No abstract available.
Hantaan virus* ; RNA* ; RNA, Messenger* ; Trinucleotide Repeats*

Activation of the NLRP3 inflammasome is critical for host defense as well as the progression of inflammatory diseases through the production of the proinflammatory cytokine IL-1β, which is cleaved by active caspase-1. It has been reported that overactivation of the NLRP3 inflammasome contributes to the development and pathology of acne vulgaris. Therefore, inhibiting activation of the NLRP3 inflammasome may provide a new therapeutic strategy for acne vulgaris. In this study, we investigated whether auranofin, an anti-rheumatoid arthritis agent, inhibited NLRP3 inflammasome activation, thereby effectively treating acne vulgaris.Auranofin suppressed NLRP3 inflammasome activation induced by Propionibacterium acnes, reducing the production of IL-1β in primary mouse macrophages and human sebocytes. In a P. acnes-induced acne mouse model, injection of P. acnes into the ears of mice induced acne symptoms such as redness, swelling, and neutrophil infiltration. Topical application of auranofin (0.5 or 1%) to mouse ears significantly reduced the inflammatory symptoms of acne vulgaris induced by P. acnes injection. Topical application of auranofin led to the downregulation of the NLRP3 inflammasome activated by P. acnes in mouse ear skin. These results show that auranofin inhibits the NLRP3 inflammasome, the activation of which is associated with acne symptoms. The results further suggest that topical application of auranofin could be a new therapeutic strategy for treating acne vulgaris by targeting the NLRP3 inflammasome.

OBJECTIVE: Wine has been the focus in the prevention of epithelial ovarian cancer (EOC) development because resveratrol abundant in wine has anti-carcinogenic properties. However, epidemiologic results have been heterogenous in the chemopreventive effect of wine on the development of EOC. Thus, we performed a meta-analysis for comparing EOC risk between wine and never drinkers using previous related studies. METHODS: After extensive search of the literature between January 1986 and December 2008, we analyzed 10 studies (3 cohort and 7 case control studies) with 135,871 women, who included 65,578 of wine and 70,293 of never drinkers. RESULTS: In all studies, there was no significant difference in EOC risk between wine and never drinkers (odds ratio [OR], 1.13; 95% confidence interval [CI], 0.92 to 1.38; random effects). When we performed re-analysis according to the study design, 3 cohort and 7 case control studies showed that there were also no significant differences in EOC risk between wine and never drinkers, respectively (OR, 1.44 and 1.04; 95% CI, 0.74 and 2.82 and 0.88 to 1.22; random effects). In sub-analyses using 2 case-control studies, EOC risk was not different between former and never drinkers (OR, 1.12; 95% CI, 0.87 to 1.44; fixed effect), and between current and former drinkers (OR, 0.74; 95% CI, 0.41 to 1.34; random effects). CONCLUSION: Although resveratrol, abundantly found in wine, is a promising naturally occurring compound with chemopreventive properties on EOC in preclinical studies, this meta-analysis suggests the epidemiologic evidence shows no association between wine drinking and EOC risk.
Case-Control Studies ; Cohort Studies ; Drinking ; Female ; Humans ; Neoplasms, Glandular and Epithelial ; Ovarian Neoplasms ; Stilbenes ; Wine

Spermatogonial stem cells (SSCs) are essential for spermatogenesis throughout the lifespan of the male. However, the rarity of SSCs has raised the need for an efficient selection method, but little is known about culture conditions that stimulate monkey SSC proliferation in vitro. In this study, we report the development of effective enrichment techniques and in vitro culturing of germ cells from pre-pubertal monkey testes. Testis cells were analyzed by fluorescence-activated cell sorting techniques and were transplanted into the testes of nude mice to characterize SSCs. Thy-1-positive cells showed a higher number of colonies than the unselected control after xenotransplantation. Extensive colonization of monkey cells in the mouse testes indicated the presence of highly enriched populations of SSCs in the Thy-1-positive sorted cells. Furthermore, monkey testis cells were enriched by differential plating using extracellular matrix, laminin, and gelatin, and then cultured under various conditions. Isolation of monkey testicular germ cells by differential plating increased germ cell purity by 2.7-fold, following the combinational isolation method using gelatin and laminin. These enriched germ cells actively proliferated under culture conditions involving StemPro medium supplemented with bFGF, GDNF, LIF, and EGF at 37 ℃. These results suggest that the enrichment and in vitro culture method proposed in the present study for harvesting a large number of functionally active monkey SSCs can be applied as the basis for efficient in vitro expansion of human SSCs.
Animals ; Colon ; Epidermal Growth Factor ; Extracellular Matrix ; Flow Cytometry ; Gelatin ; Germ Cells ; Glial Cell Line-Derived Neurotrophic Factor ; Haplorhini* ; Humans ; In Vitro Techniques* ; Laminin ; Male ; Methods ; Mice ; Mice, Nude ; Spermatogenesis ; Stem Cells* ; Testis* ; Transplantation, Heterologous

PURPOSE: Several risk factors for development of reexpansion pulmonary edema (REPE) after drainage of pneumothoraces have been reported, but the association between the method of thoracostomy and the development of REPE is unknown. The aim of this study was to compare the frequency of REPE after treatment of spontaneous pneumothorax with trocar or hemostat assisted closed thoracostomy. MATERIALS AND METHODS: We performed a prospective, observational study including 173 patients with spontaneous pneumothorax who visited the emergency department from January 2007 to December 2008. In 2007, patients were treated with hemostat-assisted drainage, whereas patients in 2008 were treated with trocar-assisted drainage. The main outcome was the development of REPE, determined by computed tomography of the chest 8 hours after closed thoracostomy. Outcomes in both groups were compared using univariate and multivariate analyses. RESULTS: Ninety-two patients were included, 48 (42 males) of which underwent hemostat-assisted drainage and 44 (41 males) underwent trocar-assisted drainage. The groups were similar in mean age (24+/-10 vs. 26+/-14 respectively). The frequencies of REPE after hemostat- and trocar-assisted drainage were 63% (30 patients) and 86% (38 patients) respectively (p=0.009). In multivariate analysis, trocar-assisted drainage was the major contributing factor for developing REPE (odds ratio=5.7, 95% confidence interval, 1.5-21). Age, gender, size of pneumothorax, symptom duration and laboratory results were similar between the groups. CONCLUSION: Closed thoracostomy using a trocar is associated with an increased risk of REPE compared with hemostat-assisted drainage in patients with spontaneous pneumothorax.
Adult ; Female ; Hemostatic Techniques ; Humans ; Male ; Multivariate Analysis ; Pneumothorax/*complications/*surgery ; Prospective Studies ; Pulmonary Edema/*diagnosis/etiology/*surgery ; Risk Factors ; Surgical Instruments ; Thoracostomy/*adverse effects/*methods ; Tomography, X-Ray Computed ; Treatment Outcome ; Young Adult

Lapatinib, a dual inhibitor of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) tyrosine kinases, has shown promising results as a growth inhibitor of HER2-positive cancer cells in vitro. However, similar to other EGFR-targeting drugs, acquired resistance to lapatinib by HER2-positive cancer cells remains a major clinical challenge. To elucidate resistance mechanisms to EGFR/HER2-targeting agents, we performed a systematic quantitative comparison of the phosphoproteome of lapatinib-resistant (LR) human gastric cancer cells (SNU216-LR) versus parental cells (SNU216) using a titanium dioxide (TiO2) phosphopeptide enrichment method and analysis with a Q-Exactive hybrid quadrupole-Orbitrap mass spectrometer. Biological network analysis of differentially expressed phosphoproteins revealed apparent constitutive activation of the MET-axis phosphatidylinositide 3-kinase (PI3K)/alpha-serine/threonine-protein kinase (AKT) and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling pathways in SNU216-LR. Inhibition of the PI3K/AKT and MAPK/ERK signaling pathways in SNU216-LR also leads to cell cycle arrest, confirming the biological network analysis. Lapatinib sensitivity was restored when cells were treated with several molecular targeting agents in combination with lapatinib. Thus, by integrating phosphoproteomic data, protein networks and effects of signaling pathway modulation on cell proliferation, we found that SNU216-LR maintains constitutive activation of the PI3K/AKT and MAPK/ERK pathways in a MET-dependent manner. These findings suggest that pathway activation is a key compensatory intracellular phospho-signaling event that may govern gastric cancer cell resistance to drug treatment.
Antineoplastic Agents/*pharmacology ; Cell Line, Tumor ; Drug Resistance, Neoplasm ; Humans ; *MAP Kinase Signaling System ; Mitogen-Activated Protein Kinase Kinases/metabolism ; Mitogen-Activated Protein Kinases/metabolism ; Phosphatidylinositol 3-Kinases/*metabolism ; Phosphorylation ; Proteomics ; Proto-Oncogene Proteins c-akt/*metabolism ; Proto-Oncogene Proteins c-met/*metabolism ; Quinazolines/*pharmacology

OBJECTIVETo determine the prevalence of a common GJB2 mutation in a big Chinese population of deaf children and the features of its distribution in regions all over the nation and to provide epidemiology data and expertise for genetic testing of deafness in China.

METHODSThe DNA samples of NSHI patients and normal controls were collected from different typical areas of China. The method of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) with ApaI was used to determine the genotype of GJB2 235 site.

RESULTSTotally 16.3% of patients carried at least one 235 delC mutant allele. Among them, 7.8% was homozygous and 8.5% was heterozygous. The prevalence of GJB2 235delC mutation in China was evident, and the significant difference of 235delC mutation frequency was found in sub-population from different areas and different ethnic groups.

CONCLUSIONSBased upon the result of this screening as stated, Chinese NSHI patients appear to have 235delC frequency and the number of GJB2 related deafness was estimated to be huge. The testing of GJB2 235delC mutation would play an important role in genetic diagnosis and screening in China. As high as 15% of patients could be diagnosed as GJB2 caused deafness (bi-allelic mutation) only by means of this simple, fast and economic assay. In addition, patients were negative for 235delC mutation would be candidates for further mutational analysis of GJB2 or other deafness related genes.

Adolescent ; Adult ; Alleles ; Asian Continental Ancestry Group ; genetics ; Child ; Child, Preschool ; China ; epidemiology ; Connexin 26 ; Connexins ; genetics ; Female ; Genotype ; Hearing Loss, Sensorineural ; epidemiology ; genetics ; Heterozygote ; Homozygote ; Humans ; Male ; Point Mutation ; Prevalence ; Young Adult

Purpose: Although advancements in medical treatments have been made, approximately half of patients with intestinal Crohn’s disease (CD) require intestinal resections during their lifetime. It is well-known that the nutritional status of CD patients can impact postoperative morbidity. The objective of this study was to evaluate the clinical significance of prognostic nutritional index (PNI) in patients with intestinal CD who underwent primary bowel resection. Materials and Methods: We retrospectively investigated patients who were diagnosed with CD and underwent intestinal surgery at Severance Hospital between January 2005 and October 2018. The patients were divided into two groups: PNI ≤40 (n=150) and PNI >40 (n=77). We assessed the clinical significance of PNI in terms of the incidence of postoperative infectious complications (PICs) and the postoperative recurrence of CD. Results: The low PNI group had significantly higher rates of infectious complications (32.0% vs. 10.4%, p=0.001) compared to the high PNI group. Multivariable analysis identified low PNI (≤40) and longer operation time (>180 min) as independent risk factors associated with PICs [odds ratio (OR)=2.754, 95% confidence interval (CI)=1.140–6.649, p=0.024; OR=2.986, 95% CI=1.451–6.143, p=0.003]. PICs were significantly associated with surgical recurrence (hazard ratio=2.217, 95% CI=1.064–4.617, p=0.034). Conclusion Preoperative PNI could serve as a predictive factor for PICs in CD patients who undergo intestinal resection. Additionally, PICs are significantly associated with a higher risk of surgical recurrence in CD.

Introduction: The rising prevalence of human immunodeficiency virus (HIV) among people who inject drugs is a major public health issue. This study intends to explore education and demographic correlates of use of condoms among male drug users in Malaysia. Methods: Data were extracted from the Integrated Biological and Behavioral Surveillance Survey 2017. Pearson’s chi-square tests and a logistic regression were used to examine the associations between condom use and education, and demographic factors. Results: Only a small proportion of drug users used condoms (25.7%). Educational backgrounds, age, ethnicity and marital status were associated with condom use. The likelihood of using condoms was lower among less educated drug users (aOR: 0.308–0.339). There was an interaction effect of education and age on condom use (aOR: 0.116–0.308). Chinese (aOR: 3.117) and those of other ethnicities (aOR: 2.934) were more likely to use condoms when compared with Malays. Being married (aOR: 0.291) or divorced/widowed (aOR: 0.346) was associated with reduced odds of using condoms. Conclusion: Education and demographic factors play an important role in influencing the decisions of Malaysian drug users to use condoms. Therefore, HIV-preventive measures targeting drug users could benefit by paying special attention to these factors.

Background: and Purpose The rate of donepezil discontinuation and the underlying reasons for discontinuation in Asian patients with Alzheimer’s disease (AD) are currently unknown. We aimed to determine the treatment discontinuation rates in AD patients who had newly been prescribed donepezil in routine clinical practice in Asia. Methods: This 1-year observational study involved 38 institutions in seven Asian countries, and it evaluated 398 participants aged 50–90 years with a diagnosis of probable AD and on newly prescribed donepezil monotherapy. The primary endpoint was the rate of donepezil discontinuation over 1 year. Secondary endpoints included the reason for discontinuation,treatment duration, changes in cognitive function over the 1-year study period, and compliance as assessed using a clinician rating scale (CRS) and visual analog scale (VAS). Results: Donepezil was discontinued in 83 (20.9%) patients, most commonly due to an adverse event (43.4%). The mean treatment duration was 103.67 days in patients who discontinued. Among patients whose cognitive function was assessed at baseline and 1 year, there were no significant changes in scores on the Mini-Mental State Examination, Montreal Cognitive Assessment, and Trail-Making Test–Black and White scores, whereas the Clinical Dementia Rating score increased significantly (p<0.001). Treatment compliance at 1 year was 96.8% (306/316) on the CRS and 92.6±14.1% (mean±standard deviation) on the VAS. Conclusions In patients on newly prescribed donepezil, the primary reason for discontinuation was an adverse event. Cognitive assessments revealed no significant worsening at 1 year, indicating that continuous donepezil treatment contributes to the maintenance of cognitive function.