Synergistic effect of interleukin 1 alpha on nontypeable Haemophilus influenzae-induced up-regulation of human beta-defensin 2 in middle ear epithelial cells

BACKGROUND: We recently showed that beta-defensins have antimicrobial activity against nontypeable Haemophilus influenzae (NTHi) and that interleukin 1 alpha (IL-1 alpha) up-regulates the transcription of beta-defensin 2 (DEFB4 according to new nomenclature of the Human Genome Organization) in human middle ear epithelial cells via a Src-dependent Raf-MEK1/2-ERK signaling pathway. Based on these observations, we investigated if human middle ear epithelial cells could release IL-1 alpha upon exposure to a lysate of NTHi and if this cytokine could have a synergistic effect on beta-defensin 2 up-regulation by the bacterial components. METHODS: The studies described herein were carried out using epithelial cell lines as well as a murine model of acute otitis media (OM). Human cytokine macroarray analysis was performed to detect the released cytokines in response to NTHi exposure. Real time quantitative PCR was done to compare the induction of IL-1 alpha or beta-defensin 2 mRNAs and to identify the signaling pathways involved. Direct activation of the beta-defensin 2 promoter was monitored using a beta-defensin 2 promoter-Luciferase construct. An IL-1 alpha blocking antibody was used to demonstrate the direct involvement of this cytokine on DEFB4 induction. RESULTS: Middle ear epithelial cells released IL-1 alpha when stimulated by NTHi components and this cytokine acted in an autocrine/paracrine synergistic manner with NTHi to up-regulate beta-defensin 2. This synergistic effect of IL-1 alpha on NTHi-induced beta-defensin 2 up-regulation appeared to be mediated by the p38 MAP kinase pathway. CONCLUSION: We demonstrate that IL-1 alpha is secreted by middle ear epithelial cells upon exposure to NTHi components and that it can synergistically act with certain of these molecules to up-regulate beta-defensin 2 via the p38 MAP kinase pathway

The relationship between genetic variants associated with primary ovarian insufficiency and lipid profile in women recruited from MASHAD cohort study

Background and aim: Primary Ovarian Insufficiency (POI) is defined by the occurrence of menopause before the age of 40 years. It is often associated with cardiovascular disease (CVD). The purpose of this study was to explore the relationship between POI-associated genotypes cardiometabolic disorder risk factors. Methods: One hundred seventeen women with POI and one hundred eighty-three healthy women without POI were recruited in this study. DNA was extracted and analyzed using ASO-PCR or Tetra ARMS-PCR. Lipid profiles were also assessed. Results: Multivariate logistic regression analysis showed that individuals with GG vs. TT genotype of the rs1046089 SNP were more likely to have a higher serum LDL (p = 0.03) compared to the control group. There was also a significant association between low serum HDL and rs2303369 and rs4806660 SNP genotypes in the POI group. In the POI group, the percentage of those with high total cholesterol was lower in those with a CC genotype compared to those with a TT genotype (p = 0.03). Conclusion: Some SNPs reported to be associated with POI appear to be independently associated with dyslipidemia. These results may be helpful to identify subjects with POI who may be susceptible to CVD

Symptom and Age Homophilies in SARS-CoV-2 Transmission Networks during the Early Phase of the Pandemic in Japan

Kanagawa and Hokkaido were affected by COVID-19 in the early stage of the pandemic. Japan’s initial response included contact tracing and PCR analysis on anyone who was suspected of having been exposed to SARS-CoV-2. In this retrospective study, we analyzed publicly available COVID-19 registry data from Kanagawa and Hokkaido (n = 4392). Exponential random graph model (ERGM) network analysis was performed to examine demographic and symptomological homophilies. Age, symptomatic, and asymptomatic status homophilies were seen in both prefectures. Symptom homophilies suggest that nuanced genetic differences in the virus may affect its epithelial cell type range and can result in the diversity of symptoms seen in individuals infected by SARS-CoV-2. Environmental variables such as temperature and humidity may also play a role in the overall pathogenesis of the virus. A higher level of asymptomatic transmission was observed in Kanagawa. Moreover, patients who contracted the virus through secondary or tertiary contacts were shown to be asymptomatic more frequently than those who contracted it from primary cases. Additionally, most of the transmissions stopped at the primary and secondary levels. As expected, significant viral transmission was seen in healthcare settings

A research on ways to get rid of usury with an emphasis on sale of the object

Usury is one of the most important issues that has plagued various human societies since ancient times and has always caused significant economic and social harm to members of society. Accordingly, in the religion of Islam, many texts have ruled that usury is forbidden. However, some Muslim jurists and thinkers have included a chapter in their works entitled "The Trick of Usury" in which they have introduced methods through which transactions are made that appear to be similar to non-usury transactions. They have usury and accordingly, they are not subject to the ruling on the sanctity of usury. The most important question in this regard is the ruling on using the trick of usury. There has been disagreement among jurists about the ruling on methods of escaping the usury deal, and some, citing the conflict between the use of these methods and the philosophy of the sanctity of usury, believe that this action is illegitimate, and on the other hand, some claim based on the content of certain narrations. They have said that cheating usury is out of the sanctity of usury specifically or professionally. According to research, not only is the use of usury tricks free of problems, but also the sale of object can be used as a way to avoid committing usury transactions

Students, View Points on Internship Community Medicine Course in Tehran Medical Universities

Introduction: Community-Based Medical Education (CBE) is considered as a new educational approach in the school of medicine. This study was designed to determine the quality of education during the internship in community medicine course in medical universities in Tehran. Methods: This is a descriptive cross-sectional study conducted on community medicine internship in medical schools of Tehran during 2008-2009. A nonrandom sample of 180 interns was selected by convenience. The data, collected by a researcher made questionnaire whose validity and reliability had been confirmed, were analyzed by Ҳ2, Mann-Whitney and Spearman coefficient tests. Results: Over 75% of interns were satisfied with the course planning, the applied content of the workshop, the presence of faculty members and their responsiveness to the students’ questions. In addition, 78% the students were satisfied with teaching on health care system. There was a significant correlation between students, satisfaction with internship and the university they were studying in (p<0.002). Conclusion: It seems that medical schools in Tehran follow the educational out lines well, and community medicine interns are relatively satisfied with the course