Computer-aided drug design to generate a unique antibiotic family.

The World Health Organization has identified antibiotic resistance as one of the three greatest threats to human health. The need for antibiotics is a pressing matter that requires immediate attention. Here, computer-aided drug design is used to develop a structurally unique antibiotic family targeting holo-acyl carrier protein synthase (AcpS).

Predictors of positive outcomes following resistive inspiratory muscle training in non-ambulatory persons with advanced multiple sclerosis.

Background: Inspiratory muscle training (IMT) using a threshold device improves inspiratory muscle strength. What factors influence the IMT outcome has not been examined.

Objective: To identify predictors of the positive outcome following IMT in persons with advanced multiple sclerosis (PwAMS).

Small molecule therapeutics for COVID-19: repurposing of inhaled furosemide.

The novel coronavirus SARS-CoV-2 has become a global health concern. The morbidity and mortality of the potentially lethal infection caused by this virus arise from the initial viral infection and the subsequent host inflammatory response. The latter may lead to excessive release of pro-inflammatory cytokines, IL-6 and IL-8, as well as TNF-α ultimately culminating in hypercytokinemia ("cytokine storm").

Is Inhaled Furosemide a Potential Therapeutic for COVID-19?

The potentially lethal infection caused by the novel Severe Acute Respiratory Disease Coronavirus-2 (SARS-CoV-2) has evolved into a global crisis. Following the initial viral infection is the host inflammatory response that frequently results in excessive secretion of inflammatory cytokines (e.g.

Effects of inspiratory muscle training in advanced multiple sclerosis.

Background: Respiratory training using Threshold Inspiratory Muscle Trainer (IMT) has not been examined adequately in multiple sclerosis (MS). The primary objective in this study of persons with advanced MS was to investigate the training effect of IMT. The secondary objective was to evaluate the retention of IMT benefits.

Lewis acid promoted anomerisation of alkyl O- and S-xylo-, arabino- and fucopyranosides.

Pentopyranoside and 6-deoxyhexopyranosides, such as those from d-xylose, l-arabinose and l-fucose are components of natural products, oligosaccharides or polysaccharides. Lewis acid promoted anomerisation of some of their alkyl O- and S-glycopyranosides is reported here. SnCl was more successful than TiCl, with the latter giving the glycosyl chloride by-product in some cases, and both were superior to BFOEt.

Detailed Description of Change in Serum Cholesterol Profile with Incremental Weight Loss After Restrictive Bariatric Surgery.

Introduction: Dyslipidemia affects up to 75% of morbidly obese individuals and is a key driver of cardiovascular disease. Weight loss is an established strategy to improve metabolic risk, including dyslipidemia. We aimed to determine weight loss goals for resolution of serum lipid abnormalities, by measuring improvements during progressive weight loss in obese individuals.

Stereoselective Epimerizations of Glycosyl Thiols.

Glycosyl thiols are widely used in stereoselective S-glycoside synthesis. Their epimerization from 1,2-trans to 1,2-cis thiols (e.g.

Effects of Bariatric Surgery on Liver Function Tests in Patients with Nonalcoholic Fatty Liver Disease.

Objectives: Nonalcoholic fatty liver disease (NAFLD) affects over 80% of obese patients and is fueled by the metabolic syndrome. Weight loss is strongly advocated as a central treatment for NAFLD and has been shown to induce histological improvement. We aimed to define the patterns of improvement in NAFLD with weight loss and determine target weight goals for NAFLD resolution.

Enhanced Glutathione Peroxidase Activity of Water-Soluble and Polyethylene Glycol-Supported Selenides, Related Spirodioxyselenuranes, and Pincer Selenuranes.

Diaryl selenides containing o-hydroxymethylene substituents function as peroxide-destroying mimetics of the antioxidant selenoenzyme glutathione peroxidase (GPx), via oxidation to the corresponding spirodioxyselenuranes with hydrogen peroxide and subsequent reduction back to the original selenides with glutathione. Parent selenides with 3-hydroxypropyl or 2,3-dihydroxypropyl groups produced the novel compounds 10 and 11, respectively, with greatly improved aqueous solubility and catalytic activity. The phenolic derivative 28 displayed similarly ameliorated properties and also modest radical-inhibiting antioxidant activity, as evidenced by an assay based on phenolic hydrogen atom transfer to the stable free radical DPPH.

Modified thresholds for fibrosis risk scores in nonalcoholic fatty liver disease are necessary in the obese.

Background: Obesity and its related comorbidities are significant risk factors for nonalcoholic fatty liver disease (NAFLD). Liver fibrosis is the major determinant of long-term outcomes in NAFLD. A non-invasive tool that accurately identifies obese patients at elevated risk of liver fibrosis would be of significant value.

Role of heme oxygenase-1 in the pathogenesis and tumorigenicity of Kaposi's sarcoma-associated herpesvirus.

Kaposi's Sarcoma-associated Herpesvirus (KSHV) is the etiologic agent of several malignancies, including Kaposi's Sarcoma (KS), which preferentially arise in immunocompromised patients such as HIV+ subpopulation and lack effective therapeutic options. Heme oxygenase-1 (HO-1) has been reported as an important regulator of endothelial cell cycle control, proliferation and angiogenesis. HO-1 has also been found to be highly expressed in KSHV-infected endothelial cells and oral AIDS-KS lesions.

Targeting HGF/c-MET induces cell cycle arrest, DNA damage, and apoptosis for primary effusion lymphoma.

Kaposi sarcoma-associated herpesvirus (KSHV) is a principal causative agent of primary effusion lymphoma (PEL) with a poor prognosis in immunocompromised patients. However, it still lacks effective treatment which urgently requires the identification of novel therapeutic targets for PEL. Here, we report that the hepatocyte growth factor (HGF)/c-MET pathway is highly activated by KSHV in vitro and in vivo.

Defining Plasma MicroRNAs Associated With Cognitive Impairment In HIV-Infected Patients.

Human Immunodeficiency Virus (HIV)-infected individuals are at increased risk for developing neurocognitive disorders and depression. These conditions collectively affect more than 50% of people living with HIV/AIDS and adversely impact adherence to HIV therapy. Thus, identification of early markers of neurocognitive impairment could lead to interventions that improve psychosocial functioning and slow or reverse disease progression through improved treatment adherence.

Induction of hyaluronan production by oncogenic KSHV and the contribution to viral pathogenesis in AIDS patients.

Kaposi sarcoma-associated herpesvirus (KSHV) is the etiologic agent for Kaposi's sarcoma (KS) and primary effusion lymphoma (PEL), malignancies arising primarily in immunocompromised patients particularly AIDS-patients, which still lack effective therapy. Hyaluronan (HA) is a large glucuronic acid and has been found closely related to multiple functions in cancer cells, although its role in viral oncogenesis remains largely unknown. Here we provide first evidence that KSHV de novo infection induces HA production from primary endothelial cells through upregulation of HA synthase gene 1 (Has1) and a multifunctional glycoprotein, CD147.

Pro-inflammatory CD11c+CD206+ adipose tissue macrophages are associated with insulin resistance in human obesity.

Objective: Insulin resistance and other features of the metabolic syndrome have been causally linked to adipose tissue macrophages (ATMs) in mice with diet-induced obesity. We aimed to characterize macrophage phenotype and function in human subcutaneous and omental adipose tissue in relation to insulin resistance in obesity.

Research Design And Methods: Adipose tissue was obtained from lean and obese women undergoing bariatric surgery.

Pediatric procedural sedation and analgesia.

Children often present with painful conditions that require painful interventions. Procedural sedation and analgesia refers to the pharmacologic technique of managing a child's pain and anxiety. Procedural sedation is a safe, effective, and humane way to facilitate appropriate medical care.

Second primary oesophageal cancer following radiation for breast cancer.

The management of 12 women who presented with a second primary oesophageal cancer following radiotherapy for breast cancer was reviewed. It was concluded that nine cases fitted the classical description of a radiation-induced malignancy. Most cases were successfully managed with combined modality therapy in spite of their previous radiotherapy.