Single nucleotide polymorphism of CD40 in the 5′-untranslated region is associated with ischemic stroke

Objectives

Ischemic stroke is influenced by both environmental and genetic factors. The CD40/CD40L system is related to proinflammatory and prothrombogenic responses, which are involved in the pathophysiology of ischemic stroke. The aim of this study was to evaluate association between the CD40 -1C/T single nucleotide polymorphism (SNP) and ischemic stroke in a Chinese population.

Methods

We conducted a case–control study including 286 ischemic stroke patients and 336 controls. CD40 -1C/T SNP was genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing methods, and evaluated its relevance to ischemic stroke susceptibility.

Results

Significantly increased ischemic stroke risk was found to be associated with the T allele of CD40 -1C/T (OR = 1.273, 95% CI = 1.016–1.594). The frequencies of CT and TT/CT genotypes of CD40 -1C/T in ischemic stroke patients were significantly higher than those of controls, respectively (for CT: OR = 2.350, 95% CI = 1.601–3.449; for TT/CT: OR = 2.148, 95% CI = 1.479–3.119). And, similar results were obtained after adjusting non-matched variables. We found that the frequency of carried T genotypes (TT and TT/CT) was significantly increased in patients with history of stroke compared with patients without (for TT: OR = 6.538, 95%CI = 1.655–25.833; for TT/CT: OR = 3.469, 95%CI = 1.031–11.670), respectively.

Conclusions

The findings suggested that the CD40 -1C/T polymorphism might contribute to the susceptibility to ischemic stroke in the Chinese population, and might be associated with history of previous stroke.     

Multi-drug resistance-1 gene polymorphisms in nephrotic syndrome: Impact on susceptibility and response to steroids

Background

Role of multidrug resistance-1 (MDR-1) gene polymorphisms has not been clarified in nephrotic syndrome (NS). Additionally, researchers studied several genetic polymorphisms to explain their influence on different patients' responses to steroid; however the data were inconsistent. Therefore, we aimed to investigate the association of MDR-1 gene polymorphisms [C1236T, G2677T/A, C3435T] and haplotypes with susceptibility to childhood nephrotic syndrome, and whether they influence steroid response.

Methods

We detected MDR-1 gene polymorphisms using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) in 138 NS patients and 140 age and sex matched healthy children.

Results

The frequencies of MDR1 G2677T/A GT, GA, TT + AA genotypes or T allele, MDR1 C3435T TT genotype, and T allele genotype frequencies were significantly increased in NS group. While no significant differences were observed in distributions of C1236T genotypes or allele between NS patients and healthy children. Moreover, steroid non-responder NS patients had significantly higher frequencies of MDR1 G2677T/A GT, GA, and TT + AA genotypes than steroid responsive NS patients. We observed also that NS patients with age less than 6 years old had increased frequencies of MDR1 G2677T/A GT, GA, TT + AA genotypes or T allele MDR1 C3435T CT, TT genotypes and T allele. Interestingly the frequency of the TGC haplotype of MDR1 was lower in the initial steroid responders than in non-responders NS patients. On the contrary, there were no any association between the MDR1 haplotypes with NS susceptibility and they did not influence renal pathological findings.

Conclusion

Our data suggested that MDR1 C3435T or G2677T/A gene polymorphisms are risk factors of increased susceptibility, earlier onset of NS, and steroid resistance.     

Polymorphisms in the IL-18 and IL-12B genes and their association with the clinical outcome in Croatian patients with Type 1 diabetes

Genetic variants of IL-18 and IL-12B may be important in immunoregulatory abnormalities, observed in the patients with Type 1 diabetes mellitus (T1DM), that contribute to individual differences in response to a treatment. Therefore, we examined the significance of IL-18-137G/C, IL-18-607C/A, and IL-12B A/C polymorphisms in Croatians (187 patients, 236 controls), not only as factors that contribute to susceptibility to T1DM, but also as determinants of the clinical presentation of disease.     

THE EFFECTS OF EXTENDED WORKING HOURS ON HEALTH AND SOCIAL WELL-BEING—A COMPARATIVE ANALYSIS OF FOUR INDEPENDENT SAMPLES

Using structural equation modeling, it can be shown that long weekly working hours and work on weekends, nights, and in shifts have detrimental effects on psychovegetative health. Employees' reported subjective work-life balance also decreases with increasing number of hours worked/week, days worked on weekends, or at nights, and with working shifts. A decrease in work-life balance in turn increases the risk of psychovegetative impairments (PVIs). Thus, long and unusual working hours increase the risk of psychovegetative health impairments both directly and indirectly, moderated by the subjective work-life balance. In fact, the indirect effects of working time on PVIs via the work-life balance seem to be stronger than the direct effects. Results of a cross-validation study of four independent and representative samples from Germany and the European Union (N?>?50,000) indicate high structural stability of these results and thus an increased validity and range for generalization. (Author correspondence: anna.wirtz@gawo-ev.de)     

Working on Sundays–Effects on Safety,Health, and Work-life Balance

Several attributes of the work schedule can increase the risk of occupational injuries and accidents, health impairments, and reduced social participation. Although previous studies mainly focused on the effects of shiftwork and long working hours on employee health and safety, there is little evidence of a potential negative impact of working Sundays on the incidence of occupational accidents, health impairments, and work-life balance. A representative sample of employed workers in 31 member and associated states of the European Union (n?=?23,934) served as the database for a cross-sectional analysis. The sample was collected via face-to-face interviews in the year 2005. The association of the risks of occupational accidents, health impairments, and decreases in work-life balance with working Sundays was calculated using logistic regression models, controlling for potential confounders, such as shiftwork, workload, and demographic characteristics. The results indicated that working one or more Sundays/month was associated with increase both in the risk of reporting one or more health impairments (odds ratio [OR]: 1.17, 95% confidence interval [CI]: 1.06–1.29) and poorer work-life balance (OR: 1.15, 95% CI: 1.02–1.28). These effects remained after controlling for potentially confounding factors, such as other work schedule attributes, intensity of physical and mental workload, and individual characteristics. Furthermore, working Sundays was also related to increased risk of occupational accidents within the last year (OR: 1.34, 95% CI: 1.03–1.73). Controlling again for individual, workload, and working-time characteristics, a significant association with accident risk, however, remained only in work sectors with low a priori risk of occupational accidents (OR: 1.40, 95% CI: 1.02–1.91), although the increased risk could be observed for both medium and high a priori risk sectors working Sundays (without controlling for additional confounders). The results thus indicate that the detrimental effects of working Sundays on safety, health, and social well-being should be taken into account when designing work schedules. The potential hazards to employees' safety, health, and work-life balance, in particular, should be considered in discussions concerning extending work on Sundays in certain sectors, e.g., retail. (Author correspondence: awirtz@hsph.harvard.edu)     

Three-Dimensional Structure of CAP-Gly Domain of Mammalian Dynactin Determined by Magic Angle Spinning NMR Spectroscopy: Conformational Plasticity and Interactions with End-Binding Protein EB1

Microtubules and their associated proteins play important roles in vesicle and organelle transport, cell motility and cell division. Perturbation of these processes by mutation typically gives rise to severe pathological conditions. In our efforts to obtain atomic information on microtubule-associated protein/microtubule interactions with the goal to understand mechanisms that might potentially assist in the development of treatments for these diseases, we have determined the three-dimensional structure of CAP-Gly (cytoskeleton-associated protein, glycine-rich) domain of mammalian dynactin by magic angle spinning NMR spectroscopy. We observe two conformations in the β2 strand encompassing residues T43-V44-A45, residues that are adjacent to the disease-associated mutation, G59S. Upon binding of CAP-Gly to microtubule plus-end tracking protein EB1, the CAP-Gly shifts to a single conformer. We find extensive chemical shift perturbations in several stretches of residues of CAP-Gly upon binding to EB1, from which we define accurately the CAP-Gly/EB1 binding interface. We also observe that the loop regions may exhibit unique flexibility, especially in the GKNDG motif, which participates in the microtubule binding. This study in conjunction with our previous reports suggests that conformational plasticity is an intrinsic property of CAP-Gly likely due to its unusually high loop content and may be required for its biological functions.     

Effects of Supplemental Fructooligosaccharides Plus Mannanoligosaccharides on Immune Function and Ileal and Fecal Microbial Populations in Adult Dogs

The goal of this study was to examine whether supplemental fructooligosaccharides (FOS) plus mannanoligosaccharides (MOS) influenced immune function and ileal and fecal microbial populations of adult dogs. Eight adult dogs surgically fitted with ileal cannulas were used in a crossover design. Dogs were fed 200g of a dry, extruded, kibble diet twice daily. At each feeding, dogs were dosed with either 1g sucrose (placebo) or 2g FOS plus 1g MOS orally via gelatin capsule. Fecal, ileal, and blood samples were collected at the end of each 14-d period to measure microbial populations and immune characteristics. Treatment least squares means were compared using the GLM procedure of SAS. Supplementation of FOS plus MOS increased fecal bifidobacteria and fecal and ileal lactobacilli concentrations. Dogs fed FOS plus MOS also tended to have lower blood neutrophils and greater blood lymphocytes vs placebo. Serum, fecal, and ileal immunoglobulin concentrations were unchanged by treatment. Supplementation of FOS plus MOS beneficially altered indices of gut health by improving ileal and fecal microbial ecology. Supplementation of FOS plus MOS also altered immune function by causing a shift in blood immune cells.     

白癜风患者求医行为的调查研究

目的:本文的目的是研究白癜风患者的求医行为及男女性别之间的差异,分析患者选择医疗机构的原因并指导他们正确就医.方法:我们对210例白癜风患者进行问卷调查分析.访谈问卷内容包括人口统计学特征、白癜风知识、求医行为及原因、疾病的发展及心理状态的调查等.结果:仅14.3％的患者对自身疾病的基本知识回答正确,并且患者主要通过医生获得疾病知识;81.0％的患者首诊时选择公立综合医院,医疗技术水平(占69.9％)是患者在首诊时选择医疗机构的主要考虑方面,50.5％的患者存在多处求医的现象;81 4％的患者存在不同程度的心理压力.结论:白癜风患者普遍存在多处求医及不良求医行为,公立医院是目前白癜风患者的主要流向;白癜风患者的认知程度、心理状态等不容乐观;我们应针对白癜风患者多次求医和乱求医的行为及其原因开展白癜风健康教育,正规医疗机构应通过改善服务质量、提高疗效、加强宣传等促进白癜风患者正确求医.     

某部队男性官兵前列腺炎及其相关因素的调查研究

目的：了解部队男性官兵前列腺炎的发病情况及影响因素调查。方法：采用整群分层,随机抽样,对某高原部队300名男性官兵进行问卷调查,并对官兵的生殖系统、前列腺液等进行相关检查。结果：发现前列腺炎12人,多数为已婚的干部及入伍前有女朋友的战士。约66%官兵了解生殖健康概念及内容,与被调查者的学历、职务、是否来自城市等有关;对性传播疾病的病种及传播途径了解不够的官兵达20%。结论：部队官兵的生殖健康良好,少数有前列腺炎,最好定期进行生殖系统疾病筛查;部队官兵对生殖健康概念及内容了解尚可,但还应加强宣传教育。