The European General Practice Research Network Presents the Translations of Its Comprehensive Definition of Multimorbidity in Family Medicine in Ten European Languages

Background

Multimorbidity, according to the World Health Organization, exists when there are two or more chronic conditions in one patient. This definition seems inaccurate for the holistic approach to Family Medicine (FM) and long-term care. To avoid this pitfall the European General Practitioners Research Network (EGPRN) designed a comprehensive definition of multimorbidity using a systematic literature review.

Objective

To translate that English definition into European languages and to validate the semantic, conceptual and cultural homogeneity of the translations for further research.

Method

Forward translation of the EGPRN’s definition of multimorbidity followed by a Delphi consensus procedure assessment, a backward translation and a cultural check with all teams to ensure the homogeneity of the translations in their national context. Consensus was defined as 70% of the scores being higher than 6. Delphi rounds were repeated in each country until a consensus was reached

Results

229 European medical expert FPs participated in the study. Ten consensual translations of the EGPRN comprehensive definition of multimorbidity were achieved.

Conclusion

A comprehensive definition of multimorbidity is now available in English and ten European languages for further collaborative research in FM and long-term care.     

Low species diversity and high interindividual variability in faeces of preterm infants as revealed by sequences of 16S rRNA genes and PCR-temporal temperature gradient gel electrophoresis profiles

Little information regarding the composition of the gut microbiota in preterm infants is available. The purpose of this study was to investigate the bacterial diversity in faeces of preterm infants, using analysis of randomly cloned 16S rRNA genes and PCR-TTGE (temporal temperature gradient gel electrophoresis) profiles, to determine whether noncultivated bacteria represented an important part of the community. The 288 clones obtained from faecal samples of 16 preterm infants were classified into 25 molecular species. All but one molecular species had a cultivated representative in public databases: molecular tools did not reveal any unexplored diversity. The mean number of molecular species per infant was 3.25, ranging from one to eight. There was a high interindividual variability. The main groups encountered were the Enterobacteriaceae family and the genera Enterococcus, Streptococcus and Staphylococcus. Seven preterm infants were colonized by anaerobes and only four by bifidobacteria. TTGE profiles were composed of one to nine bands (mean value: 4.3). Furthermore, 51 of 59 clones (86%) comigrated with a band of the corresponding faecal sample. This study will form a comparative framework for other studies, e.g. on the faecal microbiota of preterm infants with different pathologies or the impact of diet on colonization.     

Phylogeny of the genus Turris: correlating molecular data with radular anatomy and shell morphology

There are over 10,000 species of venomous marine molluscs, the vast majority of these, which are generally referred to as "turrids", are traditionally assigned to a single family, Turridae (Powell 1966). Here, we provide an initial molecular analysis of the type genus of the family, Turris R?ding, 1798, thought to be among the most well characterized groups in the family. We show that the type genus is not monophyletic. We analyzed specimens conventionally assigned to 9 different Turris species using molecular markers, combined with the shell morphology and radular anatomy whenever feasible. The results suggest that species assigned to the genus Turris, provisionally assigned to two different subgenera are not monophyletic. Five previously described species belong to the subgenus Turris (s.s.) R?ding 1798: Turris babylonia, (Linne, 1758), Turris grandis, (J. E. Gray, 1834), Turris dollyae, (Olivera, 1999), Turris normandavidsoni (Olivera, 1999) and Turris spectabilis (Reeve, 1843). With a change in species designation, Turris assyria (formerly T. babylonia1010) is added to a well-defined clade, which is in turn more closely related to Lophiotoma and Gemmula species than to the other five Turris species. We show that these five species conventionally assigned to Turris do not belong in the same subgenus, and form a clade provisionally designated as AnnulaturrisPowell, 1966: Turris annulata, (Reeve, 1843), Turris undosa, (Lamarck, 1816), Turris cristata, (Vera-Peláez, Vega-Luz, and Lozano-Francisco 2000) Turris cryptorrhaphe (G. B. Sowerby, 1825) and Turris nadaensis (Azuma, 1973). Implications of the molecular phylogenetic results and its correlation with radular morphology are discussed.     

The Activator of Apoptosis Smac-DIABLO Acts as a Tetramer in Solution

Smac-DIABLO in its mature form (20.8 kDa) binds to baculoviral IAP repeat (BIR) domains of inhibitor of apoptosis proteins (IAPs) releasing their inhibitory effects on caspases, thus promoting cell death. Despite its apparent molecular mass (∼100 kDa), Smac-DIABLO was held to be a dimer in solution, simultaneously targeting two distinct BIR domains. We report an extensive biophysical characterization of the protein alone and in complex with the X-linked IAP (XIAP)-BIR2-BIR3 domains. Our data show that Smac-DIABLO adopts a tetrameric assembly in solution and that the tetramer is able to bind two BIR2-BIR3 pairs of domains. Our small-angle x-ray scattering-based tetrameric model of Smac-DIABLO/BIR2-BIR3 highlights some conformational freedom of the complex that may be related to optimization of IAPs binding.     

Probing the role of divalent metal ions in a bacterial psychrophilic metalloprotease: binding studies of an enzyme in the crystalline state by x-ray crystallography

The psychrophilic alkaline metalloprotease (PAP) produced by a Pseudomonas bacterium isolated in Antarctica belongs to the clan of metzincins, for which a zinc ion is essential for catalytic activity. Binding studies in the crystalline state have been performed by X-ray crystallography in order to improve the understanding of the role of the zinc and calcium ions bound to this protease. Cocrystallization and soaking experiments with EDTA in a concentration range from 1 to 85 mM have resulted in five three-dimensional structures with a distinct number of metal ions occupying the ion-binding sites. Evolution of the structural changes observed in the vicinity of each cation-binding site has been studied as a function of the concentration of EDTA, as well as of time, in the presence of the chelator. Among others, we have found that the catalytic zinc ion was the first ion to be chelated, ahead of a weakly bound calcium ion (Ca 700) exclusive to the psychrophilic enzyme. Upon removal of the catalytic zinc ion, the side chains of the active-site residues His-173, His-179 and Tyr-209 shifted approximately 4, 1.0, and 1.6 A, respectively. Our studies confirm and also explain the sensitivity of PAP toward moderate EDTA concentrations and propose distinct roles for the calcium ions. A new crystal form of native PAP validates our previous predictions regarding the adaptation of this enzyme to cold environments as well as the proteolytic domain calcium ion being exclusive for PAP independent of crystallization conditions.     

HETEROZYGOSITY‐FITNESS CORRELATIONS: A TIME FOR REAPPRAISAL

Owing to the remarkable progress of molecular techniques, heterozygosity‐fitness correlations (HFCs) have become a popular tool to study the impact of inbreeding in natural populations. However, their underlying mechanisms are often hotly debated. Here we argue that these “debates” rely on verbal arguments with no basis in existing theory and inappropriate statistical testing, and that it is time to reconcile HFC with its historical and theoretical fundaments. We show that available data are quantitatively and qualitatively consistent with inbreeding‐based theory. HFC can be used to estimate the impact of inbreeding in populations, although such estimates are bound to be imprecise, especially when inbreeding is weak. Contrary to common belief, linkage disequilibrium is not an alternative to inbreeding, but rather comes with some forms of inbreeding, and is not restricted to closely linked loci. Finally, the contribution of local chromosomal effects to HFC, while predicted by inbreeding theory, is expected to be small, and has rarely if ever proven statistically significant using adequate tests. We provide guidelines to safely interpret and quantify HFCs, and present how HFCs can be used to quantify inbreeding load and unravel the structure of natural populations.     

Safety of TNF-blocking agents in rheumatic patients with serology suggesting past hepatitis B state: results from a cohort of 21 patients

Introduction  

Reactivation of hepatitis B virus (HBV) infection in patients with past infection has been described in 5% to 10% of individuals undergoing immunosuppressive therapies. No data are available to date on the outcome of patients treated by tumour necrosis factor-alpha (TNFα) inhibitors for chronic arthritis with a serological pattern of past HBV infection. The aim of our study was to monitor HBV markers in HBV surface antigen (HBsAg)-negative/anti-HBcAb-positive patients treated with a TNFα inhibitor for inflammatory arthritides.     

A new lectin family with structure similarity to actinoporins revealed by the crystal structure of Xerocomus chrysenteron lectin XCL

A newly defined family of fungal lectins displays no significant sequence similarity to any protein in the databases. These proteins, made of about 140 amino acid residues, have sequence identities ranging from 38% to 65% and share binding specificity to N-acetyl galactosamine. One member of this family, the lectin XCL from Xerocomus chrysenteron, induces drastic changes in the actin cytoskeleton after sugar binding at the cell surface and internalization, and has potent insecticidal activity. The crystal structure of XCL to 1.4 A resolution reveals the architecture of this new lectin family. The fold of the protein is not related to any of the several lectin folds documented so far. Unexpectedly, the structure similarity is significant with actinoporins, a family of pore-forming toxins. The specific structural features and sequence signatures in each protein family suggest a potential sugar binding site in XCL and a possible evolutionary relationship between these proteins. Finally, the tetrameric assembly of XCL reveals a complex network of protomer-protomer interfaces and generates a large, hydrated cavity of 1000 A3, which may become accessible to larger solutes after a small conformational change of the protein.     

Synthesis of ruthenium(II) monosubstituted squarates: 1. Procedural considerations

Attempted syntheses of ruthenium(II) monosubstituted squarate complexes in acetonitrile using cis-[RuCl₂(dmso)₄] and anisole-, methoxy-, methyl- and diphenylamino-squarate ligands, respectively, resulted in the formation in each case of the monomer cis, fac-Ru(CH₃CN)Cl₂(dmso)₃ (1) with the ruthenium atom in a distorted octahedral environment. A second crop of crystals harvested from the reaction with the methoxysquarate ligand was identified as the oxalato-bridged dimer [{cis-(CH₃CN)(Cl)(dmso)₂Ru}₂(μ-C₂O₄)] (2). When cis-[RuCl₂(dmso)₄] and methylsquarate were reacted in aqueous solution instead of acetonitrile, the dimer [{fac-(Cl)(dmso)₃Ru}₂(μ-C₂O₄)] (3) was produced. The dimers 2 and 3 are formed from oxidation/ring opening of the methoxy- and methyl-squarate ligands, respectively. Use of the salts of these ligands instead of their non-ionised forms under different reaction conditions, afforded [Na] fac-[RuCl₃(dmso)₃] (4) and [(C₄H₉)₄N]₂[(C₄O₄)(C₄H₂O₄)₂] (7), respectively, which were shown to be products of competing reactions. The information acquired from these failed attempts has provided the basis for the development of a strategy to overcome these problems and lead to a successful synthetic route to ruthenium(II) monosubstituted squarates.