Modulation of OPRM1 Alternative Splicing by Morphine and HIV-1 Nef.

Clinically used opioids, such as morphine, activate the mu opioid receptor (MOR) encoded by Opioid Receptor Mu 1 (OPRM1) gene. Examination of the opioid receptor genes showed that the human OPRM1 pre-mRNA undergoes extensive alternative splicing events and capable of expressing 21 isoforms. However, characterization of OPRM1 signaling is generalized, and only one isoform (MOR-1) has been extensively studied.

Characterization of Nef expression in different brain regions of SIV-infected macaques.

Objective: HIV-associated CNS dysfunction is a significant problem among people with HIV (PWH), who now live longer due to viral suppression from combined anti-retroviral therapy (ART). Over the course of infection, HIV generates toxic viral proteins and induces inflammatory cytokines that have toxic effects on neurons in the CNS. Among these viral proteins, HIV Nef has been found in neurons of postmortem brain specimens from PWH.

Emerging Role of Nef in the Development of HIV Associated Neurological Disorders.

Despite adherence to treatment, individuals living with HIV have an increased risk for developing cognitive impairments, referred to as HIV-associated neurological disorders (HAND). Due to continued growth in the HIV population, particularly amongst the aging cohort, the neurobiological mechanisms of HAND are increasingly relevant. Similar to other viral proteins (e.

Molecular and Cellular Impact of Inflammatory Extracellular Vesicles (EVs) Derived from M1 and M2 Macrophages on Neural Action Potentials.

Several factors can contribute to neuroinflammatory disorders, such as cytokine and chemokines that are produced and released from peripherally derived immune cells or from locally activated cells such as microglia and perivascular macrophages in the brain. The primary function of these cells is to clear inflammation; however, following inflammation, circulating monocytes are recruited to the central nervous system (CNS). Monocyte-derived macrophages in the CNS play pivotal roles in mediating neuroinflammatory responses.

Intestinal Bacteria Maintain Adult Enteric Nervous System and Nitrergic Neurons via Toll-like Receptor 2-induced Neurogenesis in Mice.

Background & Aims: The enteric nervous system (ENS) exists in close proximity to luminal bacteria. Intestinal microbes regulate ENS development, but little is known about their effects on adult enteric neurons. We investigated whether intestinal bacteria or their products affect the adult ENS via toll-like receptors (TLRs) in mice.

Quality of Life and Functional Outcome After Transanal Abdominal Transanal Proctectomy for Low Rectal Cancer.

Background: Transanal abdominal transanal proctectomy is a sphincter-preserving procedure designed to avoid colostomy in patients with cancer in the distal third of the rectum. Oncologic outcomes of this procedure have been established. However, data regarding patient satisfaction and quality of life are scant.

Modulatory Effects of Gut Microbiota on the Central Nervous System: How Gut Could Play a Role in Neuropsychiatric Health and Diseases.

Gut microbiome is an integral part of the Gut-Brain axis. It is becoming increasingly recognized that the presence of a healthy and diverse gut microbiota is important to normal cognitive and emotional processing. It was known that altered emotional state and chronic stress can change the composition of gut microbiome, but it is becoming more evident that interaction between gut microbiome and central nervous system is bidirectional.

IFN-Gamma Inhibits JC Virus Replication in Glial Cells by Suppressing T-Antigen Expression.

Objective: Patients undergoing immune modulatory therapies for the treatment of autoimmune diseases such as multiple sclerosis, and individuals with an impaired-immune system, most notably AIDS patients, are in the high risk group of developing progressive multifocal leukoencephalopathy (PML), an often lethal disease of the brain characterized by lytic infection of oligodendrocytes in the central nervous system (CNS) with JC virus (JCV). The immune system plays an important regulatory role in controlling JCV reactivation from latent sites by limiting viral gene expression and replication. However, little is known regarding the molecular mechanisms responsible for this regulation.

Increased Incidence of Benign Pancreatic Pathology following Pancreaticoduodenectomy for Presumed Malignancy over 10 Years despite Increased Use of Endoscopic Ultrasound.

Despite using imaging studies, tissue sampling, and serologic tests about 5-10% of surgeries done for presumed pancreatic malignancies will have benign findings on final pathology. Endoscopic ultrasound (EUS) is used with increasing frequency to study pancreatic masses. The aim of this study is to examine the effect of EUS on prevalence of benign diseases undergoing Whipple over the last decade.

A comparison of abdominal surgical outcomes between African-American and Caucasian Crohn's patients.

Background And Objective: Whether race affects the natural history of Crohn's disease is a matter of debate. The aim of the current study was to evaluate the differences in surgical outcomes between African-American (AA) and Caucasian (C) Crohn's patients undergoing surgery at a tertiary care referral center.

Methods: With Institutional Review Board approval, the medical records of our institution were queried to identify consecutive AA and C patients who underwent surgery for Crohn's disease from December 1, 2009 to December 15, 2011.

Diabetic gastrointestinal motility disorders and the role of enteric nervous system: current status and future directions.

Background: Gastrointestinal manifestations of diabetes are common and a source of significant discomfort and disability. Diabetes affects almost every part of gastrointestinal tract from the esophagus to the rectum and causes a variety of symptoms including heartburn, nausea, vomiting, abdominal pain, diarrhea and constipation. Understanding the underlying mechanisms of diabetic gastroenteropathy is important to guide development of therapies for this common problem.

Optic neuropathy, myelopathy, anemia, and neutropenia caused by acquired copper deficiency after gastric bypass surgery.

Malabsorptive bariatric surgery is rapidly becoming a major cause of copper deficiency given the increasing prevalence of these procedures for morbid obesity. Acquired copper deficiency can present with clinically significant hematologic and neurological manifestations. Although hematologic manifestations of copper deficiency are rapidly reversible, significant neurological improvement after copper supplementation therapy is unusual and many patients remain debilitated and may only experience, at best, stabilization of the neurological manifestations.

MicroRNA 375 mediates palmitate-induced enteric neuronal damage and high-fat diet-induced delayed intestinal transit in mice.

Background & Aims: A high-fat diet (HFD) can cause serious health problems, including alteration of gastrointestinal transit, the exact mechanism of which is not clear. Several microRNAs (miRNAs) are involved in energy homeostasis, lipid metabolism, and HFD-induced weight gain. We investigated the role of miRNAs in HFD-induced damage to the enteric nervous system.

Quality of life and fecal incontinence after transanal endoscopic microsurgery for benign and malignant rectal lesions.

Background: Transanal endoscopic microsurgery (TEM) is a minimally invasive treatment used to excise a variety of rectal lesions. Potential overstretching of the sphincter's musculature due to dilation of the anal canal to allow placement of a 40-mm-wide scope combined with partial resection of the rectum and subsequent loss of rectal volume creates a concern regarding anorectal function postoperatively. Data regarding patient satisfaction with anorectal function and quality of life after TEM are scant.

Functional Dyspepsia in Review: Pathophysiology and Challenges in the Diagnosis and Management due to Coexisting Gastroesophageal Reflux Disease and Irritable Bowel Syndrome.

Functional dyspepsia is a common disorder which imposes significant diagnostic and treatment challenges for patients and physicians. The most recent update of the diagnostic criteria subdivides functional dyspepsia into two subcategories based on the main symptom of epigastric pain or postmeal fullness. As we discuss in this review, several studies have shown significant overlap in symptoms and pathophysiology between functional dyspepsia, irritable bowel syndrome, and the spectrum of reflux disorders.

Update on diabetes in the elderly and in nursing home residents.

Diabetes is common in the elderly population and in nursing home residents. More than 20% of adults aged 65 to 75 years and 40% of adults older than 80 years suffer from diabetes. Physiological changes in elderly individuals, such as decreased physical activity, abdominal obesity, and increased inflammatory state, increase insulin resistance in peripheral tissue and reduce glucose-dependent insulin release, leading to carbohydrate intolerance and diabetes.

Hypopituitarism caused by carotid cavernous fistula.

Here we report a 79-year-old woman who presented with a 7-day history of headache, nausea, vomiting, and was found to have proptosis and ptosis. Laboratory findings showed hyponatremia, hypocortisolism, secondary hypothyroidism and low follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels. CT angiography (CTA) showed a vascular lesion in sella causing a mass affect on the pituitary gland which proved to be a carotid cavernous fistula (CCF) by conventional angiography.

Amino acid composition in parenteral nutrition: what is the evidence?

Purpose Of Review: Complete parenteral nutrition solutions contain mixed amino acid products providing all nine essential amino acids and a varying composition of nonessential amino acids. Relatively little rigorous comparative efficacy research on altered parenteral nutrition amino acid composition has been published in recent years.

Recent Findings: Limited data from randomized, double-blind, adequately powered clinical trials to define optimal doses of total or individual amino acids in parenteral nutrition are available.

Diverse roles of leptin in the gastrointestinal tract: modulation of motility, absorption, growth, and inflammation.

Objective: Leptin was discovered in 1994 as a hormone produced by adipose tissue with a modulatory effect on feeding behavior and weight control. Recently, the stomach has been identified as an important source of leptin and growing evidence has shown diverse functions for leptin in the gastrointestinal tract.

Methods: Using leptin as a keyword in PubMed, more than 17 000 articles were identified, of which more than 500 articles were related to the role of leptin in the gastrointestinal tract.

Management of intractable hypoglycemia with Yttirum-90 radioembolization in a patient with malignant insulinoma.

Metastatic insulinomas may present with recurrent life-threatening hypoglycemia. Treatment of hypoglycemia in such patients is difficult and frequently fails to respond to numerous therapeutic agents, requiring continuous dextrose infusion. The authors present our experience with Yttirum-90 radioembolization in a patient with metastatic malignant insulinoma who failed to respond to distal pancreatectomy, systemic chemotherapy with capecitabine and everolimus and medical treatment with somatostatin analogues, diazoxide and corticosteroids.

Overlapping gastroesophageal reflux disease and irritable bowel syndrome: increased dysfunctional symptoms.

Aim: To investigate the association of gastroesophageal reflux disease (GERD) and irritable bowel syndrome (IBS) in Iranian patients and examine the prevalence of functional symptoms of the gastrointestinal tract in patients presenting with either IBS, GERD or both.

Methods: Six thousand four hundred and seventy six patients presented to the Gastro-intestinal (GI) clinic with symptoms of functional dysfunction of GI tract, 1419 patients (62.0% women, 38.

Transanal endoscopic microsurgery for the treatment of rectal cancer: comparison of wound complication rates with and without neoadjuvant radiation therapy.

Background: Neoadjuvant therapy for rectal cancer has led to improved tumor downstaging and higher complete pathologic response rates. At the same time, the introduction of transanal endoscopic microsurgery (TEM) technique has renewed interest in local excision of rectal cancer. There has been concern that radiation may make the more radical local excision with TEM unsuitable.