9,405 results match your criteria: "Medical College of Virginia.[Affiliation]"

Sulfonium Moieties as Ammonium Bioisosteres: Novel Ligands for the Alpha7 Nicotinic Acetylcholine Receptor.

J Med Chem

January 2025

Department of Pharmaceutical Sciences, Medicinal Chemistry Section "Pietro Pratesi", University of Milan, Via L. Mangiagalli 25, Milan 20133, Italy.

In the pressing quest of novel treatments for chronic pain, α7 nAChR silent agonists show efficacy as anti-inflammatory modulators and represent a promising strategy. Recent findings reveal that a sulfonium ion can replace the quaternary ammonium nitrogen as an alternative pharmacophore for nAChR silent activation. This study reports the design, synthesis, and electrophysiological evaluation of a new series of sulfonium-based derivatives inspired by the archetypal silent agonist NS6740.

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Oxygen transport across the lifespan of male Sprague Dawley rats.

Biogerontology

January 2025

Song Biotechnologies LLC., Baltimore, MD, 21030, USA.

Human populations are experiencing unprecedented growth and longevity with lingering knowledge gaps of the characteristics, mechanisms, and pathologies of senescence. Invasive measurements and long-term control conditions for longitudinal studies are infeasible, necessitating the need for surrogate animal models. Rats have short lifespans (2-3 years) with translatable cardiovascular systems, and Sprague Dawley microcirculatory preparations are key to studying the oxygen transport mechanisms critical to the loss of skeletal muscle function in aging.

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Background: Sphingosine-1 phosphate (S1P) is a bioactive lipid molecule that modulates inflammation and hepatic lipid metabolism in MASLD, which affects 1 in 3 people and increases the risk of liver fibrosis and hepatic cancer. S1P can be generated by 2 isoforms of sphingosine kinase (SphK). SphK1 is well-studied in metabolic diseases.

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Discriminative stimulus properties of α-ethyltryptamine (α-ET) in rats: α-ET-like effects of MDMA, MDA and aryl-monomethoxy substituted derivatives of α-ET.

Psychopharmacology (Berl)

December 2024

Department of Medicinal Chemistry, School of Pharmacy, Medical College of Virginia Campus, Virginia Commonwealth University, 800 E. Leigh St., STE 205, Richmond, VA, 23219-0540, USA.

Rationale α-ET (α-ethyltryptamine), a homolog of the classical hallucinogen α-methyltryptamine, was once prescribed clinically as an antidepressant. Classical psychedelic drugs are currently of interest as potential pharmacotherapy for psychiatric disorders. Objectives Drug discrimination was used to (a) determine if α-ET-like stimulus effects could be engendered by the prototypical phenylalkylamines MDMA ("Ecstasy") or MDA ("Love Drug") and (b) evaluate the α-ET-like stimulus effects of four synthesized aryl-substituted monomethoxy analogs of α-ET (4-OMe-, 5-OMe-, 6-OMe- and 7-OMe-α-ET).

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Gut Microbiome and Bile Acid Interactions: Mechanistic Implications for Cholangiocarcinoma Development, Immune Resistance, and Therapy.

Am J Pathol

December 2024

Department of Microbiology and Immunology, Virginia Commonwealth University and Richmond VA Medical Center, Richmond, Virginia; Stravitz-Sanyal Institute for Liver Disease and Metabolic Health, School of Medicine, Virginia Commonwealth University, Richmond, Virginia. Electronic address:

Cholangiocarcinoma (CCA) is a rare but highly malignant carcinoma of bile duct epithelial cells with a poor prognosis. The major risk factors of CCA carcinogenesis and progression are cholestatic liver diseases. The key feature of primary sclerosing cholangitis and primary biliary cholangitis is chronic cholestasis, which means a slowdown of hepatocyte secretion of biliary lipids and metabolites into bile as well as a slowdown of enterohepatic circulation (bile acid recirculation) of bile acids with dysbiosis of the gut microbiome, which was shown to lead to enterohepatic recirculation and an increase of toxic secondary bile acids.

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Congenital syphilis is becoming increasingly common in the United States. Early identification and treatment are critical in preventing long-term sequelae, such as musculoskeletal deformity, and neurologic deficits. At our North American institution, two recent cases of congenital syphilis were identified primarily by their musculoskeletal manifestations.

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Sex related differences in cognitive deficits: Disrupted Arc/Arg3.1 signaling in an HIV model.

Neurosci Lett

January 2025

Department of Anatomy and Neurobiology, Virginia Commonwealth University, School of Medicine, Richmond, VA 23298-0709, USA; Department of Pharmacology and Toxicology, Virginia Commonwealth University, School of Medicine, P.O. Box 980613, Richmond, VA 23298-0613, USA; Institute for Drug and Alcohol Studies, Virginia Commonwealth University, Medical College of Virginia (MCV) Campus, P.O. Box 980059, Richmond, VA 23298-0059, USA. Electronic address:

Combined and highly active anti-retroviral therapies (cART) have transitioned HIV into a more chronic disease. Roughly half of people living with HIV (PLWH) still experience neurocognitive disorders, albeit less severely than in the pre-cART era. Sex-related effects on memory/cognition remain understudied, although the percentage of PLWH that are female has increased.

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Voluntary nicotine consumption and reward in a subset of diversity outbred founder strains.

J Psychopharmacol

November 2024

Department of Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA, USA.

Background: Nicotine is largely responsible for the initiation and maintenance of tobacco dependence and contributes to a global health problem.

Aims: This study characterizes nicotine oral consumption and preference in male and female mice of several Diversity Outbred (DO) founder strains: C57BL/6J, A/J, 129S1/SvImJ, PWK/PhJ, NOD/ShiLtJ, and CAST/EiJ. It assesses the impact of nicotine concentration on intake and preference, the potential interaction of strain with sex, and estimates the degree of heritable variation in nicotine consumption.

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Background: Despite their improved safety, by and large, cardiac electrophysiology procedures including catheter ablation (CA), are presently performed in hospital outpatient departments.

Objective: This large multicenter study investigated the safety and outcomes associated with various cardiac electrophysiology procedures performed at 6 ambulatory surgery centers (ASCs), primarily during the coronavirus disease 2019 pandemic under the Center for Medicare and Medicaid Services Hospitals Without Walls program.

Methods: We retrospectively analyzed the outcomes from consecutive electrophysiology procedures performed in ASCs with same-day discharge, including transesophageal echocardiography, cardioversion, cardiac implantable electronic device (CIED) implantation, electrophysiology studies, and CA for atrial fibrillation (AF), atrial flutter (AFL)/supraventricular tachycardia, ventricular premature complexes (VPCs), and atrioventricular node.

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The DSM-III symptomatic criteria for major depression (MD) were derived from those proposed by Feighner and colleagues in 1972, which closely resembled those published by Cassidy in 1957. I here present a counter-factual history in which Feighner carefully read a key reference in Cassidy, a large 1953 follow-up study by Campbell of depressed patients with detailed tables of depressive signs and symptoms. In this alternative timeline, the Feighner criteria for MD were modified by Campbell's results, which then changed DSM-III and subsequent MD criteria sets.

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We investigated the functional classes of genomic regions containing SNPS contributing most to the SNP-heritability of important psychiatric and neurological disorders and behavioral traits, as determined from recent genome-wide association studies. We employed linkage-disequilibrium score regression with several brain-specific genomic annotations not previously utilized. The classes of genomic annotations conferring substantial SNP-heritability for the psychiatric disorders and behavioral traits differed systematically from the classes associated with neurological disorders, and both differed from the classes enriched for height, a biometric trait used here as a control outgroup.

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Reflections on philosophy of psychiatry.

World Psychiatry

June 2024

Virginia Institute of Psychiatric and Behavioral Genetics, and Department of Psychiatry, Medical College of Virginia/Virginia Commonwealth University, Richmond, VA, USA.

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The burden of cardiovascular disease (CVD) in patients with metabolic dysfunction-associated steatohepatitis (MASH) is poorly characterized, particularly other liver diseases including metabolic dysfunction-associated steatotic liver disease (MASLD). To identify available evidence, Embase, MEDLINE, and Cochrane database searches (main search: 2011-September 6, 2021; additional search [MEDLINE only]: September 7, 2021-February 15, 2023), plus manual searches (2019-September 2021), were performed. Studies reporting CVD outcomes (angina, coronary artery disease [CAD], heart failure, myocardial infarction, peripheral artery disease, stroke, venous thromboembolic disease, and CV mortality) in adults with histologically confirmed MASH and MASLD or other liver diseases were identified, with studies of MASLD without confirmed MASH excluded.

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Objective: This study was undertaken to determine whether hippocampal T2 hyperintensity predicts sequelae of febrile status epilepticus, including hippocampal atrophy, sclerosis, and mesial temporal lobe epilepsy.

Methods: Acute magnetic resonance imaging (MRI) was obtained within a mean of 4.4 (SD = 5.

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Genome-wide analysis of hepatic DNA methylation reveals impact of epigenetic aging on xenobiotic metabolism and transport genes in an aged mouse model.

Geroscience

December 2024

Department of Pharmacotherapy and Outcomes Science, School of Pharmacy, Virginia Commonwealth University, Dr. Joseph L. McClay, 6Th floor Smith Building, 410 North 12Th Street, Medical College of Virginia Campus, Richmond, VA, 23298-0533, USA.

Hepatic xenobiotic metabolism and transport decline with age, while intact xenobiotic metabolism is associated with longevity. However, few studies have examined the genome-wide impact of epigenetic aging on these processes. We used reduced representation bisulfite sequencing (RRBS) to map DNA methylation changes in liver DNA from mice ages 4 and 24 months.

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Genetic factors contribute to the susceptibility of psychotic disorders, but less is known how they affect psychotic disease-course development. Utilizing polygenic scores (PGSs) in combination with longitudinal healthcare data with decades of follow-up we investigated the contributing genetics to psychotic disease-course severity and diagnostic shifts in the SUPER-Finland study, encompassing 10 403 genotyped individuals with a psychotic disorder. To longitudinally track the study participants' past disease-course severity, we created a psychiatric hospitalization burden metric using the full-coverage and nation-wide Finnish in-hospital registry (data from 1969 and onwards).

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Generation of induced pluripotent stem cells from rat fibroblasts and optimization of its differentiation into mature functional neurons.

J Neurosci Methods

June 2024

Department of Anatomy and Neurobiology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298, USA. Electronic address:

Background: Induced pluripotent stem cells (iPSCs) derived neural stem cells (NSCs) provide a potential for autologous neural transplantation therapy following neurological insults. Thus far, in preclinical studies the donor iPSCs-NSCs are mostly of human or mouse origin with concerns centering around graft rejection when applied to rat brain injury models. For better survival and integration of transplanted cells in the injured brain in rat models, use of rat-iPSC-NSCs and in combination with biomaterials is of advantageous.

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Investigating the role of nicotinic acetylcholine receptors in menthol's effects in mice.

Drug Alcohol Depend

April 2024

Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA, USA.

The use of menthol in tobacco products has been linked to an increased likelihood of developing nicotine dependence. The widespread use of menthol can be attributed to its unique sensory characteristics; however, emerging evidence suggests that menthol also alters sensitivity to nicotine through modulation of nicotinic acetylcholine receptors (nAChRs). Nicotinic subunits, such as β2 and α5, are of interest due to their implications in nicotine reward, reinforcement, intake regulation, and aversion.

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Luxenburger's 1939 Essay on "Schizophrenia and its Hereditary Circle".

Am J Med Genet B Neuropsychiatr Genet

September 2024

Department of Germanic Languages and Literatures, University of Toronto, Toronto, Canada.

In 1939, Hans Luxenburger published a detailed overview of the current status of schizophrenia genetics research, reaching six major conclusions. First, schizophrenia is clearly a hereditary disease. Second, however, schizophrenia is not the hereditary trait itself but rather the consequences of a slowly developing biological progress, the nature of which remains entirely unknown.

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Bruno Schulz's 1930 article "The Hereditary Relationships of Old-Age Paranoid Psychosis".

Am J Med Genet B Neuropsychiatr Genet

June 2024

Department of Germanic Languages and Literatures, University of Toronto, Toronto, Ontario, Canada.

In the 1899 6th edition of his influential textbook, Kraepelin proposed a diagnostic category of "Old-Age Paranoid Psychosis." In this 1930 article, Bruno Schulz studied the morbid risk (MR) of several disorders and traits in the parents, siblings, offspring, and nieces/nephews of 51 probands with "Old-Age Paranoid Psychosis." His results permitted an evaluation of the validity of Kraepelin's category of Old-Age Paranoid Psychosis, in particular, whether it was a form of psychosis resulting from "senile changes" or late-onset schizophrenia.

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Bruno Schulz's 1936 book "Methodology of medical genetic research particularly with regard to psychiatry".

Am J Med Genet B Neuropsychiatr Genet

April 2024

Department of Germanic Languages and Literatures, University of Toronto, Toronto, Ontario, Canada.

In 1936, Bruno Schulz published the first detailed, book-length review of the methodology of psychiatric genetic research, based on his experiences at the German Research Institute of Psychiatry. Emphasis is placed on proper selection of relatives and the ascertainment corrections required for Mendelian transmission models. Twin studies are considered as is the impact of reduced fertility on patterns of risk.

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William Boven's 1915 thesis "Similarity and Mendelism in the heredity of dementia praecox and manic-depressive insanity".

Am J Med Genet B Neuropsychiatr Genet

April 2024

Department of Psychiatry, The Virginia Institute of Psychiatric and Behavioral Genetics, Medical College of Virginia/Virginia Commonwealth University, Richmond, Virginia, USA.

Article Synopsis
  • Boven's 1915 MD thesis investigated the hereditary nature of dementia praecox (DP) and manic-depressive insanity (MDI) using 60 multigenerational family histories from patients.
  • He concluded that both disorders are inherited, with MDI showing direct family transmission while DP was more commonly seen in collateral relatives.
  • Utilizing modern statistical methods in collaboration with Wilhelm Weinberg, Boven found that the inheritance patterns of these disorders did not fit Mendelian transmission, indicating a complex familial relationship.
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