Isolation and characterization of human fetal liver progenitor stem cells

Ph.DDOCTOR OF PHILOSOPH

Defective DNA Strand Break Repair Causes Chromosomal Instability and Accelerates Liver Carcinogenesis in Mice

Chromosomal instability is a characteristic feature of hepatocellular carcinoma (HCC) but its origin and role in liver carcinogenesis are undefined. We tested whether a defect in the nonhomologous end-joining (NHEJ) DNA repair gene Ku70 was associated with chromosomal abnormalities and enhanced liver carcinogenesis. Male Ku70 NHEJ-deficient (Ku70-/-), heterozygote (Ku70 +/-), and wild-type (WT) mice were injected with diethylnitrosamine (DEN), a liver carcinogen, at age 15 days. Animals were killed at 3, 6, and 9 months for assessment of tumorigenesis and hepatocellular proliferation. For karyotype analysis, primary liver tumor cell cultures were prepared from HCCs arising in Ku70 mice of all genotypes. Compared to WT littermates, Ku70-/- mice injected with DEN displayed accelerated HCC development. Ku70-/- HCCs harbored clonal increases in numerical and structural aberrations of chromosomes 4, 5, 7, 8, 10, 14, and 19, many of which recapitulated the spectrum of equivalent chromosomal abnormalities observed in human HCC. Ku70-/- HCCs showed high proliferative activity with increased cyclin D1 and proliferating cell nuclear antigen expression, Aurora A kinase activity, enhanced ataxia telangiectasia mutated kinase and ubiquitination, and loss of p53 via proteasomal degradation, features which closely resemble those of human HCC. Conclusion: These findings demonstrate that defects in the NHEJ DNA repair pathway may participate in the disruption of cell cycle checkpoints leading to chromosomal instability and accelerated development of HCC

Cost-effectiveness Analysis of Hospital Infection Control Response to an Epidemic Respiratory Virus Threat

Pandemic (H1N1) 2009 can be contained with less expensive measures than some other viruses

A cost-effectiveness analysis evaluating endoscopic surveillance for gastric cancer for populations with low to intermediate risk

10.1371/journal.pone.0083959PLoS ONE812-POLN

Consensus cost-effectiveness model for treatment of chronic hepatitis B in Asia Pacific countries

The Asian Pacific Association for the Study of the Liver (APASL) convened an international working party to develop a consensus cost-effectiveness model for treatment of Hepatitis B in Asia Pacific countries in March 2010. ;The working party consisted of expert hepatologists, virologists and epidemiologists from 11 representative countries in the Asia Pacific region. Meetings were conducted at the 20th APASL Annual Meeting in 2010 to determine consensus estimates for modeling and at the 21st and 22nd APASL meetings in 2011 and 2012, respectively to review and approve the models. ;The consensus cost-effectiveness model used Singapore as base case analysis and was validated using actual data from the Singapore Cancer, Diseases and Death Registries. Simulation for Singapore, China, Thailand, Pakistan, Taiwan and Korea were performed. Antivirals with high resistance barriers like entecavir and tenofovir had the highest retail cost but were the most cost-effective therapy in developed countries such as Singapore, Taiwan and Korea while generic tenofovir was most cost effective in Thailand and Pakistan. The cost effectiveness of different treatment strategies varied significantly between countries and was affected by medication cost, economic affordability, access to liver transplantation and the prevailing health of the general population. ;Choosing treatment strategies for hepatitis B based on low retail drug cost can be misleading because more expensive drugs may be more cost effective when considering long-term health outcomes and costs. Cost-effectiveness data should be individualized to countries based on their unique socio-economic conditions. Governmental policies which subsidize more costly drugs that have lower risk of drug resistance can benefit more patients

Coronavirus 2019 Silver Linings

10.1093/ofid/ofaa230OPEN FORUM INFECTIOUS DISEASES7