Outbreaks of mumps: an observational study over two decades in a single hospital in Korea

PurposeThe introduction of the mumps vaccine has dramatically reduced the number of mumps cases, but outbreaks have recently occurred among highly vaccinated populations in developed countries. Epidemiological and clinical characteristics of patients with mumps admitted between 1989 and 2012 in a single hospital in Korea are described in the present study.MethodsWe retrospectively evaluated inpatients with mumps between 1989 and 2012 and outpatients and inpatients with mumps in 2011-2012.ResultsA total of 152 patients with mumps were admitted between 1989 and 2012, and 163 patients were recorded in 2011-2012. The highest number of admitted cases occurred in 1998 and 2012 (35 and 34 cases, respectively). Among the patients admitted in 2011-2012, the highest frequency was observed among people aged 15-19 years, and low frequency was observed in those aged 20 years, compatible to the city data and national data. In patients admitted to our department in 1998 (35 cases) and in 2010-2012 (27 cases), there were significant differences in the mean age and the rate of secondary measles-mumps-rubella (MMR) vaccination, but had similar clinical features, including complications, except aseptic meningitis. Antimumps immunoglobulin (Ig) G was positive in 83% and 100%, and IgM was positive in 67% and 41%, respectively, in the two periods.ConclusionIn Korea, recent mumps outbreaks have occurred mainly among secondary school students who received two doses of the MMR vaccine. The vaccinees might have a modified immune reaction to viral insults, manifesting modified epidemiological and clinical features

Efficacy and Tolerability of GCSB-5 for Hand Osteoarthritis: A Randomized, Controlled Trial

AbstractPurposeThe aim of this study was to investigate the efficacy and tolerability of GCSB-5, a mixture of 6 purified herbal extracts, in treating hand osteoarthritis (OA).MethodsA randomized, double-blind, placebo-controlled trial enrolled 220 patients with hand OA who had baseline a visual analog scale joint pain score of >30 of 100 mm at 3 hospitals between September 2013 and November 2014. After randomization, patients were allocated to receive oral GCSB-5 600 mg or placebo, bid for 12 weeks. The primary end point was the change in the Australian/Canadian OA Hand Index (AUSCAN)-defined pain score at 4 weeks relative to baseline. Secondary end points included the frequency Outcome Measures in Rheumatology–OA Research Society International (OMERACT-OARSI)-defined response at 4, 8, 12, and 16 weeks after randomization.FindingsThe allocated treatment was received by 109 and 106 patients in the GCSB-5 and placebo groups, respectively. At 4 weeks, the median (interquartile range) change in AUSCAN pain score relative to baseline was significantly greater in the GCSB-5 group than in the placebo group (–9.0 [–23.8 to –0.4] vs –2.2 [–16.7 to 6.0]; P = 0.014), with sustained improvement at 8, 12, and 16 weeks (P = 0.039). The GCSB-5 group also had a significantly greater OMERACT-OARSI–defined response rate than did the placebo group at 4 weeks (44.0% vs 30.2%), 8 weeks (51.4% vs 35.9%), 12 weeks (56.9% vs 40.6%), and 16 weeks (50.5% vs 37.7%) (P = 0.0074). The 2 treatments exhibited comparable safety profiles.ImplicationsGCSB-5 was associated with improved symptoms of hand OA, with good tolerability, in these patients. GCSB-5 may be a well-tolerated alternative of, or addition to, the treatment of hand OA. ClinicalTrials.gov identifier: NCT01910116

Risk of Atrial Fibrillation and Adverse Outcomes in Patients With Cardiac Implantable Electronic Devices.

Background and objectives: Comprehensive epidemiological data are lacking on the incident atrial fibrillation (AF) in patients with cardiac implantable electronic devices (CIEDs). This study aimed to examine the incidence, risk factors, and AF-related adverse outcomes of patients with CIEDs.Methods: This was an observational cohort study that analyzed patients without prevalent AF who underwent CIED implantation in 2009-2018 using a Korean nationwide claims database. The subjects were divided into three groups by CIED type and indication: pacemaker (n=21,438), implantable cardioverter defibrillator (ICD)/cardiac resynchronization therapy (CRT) with heart failure (HF) (n=3,450), and ICD for secondary prevention without HF (n=2,146). The incidence of AF, AF-associated predictors, and adverse outcomes were evaluated.Results: During follow-up, the incidence of AF was 4.3, 7.3, and 5.1 per 100 person-years in the pacemaker, ICD/CRT with HF, and ICD without HF cohorts, respectively. Across the three cohorts, older age and valvular heart disease were commonly associated with incident AF. Incident AF was consistently associated with an increased risk of ischemic stroke (3.8-11.4-fold), admission for HF (2.6-10.5-fold), hospitalization for any cause (2.4-2.7-fold), all-cause death (4.1-5.0-fold), and composite outcomes (3.4-5.7-fold). Oral anticoagulation rates were suboptimal in patients with incident AF (pacemaker, 51.3%; ICD/CRT with HF, 51.7%; and ICD without HF, 33.8%, respectively).Conclusions: A substantial proportion of patients implanted CIED developed newly diagnosed AF. Incident AF was associated with a higher risk of adverse events. The importance of awareness, early detection, and appropriate management of AF in patients with CIED should be emphasized

Loss of the tumor suppressor, Tp53, enhances the androgen receptor-mediated oncogenic transformation and tumor development in the mouse prostate.

Recent genome analysis of human prostate cancers demonstrated that both AR gene amplification and TP53 mutation are among the most frequently observed alterations in advanced prostate cancer. However, the biological role of these dual genetic alterations in prostate tumorigenesis is largely unknown. In addition, there are no biologically relevant models that can be used to assess the molecular mechanisms for these genetic abnormalities. Here, we report a novel mouse model, in which elevated transgenic AR expression and Trp53 deletion occur simultaneously in mouse prostatic epithelium to mimic human prostate cancer cells. These compound mice developed an earlier onset of high-grade prostatic intraepithelial neoplasia and accelerated prostate tumors in comparison with mice harboring only the AR transgene. Histological analysis showed prostatic sarcomatoid and basaloid carcinomas with massive squamous differentiation in the above compound mice. RNA-sequencing analyses identified a robust enrichment of the signature genes for human prostatic basal cell carcinomas in the above prostate tumors. Master regulator analysis revealed SOX2 as a transcriptional regulator in prostatic basal cell tumors. Elevated expression of SOX2 and its downstream target genes were detected in prostatic tumors of the compound mice. Chromatin immunoprecipitation analyses implicate a coregulatory role of AR and SOX2 in the expression of prostatic basal cell signature genes. Our data demonstrate a critical role of SOX2 in prostate tumorigenesis and provide mechanistic insight into prostate tumor aggressiveness and progression mediated by aberrant AR and p53 signaling pathways

Mitogenesis of Vascular Smooth Muscle Cell Stimulated by Platelet-Derived Growth Factor-bb Is Inhibited by Blocking of Intracellular Signaling by Epigallocatechin-3- O

Epigallocatechin gallate (EGCG) is known to exhibit antioxidant, antiproliferative, and antithrombogenic effects and reduce the risk of cardiovascular diseases. Key events in the development of cardiovascular disease are hypertrophy and hyperplasia according to vascular smooth muscle cell proliferation. In this study, we investigated whether EGCG can interfere with PDGF-bb stimulated proliferation, cell cycle distribution, and the gelatinolytic activity of MMP and signal transduction pathways on RAOSMC when it was treated in two different ways—cotreatment with PDGF-bb and pretreatment of EGCG before addition of PDGF-bb. Both cotreated and pretreated EGCG significantly inhibited PDGF-bb induced proliferation, cell cycle progression of the G0/G1 phase, and the gelatinolytic activity of MMP-2/9 on RAOSMC. Also, EGCG blocked PDGF receptor-β (PDGFR-β) phosphorylation on PDGF-bb stimulated RAOSMC under pretreatment with cells as well as cotreatment with PDGF-bb. The downstream signal transduction pathways of PDGFR-β, including p42/44 MAPK, p38 MAPK, and Akt phosphorylation, were also inhibited by EGCG in a pattern similar to PDGFR-β phosphorylation. These findings suggest that EGCG can inhibit PDGF-bb stimulated mitogenesis by indirectly and directly interrupting PDGF-bb signals and blocking the signaling pathway via PDGFR-β phosphorylation. Furthermore, EGCG may be used for treatment and prevention of cardiovascular disease through blocking of PDGF-bb signaling

Cancer Statistics in Korea: Incidence, Mortality and Survival in 2006-2007

Cancer has been the leading cause of death in Korea. Korea is facing a very rapid change and increase in cancer incidence, which draws much attention in public health. This paper overviews the nationwide cancer statistics, including incidence, mortality, and survival rates, and their trends in Korea based on the cancer incidence data from The Korea Central Cancer Registry (KCCR) in year 2006 and 2007. In Korea, there were 153,237 cancer cases and 65,519, cancer deaths observed in 2006, and 161,920 cancer cases and 67,561 cancer deaths in 2007, respectively. The incidence rate for all cancer combined showed an annual increase of 2.8% from 1999 to 2007. Specifically, there was significant increase in the incidence of colorectal, thyroid, female breast, and prostate cancers. The number of cancer deaths has increased over the past two decades, due mostly to population aging, while the age-standardized mortality rates have decreased in both men and women since 2002. Notable improvement has been observed in the 5-yr relative survival rates for most major cancers and for all cancer combined, with the exception of pancreatic cancer. The nationwide cancer statistics in this paper will provide essential data for cancer research and evidence-based health policy in Korea

miR-140-5p suppresses BMP2-mediated osteogenesis in undifferentiated human mesenchymal stem cells

AbstractHuman mesenchymal stem cells (hMSCs) have self-renewal and differentiation capabilities but the regulatory mechanisms of MSC fate determination remain poorly understood. Here, we aimed to identify microRNAs enriched in hMSCs that modulate differentiation commitments. Microarray analysis revealed that miR-140-5p is commonly enriched in undifferentiated hMSCs from various tissue sources. Moreover, bioinformatic analysis and luciferase reporter assay validated that miR-140-5p directly represses bone morphogenic protein 2 (BMP2). Furthermore, blocking miR-140-5p in hMSCs increased the expression of BMP signaling components and critical regulators of osteogenic differentiation. We propose that miR-140-5p functionally inhibits osteogenic lineage commitment in undifferentiated hMSCs

Bacterial Uracil Modulates Drosophila DUOX-Dependent Gut Immunity via Hedgehog-Induced Signaling Endosomes

SummaryGenetic studies in Drosophila have demonstrated that generation of microbicidal reactive oxygen species (ROS) through the NADPH dual oxidase (DUOX) is a first line of defense in the gut epithelia. Bacterial uracil acts as DUOX-activating ligand through poorly understood mechanisms. Here, we show that the Hedgehog (Hh) signaling pathway modulates uracil-induced DUOX activation. Uracil-induced Hh signaling is required for intestinal expression of the calcium-dependent cell adhesion molecule Cadherin 99C (Cad99C) and subsequent Cad99C-dependent formation of endosomes. These endosomes play essential roles in uracil-induced ROS production by acting as signaling platforms for PLCβ/PKC/Ca2+-dependent DUOX activation. Animals with impaired Hh signaling exhibit abolished Cad99C-dependent endosome formation and reduced DUOX activity, resulting in high mortality during enteric infection. Importantly, endosome formation, DUOX activation, and normal host survival are restored by genetic reintroduction of Cad99C into enterocytes, demonstrating the important role for Hh signaling in host resistance to enteric infection

Clinical characteristics and outcomes of COVID-19 in children and adolescents with diabetes in Daegu, South Korea

Purpose Children with comorbidities have a higher risk of severe, coronavirus disease 2019 (COVID-19). This study investigated the clinical features and outcomes of COVID-19 in children and adolescents with diabetes between January and March 2022. Methods We retrospectively reviewed the medical records of 123 children and adolescents (73 with type 1 diabetes and 50 with type 2 diabetes, 59 males and 64 females) aged <18 years who had been diagnosed with diabetes. Data were collected from 7 academic medical centers in Daegu, South Korea. Results Thirty-five children with diabetes were diagnosed with COVID-19 (18 with type 1 and 17 with type 2 diabetes). Eighteen of the 35 children with diabetes and COVID-19 and 50 of the 88 children with diabetes alone received a COVID-19 vaccination. No significant differences were observed between patients with diabetes and COVID-19 and patients with diabetes alone in the type of diabetes diagnosed, sex, age, body mass index, hemoglobin A1c, or vaccination status. All children with diabetes and COVID-19 had mild clinical features and were safely managed in their homes. Fourteen children had a fever of 38℃ or higher that lasted for more than 2 days, 11 of whom were not vaccinated (p=0.004). None experienced post-COVID-19 conditions. Conclusions All children and adolescents with pre-existing diabetes had mild symptoms of COVID-19 due to low disease severity, high vaccination rates, uninterrupted access to medical care, and continuous glucose monitoring. Unvaccinated children with diabetes who experienced COVID-19 presented with higher and more frequent fevers compared to vaccinated children

Biomarkers of thyroid function and autoimmunity for predicting high-risk groups of thyroid cancer: a nested case–control study

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.Abstract Background A remarkable increase in the number of thyroid cancer cases has been reported in recent years; however, the markers to predict high-risk groups have not been fully established. Methods We conducted a case–control study (257 cases and 257 controls) that was nested in the Cancer Screenee Cohort Study between August 2002 and December 2010; the mean follow-up time for this study was 3.1 ± 2.2 years. The levels of total triiodothyronine (TT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), thyroglobulin (Tg), anti-thyroperoxidase antibody (TPOAb), and anti-thyroglobulin antibody (TgAb) were measured using samples with pre-diagnostic status. Logistic regression models were used to examine the association between thyroid function/autoimmunity and thyroid cancer risk. Results When the markers were categorized by the tertile distributions of the control group, the highest tertile of FT4 (OR = 1.73, 95% CI = 1.11 - 2.69) and the middle tertile of TSH (OR = 1.77, 95% CI = 1.14 - 2.74) were associated with an increased risk of thyroid cancer by multivariate analyses. In addition, an elevated risk for thyroid cancer was found in subjects with TPOAb levels above 30 IU/mL (OR = 8.47, 95% CI = 5.39 - 13.33 for 30–60 IU/mL and OR = 4.48, 95% CI = 2.59 - 7.76 for ≥60 IU/mL). Stratified analyses indicated that some of these associations differed by sex, BMI, smoking status, and the duration of follow-up. Conclusions This study demonstrated that the levels of biomarkers of thyroid function/autoimmunity, particularly the presence of TPOAb, might be used as diagnostic markers for predicting thyroid cancer risk. Our findings suggest that careful monitoring of thyroid biomarkers may be helpful for identifying Korean populations at high-risk for thyroid cancer