Chronic obstructive pulmonary disease severity and cardiovascular outcomes

Objective: To identify predictors of chronic obstructive pulmonary disease (COPD) severity and assess the relation between COPD severity and risk of cardiovascular outcomes. Study design and setting: A␣cohort of patients with diagnosed and treated COPD was compiled from the Saskatchewan Health longitudinal databases. We used multivariate modeling to identify predictors of hospitalization for COPD as an indicator of COPD severity, and we used the model to characterize patients according to quintiles of COPD severity. These severity levels were used as independent variables in multivariate models of cardiovascular outcomes. Results: Determinants of COPD severity included emphysema, recent nebulizer use, home oxygen services, corticosteroid use, frequent bronchodilator use, pneumonia and prior COPD exacerbation. The 20% of patients with the highest COPD severity were 1.27 (CI: 1.07–1.50) times more likely to have arrhythmia, 1.25 (CI: 1.07–1.46) times more likely to have ischemic heart disease, 1.38 (CI: 1.11–1.71) times more likely to have angina, 2.28 (CI: 1.95–2.66) times more likely to have congestive heart failure, and 1.63 (CI: 1.22–2.16) times more likely to die of cardiovascular causes than the least severe 20% of patients. Conclusions: Patients with more severe COPD, as defined by our model, had higher cardiovascular morbidity and mortality than patients with less severe COPD.     

Untersuchungen über die Hefeflora auf gesunder Haut*

Zusammenfassung: Das Hefevorkommen auf intakter Haut verlangt Beachtung, da die fakulta-tiv pathogenen Hefepilze unter besonderen Bedingungen klinische Bedeutung als Krankheits-erreger erlangen. Durch die genaue mykologische Differenzierung der isolierten Hefestämme, die Ermittlung ihrer Häufigkeit und ihrer speziellen iokalen Verteilung konnten wir die notwen-dige Vergleichsbasis schaffen, die im Fall tatsSchlich entstandener Hefemykosen Aussagen über die pathogene Rolle dieser Pilze ermöglicht. Summary: The occurence of yeasts on healthy skin is of practical importance as some yeasts may become pathogens under special clinical conditions. 651 yeast strains were isolated from 135 persons without skin lesions by taking swabs from 24 different skin regions. 126 strains of the genus Candida and among these only 18 strains of C. albicans were found. The data obtained may serve as a basis for comparison with isolates from yeast mycoses of the skin and thus contribute to our knowledge of the pathogenic role of yeasts.     

Veränderungen im Chromosomensatz heterolog wachsender Tumoren

Zusammenfassung Der Chromosomensatz einer Walker-Carcinom-Linie, welche auf Ratten, Mäusen und Goldhamstern wächst, wurde untersucht. Die Morphologie der Chromosomen und ihre Zahl ist auf allen drei Tierarten in dieser Tumorlinie gleich. Ein auftretendes submetazentrisches Marker-Chromosom mit heterochromatischem Abschnitt findet sich in gleich hohem Prozentsatz in Tumor-zellen aller drei Tierarten.

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Summary The chromosome-sets of a Walker carcinoma line were studied while growing in rats, mice, and gold hamsters. The morphology of the chromosomes and their number for this tumor-line were the same in all three types of animals. A submetacentric marker-chromosome appearing with heterochromatic segments was found in the same high percentage in the tumor cells of all three types of animal.

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Der Deutschen Forschungsgemeinschaft danken wir für die Unterstützung bei Durchführung der Arbeit.     

The where, what and why of the developing renal stroma

In recent years, a great deal has been learnt about the molecular regulation of kidney development. While most research has focused on the molecular regulation of ureteric branching morphogenesis and nephron formation, significant insights into the definition and functions of the renal stroma have emerged. Many molecules expressed in the developing renal stroma are now known to play significant regulatory roles in kidney development. However, the term 'renal stroma' continues to have different meanings to different researchers. This review clarifies this situation and defines the derivation, location and functions of the stroma in the developing metanephros.     

Irreversible inactivation of trypanothione reductase by unsaturated Mannich bases: a divinyl ketone as key intermediate

Trypanothione reductase is a flavoenzyme unique to trypanosomatid parasites. Here we show that unsaturated Mannich bases irreversibly inactivate trypanothione reductase from Trypanosoma cruzi, the causative agent of Chagas' disease. The inhibitory potency of the compounds strongly increased upon storage of the DMSO stock solutions. HPLC, NMR, and mass spectrometry data of potential intermediates revealed a divinyl ketone as the active compound inactivating the enzyme. ESI- and MALDI-TOF mass spectrometry of trypanothione reductase modified by the Mannich base or the divinyl ketone showed specific alkylation of the active site Cys52 by a 5-(2'chlorophenyl)-3-oxo-4-pentenyl substituent. The reaction mechanism and the site of alkylation differ from those in Plasmodium falciparum thioredoxin reductase where the C-terminal redox active dithiol is modified. After deamination, unsaturated Mannich bases are highly reactive in polycondensation with trypanothione. Interaction of these compounds with both trypanothione and trypanothione reductase could account for their potent trypanocidal effect against Trypanosoma brucei.     

Genetics and animal modeling of autism spectrum disorders. New developments

Autism spectrum disorders (ASD) are pervasive developmental disorders with a complex phenotype in respect to communication, verbal development, and social behavior. Manifold molecular genetic analyses point towards a multifactorial genetic predisposition. For the identification of central key mechanisms large consortia have performed linkage analysis, genome-wide association, and copy number variation (CNV) studies, which led to the characterization of risk factors for ASD like CNV and single nucleotide polymorphisms but also single rare mutations. The so far associated genomic regions and candidate genes impact neuronal development especially the establishment of the synaptic cleft, secretion of surface proteins, or dendritic translation. These findings point towards deficits of translation-dependent cell-cell connectivity and synaptic plasticity for ASD. Animal models are relevant to analyze the pathomechanisms of single genetic risk variants at the cellular, tissue-specific, and behavioral levels.     

Electromagnetic evidence of altered visual processing in autism

Individuals with autism spectrum disorder (ASD) demonstrate intact or superior local processing of visual-spatial tasks. We investigated the hypothesis that in a disembedding task, autistic individuals exhibit a more local processing style than controls, which is reflected by altered electromagnetic brain activity in response to embedded stimuli and enhanced activity of early visual areas. Ten autistic and ten matched control participants underwent 151-channel whole-head magnetoencephalography. Participants were presented with 400 embedded or isolated letters (‘S’ or ‘H’) and asked to indicate which of the two letters was shown. Performance was equal in both groups, but event-related magnetic fields differed between groups in an early (100–150 ms) and a later (350–400 ms) time window. In the early time window, autistic individuals differed from control participants in the embedded, but not in the isolated condition, reflecting reduced processing of the irrelevant context in autistic individuals. In the later time window, amplitude differences between the embedded and isolated conditions were measured in control participants only, suggesting that “disembedding” processes were not required in autistic individuals. Source localisation indicated that activity in individuals with ASD peaked in the primary visual cortex in both conditions and time windows indicating an effortless (automatic, bottom-up) local process, whereas activity in controls peaked outside the visual cortex.     

Cognitive behavioral therapy of socially phobic children focusing on cognition: a randomised wait-list control study

Background  

Although literature provides support for cognitive behavioral therapy (CBT) as an efficacious intervention for social phobia, more research is needed to improve treatments for children.