Design and synthesis of new drugs inhibitors of Candida albicans hyphae and biofilm formation by upregulating the expression of TUP1 transcription repressor gene.

Candida albicans is a common human fungal pathogen that causes disease ranging from superficial to lethal infections. C. albicans grows as budding yeast which can transform into hyphae in response to various environmental or biological stimuli.

The REMAP-CAP (Randomized Embedded Multifactorial Adaptive Platform for Community-acquired Pneumonia) Study. Rationale and Design.

There is broad interest in improved methods to generate robust evidence regarding best practice, especially in settings where patient conditions are heterogenous and require multiple concomitant therapies. Here, we present the rationale and design of a large, international trial that combines features of adaptive platform trials with pragmatic point-of-care trials to determine best treatment strategies for patients admitted to an intensive care unit with severe community-acquired pneumonia. The trial uses a novel design, entitled "a randomized embedded multifactorial adaptive platform.

Cardiovascular Outcomes in Relation to Antihypertensive Medication Use in Women with and Without Cancer: Results from the Women's Health Initiative.

Background: Recent clinical trials have evaluated angiotensin-converting enzyme (ACE) inhibitors (ACEis), angiotensin receptor blockers (ARBs), and beta blockers (BBs) in relation to cardiotoxicity in patients with cancer, typically defined by ejection fraction declines. However, these trials have not examined long-term, hard clinical endpoints. Within a prospective study, we examined the risk of heart failure (HF) and coronary heart disease (CHD) events in relation to use of commonly used antihypertensive medications, including ACEis/ARBs, BBs, calcium channel blockers (CCB), and diuretics, comparing women with and without cancer.

Relationship of fibroblast growth factor 21 levels with inflammation, lipoproteins and non-alcoholic fatty liver disease.

Background And Aims: Non-alcoholic fatty liver disease (NAFLD) is associated with inflammation and atherogenic lipoprotein abnormalities. Previous studies suggest an association of fibroblast growth factor 21 (FGF21) with NAFLD. Therefore, we assessed the association of circulating FGF21 levels with inflammatory markers, lipoprotein profile and NAFLD in the Multi-Ethnic Study of Atherosclerosis (MESA).

Fosmanogepix (APX001) Is Effective in the Treatment of Pulmonary Murine Mucormycosis Due to Rhizopus arrhizus.

Mucormycosis is a life-threatening infection with high mortality that occurs predominantly in immunocompromised patients. Manogepix (MGX) is a novel antifungal that targets Gwt1, a protein involved in an early step in the conserved glycosylphosphotidyl inositol (GPI) posttranslational modification pathway of surface proteins in eukaryotic cells. Inhibition of fungal inositol acylation by MGX results in pleiotropic effects, including inhibition of maturation of GPI-anchored proteins necessary for growth and virulence.

Tranilast induces MiR-200c expression through blockade of RelA/p65 activity in leiomyoma smooth muscle cells.

Objective: To determine the mechanism by which tranilast induces miR-200c expression in leiomyoma smooth muscle cells (LSMCs).

Design: Experimental study.

Setting: Academic research laboratory.

A randomized trial of a behavioral intervention to decrease hospital length of stay by decreasing bedrest.

Background: Approximately half of hospitalized patients suffer functional decline due to spending the vast majority of their time in bed. Previous studies of early mobilization have demonstrated improvement in outcomes, but the interventions studied have been resource-intensive. We aimed to decrease the time hospital inpatients spend in bed through a pragmatic mobilization protocol.

Correction to: Racial Differences in the Utilization of Guideline-Recommended and Life-Sustaining Procedures During Hospitalizations for Out-of-Hospital Cardiac Arrest.

There was an error in Fig. 1 as published in this article, and the Hemodialysis and Palliative Care titles in the figure are reversed.

Racial Differences in the Utilization of Guideline-Recommended and Life-Sustaining Procedures During Hospitalizations for Out-of-Hospital Cardiac Arrest.

Background: Racial and ethnic minorities are at risk for disparities in quality of care after out-of-hospital cardiopulmonary arrest (OHCA). As such, we examined associations between race and ethnicity and use of guideline-recommended and life-sustaining procedures during hospitalizations for OHCA.

Methods: This was a retrospective study of hospitalizations for OHCA in all acute-care, non-federal California hospitals from 2009 to 2011.

Cross-talk between miR-29c and transforming growth factor-β3 is mediated by an epigenetic mechanism in leiomyoma.

Objective: To determine the expression of miR-29c and its target gene transforming growth factor-β3 (TGF-β3) in leiomyoma and the mechanisms of their reciprocal regulation.

Design: Experimental study.

Setting: Academic research laboratory.

Fosmanogepix (APX001) Is Effective in the Treatment of Immunocompromised Mice Infected with Invasive Pulmonary Scedosporiosis or Disseminated Fusariosis.

There are limited treatment options for immunosuppressed patients with lethal invasive fungal infections due to and Manogepix (MGX; APX001A) is a novel antifungal that targets the conserved Gwt1 enzyme required for localization of glycosylphosphatidylinositol-anchored mannoproteins in fungi. We evaluated the activity of MGX and the efficacy of the prodrug fosmanogepix (APX001) in immunosuppressed murine models of hematogenously disseminated fusariosis and pulmonary scedosporiosis. The MGX minimum effective concentration (MEC) for isolates was 0.

Time-Limited Trials Among Critically Ill Patients With Advanced Medical Illnesses to Reduce Nonbeneficial Intensive Care Unit Treatments: Protocol for a Multicenter Quality Improvement Study.

Background: Invasive intensive care unit (ICU) treatments for patients with advanced medical illnesses and poor prognoses may prolong suffering with minimal benefit. Unfortunately, the quality of care planning and communication between clinicians and critically ill patients and their families in these situations are highly variable, frequently leading to overutilization of invasive ICU treatments. Time-limited trials (TLTs) are agreements between the clinicians and the patients and decision makers to use certain medical therapies over defined periods of time and to evaluate whether patients improve or worsen according to predetermined clinical parameters.

Associations of recreational and non-recreational physical activity with coronary artery calcium density vs. volume and cardiovascular disease events: the Multi-Ethnic Study of Atherosclerosis.

Aims: The benefits of physical activity (PA) on cardiovascular disease (CVD) are well known. However, studies suggest PA is associated with coronary artery calcium (CAC), a subclinical marker of CVD. In this study, we evaluated the associations of self-reported recreational and non-recreational PA with CAC composition and incident CVD events.

Effect of Weight Loss via Severe vs Moderate Energy Restriction on Lean Mass and Body Composition Among Postmenopausal Women With Obesity: The TEMPO Diet Randomized Clinical Trial.

Importance: Severely energy-restricted diets are the most effective dietary obesity treatment. However, there are concerns regarding potential adverse effects on body composition.

Objective: To compare the long-term effects of weight loss via severe vs moderate energy restriction on lean mass and other aspects of body composition.

Daily Physical Activity in Patients With COPD After Hospital Discharge in a Minority Population.

Background: Low physical activity in patients with chronic obstructive pulmonary disease (COPD) is associated with increased morbidity and mortality. To inform the design of a home-based physical activity promotion program for patients with COPD recently discharged from a minority-serving hospital, we conducted a cohort study to evaluate objectively measured daily physical activity and patient-reported outcomes.

Methods: This was a 12-week prospective cohort study of patients with a physician diagnosis of COPD recently hospitalized (≤ 12 weeks) for respiratory symptoms.

Video Versus Direct and Augmented Direct Laryngoscopy in Pediatric Tracheal Intubations.

Objectives: With respect to first-attempt intubation success, the pediatric literature demonstrates either clinical equipoise or superiority of direct laryngoscopy (DL) when compared to video laryngoscopy (VL). Furthermore, it is unknown how VL compares to DL, when DL is "augmented" by maneuvers, such as optimal external laryngeal manipulation (OELM), upright or ramped positioning, or the use of the bougie. The objective of our study was to compare first-attempt success between VL and all DL, including "augmented DL" for pediatric intubations.

Optimizing Contact Precautions to Curb the Spread of Antibiotic-resistant Bacteria in Hospitals: A Multicenter Cohort Study to Identify Patient Characteristics and Healthcare Personnel Interactions Associated With Transmission of Methicillin-resistant Staphylococcus aureus.

Background: Healthcare personnel (HCP) acquire antibiotic-resistant bacteria on their gloves and gowns when caring for intensive care unit (ICU) patients. Yet, contact precautions for patients with methicillin-resistant Staphylococcus aureus (MRSA) remains controversial despite existing guidelines. We sought to understand which patients are more likely to transfer MRSA to HCP and to identify which HCP interactions are more likely to lead to glove or gown contamination.

The Kronos Early Estrogen Prevention Study (KEEPS): what have we learned?

Objective: The Kronos Early Estrogen Prevention Study (KEEPS) was designed to address gaps in understanding the effects of timely menopausal hormone treatments (HT) on cardiovascular health and other effects of menopause after the premature termination of the Women's Health Initiative.

Method: The KEEPS was a randomized, double-blinded, placebo-controlled trial to test the hypothesis that initiation of HT (oral conjugated equine estrogens [o-CEE] or transdermal 17β-estradiol [t-E2]) in healthy, recently postmenopausal women (n = 727) would slow the progression of atherosclerosis as measured by changes in carotid artery intima-media thickness (CIMT).

Results: After 4 years, neither HT affected the rate of increase in CIMT.

Genomic and transcriptomic association studies identify 16 novel susceptibility loci for venous thromboembolism.

Venous thromboembolism (VTE) is a significant contributor to morbidity and mortality. To advance our understanding of the biology contributing to VTE, we conducted a genome-wide association study (GWAS) of VTE and a transcriptome-wide association study (TWAS) based on imputed gene expression from whole blood and liver. We meta-analyzed GWAS data from 18 studies for 30 234 VTE cases and 172 122 controls and assessed the association between 12 923 718 genetic variants and VTE.

Identifying Smoking-Related Disease on Lung Cancer Screening CT Scans: Increasing the Value.

Background: Lung cancer screening (LCS) via chest computed tomography (CT) scans can save lives by identifying early-stage tumors. However, most smokers die of comorbid smoking-related diseases. LCS scans contain information about smoking-related conditions that is not currently systematically assessed.

Insulin Resistance Exacerbates Genetic Predisposition to Nonalcoholic Fatty Liver Disease in Individuals Without Diabetes.

The accumulation of excess fat in the liver (hepatic steatosis) in the absence of heavy alcohol consumption causes nonalcoholic fatty liver disease (NAFLD), which has become a global epidemic. Identifying metabolic risk factors that interact with the genetic risk of NAFLD is important for reducing disease burden. We tested whether serum glucose, insulin, insulin resistance, triglyceride (TG), low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, body mass index (BMI), and waist-to-hip ratio adjusted for BMI interact with genetic variants in or near the patatin-like phospholipase domain containing 3 () gene, the glucokinase regulatory protein () gene, the neurocan/transmembrane 6 superfamily member 2 () gene and the lysophospholipase-like 1 () gene to exacerbate hepatic steatosis, estimated by liver attenuation.