Herringstone3731

The causative factors of occult hepatitis B infection are complicated and not yet been fully elucidated. Mutations in hepatitis B virus (HBV) S gene are one of the factors may contributing to occult infection. In this study, 89 blood donors with genotype B occult HBV infection were investigated. Fifty-seven hepatitis B surface antigen (HBsAg)-positive/HBV DNA-positive blood donors served as control group for comparison. Occult HBV-related mutations with a high incidence (P  less then  .05) in the S gene were identified. To further verify these occult infection-related mutations, a conservative full-gene expression vector of HBV B genotype (pHBV1.3B) was constructed. Then, the mutant plasmids on the basis of pHBV1.3B were constructed and transfected into HepG2 cells. Extracellular as well as intracellular HBsAg was analysed by electrochemical luminescence and cellular immunohistochemistry. Ten occult infection-related mutations (E2G, Q101R, K122R, M133T, D144E, G145R, V168A, S174N, L175S and I226S) were significantly more frequent in the occult infection group (P  less then  .05). Five of the ten mutations (E2G, D144E, G145R, V168A and S174N) strongly decreased extracellular HBsAg level (P  less then  .05) in the transfection system. Notably, the E2G mutation had the most significant impact on the ratio of extracellular HBsAg (3.8% vs pHBV1.3B) and intracellular HBsAg (239.3% vs pHBV1.3B) (P  less then  .05), and the fluorescence density of E2G mutant HBsAg was significantly higher than that of pHBV1.3B (P  less then  .0001). Hence, ten mutations were associated with genotype B occult HBV infection; E2G and V168A were novel mutations which we confirmed significantly affect HBsAg detection. E2G might cause HBsAg secretion impairment that results in intracellular accumulation and a decrease in HBsAg secretion. © 2020 John Wiley & Sons Ltd.To measure HU and HRQOL in pediatric liver transplant (LT) recipients, a cross-sectional study of patient-parent dyads was conducted. Direct HU were assessed in 48 adolescents ≥12 years using SG and TTO techniques. Indirect HU were measured by Health Utility Index 2 and HUI3 for subjects ≥12 years and CHU9D for ≥7 years. Patients reported HRQOL using PedsQL™ GC and PedsQL™ TM. A total of 108 dyads participated (55.6% female; 73.2% Caucasian; 42.6% biliary atresia; 35.2% living donor; 37.0% Medicaid). Mean age at survey was 13.6 ± 3.5 years, and time from LT was 8.9 ± 4.9 years. 61.2% were on monotherapy, 25 (23.2%) had acute rejection within 3 years, and 15 (13.9%) had a biliary obstruction within 5 years. Mean indirect HU and HRQOL scores by child report were lower than norms (P  less then  .001). LRD recipients had higher PedsQL™ GC, PedsQL™ TM, and HUI3 scores (P  less then  .01). HU in pediatric LT recipients are lower than norms. Availability of HU scores for post-transplant health states will enable measurement of quality-adjusted life years for future comparative effectiveness studies. © 2020 Wiley Periodicals, Inc.OBJECTIVES To evaluate treatment patterns and associated outcomes of patients with urethral cancer. PATIENTS AND METHODS After obtaining IRB approval we identified 165 patients treated for primary urethral cancer between 1956-2017. Treatment included monotherapy (surgery or radiation), dual-therapy (surgery+radiation, surgery+chemotherapy, or chemotherapy+radiation) or triple-therapy (surgery+radiation+chemotherapy). Rates of different treatments were described by treatment year. The association between treatment type and outcomes was evaluated with multivariate Cox-regression models adjusting for disease characteristics. RESULTS The study cohort included 74 males and 91 females with a median age of 61 years. Common histologies were squamous-cell (36%), urothelial (27%) and adenocarcinoma (25%). At presentation, 72% of patients had invasive disease, 24% had nodal involvement, and 5% had metastases. Treatment included monotherapy (57%), dual-therapy (21%), and triple-therapy (10%). The use of monotherapy decreased over time, while rates of dual-therapy remained consistent, and rates of triple-therapy increased. Median followup was 4.7 years. Estimated five-year local recurrence-free, disease-specific and overall survival were 51%, 48% and 41%, respectively. Monotherapy was associated with decreased local recurrence-free survival after adjusting for stage, histology, sex and year of treatment (p=0.017). There was no evidence that treatment type was associated with distant recurrence, cancer-specific and overall survival. CONCLUSIONS We found preliminary evidence that multimodal therapy, more commonly used in recent years, was of benefit in patients with primary urethral cancer. This finding should be confirmed in further studies involving multiple centers due to the low incidence of the disease. This article is protected by copyright. All rights reserved.AIM The aim of this single institution study was to analyse the diagnostic methods, pre-operative work-up and outcomes of 52 retrorectal tumours. METHOD All patients treated for retro-rectal tumours from 2012 to 2017 were included. RESULTS Out of 52 patients, 40 (77%) were women. The patients' median age at the time of surgery was 43 (19-76) years, and 30 (58%) of the patients were asymptomatic at the time of diagnosis. All tumours were visible on magnetic resonance imaging (MRI) prior to surgery. The sensitivity and specificity for predicting malignancy on pre-operative imaging for retro-rectal tumours were 25% and 98%, respectively. Forty-four procedures (85%) were performed using the perineal approach. The median hospital stay was three (1-18) days. There was no 30-day post-operative mortality. Eleven (21%) patients developed post-operative complications, mostly surgical site infections. Twenty-nine tumours (56%) were benign tailgut cysts. Four (8%) tumours were malignant and were considered to be removed with a tumour-free resection margin. Local recurrent disease was detected on MRI in 14 (27%) patients at a median of 1.05 (range 0.78-1.77) years after primary surgery. Only the multi-lobular shape of the tumour was found to be an independent risk factor for recurrence (p=0.030). CONCLUSION A pre-operative MRI is mandatory in order to plan the surgical strategy for retro-rectal tumours. Symptomatic, solid, large tumours should be removed because of the risk of malignancy. Minor cystic lesions with thin walls as well as asymptomatic recurrences of benign tumours are suitable to be followed conservatively. This article is protected by copyright. All rights reserved.Pancreatic ductal adenocarcinoma (PDAC) will soon belong to the top three cancer killers. The only approved specific PDAC therapy targets the epidermal growth factor receptor (EGFR). Although EGFR is a crucial player in PDAC development, EGFR-based therapy is disappointing. In this study, we evaluated the role of the EGFR ligand betacellulin (BTC) in PDAC. The expression of BTC was investigated in human pancreatic cancer specimen. Then, we generated a BTC knockout mouse model by CRISPR/Cas9 technology and a BTC overexpression model. Both models were crossed with the Ptf1aCre/+ ;KRASG12D/+ (KC) mouse model (B-/- KC or BKC, respectively). In addition, EGFR, ERBB2, and ERBB4 were investigated by the pancreas-specific deletion of each receptor using the Cre-loxP system. Tumor initiation and progression were analyzed in all mouse lines and the underlying molecular biology of PDAC was investigated at different time points. BTC is expressed in human and murine PDAC. B-/- KC mice showed a decelerated PDAC progression, associated with decreased EGFR activation. BKC mice developed severe PDAC with a poor survival rate. The dramatically increased BTC-mediated tumor burden was EGFR-dependent, but also ERBB4 and ERBB2 were involved in PDAC development or progression, as depletion of EGFR, ERBB2 or ERBB4 significantly improved the survival rate of BTC-mediated PDAC. BTC increases PDAC tumor burden dramatically by enhanced RAS activation. EGFR-, ERBB2-, and ERBB4-signaling are involved in accelerated PDAC development mediated by BTC indicating that targeting the whole ERBB family, instead of a single receptor, is a promising strategy for the development of future PDAC therapies. This article is protected by copyright. All rights reserved.Linc-ROR is reported to be a potential biomarker of breast cancer, but the detailed mechanism of linc-ROR-mediated breast cancer regulation has not been fully studied. We aimed to explore how linc-ROR affects proliferation, metastasis and drug sensitivity in breast cancer. Cell lines in which linc-ROR was overexpressed or knocked down were constructed, and the cell proliferation, colony formation, cell migration and invasion abilities of these lines were explored. A CCK-8 assay was performed to determine the sensitivity of the breast cancer cells to rapamycin. Next-generation sequencing was conducted to explore the detailed regulatory mechanism of linc-ROR; differentially expressed RNAs in the linc-ROR-overexpressing cell line compared with the negative control were screened out and their target genes were chosen to perform Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, protein-protein interaction (PPI) network analysis and competing endogenous RNA (ceRNA) network analysmycin treatment by functioning as a ceRNA sponge for miR-194-3p, which targets MECP2. This article is protected by copyright. All rights reserved.IMPORTANCE Improving representation of indigenous ophthalmologists in New Zealand. BACKGROUND Māori, indigenous to New Zealand/Aotearoa and Pacific Peoples indigenous to Pacific Island Nations living in New Zealand, experience poorer health outcomes across several ophthalmic conditions. The Royal Australian and New Zealand College of Ophthalmologists has identified indigenous workforce development as a priority. DESIGN Mixed-methods study, utilising retrospective analysis of Medical Schools Outcomes Database and Longitudinal Tracking Project responses, and prospective interviews with Māori/Pasifika medical graduates. PARTICIPANTS This study involved 64 medical graduates from the University of Auckland and University of Otago, and six Māori/Pasifika medical postgraduates in New Zealand. METHODS Retrospective analysis of medical graduate responses who ranked ophthalmology among their top-three preferred specialties in the Medical Schools Outcomes Database and Longitudinal Tracking Project. Prospective semi-strue insights include enhancing specialty exposure, mentor development, promoting Māori/Pasifika connections and clarifying training pathways for future graduates. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.OBJECTIVE To explore the mediating role of visceral adiposity, as assessed by the visceral adiposity index (VAI), in the relationship among schooling, physical inactivity, and unhealthy metabolic phenotype (UMP). METHODS A cross-sectional population-based study was conducted with 854 adult individuals of both sexes from a Brazilian city. Data were collected through interviews, anthropometric evaluation, and clinical and laboratorial tests. We used multivariate path analysis, which simultaneously analyzes multiple relationships between variables. The analyses were adjusted by sex and age and stratified according to nutritional status. RESULTS A positive direct effect of visceral adiposity on the UMP was observed for normal weight, standardized estimate (SE) = 0.632; confidence interval (CI 95%) = 0.547, 0.707) and overweight individuals (SE = 0.732; CI 95% = 0.647, 0.808), and negative direct effect of schooling on physical inactivity (normal weight SE = -0.408; CI 95% = -0.550, -0.265) and overweight (SE = -0.