level clusters relative to a model that embeds notions of similarity.

High-dose rifapentine with or without moxifloxacin for shortening treatment of pulmonary tuberculosis: Study protocol for TBTC study 31/ACTG A5349 phase 3 clinical trial.

Introduction: Phase 2 clinical trials of tuberculosis treatment have shown that once-daily regimens in which rifampin is replaced by high dose rifapentine have potent antimicrobial activity that may be sufficient to shorten overall treatment duration. Herein we describe the design of an ongoing phase 3 clinical trial testing the hypothesis that once-daily regimens containing high dose rifapentine in combination with other anti-tuberculosis drugs administered for four months can achieve cure rates not worse than the conventional six-month treatment regimen.

Methods/design: S31/A5349 is a multicenter randomized controlled phase 3 non-inferiority trial that compares two four-month regimens with the standard six-month regimen for treating drug-susceptible pulmonary tuberculosis in HIV-negative and HIV-positive patients.