Genotype-Phenotype Associations of the CD-Associated Single Nucleotide Polymorphism within the Gene Locus Encoding Protein Tyrosine Phosphatase Non-Receptor Type 22 in Patients of the Swiss IBD Cohort.

Protein tyrosine phosphatase non-receptor type 22 (PTPN22) plays an important role in immune cell function and intestinal homeostasis. The single nucleotide polymorphism (SNP) rs2476601 within the PTPN22 gene locus results in aberrant function of PTPN22 protein and protects from Crohn's disease (CD). Here, we investigated associations of PTPN22 SNP rs2476601 in inflammatory bowel disease (IBD) patients in the Swiss IBD Cohort Study (SIBDCS). 2'028 SIBDCS patients (1173 CD and 855 ulcerative colitis (UC) patients) were included. The clinical characteristics were analysed for an association with the presence of the PTPN22 SNP rs2476601 genotypes 'homozygous variant' (AA), 'heterozygous' (GA) and 'homozygous wild-type' (GG). 13 patients (0.6%) were homozygous variant (AA) for the PTPN22 polymorphism, 269 (13.3%) heterozygous variant (GA) and 1'746 (86.1%) homozygous wild-type (GG). In CD, AA and GA genotypes were associated with less use of steroids and antibiotics, and reduced prevalence of vitamin D and calcium deficiency. In UC the AA and GA genotype was associated with increased use of azathioprine and anti-TNF antibodies, but significantly less patients with the PTPN22 variant featured malabsorption syndrome (p = 0.026). Our study for the first time addressed how presence of SNP rs2476601 within the PTPN22 gene affects clinical characteristics in IBD-patients. Several factors that correlate with more severe disease were found to be less common in CD patients carrying the A-allele, pointing towards a protective role for this variant in affected CD patients. In UC patients however, we found the opposite trend, suggesting a disease-promoting effect of the A-allele

Compact silicon-based attenuated total reflection (ATR) sensor module for liquid analysis

Infrared attenuated total reflection (ATR) spectroscopy is a common laboratory technique for the analysis of highly absorbing liquids and solids, and a variety of ATR accessories for laboratory FTIR spectrometers are available. However, ATR spectroscopy is rarely found in industrial processes, where compact, robust, and cost-effective sensors for continuous operation are required. Here, narrowband photometers are more appropriate than FTIR instruments. We show the concept and implementation of a compact Si-based ATR module with a four-channel microelectromechanical systems (MEMS) detector. Measurements of liquid mixtures demonstrate the suitability for applications in the chemical industry. Apart from sapphire (for wavelengths below 5 µm) and diamond (extending to the far-infrared region), most materials for ATR elements do not have either high enough infrared transmission or sufficient mechanical and chemical stability to be exposed to process fluids, abrasive components, or aggressive cleaning agents. However, using diamond coatings on Si improves the stability of the sensor surface. In addition, by proper choice of incidence angle and coating thickness, an enhancement of the ATR absorbance is theoretically expected and demonstrated by first experiments using a compact sensor module with a diamond-coated Si ATR element.</p

Neuropsychological effects of chronic low-dose exposure to polychlorinated biphenyls (PCBs): A cross-sectional study

BACKGROUND: Exposure to indoor air of private or public buildings contaminated with polychlorinated biphenyls (PCBs) has raised health concerns in long-term users. This exploratory neuropsychological group study investigated the potential adverse effects of chronic low-dose exposure to specific air-borne low chlorinated PCBs on well-being and behavioral measures in adult humans. METHODS: Thirty employees exposed to indoor air contaminated with PCBs from elastic sealants in a school building were compared to 30 non-exposed controls matched for education and age, controlling for gender (age range 37–61 years). PCB exposure was verified by external exposure data and biological monitoring (PCB 28, 101, 138, 153, 180). Subjective complaints, learning and memory, executive function, and visual-spatial function was assessed by standardized neuropsychological testing. Since exposure status depended on the use of contaminated rooms, an objectively exposed subgroup (N = 16; PCB 28 = 0.20 μg/l; weighted exposure duration 17.9 ± 7 years) was identified and compared with 16 paired controls. RESULTS: Blood analyses indicated a moderate exposure effect size (d) relative to expected background exposure for total PCB (4.45 ± 2.44 μg/l; d = 0.4). A significant exposure effect was found for the low chlorinated PCBs 28 (0.28 ± 0.25 μg/l; d = 1.5) and 101 (0.07 ± 0.09 μg/l; d = 0.7). Although no neuropsychological effects exceeded the adjusted significance level, estimation statistics showed elevated effect sizes for several variables. The objectively exposed subgroup showed a trend towards increased subjective attentional and emotional complaints (tiredness and slowing of practical activities, emotional state) as well as attenuated attentional performance (response shifting and alertness in a cued reaction task). CONCLUSION: Chronic inhalation of low chlorinated PCBs that involved elevated blood levels was associated with a subtle attenuation of emotional well-being and attentional function. Extended research is needed to replicate the potential long-term low PCB effects in a larger sample

Somatic mosaicism and common genetic variation contribute to the risk of very-early-onset inflammatory bowel disease

Abstract: Very-early-onset inflammatory bowel disease (VEO-IBD) is a heterogeneous phenotype associated with a spectrum of rare Mendelian disorders. Here, we perform whole-exome-sequencing and genome-wide genotyping in 145 patients (median age-at-diagnosis of 3.5 years), in whom no Mendelian disorders were clinically suspected. In five patients we detect a primary immunodeficiency or enteropathy, with clinical consequences (XIAP, CYBA, SH2D1A, PCSK1). We also present a case study of a VEO-IBD patient with a mosaic de novo, pathogenic allele in CYBB. The mutation is present in ~70% of phagocytes and sufficient to result in defective bacterial handling but not life-threatening infections. Finally, we show that VEO-IBD patients have, on average, higher IBD polygenic risk scores than population controls (99 patients and 18,780 controls; P < 4 × 10−10), and replicate this finding in an independent cohort of VEO-IBD cases and controls (117 patients and 2,603 controls; P < 5 × 10−10). This discovery indicates that a polygenic component operates in VEO-IBD pathogenesis

Analyse des Rechtsrahmens für den Einsatz von On-demand Fahrzeugen im ÖV

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