Direct endoscopic placement of percutaneous endoscopic gastrostomies with jejunal extension tubes (PEG-J) using ultra-thin endoscopes - long-term outcomes from a U.S. tertiary referral center.

Introduction: Several techniques for PEG-J tube placement have been described, commonly requiring fluoroscopic guidance and/or fixation of the jejunostomy tube (J-tube) into the small intestine. We describe a modified technique for placing jejunostomy tubes under direct visualization through a PEG with the use of ultra-thin endoscopes and steel guidewire.

Methods: A retrospective study at a single tertiary academic center evaluating patients who underwent PEG-J placement between 2010 and 2020.

Susac Syndrome and Pregnancy.

Susac syndrome (SuS) is a rare poorly characterised disorder that affects the brain, retina, and cochlea. Here, we present a case of a 31-year-old pregnant female with a new diagnosis of SuS that was successfully managed to 36 weeks of gestation with minimal disease burden to both the mother and newborn. She was treated initially using intravenous methylprednisolone followed by oral prednisone, and intravenous immunoglobulin (IVIg).

Atypical Large Vessel Vasculitis Presenting With Cholestatic Liver Abnormalities: Case-Based Review.

Clinicians usually easily recognize cranial manifestations of giant cell arteritis (GCA) such as new-onset headache, jaw claudication, scalp tenderness, and abrupt changes in visual acuity or blindness; however, when presented with an aberrant clinical course, the diagnosis becomes more elusive. In addition to temporal arteries and other extracranial branches of the carotid arteries, large vessel vasculitis (LVV) can also affect other blood vessels including coronary arteries, aorta with its major branches, intracranial blood vessels, and hepatic arteries.Over time, the scope of the symptoms typically associated with LVV has broadened and includes cases of fever of unknown origin accompanied with other constitutional symptoms that can mimic a range of neoplastic and infectious diseases.

Viral eradication restores normal iron status in chronic hepatitis C patients with abnormal iron studies.

Introduction And Objectives: Abnormal serum iron studies are seen in a third or more of patients with chronic hepatitis C infection (HCV), where they have been linked to accelerated fibrosis progression and increased risk of hepatocellular carcinoma and sometimes lead to concern for coexisting hereditary hemochromatosis. The aim of this study was to assess the effect of HCV eradication in patients with abnormal serum iron studies prior to treatment with direct-acting antiviral agents (DAAs).

Patients: HCV-infected subjects with iron studies obtained before and after successful treatment with DAAs were identified (n=27).

Tau immunotherapies for Alzheimer's disease.

Introduction: Alzheimer's dementia (AD) is the most common form of dementia in the World. Pathologically, it is characterized by extracellular β-amyloid plaques and intraneuronal neurofibrillary tangles (NFTs). The latter is composed of irregular, pathological forms of the tau protein.

Salivary beta amyloid protein levels are detectable and differentiate patients with Alzheimer's disease dementia from normal controls: preliminary findings.

Background: Peripheral diagnostics for Alzheimer's disease (AD) continue to be developed. Diagnostics capable of detecting AD before the onset of symptoms are particularly desirable, and, given the fact that early detection is imperative for alleviating long-term symptoms of the disease, methods which enable detection in the earliest stages are urgently needed. Saliva testing is non-invasive, and saliva is easy to acquire.

Nicotinic Acetylcholine Receptor Agonists for the Treatment of Alzheimer's Dementia: An Update.

Unlabelled: A significant portion of the clinical phenotype observed in Alzheimer's disease (AD) occurs through nicotinic acetylcholine receptors (nAChRs). Degeneration of cholinergic neurons, combined with aberrant nAChR expression and activation partially through amyloid-beta peptide (Aβ)-nAChR leads to upregulation of pro-inflammatory pathways and subsequently the progressive cognitive decline of AD. Interestingly, the cholinergic anti-inflammatory pathway is also mediated through nAChR particularly α7 nAChR.

Effective Reduction in High Ethanol Drinking by Semisynthetic Tetracycline Derivatives.

Background: New pharmacotherapies to treat alcohol use disorders (AUD) are needed. Given the complex nature of AUD, there likely exist multiple novel drug targets. We, and others, have shown that the tetracycline drugs, minocycline and doxycycline, reduced ethanol (EtOH) drinking in mice.

Prenatal Hypoxia Reduces Mitochondrial Protein Levels and Cytochrome c Oxidase Activity in Offspring Guinea Pig Hearts.

Prenatal hypoxia (HPX) reduces mitochondrial cytochrome c oxidase (CCO and COX) activity in fetal guinea pig (GP) hearts. The aim of this study was to quantify the lasting effects of chronic prenatal HPX on cardiac mitochondrial enzyme activity and protein expression in offspring hearts. Pregnant GPs were exposed to either normoxia (NMX) or HPX (10.

Bioinformatics analyses reveal age-specific neuroimmune modulation as a target for treatment of high ethanol drinking.

Background: Use of in silico bioinformatics analyses has led to important leads in the complex nature of alcoholism at the genomic, epigenomic, and proteomic level, but has not previously been successfully translated to the development of effective pharmacotherapies. In this study, a bioinformatics approach led to the discovery of neuroimmune pathways as an age-specific druggable target. Minocycline, a neuroimmune modulator, reduced high ethanol (EtOH) drinking in adult, but not adolescent, mice as predicted a priori.

Functional mapping of the neuronal substrates for drug tolerance in Drosophila.

Physical dependence on alcohol and anesthetics stems from neuroadaptive changes that act to counter the effects of sedation in the brain. In Drosophila, exposure to either alcohol or solvent anesthetics have been shown to induce changes in expression of the BK-type Ca(2+)-activated K(+) channel gene slo. An increase in slo expression produces an adaptive modulation of neural activity that generates resistance to sedation and promotes drug tolerance and dependence.

Chronic hypoxia impairs cytochrome oxidase activity via oxidative stress in selected fetal Guinea pig organs.

We hypothesized that chronic hypoxia disrupts mitochondrial function via oxidative stress in fetal organs. Pregnant guinea pig sows were exposed to either normoxia or hypoxia (10.5% O2, 14 days) in the presence or absence of the antioxidant, N-acetylcysteine (NAC).

Impact of oxidative stress in fetal programming.

Intrauterine stress induces increased risk of adult disease through fetal programming mechanisms. Oxidative stress can be generated by several conditions, such as, prenatal hypoxia, maternal under- and overnutrition, and excessive glucocorticoid exposure. The role of oxidant molecules as signaling factors in fetal programming via epigenetic mechanisms is discussed.

Protective effect of N-acetylcysteine on liver damage during chronic intrauterine hypoxia in fetal guinea pig.

Chronic exposure to hypoxia during pregnancy generates a stressed intrauterine environment that may lead to fetal organ damage. The objectives of the study are (1) to quantify the effect of chronic hypoxia in the generation of oxidative stress in fetal guinea pig liver and (2) to test the protective effect of antioxidant treatment in hypoxic fetal liver injury. Pregnant guinea pigs were exposed to either normoxia (NMX) or 10.

A role for dynamin in triggering ethanol tolerance.

Background: A prevailing hypothesis is that the set of genes that underlie the endophenotypes of alcoholism overlap with those responsible for the addicted state. Functional ethanol tolerance, an endophenotype of alcoholism, is defined as a reduced response to ethanol caused by prior ethanol exposure. The neuronal origins of functional rapid tolerance are thought to be a homeostatic response of the nervous system that counters the effects of the drug.

Tolerance to anesthesia depends on synaptic proteins.

The hypnotic effects of anesthetics are caused by their interactions with neuronal components vital for proper signaling. An understanding of the adaptive mechanisms that lead to the development of anesthetic tolerance can offer insight into the regulation of neuroexcitability and plasticity that alter behavioral output. Here we use genetic and pharmacological manipulation of Drosophila to investigate the mechanisms of tolerance to benzyl alcohol.

slo K(+) channel gene regulation mediates rapid drug tolerance.

Changes in neural activity caused by exposure to drugs may trigger homeostatic mechanisms that attempt to restore normal neural excitability. In Drosophila, a single sedation with the anesthetic benzyl alcohol changes the expression of the slo K(+) channel gene and induces rapid drug tolerance. We demonstrate linkage between these two phenomena by using a mutation and a transgene.