脳の発達におけるKIF3Bの機能に関する分子遺伝学的研究

学位の種別: 課程博士審査委員会委員 : （主査）東京大学教授 岡部 繁男, 東京大学教授 河西 春郎, 東京大学教授 村上 誠, 東京大学講師 柳澤 春明, 東京大学教授 狩野 方伸University of Tokyo(東京大学

The influence of polygenic risk for bipolar disorder on neural activation assessed using fMRI

Genome-wide association studies (GWAS) have demonstrated a significant polygenic contribution to bipolar disorder (BD) where disease risk is determined by the summation of many alleles of small individual magnitude. Modelling polygenic risk scores may be a powerful way of identifying disrupted brain regions whose genetic architecture is related to that of BD. We determined the extent to which common genetic variation underlying risk to BD affected neural activation during an executive processing/language task in individuals at familial risk of BD and healthy controls. Polygenic risk scores were calculated for each individual based on GWAS data from the Psychiatric GWAS Consortium Bipolar Disorder Working Group (PGC-BD) of over 16 000 subjects. The familial group had a significantly higher polygene score than the control group (P=0.04). There were no significant group by polygene interaction effects in terms of association with brain activation. However, we did find that an increasing polygenic risk allele load for BD was associated with increased activation in limbic regions previously implicated in BD, including the anterior cingulate cortex and amygdala, across both groups. The findings suggest that this novel polygenic approach to examine brain-imaging data may be a useful means of identifying genetically mediated traits mechanistically linked to the aetiology of BD

Exploring Promising Therapies for Non-Alcoholic Fatty Liver Disease: A ClinicalTrials.gov Analysis

Omar E Hegazi,1,2 Samer O Alalalmeh,1,2 Moyad Shahwan,1,2 Ammar Abdulrahman Jairoun,3,4 Mansour M Alourfi,5,6 Ghfran Abdulrahman Bokhari,6 Abdullah Alkhattabi,6 Saeed Alsharif,7 Mohannad Abdulrahman Aljehani,8 Abdulmalik Mohammed Alsabban,9 Mohammad Almtrafi,9 Ysear Abdulaziz Zakri,9 Abdullah AlMahmoud,10 Khalid Mohammed Alghamdi,10 Ahmed M Ashour,11 Nasser M Alorfi11 1Center of Medical and Bio-Allied Health Sciences Research, Ajman University, Ajman, United Arab Emirates; 2Department of Clinical Sciences, College of Pharmacy and Health Sciences, Ajman University, Ajman, United Arab Emirates; 3Health and Safety Department, Dubai, United Arab Emirates; 4School of Pharmaceutical Sciences, Universiti Sains Malaysia, Pulau Pinang, Malaysia; 5Internal medicine Department, King Faisal Medical City for Southern Region, Abha, Saudi Arabia; 6Department of gastroenterology, East Jeddah hospital, Jeddah, Saudi Arabia; 7Gastroenterology Department, Armed force Hospital of southern region, Khamis Mushait, Saudi Arabia; 8Division of Gastroenterology, Department of Medicine, King Faisal Specialist Hospital and Research Centre, Jeddah, Saudi Arabia; 9Gastroenterology Section, Department of Medicine, King Abdulaziz Medical City, Jeddah, Saudi Arabia; 10Gastroenterology Section, Internal Medicine Department, King Fahad Hospital, Jeddah, Saudi Arabia; 11Department of Pharmacology and Toxicology, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi ArabiaCorrespondence: Nasser M Alorfi, Department of Pharmacology and Toxicology, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia, Email [email protected]: Non-alcoholic fatty liver disease (NAFLD) is a common disease and has been increasing in recent years. To date, no FDA-approved drug specifically targets NAFLD.Methods: The terms “Non-alcoholic Fatty Liver Disease” and “NAFLD” were used in a search of ClinicalTrials.gov on August 24, 2023. Two evaluators independently examined the trials using predetermined eligibility criteria. Studies had to be interventional, NAFLD focused, in Phase IV, and completed to be eligible for this review.Results: The ClinicalTrials.gov database was searched for trials examining pharmacotherapeutics in NAFLD. The search revealed 1364 trials, with 31 meeting the inclusion criteria. Out of these, 19 were finalized for evaluation. The dominant intervention model was Parallel. The most prevalent studies were in Korea (26.3%) and China (21.1%). The most common intervention was metformin (12.1%), with others like Exenatide and Pioglitazone accounting for 9.1%.Conclusion: Therapeutics used to manage NAFLD are limited. However, various medications offer potential benefits. Further investigations are definitely warranted.Keywords: NAFLD, hepatology, clinical trials, therapeutics, metabolic disorde