Acceptance and timeliness of standard vaccination in children with chronic neurological deficits in north-western Switzerland

There are no special recommendations for basic vaccinations in patients with chronic neurological deficits distinct from the nationwide advocated schedule in Switzerland. Reports describing adverse neurological events possibly related to vaccinations have attracted public attention. It is unclear if patients with chronic neurological deficits are more reluctantly vaccinated compared to healthy children. We therefore investigated the acceptance of vaccinations in such patients and healthy controls in a retrospective case-control study. At the University Children's Hospital, Basel, Switzerland we investigated 100 patients with chronic neurological deficits and 200 age-matched healthy controls regarding the issue of vaccination rates and ages. The total number of administered vaccinations against diphtheria, tetanus, pertussis, polio, Haemophilus influenzae type b (Hib), mumps, measles, rubella and hepatitis B were significantly lower in patients compared to healthy controls ( P <0.01 for each of the respective vaccines). Patients had an increased risk to receive the third pertussis, diphtheria, and tetanus vaccinations (relative risks (RR) for late vaccination 1.53, 1.53, and 1.54 respectively, P <0.01 for all comparisons), the second (RR=1.60, P <0.05) and third Hib vaccinations (RR=1.52, P <0.05), and the third polio vaccination (RR=1.43, P <0.05) later than controls. Conclusion:Children with chronic neurological deficits received fewer vaccinations than healthy controls. In addition, patients received vaccinations later than healthy children. Hence, it may be assumed that children with chronic neurological deficits are at an increased risk to acquire preventable infections. Therefore, vaccination should be promoted as part of the consultation during a routine appointment with the specialis

Equilibrium sampling of polychlorinated biphenyls in River Elbe sediments – Linking bioaccumulation in fish to sediment contamination

AbstractEquilibrium sampling can be applied to measure freely dissolved concentrations (cfree) of hydrophobic organic chemicals (HOCs) that are considered effective concentrations for diffusive uptake and partitioning. It can also yield concentrations in lipids at thermodynamic equilibrium with the sediment (clip⇌sed) by multiplying concentrations in the equilibrium sampling polymer with lipid to polymer partition coefficients. We have applied silicone coated glass jars for equilibrium sampling of seven ‘indicator’ polychlorinated biphenyls (PCBs) in sediment samples from ten locations along the River Elbe to measure cfree of PCBs and their clip⇌sed. For three sites, we then related clip⇌sed to lipid-normalized PCB concentrations (cbio,lip) that were determined independently by the German Environmental Specimen Bank in common bream, a fish species living in close contact with the sediment: (1) In all cases, cbio,lip were below clip⇌sed, (2) there was proportionality between the two parameters with high R2 values (0.92–1.00) and (3) the slopes of the linear regressions were very similar between the three stations (0.297; 0.327; 0.390). These results confirm the close link between PCB bioaccumulation and the thermodynamic potential of sediment-associated HOCs for partitioning into lipids. This novel approach gives clearer and more consistent results compared to conventional approaches that are based on total concentrations in sediment and biota-sediment accumulation factors. We propose to apply equilibrium sampling for determining bioavailability and bioaccumulation potential of HOCs, since this technique can provide a thermodynamic basis for the risk assessment and management of contaminated sediments

Redox amplification of apoptosis by caspase-dependent cleavage of glutaredoxin 1 and S-glutathionylation of Fas

Reactive oxygen species (ROS) increase ligation of Fas (CD95), a receptor important for regulation of programmed cell death. Glutathionylation of reactive cysteines represents an oxidative modification that can be reversed by glutaredoxins (Grxs). The goal of this study was to determine whether Fas is redox regulated under physiological conditions. In this study, we demonstrate that stimulation with Fas ligand (FasL) induces S-glutathionylation of Fas at cysteine 294 independently of nicotinamide adenine dinucleotide phosphate reduced oxidase–induced ROS. Instead, Fas is S-glutathionylated after caspase-dependent degradation of Grx1, increasing subsequent caspase activation and apoptosis. Conversely, overexpression of Grx1 attenuates S-glutathionylation of Fas and partially protects against FasL-induced apoptosis. Redox-mediated Fas modification promotes its aggregation and recruitment into lipid rafts and enhances binding of FasL. As a result, death-inducing signaling complex formation is also increased, and subsequent activation of caspase-8 and -3 is augmented. These results define a novel redox-based mechanism to propagate Fas-dependent apoptosis

Detection of pneumonia associated pathogens using a prototype multiplexed pneumonia test in hospitalized patients with severe pneumonia

Severe pneumonia remains an important cause of morbidity and mortality. Polymerase chain reaction (PCR) has been shown to be more sensitive than current standard microbiological methods--particularly in patients with prior antibiotic treatment--and therefore, may improve the accuracy of microbiological diagnosis for hospitalized patients with pneumonia. Conventional detection techniques and multiplex PCR for 14 typical bacterial pneumonia-associated pathogens were performed on respiratory samples collected from adult hospitalized patients enrolled in a prospective multi-center study. Patients were enrolled from March until September 2012. A total of 739 fresh, native samples were eligible for analysis, of which 75 were sputa, 421 aspirates, and 234 bronchial lavages. 276 pathogens were detected by microbiology for which a valid PCR result was generated (positive or negative detection result by Curetis prototype system). Among these, 120 were identified by the prototype assay, 50 pathogens were not detected. Overall performance of the prototype for pathogen identification was 70.6% sensitivity (95% confidence interval (CI) lower bound: 63.3%, upper bound: 76.9%) and 95.2% specificity (95% CI lower bound: 94.6%, upper bound: 95.7%). Based on the study results, device cut-off settings were adjusted for future series production. The overall performance with the settings of the CE series production devices was 78.7% sensitivity (95% CI lower bound: 72.1%) and 96.6% specificity (95% CI lower bound: 96.1%). Time to result was 5.2 hours (median) for the prototype test and 43.5 h for standard-of-care. The Pneumonia Application provides a rapid and moderately sensitive assay for the detection of pneumonia-causing pathogens with minimal hands-on time

Методические указания к выполнению индивидуальных заданий практикума по дисциплине «Энергетический потенциал природных возобновляемых энергоресурсов и эффективность его преобразования в электроэнергию»

В методических указаниях рассмотрены вопросы оценки энергетического потенциала природных возобновляемых энергоресурсов: ветра, солнечного излучения и потоков воды и эффективности их преобразования в электроэнергию. Пособие предназначено для студентов дневного обучения по направлению13.04.02 «Электроэнергетика и электротехника» по профилям магистерской подготовки «Возобновляемые источники энергии» и «Оптимизация развивающихся систем электроснабжения»

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes