We investigated cognitive function, axonal/white matter (WM) changes and glymphatic function of vascular dementia (VaD) using a multiple microinfarction (MMI) model in retired breeder (RB) rats. The MMI model induces significant (p<0.05) cognitive decline that worsens with age starting at 2 weeks, which persists until at least 6 weeks after MMI. RB rats subjected to MMI exhibit significant axonal/WM damage identified by decreased myelin thickness, oligodendrocyte progenitor cell numbers, axon density, synaptic protein expression in the cortex and striatum, cortical neuronal branching, and dendritic spine density in the cortex and hippocampus compared with age matched controls. MMI evokes significant dilation of perivascular spaces as well as water channel dysfunction indicated by decreased Aquaporin-4 (AQP-4) expression around blood vessels. MMI induced glymphatic dysfunction with delayed cerebrospinal fluid (CSF) penetration into the brain parenchyma via paravascular pathways as well as delayed waste clearance from the brain. The MMI model in RB rats decreases AQP-4 and induces glymphatic dysfunction which may play an important role in MMI induced axonal/WM damage and cognitive deficits.

In an analysis of data from patients receiving routine clinical care in Fibrotic Liver Disease Consortium health systems, we found that the prevalence of PBC increased from 2004 through 2014, despite steady incidence. Patient demographic and clinical characteristics, as well as UDCA treatment, affected mortality.

T he reported prevalence of gastrointestinal (GI) symptoms, including anorexia, diarrhea, nausea, vomiting, and abdominal pain, in severe acute respiratory syndrome coronavirus 2 infection has been highly variable, ranging from 5% to 61%. 1-7 Although the Centers for Disease Control and Prevention guidelines for testing for coronavirus disease 2019 (COVID-19) include vomiting and diarrhea, to our knowledge, all studies to date have been retrospective, and none have evaluated the prevalence of GI symptoms among patients who tested negative for COVID-19. In this prospective case-control study, we compared the prevalence of GI symptoms between those who tested positive and negative for COVID-19 and determined the association between GI symptoms and COVID-19 diagnosis or outcomes. Methods This was a prospective case-control study performed at a single tertiary care hospital in Baltimore, Maryland, after institutional review board approval. The study population included all adult patients who tested positive (case patients) or negative (control individuals) for COVID-19 by nasopharyngeal swab between March 9, 2020, and April 15, 2020. A telephone survey was conducted to obtain information including demographics, comorbid conditions, GI symptoms, respiratory symptoms, fever, gustatory symptoms, olfactory symptoms, and need for hospitalization by using a predesigned questionnaire. The primary outcome was the prevalence of GI symptoms in COVID-19-positive and-negative patients, and the secondary outcomes were to determine the utility of GI symptoms for COVID-19 screening and the association of GI symptoms with need for hospitalization. Logistic regression and univariate followed by multivariable analysis using a backward model selection approach were conducted to evaluate risk factors of COVID-19, and the area under the receiver operating characteristic (AUROC) for COVID-19 using a combination of different symptoms was determined.

No abstract

BACKGROUND & AIMS Sustained virological response (SVR) to antiviral therapy for hepatitis C virus (HCV) correlates with changes in biochemical measures of liver function. However, little is known about the long-term effects of SVR on liver fibrosis. We investigated the effects of HCV therapy on fibrosis, based on the Fibrosis-4 (FIB4) score, over a 10-year period. METHODS We collected data from participants in the Chronic Hepatitis Cohort Study—a large observational multicenter study of patients with hepatitis at 4 US health systems—from January 1, 2006, through December 31, 2013. We calculated patients’ FIB4 score and the aminotransferase-to-platelet ratio index (APRI) score over a 10-year period. Of 4731 patients with HCV infection, 1657 (35%) were treated and 755 (46%) of these patients achieved SVR. RESULTS In propensity score–adjusted analyses, we observed significant longitudinal changes in FIB4 score that varied with treatment and response to treatment. In patients achieving SVR, FIB4 scores decreased sharply, remaining significantly lower over the 10-year period than in untreated patients or patients with treatment failure (P < .001). In independent analyses, men and patients with HCV genotype 1 or 3 infections had higher FIB4 scores than women or patients with HCV genotype 2 infections (P < .01 for both). Findings were similar in a sensitivity analysis that substituted the APRI as the marker of fibrosis instead of the FIB4 score. CONCLUSIONS SVR to HCV treatment appears to induce long-term regression of fibrosis based on FIB4 scores collected over 10 years from a large observational study of US hepatitis patients. Patients receiving no treatment or with treatment failure had progressive increases in FIB4 scores.