Physiologic and structural characterization of desisobutyryl-ciclesonide, a selective glucocorticoid receptor modulator in newborn rats.

Bronchopulmonary dysplasia, the most prevalent chronic lung disease of prematurity, is often treated with glucocorticoids (GCs) such as dexamethasone (DEX), but their use is encumbered with several adverse somatic, metabolic, and neurologic effects. We previously reported that systemic delivery of the GC prodrug ciclesonide (CIC) in neonatal rats activated glucocorticoid receptor (GR) transcriptional responses in lung but did not trigger multiple adverse effects caused by DEX. To determine whether limited systemic metabolism of CIC was solely responsible for its enhanced safety profile, we treated neonatal rats with its active metabolite desisobutyryl-ciclesonide (Des-CIC).

A Brief Intervention on Alcohol Use Disorder Is Associated With Treatment Access for Inpatients With Alcohol-Associated Liver Disease.

Background: Alcohol-associated liver disease (ALD) is the most common indication for liver transplantation in the United States. Alcohol use disorder (AUD) treatment is recommended in all patients with ALD and AUD, but it remains underutilized.

Aims: To identify predictors of AUD treatment and to assess 30-day readmission, return to drinking, and 1-year transplant-free survival.

Benign prostatic hyperplasia nodules in patients treated with celecoxib and/or finasteride have reduced levels of NADH dehydrogenase [ubiquinone] iron-sulfur protein 3, a mitochondrial protein essential for efficient function of the electron transport chain.

Background: Benign prostatic hyperplasia (BPH) is a condition generally associated with advanced age in men that can be accompanied by bothersome lower urinary tract symptoms (LUTS) including intermittency, weak stream, straining, urgency, frequency, and incomplete bladder voiding. Pharmacotherapies for LUTS/BPH include alpha-blockers, which relax prostatic and urethral smooth muscle and 5ɑ-reductase inhibitors such as finasteride, which can block conversion of testosterone to dihydrotestosterone thereby reducing prostate volume. Celecoxib is a cyclooxygenase-2 inhibitor that reduces inflammation and has shown some promise in reducing prostatic inflammation and alleviating LUTS for some men with histological BPH.

Turmeric-Associated Drug-Induced Liver Injury.

Turmeric is a common herbal supplement used for its possible anti-inflammatory and other properties. It is marketed as safe with few reports of major adverse effects directly related to oral supplementation. We report a case of turmeric supplement-induced liver injury in a 49-year-old woman admitted with elevated aspartate aminotransferase and alanine aminotransferase with no history of liver disease or alcohol use disorder.

Survival characteristics of fibrolamellar hepatocellular carcinoma: A Surveillance, Epidemiology, and End Results database study.

Background: Fibrolamellar hepatocellular carcinoma (FL-HCC) is a rare and distinct type of hepatocellular carcinoma that frequently presents in an advanced stage in younger patients with no underlying liver disease. Currently, there is a limited understanding of factors that impact outcomes in FL-HCC.

Aim: To characterize the survival of FL-HCC by age, race, and surgical intervention.

A human brain vascular atlas reveals diverse mediators of Alzheimer's risk.

The human brain vasculature is of great medical importance: its dysfunction causes disability and death, and the specialized structure it forms-the blood-brain barrier-impedes the treatment of nearly all brain disorders. Yet so far, we have no molecular map of the human brain vasculature. Here we develop vessel isolation and nuclei extraction for sequencing (VINE-seq) to profile the major vascular and perivascular cell types of the human brain through 143,793 single-nucleus transcriptomes from 25 hippocampus and cortex samples of 9 individuals with Alzheimer's disease and 8 individuals with no cognitive impairment.

Exercise plasma boosts memory and dampens brain inflammation via clusterin.

Physical exercise is generally beneficial to all aspects of human and animal health, slowing cognitive ageing and neurodegeneration. The cognitive benefits of physical exercise are tied to an increased plasticity and reduced inflammation within the hippocampus, yet little is known about the factors and mechanisms that mediate these effects. Here we show that 'runner plasma', collected from voluntarily running mice and infused into sedentary mice, reduces baseline neuroinflammatory gene expression and experimentally induced brain inflammation.

A novel knockout mouse model of the noncoding antisense () gene displays increased endogenous Bdnf protein and improved memory function following exercise.

) expression is tightly controlled at the transcriptional and post-transcriptional levels. Previously, we showed that inhibition of noncoding antisense (-AS) RNA upregulates Bdnf protein. Here, we generated a -antisense knockout (AS KO) mouse model by deleting 6 kilobases upstream of -AS.

Validation of the Arabic version of the breastfeeding behavior questionnaire among Lebanese women.

Background: The Breastfeeding Behavior Questionnaire (BBQ) assesses women's perceptions of their breastfeeding behavior. It was adapted to several languages and used in different settings, but has not been validated in Arabic-speaking populations. None of the previous studies that used the BBQ in other cultures examined its ability to predict the actual breastfeeding behaviors of mothers postpartum.

Knowledge and attitudes towards E-cigarette use in Lebanon and their associated factors.

Background: Despite the misconceptions regarding E-cigarettes (ECs), only a few studies have been conducted in the Middle East that focused on this topic. This study assesses the knowledge of and attitudes towards ECs in Lebanon, determines how these two measures are associated, and identifies the variables that explain each of these measures.

Methods: A cross sectional study was conducted on a convenience sample of Lebanese pedestrians aged between 18 and 64 inclusive.

Cell-Type-Specific Analysis of Molecular Pathology in Autism Identifies Common Genes and Pathways Affected Across Neocortical Regions.

Despite its heterogeneity, autism is characterized by a defined behavioral phenotype, suggesting that the molecular pathology affects specific neural substrates to cause behavioral dysfunction. Previous studies identified genes dysregulated in autism cortex but did not address their cell-type specificity. Moreover, it is unknown whether there is a core of genes dysregulated across multiple neocortical regions.

Musculoskeletal disorders in hemodialysis patients: different disease clustering according to age and dialysis vintage.

Musculoskeletal disorders remain a major problem in hemodialysis patients. The aim of the study was to estimate the prevalence of musculoskeletal manifestations in hemodialysis patients and identify disease cluster profiles. We performed a cross-sectional study including all adult patients in the hemodialysis unit at Hotel-Dieu de France Hospital.

Ischemic Neuroprotectant PKCε Restores Mitochondrial Glutamate Oxaloacetate Transaminase in the Neuronal NADH Shuttle after Ischemic Injury.

The preservation of mitochondrial function is a major protective strategy for cerebral ischemic injuries. Previously, our laboratory demonstrated that protein kinase C epsilon (PKCε) promotes the synthesis of mitochondrial nicotinamide adenine dinucleotide (NAD). NAD along with its reducing equivalent, NADH, is an essential co-factor needed for energy production from glycolysis and oxidative phosphorylation.

Brain SIRT1 Mediates Metabolic Homeostasis and Neuroprotection.

Sirtuins are evolutionarily conserved proteins that use nicotinamide adenine dinucleotide (NAD) as a co-substrate in their enzymatic reactions. There are seven proteins (SIRT1-7) in the human sirtuin family, among which SIRT1 is the most conserved and characterized. SIRT1 in the brain, in particular, within the hypothalamus, plays crucial roles in regulating systemic energy homeostasis and circadian rhythm.

Resveratrol Preconditioning Induces Genomic and Metabolic Adaptations within the Long-Term Window of Cerebral Ischemic Tolerance Leading to Bioenergetic Efficiency.

Neuroprotective agents administered post-cerebral ischemia have failed so far in the clinic to promote significant recovery. Thus, numerous efforts were redirected toward prophylactic approaches such as preconditioning as an alternative therapeutic strategy. Our laboratory has revealed a novel long-term window of cerebral ischemic tolerance mediated by resveratrol preconditioning (RPC) that lasts for 2 weeks in mice.

Comparative Efficacy of Anti-TNF Therapies For The Prevention of Postoperative Recurrence of Crohn's Disease: A Systematic Review and Network Meta-Analysis of Prospective Trials.

Introduction: There is a lack of studies on the optimal anti-tumor necrosis factor (anti-TNF) agent for postoperative prophylaxis of Crohn's disease (CD) recurrence. Therefore, we conducted a network meta-analysis (NMA) of prospective trials to compare the efficacy of anti-TNF agents in the prevention of postoperative endoscopic and clinical recurrence of CD following ileocolonic resection.

Methods: We searched PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and recent American gastroenterology association (AGA) meeting abstracts through August 2017.

Metabolomics Based Identification of SIRT5 and Protein Kinase C Epsilon Regulated Pathways in Brain.

The role of Sirtuins in brain function is emerging, yet little is known about SIRT5 in this domain. Our previous work demonstrates that protein kinase C epsilon (PKCε)-induced protection from focal ischemia is lost in SIRT5 mice. Thus, metabolic regulation by SIRT5 contributes significantly to ischemic tolerance.

Neuronal SIRT1 (Silent Information Regulator 2 Homologue 1) Regulates Glycolysis and Mediates Resveratrol-Induced Ischemic Tolerance.

Background And Purpose: Resveratrol, at least in part via SIRT1 (silent information regulator 2 homologue 1) activation, protects against cerebral ischemia when administered 2 days before injury. However, it remains unclear if SIRT1 activation must occur, and in which brain cell types, for the induction of neuroprotection. We hypothesized that neuronal SIRT1 is essential for resveratrol-induced ischemic tolerance and sought to characterize the metabolic pathways regulated by neuronal Sirt1 at the cellular level in the brain.

The NAD-Dependent Family of Sirtuins in Cerebral Ischemia and Preconditioning.

Sirtuins are an evolutionarily conserved family of NAD-dependent lysine deacylases and ADP ribosylases. Their requirement for NAD as a cosubstrate allows them to act as metabolic sensors that couple changes in the energy status of the cell to changes in cellular physiological processes. NAD levels are affected by several NAD-producing and NAD-consuming pathways as well as by cellular respiration.

Protein kinase C epsilon delays latency until anoxic depolarization through arc expression and GluR2 internalization.

Global cerebral ischemia is a debilitating injury that damages the CA1 region of the hippocampus, an area important for learning and memory. Protein kinase C epsilon (PKCɛ) activation is a critical component of many neuroprotective treatments. The ability of PKCɛ activation to regulate AMPA receptors (AMPARs) remains unexplored despite the role of AMPARs in excitotoxicity after brain ischemia.

Febuxostat-associated eosinophilic polymyositis in marginal zone lymphoma.

Febuxostat is an orally administered selective inhibitor of xanthine oxidase approved for the treatment of gout and prevention of tumor lysis syndrome. It is a relatively safe medication. Hypersensitivity reactions associated with the use of febuxostat are quite rare with only one reported case of DRESS syndrome.

Long-term window of ischemic tolerance: An evolutionarily conserved form of metabolic plasticity regulated by epigenetic modifications?

In the absence of effective neuroprotective agents in the clinic, ischemic and pharmacological preconditioning are gaining increased interest in the field of cerebral ischemia. Our lab recently reported that resveratrol preconditioning affords tolerance against a focal cerebral ischemic insult in mice that can last for at least 14 days in vivo making it the longest window of ischemic tolerance discovered to date by a single administration of a pharmacological agent. The mechanism behind this novel extended window of ischemic tolerance remains elusive.