Comorbidity patterns in patients with chronic diseases in general practice

Introduction

Healthcare management is oriented toward single diseases, yet multimorbidity is nevertheless the rule and there is a tendency for certain diseases to occur in clusters. This study sought to identify comorbidity patterns in patients with chronic diseases, by reference to number of comorbidities, age and sex, in a population receiving medical care from 129 general practitioners in Spain, in 2007.

Methods

A cross-sectional study was conducted in a health-area setting of the Madrid Autonomous Region (Comunidad Autónoma), covering a population of 198,670 individuals aged over 14 years. Multiple correspondences were analyzed to identify the clustering patterns of the conditions targeted.

Results

Forty-two percent (95% confidence interval [CI]: 41.8–42.2) of the registered population had at least one chronic condition. In all, 24.5% (95% CI: 24.3–24.6) of the population presented with multimorbidity.In the correspondence analysis, 98.3% of the total information was accounted for by three dimensions. The following four, age- and sex-related comorbidity patterns were identified: pattern B, showing a high comorbidity rate; pattern C, showing a low comorbidity rate; and two patterns, A and D, showing intermediate comorbidity rates.

Conclusions

Four comorbidity patterns could be identified which grouped diseases as follows: one showing diseases with a high comorbidity burden; one showing diseases with a low comorbidity burden; and two showing diseases with an intermediate comorbidity burden.     

Pyrazine-based Syk kinase inhibitors

A series of aminopyrazines as inhibitors of Syk kinase activity and showing inhibition of LAD2 cells degranulation is described. Optimization of the carboxamide motif with aminomethylpiperidines provided high potency inhibiting Syk but low cellular activity. Amides of cis and trans adamantanol showed good inhibitory activity against Syk as well as remarkable activity in LAD2 cells degranulation assay.     

Systematic significance of seed morphology in veronica (plantaginaceae): a phylogenetic perspective

BACKGROUND AND AIMS: A new infrageneric rearrangement for Veronica has been proposed based on the most recent evidence from DNA sequence data, morphological evidence, and biogeographical considerations. Looking for morphological synapomorphies for each monophyletic subgenus has been problematic, due to difficulties arising from widespread homoplasy (mainly parallel evolution). In an attempt to overcome these difficulties, previously underexplored morphological characters are starting to be studied in more depth. METHODS: A molecular phylogenetic hypothesis was used based on sequences of ITS (nuclear ribosomal DNA) and plastid trnL-F regions, as a framework to test the use of seed coat ultrastructure (studied under scanning electron microscope) in the systematics of the genus. A sample of 132 taxa representing ten of the 13 subgenera in Veronica, excluding the species of the southern hemisphere Hebe complex and the exclusively North American subgenus Synthyris, was studied. KEY RESULTS AND CONCLUSIONS: The results demonstrate that, in many cases, the ultrastucture of the testa can be employed to assess relationships of taxa within the genus, and the character provides additional support for molecular trees. Further characters relevant for the classification of Veronica, i.e. base chromosome number, iridoid chemical data, life cycle, inflorescence position, have been taken into consideration in a discussion where an attempt is made to highlight the best traits to characterize each subgenus investigated.     

Male fertility in natural populations of red deer is determined by sperm velocity and the proportion of normal spermatozoa

Male reproductive success is determined by the ability of males to gain sexual access to females and by their ability to fertilize ova. Among polygynous mammals, males differ markedly in their reproductive success, and a great deal of effort has been made to understand how selective forces have shaped traits that enhance male competitiveness both before and after copulation (i.e., sperm competition). However, the possibility that males also may differ in their fertility has been ignored under the assumption that male infertility is rare in natural populations because selection against it is likely to be strong. In the present study, we examined which semen traits correlate with male fertility in natural populations of Iberian red deer (Cervus elaphus hispanicus). We found no trade-offs between semen traits. Our analyses revealed strong associations between sperm production and sperm swimming velocity, sperm motility and proportion of morphologically normal spermatozoa, and sperm viability and acrosome integrity. These last two variables had the lowest coefficients of variation, suggesting that these traits have stabilized at high values and are unlikely to be related to fitness. In a fertility trial, our results show a large degree of variation in male fertility, and differences in fertility were determined mainly by sperm swimming velocity and by the proportion of morphologically normal sperm. We conclude that male fertility varies substantially in natural populations of Iberian red deer and that, when sperm numbers are equal, it is determined mainly by sperm swimming velocity and sperm morphology.     

Transcriptional regulation of matrix metalloproteinase-1 and collagen 1A2 explains the anti-fibrotic effect exerted by proteasome inhibition in human dermal fibroblasts

Introduction  

Extracellular matrix (ECM) turnover is controlled by the synthetic rate of matrix proteins, including type I collagen, and their enzymatic degradation by matrix metalloproteinases (MMPs). Fibrosis is characterized by an unbalanced accumulation of ECM leading to organ dysfunction as observed in systemic sclerosis. We previously reported that proteasome inhibition (PI) in vitro decreases type I collagen and enhances MMP-1 production by human fibroblasts, thus favoring an antifibrotic fibroblast phenotype. These effects were dominant over the pro-fibrotic phenotype induced by transforming growth factor (TGF)-β. Here we investigate the molecular events responsible for the anti-fibrotic phenotype induced in fibroblasts by the proteasome inhibitor bortezomib.