Anxiety and Depression in Patients with Primary Biliary Cholangitis: Current Insights and Impact on Quality of Life.

Primary biliary cholangitis (PBC), formerly known as primary biliary cirrhosis, is a chronic cholestatic immune-mediated liver disease characterized by injury to intrahepatic bile ducts that may ultimately progress to cirrhosis and liver failure and result in the need for liver transplant or death without treatment. Ursodeoxycholic acid (UDCA) and obeticholic acid (OCA) are approved therapies for PBC and are associated with a reduced risk of progression of disease, although patients may continue to experience significant symptoms of pruritus and fatigue independent of liver disease. The two most commonly reported symptoms among patients with PBC are fatigue and pruritus which may be debilitating, and negatively impact physical, mental, emotional, and social wellbeing. Intense symptom burden has been associated with depressive symptoms, cognitive defects, poor sleep schedules, and social isolation. This literature review explores the presence of anxiety and depressive symptoms in chronic liver disease, the impact of symptom burden on patients' wellbeing, and available pharmaceutical and natural therapies.

Evidence of disrupted rhombic lip development in the pathogenesis of Dandy-Walker malformation.

Dandy-Walker malformation (DWM) and Cerebellar vermis hypoplasia (CVH) are commonly recognized human cerebellar malformations diagnosed following ultrasound and antenatal or postnatal MRI. Specific radiological criteria are used to distinguish them, yet little is known about their differential developmental disease mechanisms. We acquired prenatal cases diagnosed as DWM and CVH and studied cerebellar morphobiometry followed by histological and immunohistochemical analyses. This was supplemented by laser capture microdissection and RNA-sequencing of the cerebellar rhombic lip, a transient progenitor zone, to assess the altered transcriptome of DWM vs control samples. Our radiological findings confirm that the cases studied fall within the accepted biometric range of DWM. Our histopathological analysis points to reduced foliation and inferior vermian hypoplasia as common features in all examined DWM cases. We also find that the rhombic lip, a dorsal stem cell zone that drives the growth and maintenance of the posterior vermis is specifically disrupted in DWM, with reduced proliferation and self-renewal of the progenitor pool, and altered vasculature, all confirmed by transcriptomics analysis. We propose a unified model for the developmental pathogenesis of DWM. We hypothesize that rhombic lip development is disrupted through either aberrant vascularization and/or direct insult which causes reduced proliferation and failed expansion of the rhombic lip progenitor pool leading to disproportionate hypoplasia and dysplasia of the inferior vermis. Timing of insult to the developing rhombic lip (before or after 14 PCW) dictates the extent of hypoplasia and distinguishes DWM from CVH.