Effects of lactisole on pancreatic islet B-cells electrophysiology

Sucralose mimics the effects of glucose upon several variables of pancreatic islet B-cell metabolism and function, including bioelectrical activity. The present study aimed at investigating whether lactisole, which was recently found to act as an antagonist of the sweet taste receptor TIR3 in pancreatic islet B-cells, also opposes the effects of glucose and/or sucralose upon B-cell electrophysiology. A dual effect of lactisole, both inhibitory and stimulatory, was observed upon the electrical activity of mouse pancreatic islet B-cells. The present findings thus document that agents supposed to act specifically on the TIR3 sweet receptor may either mimic or oppose the effect of glucose upon islet B-cell electrical activity

Adaptive short-term associative conditioning in the pancreatic β-cell

This study associates cholinergic stimulation of the pancreatic β-cell electrical activity with a short-term memory phenomenon. Glucose pulses applied to a basal glucose concentration induce depolarizing waves which are used to estimate the evolution of the β-cell glucose sensitivity. Exposure to carbamoylcholine (carbachol) increases the size of the glucose-induced depolarizing waves. This change appears after carbachol withdrawal and implies a temporal potentiation of sensitivity (TPS) lasting up to one hour. TPS induction requires the simultaneous action of carbachol and glucose. The substitution of glucose with the secretagogues glyceraldehyde or 2-ketoisocaproate mimics glucose-induced TPS, while palmitate does not. TPS is not produced if the membrane is kept hyperpolarized by diazoxide. Glucose can be replaced by tolbutamide, suggesting a role of depolarization and a subsequent increase in intracellular calcium concentration. A role for kinases is suggested because staurosporine prevents TPS induction. Cycloheximide does not impair TPS induction, indicating that de novo protein synthesis is not required. The fact that the two inputs acting simultaneously produce an effect that lasts up to one hour without requiring de novo protein synthesis suggests that TPS constitutes a case of short-term associative conditioning in non-neural tissue. The convergence of basal glucose levels and muscarinic activation happens physiologically during the cephalic phase of digestion, in order to later absorb incoming fuels. Our data reveals that the role of the cephalic phase may be extended, increasing nutrient sensitivity during meals while remaining low between them

Parkinson’s disease and autophagy

It is generally accepted that a correlation between neurodegenerative disease and protein aggregation in the brain exists; however, a causal relationship has not been elucidated. In neurons, failure of autophagy may result in the accumulation of aggregate-prone proteins and subsequent neurodegeneration. Thus, pharmacological induction of autophagy to enhance the clearance of intracytoplasmic aggregate-prone proteins has been considered as a therapeutic strategy to ameliorate pathology in cell and animal models of neurodegenerative disorders. However, autophagy has also been found to be a factor in the onset of these diseases, which raises the question of whether autophagy induction is an effective therapeutic strategy, or, on the contrary, can result in cell death. In this paper, we will first describe the autophagic machinery, and we will consider the literature to discuss the neuroprotective effects of autophagy

Los desafíos del profesorado clínico en la educación médica

Background: There is a unique particularity of clinical teaching in medical education that isbeyond knowledge, skills or teaching methods of each clinician: this is clinical teaching context.This study aimed to analyze the main barriers in clinical teaching in a single medical school in Spain. Methods: This was a descriptive study in which all the clinical teachers (all of them associateprofessors) of a single and novel faculty of medicine were asked to answer an online, anonymousand voluntary questionnaire about aspects of support to clinical work, promotion of clinicalresearch and recognition of their professional careers. The questionnaires were organized andanalyzed into these three main issues.Results: 61 clinical teachers (42%) answered the questionnaire. The main findings that emergedwere: (i) lack of protected time for practical teaching at hospital; (ii) lack of support for clinicalresearch from hospital or faculty; and (iii) lack of recognition of their professional careers.Conclusions: The clinical teaching in medical education is a continuing challenge for busyclinicians. Further studies on this topic are needed.Antecedentes: La enseñanza clínica en la educación médica tiene una particularidad única:el contexto clínico. Este estudio tiene como objetivo analizar las principales barreras de laense˜nanza clínica en una facultad joven de Medicina de Espa˜na.Métodos: Se trata de un estudio transversal descriptivo en el que se solicitó a todos losprofesores clínicos (todos ellos profesores asociados) de una facultad joven de Medicina que res-pondieran a un cuestionario en línea, anónimo y voluntario sobre aspectos de carga asistencial,promoción de la investigación clínica y reconocimiento de sus carreras profesionales.Resultados: Sesenta y un profesores (42%) respondieron al cuestionario. Los principales hallaz-gos que se obtuvieron fueron: 1) la falta de tiempo protegido para la ense˜nanza práctica en lainstitución sanitaria; 2) el escaso apoyo para la investigación clínica por parte de la instituciónsanitaria o de la facultad; y 3) el escaso de reconocimiento de la carrera profesional.Conclusiones: La ense˜nanza clínica en la educación médica es un desafío continuo para elclínico. Son necesarios futuros estudios que analicen estos aspectos de forma más exhaustiva

A Fast 0.5 T Prepolarizer Module for Preclinical Magnetic Resonance Imaging

We present a magnet and high power electronics for Prepolarized Magnetic Resonance Imaging (PMRI) in a home-made, special-purpose preclinical system designed for simultaneous visualization of hard and soft biological tissues. The sensitivity of MRI systems grows with field strength, but so do their costs. PMRI can boost the signal-to-noise ratio (SNR) in affordable low-field scanners by means of a long and strong magnetic pulse. However, this must be rapidly switched off prior to the imaging pulse sequence, in timescales shorter than the spin relaxation (or T1) time of the sample. We have operated our prepolarizer at up to 0.5 T and demonstrated enhanced magnetization, image SNR and tissue contrast with PMRI of tap water, an ex vivo mouse brain and food samples. These have T1 times ranging from hundreds of milli-seconds to single seconds, while the preliminary high-power electronics setup employed in this work can switch off the prepolarization field in tens of milli-seconds. In order to make this system suitable for solid-state matter and hard tissues, which feature T1 times as short as 10 ms, we are developing new electronics which can cut switching times to ~ 300 μs. This does not require changes in the prepolarizer module, opening the door to the first experimental demonstration of PMRI on hard biological tissues

A catalogue of structural and morphological measurements for DES Y1

We present a structural and morphological catalogue for 45 million objects selected from the first year data of the Dark Energy Survey (DES). Single Sersic fits and non-parametric ´ measurements are produced for g, r, and i filters. The parameters from the best-fitting Sersic ´ model (total magnitude, half-light radius, Sersic index, axis ratio, and position angle) are mea- ´ sured with GALFIT; the non-parametric coefficients (concentration, asymmetry, clumpiness, Gini, M20) are provided using the Zurich Estimator of Structural Types (ZEST+). To study the statistical uncertainties, we consider a sample of state-of-the-art image simulations with a realistic distribution in the input parameter space and then process and analyse them as we do with real data: this enables us to quantify the observational biases due to PSF blurring and magnitude effects and correct the measurements as a function of magnitude, galaxy size, Sersic ´ index (concentration for the analysis of the non-parametric measurements) and ellipticity. We present the largest structural catalogue to date: we find that accurate and complete measurements for all the structural parameters are typically obtained for galaxies with SEXTRACTOR MAG AUTO I ≤ 21. Indeed, the parameters in the filters i and r can be overall well recovered up to MAG AUTO ≤ 21.5, corresponding to a fitting completeness of ∼90 per cent below this threshold, for a total of 25 million galaxies. The combination of parametric and non-parametric structural measurements makes this catalogue an important instrument to explore and understand how galaxies form and evolve. The catalogue described in this paper will be publicly released alongside the DES collaboration Y1 cosmology data products at the following URL: https://des.ncsa.illinois.edu/releases

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Rate and duration of hospitalisation for acute pulmonary embolism in the real-world clinical practice of different countries : Analysis from the RIETE registry

publishersversionPeer reviewe

Canagliflozin and Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus and Chronic Kidney Disease in Primary and Secondary Cardiovascular Prevention Groups

Background: Canagliflozin reduces the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, but effects on specific cardiovascular outcomes are uncertain, as are effects in people without previous cardiovascular disease (primary prevention). Methods: In CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation), 4401 participants with type 2 diabetes mellitus and chronic kidney disease were randomly assigned to canagliflozin or placebo on a background of optimized standard of care. Results: Primary prevention participants (n=2181, 49.6%) were younger (61 versus 65 years), were more often female (37% versus 31%), and had shorter duration of diabetes mellitus (15 years versus 16 years) compared with secondary prevention participants (n=2220, 50.4%). Canagliflozin reduced the risk of major cardiovascular events overall (hazard ratio [HR], 0.80 [95% CI, 0.67-0.95]; P=0.01), with consistent reductions in both the primary (HR, 0.68 [95% CI, 0.49-0.94]) and secondary (HR, 0.85 [95% CI, 0.69-1.06]) prevention groups (P for interaction=0.25). Effects were also similar for the components of the composite including cardiovascular death (HR, 0.78 [95% CI, 0.61-1.00]), nonfatal myocardial infarction (HR, 0.81 [95% CI, 0.59-1.10]), and nonfatal stroke (HR, 0.80 [95% CI, 0.56-1.15]). The risk of the primary composite renal outcome and the composite of cardiovascular death or hospitalization for heart failure were also consistently reduced in both the primary and secondary prevention groups (P for interaction >0.5 for each outcome). Conclusions: Canagliflozin significantly reduced major cardiovascular events and kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, including in participants who did not have previous cardiovascular disease