IgA and Differentiation-associated Transcription Factors in Chronic Otitis Media with Effusion

ObjectivesInadequate antibody responses to pathogens may lead to the recurrence of otitis media with effusion (OME). Although B-cell production by antibodies is controlled by transcription factors, the status of these factors has not been assessed in patients with OME.MethodsExpression of immunoglobulin was measured by enzyme-linked immunosorbent assay. Expression of transcription factors Bcl-6, Blimp-1, Pax-5, and XBP-1 was assessed by RT-PCR in the middle-ear fluid of 29 children with >4 OME episodes in 12 months or >3 episodes in 6 months (the OME-prone group) and in 32 children with <3 OME episodes in 12 months (OME group). The relationship between recurrence of OME and expression levels of immunoglobulins and transcription factors in middle-ear fluid was determined.ResultsThe concentration of IgA in middle-ear fluid was significantly lower in the OME-prone than in the OME group, as was the expression of mRNA encoding the transcription factors Blimp-1 and XBP-1 (P<0.05 each). Expression of mRNA encoding the transcription factors Bcl-6 and Pax-5 was more intense in the OME-prone than in the OME group, but these differences were not significant (P>0.05).ConclusionLower concentrations of IgA, Blimp-1 and XBP-1 in middle ear fluid of patients with OME may be related to OME recurrence and chronicity

Issues in Developing and Evaluating a Culturally Tailored Internet Cancer Support Group

The purpose of this paper is to explore practical issues in developing and implementing a culturally tailored Internet Cancer Support Group for a group of ethnic minority cancer patients—Asian American cancer patients. Throughout the research process of the original study testing the Internet cancer support group, research team made written records of practical issues and plausible rationales for the issues. Weekly group discussion among research team members was conducted, and the discussion records were evaluated and analyzed using a content analysis (with individual words as the unit of analysis). The codes from the analysis process were categorized into idea themes, through which the issues were extracted. The issues included those in: (a) difficulties in using multiple languages; (b) collaboration with the IT department and technical challenges (c) difficulties in recruitment; (d) difficulties in retention; (e) optimal timing; and (f) characteristics of the users. Based on the findings, we suggested researchers to plan a workable translation process, check technical needs in advance, use multiple strategies to recruit and retain research participants, plan the right time for data collection, and consider characteristics of the users in the study design

Internet Recruitment of Asian American Breast Cancer Survivors

The purpose of this paper is to identify practical issues in Internet recruitment of racial/ethnic minorities by analyzing an Internet intervention study conducted with Asian American breast cancer survivors, and to propose directions for recruitment of racial/ethnic minorities for future Internet research. Six practical issues were identified: (a) a relatively fewer number of Internet communities/groups; (b) hindrances in establishing authenticity; (c) difficulties in gaining entrée from the webmasters or website owners of Internet communities/groups; (d) the necessity of racially/ethnically matched research team members; (e) flexibility required in recruitment strategies; and (f) strategies to overcome the low response rate

Curative Effects of Thiacremonone against Acetaminophen-Induced Acute Hepatic Failure via Inhibition of Proinflammatory Cytokines Production and Infiltration of Cytotoxic Immune Cells and Kupffer Cells

High doses of acetaminophen (APAP; N-acetyl-p-aminophenol) cause severe hepatotoxicity after metabolic activation by cytochrome P450 2E1. This study was undertaken to examine the preventive effects of thiacremonone, a compound extracted from garlic, on APAP-induced acute hepatic failure in male C57BL/6J. Mice received with 500 mg/kg APAP after a 7-day pretreatment with thiacremonone (10–50 mg/kg). Thiacremonone inhibited the APAP-induced serum ALT and AST levels in a dose-dependent manner, and markedly reduced the restricted area of necrosis and inflammation by administration of APAP. Thiacremonone also inhibited the APAP-induced depletion of intracellular GSH, induction of nitric oxide, and lipid peroxidation as well as expression of P450 2E1. After APAP injection, the numbers of Kupffer cells, natural killer cells, and cytotoxic T cells were elevated, but the elevated cell numbers in the liver were reduced in thiacremonone pretreated mice. The expression levels of I-309, M-CSF, MIG, MIP-1α, MIP-1β, IL-7, and IL-17 were increased by APAP treatment, which were inhibited in thiacremonone pretreated mice. These data indicate that thiacremonone could be a useful agent for the treatment of drug-induced hepatic failure and that the reduction of cytotoxic immune cells as well as proinflammatory cytokine production may be critical for the prevention of APAP-induced acute liver toxicity

A test of the submentalizing hypothesis : apes' performance in a false belief task inanimate control

Financial support came from Ministry of Education, Culture, Sports, Science and Technology (K-CONNEX to FK), Japan Society for Promotion of Science (KAKENHI 26885040, 16K21108 to FK), JSPS (KAKENHI 26245069, 24000001 to SH), and European Research Council (Synergy grant 609819 SOMICS to JC).Much debate concerns whether any nonhuman animals share with humans the ability to infer others' mental states, such as desires and beliefs. In a recent eye-tracking false-belief task, we showed that great apes correctly anticipated that a human actor would search for a goal object where he had last seen it, even though the apes themselves knew that it was no longer there. In response, Heyes proposed that apes' looking behavior was guided not by social cognitive mechanisms but rather domain-general cueing effects, and suggested the use of inanimate controls to test this alternative submentalizing hypothesis. In the present study, we implemented the suggested inanimate control of our previous false-belief task. Apes attended well to key events but showed markedly fewer anticipatory looks and no significant tendency to look to the correct location. We thus found no evidence that submentalizing was responsible for apes' anticipatory looks in our false-belief task.Publisher PDFPeer reviewe

Outcome of neonatal palliative procedure for pulmonary atresia with ventricular septal defect or tetralogy of Fallot with severe pulmonary stenosis: experience in a single tertiary center

Purpose The present study aimed to evaluate progression and prognosis according to the palliation method used in neonates and early infants aged 3 months or younger who were diagnosed with pulmonary atresia with ventricular septal defect (PA VSD) or tetralogy of Fallot (TOF) with severe pulmonary stenosis (PS) in a single tertiary hospital over a period of 12 years. Methods Twenty with PA VSD and 9 with TOF and severe PS needed initial palliation. Reintervention after initial palliation, complete repair, and progress were reviewed retrospectively. Results Among 29 patients, 14 patients underwent right ventricle to pulmonary artery (RV-PA) connection, 11 palliative BT shunt, 2 central shunt, and 2 ductal stent insertion. Median age at the initial palliation was 13 days (1–98 days). Additional procedure for pulmonary blood flow was required in 5 patients; 4 additional BT shunt operations and 1 RV-PA connection. There were 2 early deaths among patients with RV-PA connection, one from RV failure and the other from severe infection. Finally, 25 patients (86%) had a complete repair. Median age of total correction was 12 months (range, 2–31 months). At last follow-up, 2 patients had required reintervention after total correction; 1 conduit replacement and 1 right ventricular outflow tract (RVOT) patch enlargements. Conclusion For initial palliation of patients with PA VSD or TOF with severe PS, not only shunt operation but also RV-PA connection approach can provide an acceptable outcome. To select the most proper surgical strategy, we recommend thorough evaluation of cardiac anomalies such as RVOT and PA morphologies and consideration of the patient’s condition

Cerebral Infarction as a Complication of Nephrotic Syndrome: A Case Report with a Review of the Literature

Arterial thrombosis is relatively rare compared with venous thrombosis in nephrotic syndrome. However, the assessment of its pathogenesis and risk factors in individual patient with nephrotic syndrome is necessary to allow appropriate prophylactic management because it is a potentially serious problem. Hereby, with review of the literature, we report a case of a 53 yr-old man with cerebral infarction associated with nephrotic syndrome due to focal segmental glomerulosclerosis during the course of treatments with diuretics and steroid. It reveals that the hypercoagulable state in nephrotic syndrome can be associated with cerebral infarction in adults. Prophylactic anticoagulants can be considered to reduce the risk of serious cerebral infarction in nephrotic patients with risk factors such as severe hypoalbuminemia and on diuretics or steroid treatment, even in young patients regardless of types of underlying glomerular diseases

Discovery of Novel Biased Opioid Receptor Ligands through Structure-Based Pharmacophore Virtual Screening and Experiment

G_i‐protein biased agonists with minimal β‐arrestin recruitment have shown opportunities for alternative safe pain treatment to overcome the serious adverse effects of human mu opioid receptor (μ‐OR) agonists. In order to discover novel non‐morphine OR agonists, we applied hierarchical virtual screening of our in‐house database against a pharmacophore based on modeling the active conformation of ORs.We discovered Initial hit compound (4), a novel μ‐OR agonist with pyrazoloisoquinoline scaffold. We applied computational R‐group screening to compound 4 and synthesized 14 derivatives predicted to be best. Of these, the new Gi‐protein biased compound (19) shows EC50 = 179 nM at μ‐OR. This resulting in significant pain‐relief effects for mice at the phase II period in formalin tests. This study provides a new strategy to identify diverse sets of promising compounds that might prove useful for drug developments targeting other G protein‐coupled receptors (GPCRs)