A systematic literature review of studies analyzing the effect of sex, age, education, marital status, obesity, and smoking on health transitions

Sex, age, education, marital status, obesity, and smoking have been found to affect health transitions between non-disabled, disabled, and death. Our aim is to review the research literature on this topic and provide structured information, first on the availability of results for each risk factor and transition, and then on detailed study characteristics and disability measures. We use expert recommendations and the electronic databases Medline, PsycINFO, and SOCA. The search is confined to the years 1985-2005, and produced a total of 7,778 articles. Sixty-three articles met the selection criteria regarding study population, longitudinal design, risk factors, transition, and outcome measures.gender, health, mortality, obesity, review, sex, smoking, systematic review, transition

The FtsK-like motor TraB is a DNA-dependent ATPase that forms higher-order assemblies

TraB is an FtsK-like DNA translocase responsible for conjugative plasmid transfer in mycelial Streptomyces Unlike other conjugative systems, which depend on a type IV secretion system, Streptomyces requires only TraB protein to transfer the plasmid as dsDNA. The ?-domain of this protein specifically binds to repeated 8-bp motifs on the plasmid sequence, following a mechanism that is reminiscent of the FtsK/SpoIIIE chromosome segregation system. In this work, we purified and characterized the enzymatic activity of TraB, revealing that it is a DNA-dependent ATPase that is highly stimulated by dsDNA substrates. Interestingly, we found that unlike the SpoIIIE protein, the ?-domain of TraB does not confer sequence-specific ATPase stimulation. We also found that TraB binds G-quadruplex DNA structures with higher affinity than TraB-recognition sequences (TRSs). An EM-based structural analysis revealed that TraB tends to assemble as large complexes comprising four TraB hexamers, which might be a prerequisite for DNA translocation across cell membranes. In summary, our findings shed light on the molecular mechanism used by the DNA-translocating motor TraB, which may be shared by other membrane-associated machineries involved in DNA binding and translocation.Funding: This work was supported by the Spanish Ministerio de Economia y Competitividad (MINECO) grants BFU2016-78521-R (to E.C. and I.A.) and Deutsche Forschungsgemeinschaft SFB766 (to G.M)

Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy:Study protocol of a cluster randomized clinical trial (Multi-PAP project)

This study was funded by the Fondo de Investigaciones Sanitarias ISCIII (Grant Numbers PI15/00276, PI15/00572, PI15/00996), REDISSEC (Project Numbers RD12/0001/0012, RD16/0001/0005), and the European Regional Development Fund ("A way to build Europe").Background: Multimorbidity is associated with negative effects both on people's health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12months, as compared with usual care. Methods/Design: Design:pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65-74years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3months). Sample size: n=400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle. Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes. Trial registration: Clinicaltrials.gov, NCT02866799Publisher PDFPeer reviewe

Minimal information for studies of extracellular vesicles 2018 (MISEV2018):a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

A systematic literature review of studies analyzing the effect of sex, age, education, marital status, obesity, and smoking on health transitions

Sex, age, education, marital status, obesity, and smoking have been found to affect health transitions between non-disabled, disabled, and death. Our aim is to review the research literature on this topic and provide structured information, first on the availability of results for each risk factor and transition, and then on detailed study characteristics and disability measures. We use expert recommendations and the electronic databases Medline, PsycINFO, and SOCA. The search is confined to the years 1985-2005, and produced a total of 7,778 articles. Sixty-three articles met the selection criteria regarding study population, longitudinal design, risk factors, transition, and outcome measures

public | private

Diese Frage nach dem öffentlichen und privaten Raum und dessen Bedeutung mag auf den ersten Blick banal und vielleicht auch unnötig erscheinen. Lässt man sich auf diese Fragestellung allerdings ein, so wird einem schnell bewusst, wie schwierig eine klare Antwort ist - betrachtet man Aspekte, wie rechtliche Besitzverhältnisse, den Nutzungsanspruch bestimmter Personengruppen, die Funktionen hinsichtlich der Gemeinschaft, die Zugänglichkeit usw. Betrachtet man verschiedene Kontexte der römischen Antike, so stellen wir überall fest, dass es diese Dichotomie in der Definition von Räumen kaum gibt, da jeder antike Raum Aspekte des Privaten sowie des Öffentlichen enthält (paper 01). Betrachten wir z.B. Atriumshäuser: Im Gegensatz zu unserem heutigen Wohnverständnis sind diese durchaus als Räume mit besonderer öffentlicher Relevanz zu begreifen, in denen der Hausherr (patronus) seine Bittsteller (clientes) oder noch wichtiger seine Gäste zum Gelage (symposium) eingeladen hat. Andernfalls ist wohl kaum der Ausstattungsluxus zu erklären, der sich in den vor allem aristokratischen Wohnanlagen manifestiert - etwa in den großen Villenanalgen nahe Roms (horti, paper 06), in der Anlage von kleineren Badeanlagen innerhalb eines Wohnhauses (balnea, paper 07) oder eng damit verbunden in der prächtigen Ausgestaltung gar von Latrinen (paper 08). Auch gibt es vor allem an Fourmsanlagen das Phänomen, das Atriumshäuser sukzessiv mit öffentlichen, administrativen oder religiösen Funktionen besetzt oder gar in der Folgebebauung durch entsprechende öffentliche Funktionsbauten, wie den Basiliken, ersetzt wurden und damit wohl keine „privaten“ Wohnhäuser darstellten, sondern „öffentliche“ atria waren (paper 03). Das Forum Romanum stellt in diesem Zusammenhang ein besonders spannendes Areal dar, als wichtigstes öffentliches Zentrum der Stadt und Mittelpunkt des Römischen Reiches. Aber auch hier lassen sich verschiedene, ganz persönliche und private Bedürfnisse der Nutzer*innen, wie die Selbstdarstellung im öffentlichen Kontext, greifen (paper 02). Angrenzend an das Forum Romanum und die Kaiserfora befindet sich die subura, die eben je nach Veränderung in der Ausgestaltung der großen Platzanlagen, aber auch in der unterschiedlichen Wahrnehmung von Räumen je nach Zeitgeist aus den antiken Quellen unterschiedlich zu bewerten ist (paper 05). Ein interessantes Beispiel für den Übergang vom Privaten zum Öffentlichen sind auch für die subura nachzuweisende Altäre für die Laren (lares compitalis), ein Kult, der ursprünglich dezidiert zum Haus gehörte, aber vor allem ab augusteischer Zeit in den öffentlichen Bereich der Straßen transferiert wurde – quasi als Hauskult der öffentlichen Gemeinschaft, eng verbunden mit dem Kaiserhaus, dem patronus des römischen Volkes (paper 04). Dieses Spiel im Changieren der antiken Räume zwischen öffentlich und privat ist auch in seiner Rezeption interessant. Hier zeigen die inszenierten Räume in Antikenfilmen ein eigenes Spiel in der Umsetzung der Räume, wobei neben dem eigentlichen schwierigen Verständnis hinsichtlich der antiken Räume noch Unschärfen durch die eigene Wahrnehmung von Räumen aus den Zeiten, in denen die Filme entstanden sind, hinzukommen (paper 09).Not Reviewe

Pro‐inflammatory immunity supports fibrosis advancement in epidermolysis bullosa: intervention with Ang‐(1‐7)

Abstract Recessive dystrophic epidermolysis bullosa (RDEB), a genetic skin blistering disease, is a paradigmatic condition of tissue fragility‐driven multi‐organ fibrosis. Here, longitudinal analyses of the tissue proteome through the course of naturally developing disease in RDEB mice revealed that increased pro‐inflammatory immunity associates with fibrosis evolution. Mechanistically, this fibrosis is a consequence of altered extracellular matrix organization rather than that of increased abundance of major structural proteins. In a humanized system of disease progression, we targeted inflammatory cell fibroblast communication with Ang‐(1‐7)—an anti‐inflammatory heptapeptide of the renin‐angiotensin system, which reduced the fibrosis‐evoking aptitude of RDEB cells. In vivo, systemic administration of Ang‐(1‐7) efficiently attenuated progression of multi‐organ fibrosis and increased survival of RDEB mice. Collectively, our study shows that selective down‐modulation of pro‐inflammatory immunity may mitigate injury‐induced fibrosis. Furthermore, together with published data, our data highlight molecular diversity among fibrotic conditions. Both findings have direct implications for the design of therapies addressing skin fragility and fibrosis