Deciphering Adipose Tissue Extracellular Vesicles Protein Cargo and Its Role in Obesity

The extracellular vesicles (EVs) have emerged as key players in metabolic disorders rising as an alternative way of paracrine/endocrine communication. In particular, in relation to adipose tissue (AT) secreted EVs, the current knowledge about its composition and function is still very limited. Nevertheless, those vesicles have been lately suggested as key players in AT communication at local level, and also with other metabolic peripheral and central organs participating in physiological homoeostasis, and also contributing to the metabolic deregulation related to obesity, diabetes, and associated comorbidities. The aim of this review is to summarize the most relevant data around the EVs secreted by adipose tissue, and especially in the context of obesity, focusing in its protein cargo. The description of the most frequent proteins identified in EVs shed by AT and its components, including their changes under pathological status, will give the reader a whole picture about the membrane/antigens, and intracellular proteins known so far, in an attempt to elucidate functional roles, and also suggesting biomarkers and new paths of therapeutic action

Pharmaceutical companies information and antibiotic prescription patterns: A follow-up study in Spanish primary care

OBJECTIVES: To assess the impact of sources of drug information on antibiotic prescribing patterns (quantity and quality) among primary care physicians. METHODS: We conducted a cohort study on primary care physicians who were actively engaged in medical practice in 2010 in a region in north-west Spain (Galicia), fulfilling inclusion criteria (n = 2100). As the independent variable, we took the perceived utility of 6 sources of information on antibiotics, as measured by the validated KAAR-11 questionnaire. As dependent variables, we used: (1) a quality indicator (appropriate quality, defined as any case where 6 of the 12 indicators proposed by the European Surveillance of Antimicrobial Consumption Network [ESAC-Net] were better than the mean values for Spain); and, (2) a quantity indicator (high prescribing), defined as any case where defined daily doses (DDD) per 1 000 inhabitants per day of antibacterials for systemic use were higher than the mean values for Spain. The adjusted odds ratio for a change in the interquartile range (IqOR) for each sources of information on antibiotics was calculated using Generalized Linear Mixed Models. RESULTS: The questionnaire response rate was 68%. Greater perceived utility of pharmaceutical sales representatives increases the risk of having high prescribing (1/IqOR = 2.50 [95%CI: 1.63-3.66]) and reduces the probability of having appropriate quality (1/IqOR = 2.28 [95%CI: 1.77-3.01]). Greater perceived utility of clinical guidelines increases the probability of having appropriate quality (1/IqOR = 1.25 [95%CI: 1.02-1.54]) and reduces the probability of high prescribing (1/IqOR = 1.25 [95%CI: 1.02-1.54]). CONCLUSIONS: Sources of information on antibiotics are an important determinant of the quantity and quality of antibiotic prescribing in primary care. Commercial sources of information influence prescribing negatively, and clinical guidelines are associated with better indicators.Instituto de Salud Carlos IIIThe European Regional Development Fund (ERDF)Mutua Madrileñ

Association of High Serum Levels of Growth Factors with Good Outcome in Ischemic Stroke : a Multicenter Study

Altres ajuts: This project was partially supported by grants from Xunta de Galicia (Consellería Educación: GRC2014/027 and IN607A2018/3), Spanish Research Network on Cerebrovascular Diseases RETICS-INVICTUS PLUS (RD16/0019), and by the European Union FEDER program.The main objective of this research work was to study the association of serum levels of growth factors (GF) and SDF-1α with the functional outcome and reduction of lesion volume in ischemic stroke patients. In this multicenter study, 552 patients with non-lacunar stroke (male, 62.1%; mean age, 68.2 ± 11.4) were included within 24 h from symptom onset. The main outcome variable was good functional outcome (modified Rankin Scale [mRS] ≤ 2) at 12 months. Secondary outcome variable was infarct volume (in mL) after 6 ± 3 months. Serum levels of VEGF, Ang-1, G-CSF, BDNF, and SDF-1α were measured by ELISA at admission, 7 ± 1 days, at 3 ± 1 months, and 12 ± 3 months. Except for BDNF, all GF and SDF-1α serum levels showed a peak value at day 7 and remained elevated during the first 3 months (all p < 0.01). High serum levels at day 7 of VEGF (OR, 19.3), Ang-1 (OR, 14.7), G-CSF (OR, 9.6), and SDF-1α (OR, 28.5) were independently associated with good outcome at 12 months (all p < 0.0001). On the other hand, serum levels of VEGF (B, − 21.4), G-CSF (B, − 14.0), Ang-1 (B, − 13.3), and SDF-1α (B, − 44.6) measured at day 7 were independently associated with lesion volume at 6 months (p < 0.01). In summary, high serum levels of VEGF, Ang-1, G-CSF, and SDF-1α at day 7 and 3 months after ischemic stroke are associated with good functional outcome and smaller residual lesion at 1 year of follow-up

Net Efficacy Adjusted for Risk (NEAR): A Simple Procedure for Measuring Risk:Benefit Balance

BACKGROUND: Although several mathematical models have been proposed to assess the risk:benefit of drugs in one measure, their use in practice has been rather limited. Our objective was to design a simple, easily applicable model. In this respect, measuring the proportion of patients who respond favorably to treatment without being affected by adverse drug reactions (ADR) could be a suitable endpoint. However, remarkably few published clinical trials report the data required to calculate this proportion. As an approach to the problem, we calculated the expected proportion of this type of patients. METHODOLOGY/PRINCIPAL FINDINGS: Theoretically, responders without ADR may be obtained by multiplying the total number of responders by the total number of subjects that did not suffer ADR, and dividing the product by the total number of subjects studied. When two drugs are studied, the same calculation may be repeated for the second drug. Then, by constructing a 2 x 2 table with the expected frequencies of responders with and without ADR, and non-responders with and without ADR, the odds ratio and relative risk with their confidence intervals may be easily calculated and graphically represented on a logarithmic scale. Such measures represent "net efficacy adjusted for risk" (NEAR). We assayed the model with results extracted from several published clinical trials or meta-analyses. On comparing our results with those originally reported by the authors, marked differences were found in some cases, with ADR arising as a relevant factor to balance the clinical benefit obtained. The particular features of the adverse reaction that must be weighed against benefit is discussed in the paper. CONCLUSION: NEAR representing overall risk-benefit may contribute to improving knowledge of drug clinical usefulness. As most published clinical trials tend to overestimate benefits and underestimate toxicity, our measure represents an effort to change this trend

Rationale, design and preliminary results of the GALIPEMIAS study (prevalence and lipid control of familial dyslipidemia in Galicia, northwest Spain)

[Abstract] Aims. There is little information on the familial nature of dyslipidemias in the Spanish population. This knowledge could have potential diagnostic and treatment implications. The objective of the GALIPEMIAS study was to determine the prevalence of familial dyslipidemia in Galicia, as well as determine the degree of lipid control in the participants. Prevalence of atherosclerotic cardiovascular disease (ASCVD) was also estimated. This paper presents the design, methodology and selected preliminary results. Methodology. A cross‐sectional study was performed in the population aged ≥18 years using cluster sampling and then random sampling. A sample of 1000 subjects was calculated and divided into three sequential phases with a specific methodology for each one. Phase I: selection of subjects from the general population and collection of informed consent documents; Phase II: collection of data from the digital clinical history to select subjects with dyslipidemia according to study criteria; Phase III: personal interview, blood analysis, family tree, and definitive diagnosis of dyslipidemia. Prevalence of different diseases and active medication was analysed. Corrected prevalence (to the reference population) of different risk factors and ASCVD was estimated. Results. Phase I participation was 89.5%. We extracted complete information from 93% of the participants (Phase II). According to the study′s own criteria, 56.5% (n = 527) of the participants had some form of dyslipidemia and almost 33.7% of them had familial dyslipidemia with autosomal dominant inherit pattern. The corrected prevalence of ASCVD was 5.1% (95% CI 3.1‐7.2). Conclusions. Dyslipidemia was the most prevalent cardiovascular risk factor in our population with an autosomal dominant inheritance pattern in one out of every three dyslipidemia cases. Approximately, 5.1% of the sample population aged ≥18 has suffered an episode of ACVD

ECAMulticapa: Effectiveness of double-layered compression therapy for healing venous ulcers in primary care: a Study Protocol

Background: Chronic venous insufficiency, in its final stage can cause venous ulcers. Venous ulcers have a prevalence of 0.5 % to 0.8 % in the general population, and increases starting at 60 years of age. This condition often causes increased dependency in affected individuals, as well as a perceived reduced quality of life and family overload. Local Treating chronic venous ulcers has 2 components: topically healing the ulcer and controlling the venous insufficiency. There is evidence that compressive therapy favours the healing process of venous ulcers. The studies we have found suggest that the use of multilayer bandage systems is more effective than the use of bandages with a single component, these are mostly using in Spain. Multilayer compression bandages with 2 layers are equally effective in the healing process of chronic venous ulcers as 4-layer bandages and are better tolerated and preferenced by patients. More studies are needed to specifically compare the 2-layer bandages systems in the settings where these patients are usually treated. Method/design: Randomised, controlled, parallel, multicentre clinical trial, with 12 weeks of follow-up and blind evaluation of the response variable. The objective is to assess the efficacy of multilayer compression bandages (2 layers) compared with crepe bandages, based on the incidence of healed venous ulcers in individuals treated in primary care nursing consultations, at 12 weeks of follow-up. The study will include 216 individuals (108 per branch) with venous ulcers treated in primary care nursing consultations. The primary endpoint is complete healing at 12 weeks of follow-up. The secondary endpoints are the degree of healing (Resvech.2), quality of life (CCVUQ-e), adverse reactions related to the healing process. Prognosis and demographic variables are also recorder. Effectiveness analysis using Kaplan-Meier curves, a log-rank test and a Cox regression analysis. The analysis was performed by intention to treat. Discussion: The study results can contribute to improving the care and quality of life of patients with venous ulcers, decreasing healing times and healthcare expenditure and contributing to the consistent treatment of these lesions. Trial registration: This study has been recorded in the Clinical Trials.gov site with the code NCT02364921. 17 February 2015.This study was funded by PN of I + D + I 2013–2016 and the ISCIII – Subdirección General de Evaluación y Fomento de la Investigación and FEDER funds (PI13/01975). Ministerio de Economia y Competitividad

Wage inequality, segregation by skill and the price of capital in an assignment model

Some pieces of empirical evidence suggest that in the U.S., over the last few decades, (i) wage inequality between-plants has risen much more than wage inequality within-plants and (ii) there has been an increase in the segregation of workers by skill into separate plants. This paper presents a frictionless assignment model in which these two features can be explained simultaneously as the result of the decline in the relative price of capital. Additional implications of the model regarding the skill premium and the dispersion in labor productivity across plants are also consistent with the empirical evidence. [resumen de autor

Anti-tumour necrosis factor discontinuation in inflammatory bowel disease patients in remission: study protocol of a prospective, multicentre, randomized clinical trial

Background: Patients with inflammatory bowel disease who achieve remission with anti-tumour necrosis factor (anti-TNF) drugs may have treatment withdrawn due to safety concerns and cost considerations, but there is a lack of prospective, controlled data investigating this strategy. The primary study aim is to compare the rates of clinical remission at 1?year in patients who discontinue anti-TNF treatment versus those who continue treatment. Methods: This is an ongoing, prospective, double-blind, multicentre, randomized, placebo-controlled study in patients with Crohn?s disease or ulcerative colitis who have achieved clinical remission for ?6?months with an anti-TNF treatment and an immunosuppressant. Patients are being randomized 1:1 to discontinue anti-TNF therapy or continue therapy. Randomization stratifies patients by the type of inflammatory bowel disease and drug (infliximab versus adalimumab) at study inclusion. The primary endpoint of the study is sustained clinical remission at 1?year. Other endpoints include endoscopic and radiological activity, patient-reported outcomes (quality of life, work productivity), safety and predictive factors for relapse. The required sample size is 194 patients. In addition to the main analysis (discontinuation versus continuation), subanalyses will include stratification by type of inflammatory bowel disease, phenotype and previous treatment. Biological samples will be obtained to identify factors predictive of relapse after treatment withdrawal. Results: Enrolment began in 2016, and the study is expected to end in 2020. Conclusions: This study will contribute prospective, controlled data on outcomes and predictors of relapse in patients with inflammatory bowel disease after withdrawal of anti-TNF agents following achievement of clinical remission. Clinical trial reference number: EudraCT 2015-001410-1