Susceptibilities of Campylobacter jejuni isolates from Germany to ciprofloxacin,moxifloxacin, erythromycin,clindamycin, and tetracycline

To elucidate Campylobacter jejuni resistance to antibiotics in Germany, MICs of ciprofloxacin, moxifloxacin, erythromycin, clindamycin, and tetracycline were determined (using agar dilution) for 144 clinical isolates. The data indicate a considerable ciprofloxacin resistance (45.1%) without a clonal relationship of the strains and a greater in vitro activity of moxifloxacin, erythromycin, and clindamycin.     

Effects of self-esteem and stress on self-assessed health: a Swiss study from adolescence to early adulthood

Purpose

A large literature shows important effects of self-esteem and stress on mental and physical health in young adulthood. Negative life events are one type of stressor associated with poor health, but it is less clear whether more neutral stressors are also associated with poor health. This study contributes to the existing literature by investigating the association between different types of stressful life events, self-esteem, and health during the transition from adolescence to early adulthood in Switzerland.

Methods

We draw on the “Transitions from Education to Employment” (TREE) panel study, a nationally representative longitudinal survey of a cohort of Swiss young adults, using logistic regression analysis. The study includes eight waves over a 10-year period, from 2001, average age 16, to 2010, average age 26. Our dependent variable is a dichotomized health self-assessment, and key independent variables include self-esteem and three measures of cumulative significant life events (SLEs): total cumulative SLEs, cumulative negative SLEs, and cumulative neutral SLEs.

Results

Self-esteem had a significant positive impact on health, whereas cumulative SLEs had a significant negative impact. Negative SLEs had a larger negative impact than total SLEs, and neutral SLEs had a smaller impact. Considered individually, negative SLEs were more likely to have a significant negative impact on health.

Conclusions

In addition to their known influence on mental health, stress and self-esteem are important factors influencing individuals’ general health, even in adolescence and young adulthood. While all types of stressors have a negative impact on health, the negative stressors seem to have more prominent effects than neutral stressors.

     

Disease-causing dysfunctions of barttin in Bartter syndrome type IV

Bartter syndrome type IV is an inherited human condition characterized by severe renal salt wasting and sensorineural deafness. The causal gene, BSND, encodes barttin, an accessory subunit of chloride channels located in the kidney and inner ear. Barttin modulates the stability, cell surface localization, and function of ClC-K channels; distinct mutations cause phenotypes of varying severity. For definition of the molecular basis of this diversity, the functional consequences of six disease-causing mutations (R8L, R8W, G10S, Q32X, G47R, and E88X) on ClC-K channel properties were studied by heterologous expression in renal cell lines, electrophysiology, confocal imaging, and biochemical analysis. Three missense mutations (R8L, R8W, and G10S) eliminated the function of ClC-K/barttin channels but did not prevent the insertion of the channels into the surface membrane. Another mutant that produces a mild renal phenotype (G47R) was capable of performing all functions of wild-type barttin but bound to ClC-K channels less effectively. The nonsense mutation E88X affected epithelial sorting, leading to equal amounts of barttin inserting into the basolateral and apical membranes, contrasting with the preferential apical insertion of wild-type barttin. Last, the nonsense mutation Q32X allowed barttin to associate with ClC-K channels but prevented surface membrane insertion and channel activation. These results demonstrate that Bartter syndrome type IV can be caused by various derangements in the function of barttin, likely contributing to the diversity of observed phenotypes.     

Motor development in children with congenital cardiac diseases compared to their healthy peers

Their perceptual and motor experiences determine the physical and motor development of children, and impact also on their emotional, psychosocial, and cognitive development. Our aim, therefore, was to evaluate motor development in children with congenitally malformed hearts compared to their healthy peers. We compared 194 children, with a mean age of 10.0 years, and standard deviation of 2.7 years, representing the entire spectrum of congenital cardiac disease, to a control group of 455 healthy children, having a mean age 9.6 years, with standard deviation of 2.17 years. The bodily coordination test for children was used to examine motor development. Of the children with congenitally malformed hearts, 26.8% showed moderate, and 31.9% had severe disturbances of motor development, compared to 16.5% and 5.5% of the control group, the p-value for these differences being less than 0.001. The mean motor quotient adjusted for age and gender was lower in the children with congenitally malformed hearts than in their healthy peers, at 79.6, with standard deviation of 18.9 as opposed to 96.6, with standard deviation of 15, this difference having a p-value of less than 0.001. Depending on the presence, and/or the degree, of residual sequels, the children with congenitally malformed hearts were divided into two subgroups, with either no or mild residual sequels, or with significant sequels. The mean motor quotient was lower in those with significant residual sequels, at 75, with standard deviation of 19.3, as opposed to 83, with standard deviation of 17.9, the p-value for this difference being less than 0.01. In both subgroups, the mean motor quotient was lower, with a p-value of less than 0.01, than in the control group. Our findings show that children with congenitally malformed hearts have deficits in their motor development, these being found in the presence of no or mild sequels, as well as with significant residual sequels. Parental overprotection may contribute to these findings.     

T cell epitope: Friend or Foe? Immunogenicity of biologics in context

Like vaccines, biologic proteins can be very immunogenic for reasons including route of administration, dose frequency and the underlying antigenicity of the therapeutic protein. Because the impact of immunogenicity can be quite severe, regulatory agencies are developing risk-based guidelines for immunogenicity screening. T cell epitopes are at the root of the immunogenicity issue. Through their presentation to T cells, they activate the process of anti-drug antibody development. Preclinical screening for T cell epitopes can be performed in silico, followed by in vitro and in vivo validation. Importantly, screening for immunogenicity is complicated by the discovery of regulatory T cell epitopes, which suggests that immunogenicity testing must now take regulatory T cells into consideration. In this review, we address the application of computational tools for preclinical immunogenicity assessment, the implication of the discovery of regulatory T cell epitopes, and experimental validation of those assessments.