Effectiveness of Ledipasvir/Sofosbuvir with/without Ribavarin in Liver Transplant Recipients with Hepatitis C.

Background and Aims: Recurrent infection of hepatitis C virus (HCV) in liver transplant (LT) recipients is universal and associated with significant morbidity and mortality. Methods: We retrospectively evaluated the safety and efficacy of ledipasvir/sofosbuvir with and without ribavirin in LT recipients with recurrent genotype 1 hepatitis C. Results: Eighty-five LT recipients were treated for recurrent HCV with ledipasvir/sofosbuvirwith and without ribavirin for 12 or 24 weeks. The mean (± standard deviation [SD]) time from LT to treatment initiation was 68 (±71) months. The mean (± SD) age of the cohort was 63 (±8.6) years old. Most recipients were male (70%). Baseline alanine transaminase, total bilirubin, and HCV ribonucleic acid (RNA) values (± SD) were 76.8 (±126) mg/dL, 0.8 (±1.3) U/L, and 8,010,421.9 (±12,420,985) IU/mL, respectively. Five of 43 recipients who were treated with ribavirin required drug cessation due to side effects, with 4 of those being anemia complications. No recipient discontinued the ledipasvir/sofosbuvir. Eighty-one percent of recipients had undetectable viral levels at 4 weeks after starting therapy, and all recipients had complete viral suppression at the end of therapy. The sustained viral response at 12 weeks after completion of therapy was 94%. Conclusion : Ledipasvir and sofosbuvir with and without ribavirin therapy is an effective and well-tolerated interferon-free treatment for recurrent HCV infection after LT. Anemia is not uncommon in LT recipients receiving ribavirin

Acute Effects of Tai Chi Training on Cognitive and Cardiovascular Responses in Late Middle-Aged Adults: A Pilot Study

This study explored the immediate effects of Tai Chi (TC) training on attention and meditation, perceived stress level, heart rate, oxygen saturation level in blood, and palmar skin temperature in late middle-aged adults. Twenty TC practitioners and 20 nonpractitioners volunteered to join the study. After baseline measurements were taken, the TC group performed TC for 10 minutes while their cognitive states and cardiovascular responses were concurrently monitored. The control group rested for the same duration in a standing position. Both groups were then reassessed. The participants’ attention and meditation levels were measured using electroencephalography; stress levels were measured using Perceived Stress Scale; heart rate and blood oxygenation were measured using an oximeter; and palmar skin temperature was measured using an infrared thermometer. Attention level tended to increase during TC and dropped immediately thereafter (p<0.001). Perceived stress level decreased from baseline to posttest in exclusively the TC group (p=0.005). Heart rate increased during TC (p<0.001) and decreased thereafter (p=0.001). No significant group, time, or group-by-time interaction effects were found in the meditation level, palmar skin temperature, and blood oxygenation outcomes. While a 10-minute TC training could temporarily improve attention and decrease perceived stress levels, it could not improve meditation, palmar skin temperature, or blood oxygenation among late middle-aged adults

Characteristics of Adults in the Hepatitis B Research Network in North America Reflect Their Country of Origin and Hepatitis B Virus Genotype

Chronic hepatitis B virus (HBV) infection is an important cause of cirrhosis and hepatocellular carcinoma worldwide; populations that migrate to the US and Canada might be disproportionately affected. The Hepatitis B Research Network (HBRN) is a cooperative network of investigators from the United States and Canada, created to facilitate clinical, therapeutic, and translational research in adults and children with hepatitis B. We describe the structure of the network and baseline characteristics of adults with hepatitis B enrolled in the network

Design incubatees' perspectives and experiences in Hong Kong

This paper discusses the services and support from one of the government design-based business incubators in Hong Kong. The characteristics of a design business incubator are explained, and a multiple-case study indicates the perspectives of incubatees from different design disciplines after their graduation from the incubation programme. The research under discussion in this paper was based on eight design incubatees in different design disciplines within two years of incubation period, all of whom had participated in one of the government-funded business incubation programmes for designers in Hong Kong. The programme is unique because there are no other government-based incubation programmes for designers in Hong Kong. Semi-structured interviews were conducted to collect feedback from incubatees in areas ranging from terms of service to support of the incubation programme. The services of training, mentorship and finance were found to be the most important to design start-ups. Financial support and flexible funding allocation were another important issue for design incubatees, but training in these subject areas was not included in the incubation programme. However, it was confirmed that funding provided may have helped a number of the incubatees in developing their start-up businesses as a result of the reduced financial burden and office allocation. The research focused on one incubation programme because of the lack of incubation programmes for designers in Hong Kong, therefore future research which compares different types of business incubation programmes is suggested. The outcomes of the research not only identified the possible areas of development and improvement of business incubation in entrepreneurship but they will also be useful for the government, universities, institutions, designers, policy makers, entrepreneurs and practitioners. These, in addition to industry stakeholders who want to evaluate their entrepreneurship programmes and develop their plans for potential development in incubation- or entrepreneurial-related programmes or training, especially in the area of design, will find the results useful

Mutating a conserved cysteine in GPIHBP1 reduces amounts of GPIHBP1 in capillaries and abolishes LPL binding

Mutation of conserved cysteines in proteins of the Ly6 family cause human disease-chylomicronemia in the case of glycosylphosphatidylinositol-anchored HDL binding protein 1 (GPIHBP1) and paroxysmal nocturnal hemoglobinuria in the case of CD59. A mutation in a conserved cysteine in CD59 prevented the protein from reaching the surface of blood cells. In contrast, mutation of conserved cysteines in human GPIHBP1 had little effect on GPIHBP1 trafficking to the surface of cultured CHO cells. The latter findings were somewhat surprising and raised questions about whether CHO cell studies accurately model the fate of mutant GPIHBP1 proteins in vivo. To explore this concern, we created mice harboring a GPIHBP1 cysteine mutation (p.C63Y). The p.C63Y mutation abolished the ability of mouse GPIHBP1 to bind LPL, resulting in severe chylomicronemia. The mutant GPIHBP1 was detectable by immunohistochemistry on the surface of endothelial cells, but the level of expression was ∼70% lower than in WT mice. The mutant GPIHBP1 protein in mouse tissues was predominantly monomeric. We conclude that mutation of a conserved cysteine in GPIHBP1 abolishes the ability of GPIHBP1 to bind LPL, resulting in mislocalization of LPL and severe chylomicronemia. The mutation reduced but did not eliminate GPIHBP1 on the surface of endothelial cells in vivo

Effectiveness of Ledipasvir/Sofosbuvir with/without Ribavarin in Liver Transplant Recipients with Hepatitis C.

Background and Aims: Recurrent infection of hepatitis C virus (HCV) in liver transplant (LT) recipients is universal and associated with significant morbidity and mortality. Methods: We retrospectively evaluated the safety and efficacy of ledipasvir/sofosbuvir with and without ribavirin in LT recipients with recurrent genotype 1 hepatitis C. Results: Eighty-five LT recipients were treated for recurrent HCV with ledipasvir/sofosbuvirwith and without ribavirin for 12 or 24 weeks. The mean (± standard deviation [SD]) time from LT to treatment initiation was 68 (±71) months. The mean (± SD) age of the cohort was 63 (±8.6) years old. Most recipients were male (70%). Baseline alanine transaminase, total bilirubin, and HCV ribonucleic acid (RNA) values (± SD) were 76.8 (±126) mg/dL, 0.8 (±1.3) U/L, and 8,010,421.9 (±12,420,985) IU/mL, respectively. Five of 43 recipients who were treated with ribavirin required drug cessation due to side effects, with 4 of those being anemia complications. No recipient discontinued the ledipasvir/sofosbuvir. Eighty-one percent of recipients had undetectable viral levels at 4 weeks after starting therapy, and all recipients had complete viral suppression at the end of therapy. The sustained viral response at 12 weeks after completion of therapy was 94%. Conclusion : Ledipasvir and sofosbuvir with and without ribavirin therapy is an effective and well-tolerated interferon-free treatment for recurrent HCV infection after LT. Anemia is not uncommon in LT recipients receiving ribavirin

Altered Cardiac Energetics and Mitochondrial Dysfunction in Hypertrophic Cardiomyopathy

BackgroundHypertrophic cardiomyopathy (HCM) is a complex disease partly explained by the effects of individual gene variants on sarcomeric protein biomechanics. At the cellular level, HCM mutations most commonly enhance force production, leading to higher energy demands. Despite significant advances in elucidating sarcomeric structure-function relationships, there is still much to be learned about the mechanisms that link altered cardiac energetics to HCM phenotypes. In this work, we test the hypothesis that changes in cardiac energetics represent a common pathophysiologic pathway in HCM.MethodsWe performed a comprehensive multiomics profile of the molecular (transcripts, metabolites, and complex lipids), ultrastructural, and functional components of HCM energetics using myocardial samples from 27 HCM patients and 13 normal controls (donor hearts).ResultsIntegrated omics analysis revealed alterations in a wide array of biochemical pathways with major dysregulation in fatty acid metabolism, reduction of acylcarnitines, and accumulation of free fatty acids. HCM hearts showed evidence of global energetic decompensation manifested by a decrease in high energy phosphate metabolites (ATP, ADP, and phosphocreatine) and a reduction in mitochondrial genes involved in creatine kinase and ATP synthesis. Accompanying these metabolic derangements, electron microscopy showed an increased fraction of severely damaged mitochondria with reduced cristae density, coinciding with reduced citrate synthase activity and mitochondrial oxidative respiration. These mitochondrial abnormalities were associated with elevated reactive oxygen species and reduced antioxidant defenses. However, despite significant mitochondrial injury, HCM hearts failed to upregulate mitophagic clearance.ConclusionsOverall, our findings suggest that perturbed metabolic signaling and mitochondrial dysfunction are common pathogenic mechanisms in patients with HCM. These results highlight potential new drug targets for attenuation of the clinical disease through improving metabolic function and reducing mitochondrial injury