Detailed Molecular Interactions between Respiratory Syncytial Virus Fusion Protein and the TLR4/MD-2 Complex In Silico

Molecular interactions between respiratory syncytial virus (RSV) fusion protein (F protein) and the cellular receptor Toll-like receptor 4 (TLR4) and myeloid differentiation factor-2 (MD-2) protein complex are unknown. Thus, to reveal the detailed molecular interactions between them, in silico analyses were performed using various bioinformatics techniques. The present simulation data showed that the neutralizing antibody (NT-Ab) binding sites in both prefusion and postfusion proteins at sites II and IV were involved in the interactions between them and the TLR4 molecule. Moreover, the binding affinity between postfusion proteins and the TLR4/MD-2 complex was higher than that between prefusion proteins and the TLR4/MD-2 complex. This increased binding affinity due to conformational changes in the F protein may be able to form syncytium in RSV-infected cells. These results may contribute to better understand the infectivity and pathogenicity (syncytium formation) of RSV.     

Multimodal treatment including tandem high‐dose chemotherapy and autologous stem cell transplantation in children with anaplastic ependymomas

In this study, we evaluated the results of multimodal treatment that included tandem HDCT/auto‐SCT in children with anaplastic ependymomas. Fourteen patients with anaplastic ependymomas were enrolled from 2006 to 2014. Six cycles of induction chemotherapy were administered to all patients before they underwent tandem HDCT/auto‐SCT. Patients who were older than 3 years of age were administered RT after two cycles of induction chemotherapy. In patients under 3 years of age, RT was either omitted or delayed until they reached 3 years of age, if the patients experienced CR after tandem HDCT/auto‐SCT. All patients, including two who experienced disease progression during induction treatment, underwent the first HDCT/auto‐SCT, and 13 subsequently underwent the second HDCT/auto‐SCT. One patient died from hepatic VOD during the second HDCT/auto‐SCT; other toxicities occurring during tandem HDCT/auto‐SCT were manageable. Relapses or progression occurred in seven patients, and five of seven of them remain alive till date after salvage treatment, including surgery and RT. The 5‐year overall and event‐free survival rates were 85.1% ± 9.7% and 50.0% ± 13.4%, respectively. These findings suggest that multimodal treatment including tandem HDCT/auto‐SCT could be a feasible option for improving survival in children with anaplastic ependymomas.     

Pharmacological effects of green tea on the gastrointestinal system

Green tea is rich in polyphenolic compounds, with catechins as its major component. Studies have shown that catechins possess diverse pharmacological properties that include anti-oxidative, anti-inflammatory, anti-carcinogenic, anti-arteriosclerotic and anti-bacterial effects. In the gastrointestinal tract, green tea was found to activate intracellular antioxidants, inhibit procarcinogen formation, suppress angiogenesis and cancer cell proliferation. Studies on the preventive effect of green tea in esophageal cancer have produced inconsistent results; however, inverse relationships of tea consumption with cancers of the stomach and colon have been widely reported. Green tea is effective to prevent dental caries and reduce cholesterols and lipids absorption in the gastrointestinal tract, thus benefits subjects with cardiovascular disorders. As tea catechins are well absorbed in the gastrointestinal tract and they interact synergistically in their disease-modifying actions, thus drinking unfractionated green tea is the most simple and beneficial way to prevent gastrointestinal disorders.     

Pelvic Inflammatory Disease in Virgin Women With Tubo-ovarian Abscess: A Single-Center Experience and Literature Review

Study Objective

To evaluate the incidence of pelvic inflammatory disease (PID) in virgin women and investigate the clinical characteristics of the patients.

Effects of antisense oligonucleotide-mediated depletion of tumor necrosis factor (TNF) receptor 1-associated death domain protein on TNF-induced gene expression

Tumor necrosis factor (TNF) receptor 1-associated death domain protein (TRADD) is an adaptor protein known to be involved in the TNF signaling pathway as well as signaling of other members of the TNF receptor superfamily, including DR3, DR6, p75(NTR), and the Epstein-Barr virus latent membrane protein 1. Current knowledge of the function of the adaptor protein has been derived from studies examining its over-expression in either wild-type or mutated forms. In this study, we analyzed the consequences of antisense oligonucleotide (ASO)-mediated depletion of endogenous TRADD on TNF induction of inflammation-related gene products, such as intercellular adhesion molecule-1, and associated kinase signaling pathways in human umbilical vein endothelial cells. A broader perspective of TRADD's role in TNF signaling was indicated by microarray gene expression analysis, where 20 of 24 genes that showed a 5-fold or greater increase in TNF-induced mRNA expression levels displayed a reduction in TNF-induced expression as a consequence of ASO-mediated knockdown of TRADD. Reduced activation of the nuclear factor-kappaB and c-Jun NH(2)-terminal kinase pathways, as measured by IkappaB-alpha protein levels and the extent of c-Jun phosphorylation, was also observed. These results indicate usage of antisense inhibitors of TRADD expression for modulating diseases associated with TRADD-dependent signal transduction pathways.     

Characteristics of Cognitive Function Changes and Related Factors in Individuals With Cognitive Impairment During the Pandemic of COVID-19: A Retrospective Chart Review Study

ObjectiveThis study aimed to explore the characteristics and factors related to changes in cognitive function in vulnerable individuals with cognitive impairment during the coronavirus disease 2019 (COVID-19) pandemic.MethodsAmong patients who visited a local university hospital with subjective cognitive complaints, those who had been tested for cognitive function at least once after the onset of COVID-19 and tested regularly at least three times within the last 5 years were included (1st, the initial screening; 2nd, the test immediately before the COVID-19 pandemic; 3rd, the most recent test after the pandemic). Finally, 108 patients were included in this study. They were divided into groups according to whether the Clinical Dementia Rating (CDR) was maintained/improved and deteriorated. We investigated the characteristics of the changes in cognitive function and related factors during COVID-19.ResultsWhen comparing CDR changes before and after COVID-19, there was no significant difference between the two groups (p=0.317). Alternatively, the main effect of the time when the test was conducted was significant (p<0.001). There was also a significant difference in the interaction between the groups and time. When the effect of the interaction was analyzed, the CDR score of the maintained/improved group significantly decreased before COVID-19 (1st–2nd) (p=0.045). After COVID-19 (2nd–3rd), the CDR score of the deteriorated group was significantly higher than that of the maintained/improved group (p<0.001). Mini-Mental State Examination recall memory and changes in activity during COVID-19 were significantly associated with CDR deterioration.Conclusion Memory dysfunction and decreased activity during the COVID-19 pandemic are strongly related to the deterioration of cognitive impairment.     

Perioperative Concerns and Complaints of Patients Undergoing Total Hip Arthroplasty

BackgroundPreoperative concerns of patients undergoing total hip arthroplasty (THA) and their complaints during the initial postoperative period are not well investigated. We evaluated preoperative concerns of patients and patient-perceived problems during the operation and initial 5 days after the operation.MethodsOne hundred and thirty-two patients, who underwent primary THA at a tertiary referral hospital, were surveyed using a questionnaire and a face-to-face interview 1 day before the operation, operation day, and postoperative days 1, 2, 3, and 4. The severity of pain was assessed daily using a visual analog scale.ResultsThe most common preoperative concern was the severity of pain after the surgery (65.2%), followed by the need of transfusion (34.8%) and postoperative rehabilitation (32.6%). Among 29 patients who could recall the experience during the operation, 12 (41.4%) suffered from shoulder pain on the contralateral side, and 6 (20.7%) answered that hammering sound had been annoying. After returning to the ward, 29 patients (22.0%) suffered from nausea, 8 (6.1%) complained of back pain, and 7 (5.3%) had ipsilateral knee pain. On postoperative day 1, 7 patients (5.3%) had persistent back pain, 8 (6.1%) had headache, and 5 (3.8%) suffered from nausea. On postoperative day 2, nine patients (6.8%) complained of radiating pain due to aggravation of pre-existing spinal stenosis, 7 (5.3%) complained of weakness of the hip flexor due to periarticular injection of ropivacaine during the operation, and 5 (3.8%) had dressing-related skin problem at the wound. On postoperative days 3 and 4, patients had no problem other than hip pain. The mean pain score was the highest (3.1 ± 1.0) on postoperative day 1.ConclusionsThe results of this study might provide information needed to solve problems and improve satisfaction of patients undergoing THA.     

Impacts of Asthma in Patients With Bronchiectasis: Findings From the KMBARC Registry

PurposeAlthough the coexistence of asthma and bronchiectasis is common, the impacts of asthma on bronchiectastic patients (BE) have not been well evaluated because this issue using bronchiectasis cohorts has been investigated in only a few studies.MethodsIn the present study, 598 patients who were prospectively enrolled in the Korean bronchiectasis registry were evaluated. The clinical characteristics between BE with asthma and those without asthma were compared.ResultsAsthma was found in 22.4% of BE. BE with asthma had a higher body mass index (BMI) (P = 0.020), more dyspnea (P < 0.001), larger sputum volume (P = 0.015), and lower forced expiratory volume in 1 second (FEV1) (P < 0.001) than those without asthma. BE with asthma had a higher rate of previous pneumonia (P = 0.017) or measles (P = 0.037) than those without asthma. Regarding treatment, BE with asthma used inhaled corticosteroids, long-acting muscarinic antagonists, and leukotriene receptor antagonists more frequently than those without asthma. Although intergroup differences were not observed in disease severity of bronchiectasis (P = 0.230 for Bronchiectasis Severity Index and P = 0.089 for FACED), the Bronchiectasis Health Questionnaire (BHQ) scores indicating the quality of life, were significantly lower in BE with asthma than in those without asthma (61.6 vs. 64.8, P < 0.001). In a multivariable model adjusting for age, sex, body mass index, forced expiratory volume in 1 second %predicted, sputum volume, modified Medical Research Council dyspnea scale ≥ 2, and the number of involved lobes, asthma was associated with lower BHQ scores (β-coefficient = −2.579, P = 0.014).ConclusionsBE with asthma have more respiratory symptoms, worse lung function, and poorer quality of life than those without asthma. A better understanding of the impacts of asthma in BE will guide appropriate management in this population.