A hepatitis B virus-derived peptide combined with HBsAg exerts an anti-HBV effect in an HBV transgenic mouse model as a therapeutic vaccine

IntroductionFor complete or functional cure of hepatitis B virus (HBV) infection, application of immunotherapy is now being attempted. Recently, we reported that a 6-mer hepatitis B virus (HBV)-derived peptide, Poly6, exerts a strong anticancer effect in tumor-implanted mice through inducible nitric oxide synthase (iNOS)-producing DCs (Tip-DCs) in a type 1 interferon (IFN-I)-dependent manner, suggesting its potential as a vaccine adjuvant.MethodsIn this study, we explored the potential of Poly6 in combination with HBsAg as a therapeutic vaccine against hepatitis B virus infection. We investigated the immunotherapeutic potential of Poly6 combined with HBsAg vaccination against hepatitis B virus infection in C57BL/6 mice or an HBV transgenic mouse model.ResultsIn C57BL/6 mice, Poly6 enhanced DC maturation and DC migration capacity in an IFN-I-dependent manner. Moreover, the addition of Poly6 to alum in combination with HBsAg also led to enhanced HBsAg-specific cell-mediated immune (CMI) responses, suggesting its potential as an adjuvant of HBsAg-based vaccines. In HBV transgenic mice, vaccination with Poly6 combined with HBsAg exerted a strong anti-HBV effect via induction of HBV-specific humoral and cell-mediated immune responses. In addition, it also induced HBV-specific effector memory T cells (TEM).DiscussionOur data indicated that vaccination with Poly6 in combination with HBsAg exerts an anti-HBV effect in HBV transgenic mice, which is mainly mediated by HBV-specific CMI and humoral immune responses via IFN-I-dependent DC activation, suggesting the feasibility of Poly6 as an adjuvant for an HBV therapeutic vaccine

The Impact of Overactive Bladder on Health-Related Quality of Life, Sexual Life and Psychological Health in Korea

Purpose We aimed to estimate the prevalence of overactive bladder (OAB) in Korea, to assess the variation in prevalence by sex and age, and to measure the impact of OAB on quality of life. Methods A population-based, cross-sectional telephone survey was conducted between April and June 2010 with a questionnaire regarding the prevalence of OAB, demographics, and the impact of OAB on quality of life. A geographically stratified random sample of men and women aged ≥30 years was selected. Results The overall prevalence of OAB was 22.9% (male, 19%; female, 26.8%). Of a total of 458 participants with OAB, 37.6% and 19.9% reported moderate or severe impact on their daily life and sexual life (5.6% and 3.5%, respectively, in participants without OAB). Anxiety and depression were reported by 22.7% and 39.3% of participants with OAB, respectively (9.7% and 22.8%, respectively, in participants without OAB). Only 19.7% of participants with OAB had consulted a doctor for their voiding symptoms, but 50.7% of respondents with OAB were willing to visit a hospital for the management of their OAB symptoms. Conclusions This study confirmed that OAB symptoms are highly prevalent in Korea, and many sufferers appear to have actively sought medical help. OAB has severe effects on daily and sexual life as well as psychological health

Nucleosome deposition and DNA methylation at coding region boundaries

Nucleosomes and methylation have been observed to peak at both ends of protein coding units in a genome-wide survey

Phagosome Escape of Rough Mycobacterium abscessus Strains in Murine Macrophage via Phagosomal Rupture Can Lead to Type I Interferon Production and Their Cell-To-Cell Spread

Mycobacterium abscessus complex (MAB) is a rapidly growing mycobacterium(RGM) whose clinical significance as an emerging human pathogen has been increasing worldwide. It has two types of colony morphology, a smooth (S) type, producing high glycopeptidolipid (GPL) content, and a rough (R) type, which produces low levels of GPLs and is associated with increased virulence. However, the mechanism responsible for their difference in virulence is poorly known. By ultrastructural examination of murine macrophages infected, we found that MAB-R strains could replicate more actively in the macrophage phagosome than the S variants and that they could escape into cytosol via phagosomal rupture. The cytosolic access of MAB-R strains via phagosomal rupture led to enhanced Type I interferon (IFN) production and cell death, which resulted in their cell-to-cell spreading. This behavior can provide an additional niche for the survival of MAB-R strains. In addition, we found that their enhancement of cell death mediated cell spreading are dependent on Type I IFN signaling via comparison of wild-type and IFNAR1 knockout mice. In conclusion, our data indicated that a transition of MAB-S strains into MAB-R variants increased their virulence via enhanced Type I IFN production, which led to enhanced survival in infected macrophage via cell death mediated cell-to-cell spreading. This result provides not only a novel insight into the difference in virulence between MAB-R and -S variants but also hints to their treatment strategy

Male-Specific W4P/R Mutation in the Pre-S1 Region of Hepatitis B Virus, Increasing the Risk of Progression of Liver Diseases in Chronic Patients

The issue of hepatitis B virus (HBV) mutations possibly leading to a gender disparity in the progression of liver diseases has not been explored. We aimed to elucidate the relationships of the novel pre-S1 mutations, W4P/R, with the progression of liver diseases and male predominance in a South Korean chronic cohort by use of a molecular epidemiologic study. We developed a fluorescence resonance energy transfer (FRET)-based real-time PCR (RT-PCR) assay for the detection of the W4P/R mutations and applied it to 292 chronic HBV patients. The pre-S1 mutations from 247 (84.6%) of a total of 292 patients were detected by this assay. W4P/R mutants were found to be significantly related to severe liver diseases (hepatocellular carcinoma [HCC] and liver cirrhosis, 12.4% [19/153] of patients, versus chronic hepatitis and asymptomatic carriage, 1.1% [1/94] of patients) (P<0.001). All of the W4P/R mutants were found in males only. The novel HBV pre-S1 mutations, W4P/R, may be associated with disease severity in male patients chronically infected with HBV genotype C. The W4P/R mutations may provide in part an explanation for the relatively high ratio of male to female incidence in HCC generation in South Korean chronic HBV patients.OAIID:oai:osos.snu.ac.kr:snu2013-01/102/0000006653/6SEQ:6PERF_CD:SNU2013-01EVAL_ITEM_CD:102USER_ID:0000006653ADJUST_YN:YEMP_ID:A077651DEPT_CD:806CITE_RATE:4.068FILENAME:male-specific w4p_r mutation in the pre-s1.pdfDEPT_NM:의과학과EMAIL:[email protected]_YN:YCONFIRM:

Orthogonal Stability of an Additive-quartic Functional Equation in Non-Archimedean Spaces

Using fixed point method, we prove the Hyers-Ulam stability of the orthogonally additive-quartic functional equation f(2x+y)+ f(2x-y)=4 f(x+y)+ 4 f(x-y) + 10 f(x) + 14f(-x) - 3 f(y)-3f(-y) for all $x, y$ with $xperp y$, in non-Archimedean Banach spaces. Here $perp$ is the orthogonality in the sense of Rätz

Titanium Plate Fixation for a Dehisced Sternum Following Coronary Artery Bypass Grafting: A Case Report

Sternal dehiscence is one of the most troublesome complications following cardiac surgery. Treatment failure and consequent lethal results are very common, even with all the efforts to resolve sternal dehiscence such as removal of infectious tissue, muscle flap interposition, and sternal rewiring. We report on a case of sternal osteomyelitis following coronary artery bypass grafting that was successfully treated with wide sternal resection, titanium plate fixation, and pectoralis muscle flap interposition

Proposed Protocols for Artificial Intelligence Imaging Database in Acute Stroke Imaging

Purpose To propose standardized and feasible imaging protocols for constructing artificial intelligence (AI) database in acute stroke by assessing the current practice at tertiary hospitals in South Korea and reviewing evolving AI models. Materials and Methods A nationwide survey on acute stroke imaging protocols was conducted using an electronic questionnaire sent to 43 registered tertiary hospitals between April and May 2021. Imaging protocols for endovascular thrombectomy (EVT) in the early and late time windows and during follow-up were assessed. Clinical applications of AI techniques in stroke imaging and required sequences for developing AI models were reviewed. Standardized and feasible imaging protocols for data curation in acute stroke were proposed. Results There was considerable heterogeneity in the imaging protocols for EVT candidates in the early and late time windows and posterior circulation stroke. Computed tomography (CT)-based protocols were adopted by 70% (30/43), and acquisition of noncontrast CT, CT angiography and CT perfusion in a single session was most commonly performed (47%, 14/30) with the preference of multiphase (70%, 21/30) over single phase CT angiography. More hospitals performed magnetic resonance imaging (MRI)-based protocols or additional MRI sequences in a late time window and posterior circulation stroke. Diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) were most commonly performed MRI sequences with considerable variation in performing other MRI sequences. AI models for diagnostic purposes required noncontrast CT, CT angiography and DWI while FLAIR, dynamic susceptibility contrast perfusion, and T1-weighted imaging (T1WI) were additionally required for prognostic AI models. Conclusion Given considerable heterogeneity in acute stroke imaging protocols at tertiary hospitals in South Korea, standardized and feasible imaging protocols are required for constructing AI database in acute stroke. The essential sequences may be noncontrast CT, DWI, CT/MR angiography and CT/MR perfusion while FLAIR and T1WI may be additionally required

Surgical repair of descending thoracic and thoracoabdominal aortic aneurysm involving the distal arch: Open proximal anastomosis under deep hypothermia versus arch clamping technique

BackgroundSurgical repair of a descending thoracic and thoracoabdominal aortic aneurysm (DTA/TAAA) involving the distal arch is challenging and requires either deep hypothermic circulatory arrest (DHCA) or crossclamping of the distal arch. The aim of this study was to compare these 2 techniques in the treatment of DTA/TAAA involving the distal arch.MethodsFrom 1994 to 2012, 298 patients underwent open repair of DTA/TAAA through a left thoracotomy. One hundred seventy-four patients with distal arch involvement who were suitable for either DHCA (n = 81) or arch clamping (AC; n = 93), were analyzed. In-hospital outcomes were compared using propensity scores and inverse-probability-of-treatment weighting adjustment to reduce treatment selection bias.ResultsEarly mortality was 11.1% in the DHCA group and 8.6% in the AC group (P = .58). Major adverse outcomes included stroke in 16 patients (9.2%), low cardiac output syndrome in 15 (8.6%), paraplegia in 10 (5.7%), and multiorgan failure in 10 (5.7%). After adjustment, patients who underwent DHCA were at similar risk of death (odds ratio [OR], 1.14; P = .80) and permanent neurologic injury (OR, 0.95; P = .92) to those who underwent AC. Although prolonged ventilator support (>24 hours) was more frequent with DHCA than with AC (OR, 2.60; P = .003), DHCA showed a tendency to lower the risk of paraplegia (OR, 0.15; P = .057).ConclusionsCompared with AC, DHCA did not increase postoperative mortality and morbidity, except for prolonged ventilator support. However, DHCA may offer superior spinal cord protection to AC during repair of DTA/TAAA involving the distal arch

Rough colony morphology of Mycobacterium massiliense Type II genotype is due to the deletion of glycopeptidolipid locus within its genome

Background: Recently, we introduced the complete genome sequence of Mycobacterium massiliense clinical isolates, Asan 50594 belonging to Type II genotype with rough colony morphology. Here, to address the issue of whether the rough colony morphotype of M. massiliense Type II genotype is genetically determined or not, we compared polymorphisms of the glycopeptidolipid (GPL) gene locus between M. massiliense Type II Asan 50594 and other rapidly growing mycobacteria (RGM) strains via analysis of genome databases.Results: We found deletions of 10 genes (24.8 kb), in the GPL biosynthesis related gene cluster of Asan 50594 genome, but no deletions in those of other smooth RGMs. To check the presence of deletions of GPL biosynthesis related genes in Mycobacterium abscessus - complex strains, PCRs targeting 12 different GPL genes (10 genes deleted in Asan 50594 genome as well as 2 conserved genes) were applied into 76 clinical strains of the M. abscessus complex strains [54 strains (Type I: 33, and Type II: 21) of M. massiliense and 22 strains (rough morphoype: 11 and smooth morphotype: 11) of M. abscessus]. No strains of the Type II genotype produced PCR amplicons in a total of 10 deleted GPL genes, suggesting loss of GPL biosynthesis genes in the genome of M. massiliense type II genotype strains.Conclusions: Our data suggested that the rough colony morphotype of the M. massiliense Type II genotype may be acquired via deletion events at the GPL gene locus for evolutionary adaptation between the host and pathogen.OAIID:oai:osos.snu.ac.kr:snu2013-01/102/0000006653/7SEQ:7PERF_CD:SNU2013-01EVAL_ITEM_CD:102USER_ID:0000006653ADJUST_YN:YEMP_ID:A077651DEPT_CD:806CITE_RATE:4.397FILENAME:rough colony morphology of mycobacterium.pdfDEPT_NM:의과학과SCOPUS_YN:YCONFIRM: