Das Obstruktive Schlafapnoe-Syndrom als Risikofaktor für Atherosklerose – eine klinische Interventionsstudie

Das obstruktive Schlafapnoe-Syndrom (OSAS) ist als unabhängiger Risikofaktor für die Atherosklerose-Entstehung bekannt. Betroffene haben eine vergleichsweise höhere Intima-Media-Dicke (IMT) als Gesunde. Bei 25 Patienten mit einem neu diagnostizierten OSAS wurde sonographisch die IMT der Karotis-Arterien bestimmt. Nach Einleitung einer Schlafapnoe-Therapie erfolgte nach 6 Monaten die erneute IMT-Messung und der Vergleich mit den prätherapeutischen Werten. In der Gesamtgruppe fand sich unter Therapie eine signifikante Abnahme der IMT (0,70±0,09 mm vs. 0,66±0,08 mm). Die Einteilung des Gesamtkollektivs erfolgte in 2 Gruppen: Probanden mit IMT-Reduktion (64%) unterschieden sich hinsichtlich AHI, Alter, Geschlecht, BMI, Rauchen und Hypercholesterinämie nicht signifikant von Probanden ohne IMT-Reduktion (36%). Tendenziell fanden sich jedoch in der Gruppe mit IMT-Reduktion 21% mehr Hypertoniker. Die OSAS-Therapie hat somit einen sonographisch nachweisbaren anti-atherosklerotischen Effekt

TERT Promoter Mutation Detection in Cell-Free Tumor-Derived DNA in Patients with IDH Wild-Type Glioblastomas: A Pilot Prospective Study

Purpose: We conducted a pilot study to assess the feasibility and the potential implications of detecting TERT promoter (TERTp)–mutant cell-free tumor-derived DNA (tDNA) in the cerebrospinal fluid (CSF) and plasma of glioblastoma patients. Experimental Design: Matched CSF and plasma samples were collected in 60 patients with glial tumors. The CSF collection was obtained during surgery, before any surgical manipulation of the tumor. The extracted tDNA and corresponding tumor DNA samples were analyzed for TERTp and isocitrate dehydrogenase (IDH) hotspot mutations. In addition, the variant allele frequency (VAF) of TERTp mutation in the CSF-tDNA was correlated with tumor features and patients’ outcome. Results: Thirty-eight patients had TERTp-mutant/IDH wild-type glioblastomas. The matched TERTp mutation in the CSF-tDNA was successfully detected with 100% specificity (95% CI, 87.6–100%) and 92.1% sensitivity (95% CI, 78.6–98.3%) (n = 35/38). In contrast, the sensitivity in the plasma-tDNA was far lower [n = 3/38, 7.9% (95% CI, 1.6–21.4%)]. We concordantly observed a longer overall survival of patients with low VAF in the CSF-tDNA when compared with patients with high VAF, irrespective of using the lower quartile VAF [11.45%; 14.0 mo. (95% confidence interval, CI, 10.3–17.6) vs. 8.6 mo. (95% CI, 4.1–13.2), P = 0.035], the lower third VAF [13%; 15.4 mo. (95% CI, 11.6–19.2) vs. 8.3 mo. (95% CI, 2.3–14.4), P = 0.008], or the median VAF [20.3%; 14.0 mo. (95% CI, 9.2–18.7) vs. 8.6 mo. (95% CI, 7.5–9.8), P = 0.062] to dichotomize the patients. Conclusions: This pilot study highlights the value of CSF-tDNA for an accurate and reliable detection of TERTp mutations. Furthermore, our findings suggest that high TERTp mutation VAF levels in the CSF-tDNA may represent a suitable predictor of poor survival in glioblastoma patients. Further studies are needed to complement the findings of our exploratory analysis

Infection of Differentiated Porcine Airway Epithelial Cells by Influenza Virus: Differential Susceptibility to Infection by Porcine and Avian Viruses

BACKGROUND: Swine are important hosts for influenza A viruses playing a crucial role in the epidemiology and interspecies transmission of these viruses. Respiratory epithelial cells are the primary target cells for influenza viruses. METHODOLOGY/PRINCIPAL FINDINGS: To analyze the infection of porcine airway epithelial cells by influenza viruses, we established precision-cut lung slices as a culture system for differentiated respiratory epithelial cells. Both ciliated and mucus-producing cells were found to be susceptible to infection by swine influenza A virus (H3N2 subtype) with high titers of infectious virus released into the supernatant already one day after infection. By comparison, growth of two avian influenza viruses (subtypes H9N2 and H7N7) was delayed by about 24 h. The two avian viruses differed both in the spectrum of susceptible cells and in the efficiency of replication. As the H9N2 virus grew to titers that were only tenfold lower than that of a porcine H3N2 virus this avian virus is an interesting candidate for interspecies transmission. Lectin staining indicated the presence of both α-2,3- and α-2,6-linked sialic acids on airway epithelial cells. However, their distribution did not correlate with pattern of virus infection indicating that staining by plant lectins is not a reliable indicator for the presence of cellular receptors for influenza viruses. CONCLUSIONS/SIGNIFICANCE: Differentiated respiratory epithelial cells significantly differ in their susceptibility to infection by avian influenza viruses. We expect that the newly described precision-cut lung slices from the swine lung are an interesting culture system to analyze the infection of differentiated respiratory epithelial cells by different pathogens (viral, bacterial and parasitic ones) of swine

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Association of long-term exposure to local industry- and traffic-specific particulate matter with arterial blood pressure and incident hypertension

Background: Long-term exposure to fine particulate matter (PM2.5) may lead to increased blood pressure (BP). The role of industry- and traffic-specific PM2.5 remains unclear. Objective: We investigated the associations of residential long-term source-specific PM2.5 exposure with arterial BP and incident hypertension in the population-based Heinz Nixdorf Recall cohort study. Methods: We defined hypertension as systolic BP >= 140 mmHg, or diastolic BP >= 90 mmHg, or current use of BP lowering medication. Long-term concentrations of PM2.5 from all local sources (PM2.5ALL), local industry (PM2.5IND) and traffic (PM2.5TRA) were modeled with a dispersion and chemistry transport model (EURAD-CTM) with a 1 km(2) resolution. We performed a cross-sectional analysis with BP and prevalent hypertension at baseline, using linear and logistic regression, respectively, and a longitudinal analysis with incident hypertension at 5-year follow-up, using Poisson regression with robust variance estimation. We adjusted for age, sex, body mass index, lifestyle, education, and major road proximity. Change in BP (mmHg), odds ratio (OR) and relative risk (RR) for hypertension were calculated per 1 mu g/m(3) of exposure concentration. Results: PM2.5ALL was highly correlated with PM25IND. (Spearman's rho = 0.92) and moderately with PM2.5TRA (rho = 0.42). In adjusted cross-sectional analysis with 4539 participants, we found positive associations of PM2.5ALL with systolic (0.42 [95%-CI: 0.03, 0.801) and diastolic (0.25 [0.04, 0.461] BP. Higher, but less precise estimates were found for PM2.5IND (systolic: 0.55 [-0.05, 1.14]; diastolic: 0.35 [0.03, 0.671) and PM2.5TRA (systolic: 0.88 [-1.55, 3.31]; diastolic: 0.41 [-0.91, 1.731). We found crude positive association of PM2.5TRA with prevalence (OR 1.41 [1.10, 1.80]) and incidence of hypertension (RR 1.38 [1.03,1.85]), attenuating after adjustment (OR 1.19 [0.90, 1.58] and RR 1.28 [0.94, 1.72]). We found no association of PM2.5ALL and PM2.5IND with hypertension. Conclusions: Long-term exposures to all-source and industry-specific PM2.5 were positively related to BP. We could not separate the effects of industry-specific PM2.5 from all-source PM2.5. Estimates with traffic-specific PM2.5 were generally higher but inconclusive. (C) 2016 Published by Elsevier GmbH