Unified mechanism of local drivers in a percolation model of atrial fibrillation

The mechanisms of atrial fibrillation (AF) are poorly understood, resulting in disappointing success rates of ablative treatment. Different mechanisms defined largely by different atrial activation patterns have been proposed and, arguably, this dispute has slowed the progress of AF research. Recent clinical evidence suggests a unifying mechanism of local drivers based on sustained re-entrant circuits in the complex atrial architecture. Here, we present a percolation inspired computational model showing spontaneous emergence of AF that strongly supports, and gives a theoretical explanation for, the clinically observed diversity of activation. We show that the difference in surface activation patterns is a direct consequence of the thickness of the discrete network of heart muscle cells through which electrical signals percolate to reach the imaged surface. The model naturally follows the clinical spectrum of AF spanning sinus rhythm, paroxysmal and persistent AF as the decoupling of myocardial cells results in the lattice approaching the percolation threshold. This allows the model to make the novel prediction that for paroxysmal AF, re-entrant circuits emerge near the endocardium, but in persistent AF they emerge deeper in the bulk of the atrial wall. If experimentally verified, this may go towards explaining the lowering ablation success rate as AF becomes more persistent

Isolamento do vírus Influenza A em pulmões de suínos.

Projeto/Plano de Ação: 02.11.01.006

Fertilidad, desarrollo embrionario y prolificidad de conejas nulíparas alimentadas con piensos enriquecidos en ácidos grasos poliinsaturados n-3

One hundred and five nulliparous rabbit does were fed ad libitum one month before and during pregnancy with two isofibrous, isoenergetic and isoproteic diets supplemented with two different fat sources: 0.75% lard for control diet (C group: n=53) or 1.5% of a supplement (Optomega-50; Optivite International Ltd., España) containing a 50% of ether extract and 38% of n-3 polyunsaturated fatty acids (PUFA) for experimental diet (group P n-3; n=52). Fertility after artificial insemination and induction of ovulation with 20 μg of Gonadorelina (Inducel-GnRH, Ovejero) at 4.5 months of age was assessed. At parturition, pregnancy length and prolificacy (number and weight of born alive and number of stillborn) were observed. A total of 8 pregnant does from each experimental group were chosen at random to study embryo and placenta dimensions by means of ultrasonography at 8, 15 and 22 days of pregnancy. PUFA n-3 supplementation did not affect any productive results due the success on reproductive features of nulliparous does which are difficult to improve. Neither, any differences in ultrasonographic meausrements were obtained; nevertheless we have defined useful physiological parameters of rabbit embryo and placenta to future studies in this specie.Un total de 105 conejas nulíparas se alimentaron ad libitum un mes antes y durante su primera gestación con dos piensos isofibrosos, isoenergéticos e isoproteicos suplementados con dos fuentes de grasa diferentes: 0,75% de manteca para la dieta control (grupo C; n=53) ó 1,5% de un suplemento (Optomega-50; Optivite International Ltd., España) que contenía un 50% de extracto etéreo y 38% de ácidos grasos poli-insaturados (AG n-3) para la dieta experimental (grupo P; n=52). A los 4,5 meses de edad se determinó la fertilidad después de ser inseminadas artificialmente y tratadas con 20 μg de Gonadorelina (Inducel-GnRH, Ovejero) para inducirles la ovulación. Al parto se determinó la duración de la gestación, el número y peso de los gazapos nacidos vivos y muertos. Se escogieron 16 conejas al azar, 8 de cada grupo, y se realizaron ecografías a los 8, 15 y 22 días de gestación en las que se determinó las dimensiones del embrión y de los anejos fetales. La suplementación con AG n-3 no afectó a los resultados productivos determinados ya que se trata de parámetros que en nulíparas son difíciles de mejorar y suelen ser altos. Tampoco se observaron diferencias en las determinaciones ecográficas pero se han podido definir medidas fisiológicas de los fetos y anejos placentarios de gran utilidad para futuros estudios en esta especie

In Vitro Synergism of Colistin and N-acetylcysteine against Stenotrophomonas maltophilia

Stenotrophomonas maltophilia is an emerging global opportunistic pathogen, responsible for a wide range of human infections, including respiratory tract infections. Intrinsic multidrug resistance and propensity to form biofilms make S. maltophilia infections recalcitrant to treatment. Colistin is among the second-line options in case of difficult-to-treat S. maltophilia infections, with the advantage of being also administrable by nebulization. We investigated the potential synergism of colistin in combination with N-acetylcysteine (NAC) (a mucolytic agent with antioxidant and anti-inflammatory properties) against S. maltophilia grown in planktonic phase and biofilm. Eighteen S. maltophilia clinical isolates (comprising three isolates from cystic fibrosis (CF) and two trimethoprim-sulfamethoxazole (SXT)-resistant strains) were included. Checkerboard assays showed a synergism of colistin/NAC combinations against the strains with colistin Minimum Inhibitory Concentration (MIC) >2 \ub5g/mL (n = 13), suggesting that NAC could antagonize the mechanisms involved in colistin resistance. Nonetheless, time-kill assays revealed that NAC might potentiate colistin activity also in case of lower colistin MICs. A dose-dependent potentiation of colistin activity by NAC was also clearly observed against S. maltophilia biofilms, also at sub-MIC concentrations. Colistin/NAC combinations, at concentrations likely achievable by topical administration, might represent a valid option for the treatment of S. maltophilia respiratory infections and should be examined further

Effects of Aflatoxin B1 and Fumonisin B1 on the Viability and Induction of Apoptosis in Rat Primary Hepatocytes

The present study evaluated the effect of aflatoxin B1 (AFB1) and fumonisin B1 (FB1) either alone, or in association, on rat primary hepatocyte cultures. Cell viability was assessed by flow cytometry after propidium iodine intercalation. DNA fragmentation and apoptosis were assessed by agarose gel electrophoresis and acridine orange and ethidium bromide staining. At the concentrations of AFB1 and FB1 used, the toxins did not decrease cell viability, but did induce apoptosis in a concentration and time-dependent manner

Diagnosis and management of adult coeliac disease: guidelines from the British Society of Gastroenterology

A multidisciplinary panel of 18 physicians and 3 non-physicians from eight countries (Sweden, UK, Argentina, Australia, Italy, Finland, Norway and the USA) reviewed the literature on diagnosis and management of adult coeliac disease (CD). This paper presents the recommendations of the British Society of Gastroenterology. Areas of controversies were explored through phone meetings and web surveys. Nine working groups examined the following areas of CD diagnosis and management: classification of CD; genetics and immunology; diagnostics; serology and endoscopy; follow-up; gluten-free diet; refractory CD and malignancies; quality of life; novel treatments; patient support; and screening for CD

Survival of syngeneic and allogeneic iPSC–derived neural precursors after spinal grafting in minipigs

The use of autologous (or syngeneic) cells derived from induced pluripotent stem cells (iPSCs) holds great promise for future clinical use in a wide range of diseases and injuries. It is expected that cell replacement therapies using autologous cells would forego the need for immunosuppression, otherwise required in allogeneic transplantations. However, recent studies have shown the unexpected immune rejection of undifferentiated autologous mouse iPSCs after transplantation. Whether similar immunogenic properties are maintained in iPSC-derived lineage-committed cells (such as neural precursors) is relatively unknown. We demonstrate that syngeneic porcine iPSC-derived neural precursor cell (NPC) transplantation to the spinal cord in the absence of immunosuppression is associated with long-term survival and neuronal and glial differentiation. No tumor formation was noted. Similar cell engraftment and differentiation were shown in spinally injured transiently immunosuppressed swine leukocyte antigen (SLA)–mismatched allogeneic pigs. These data demonstrate that iPSC-NPCs can be grafted into syngeneic recipients in the absence of immunosuppression and that temporary immunosuppression is sufficient to induce long-term immune tolerance after NPC engraftment into spinally injured allogeneic recipients. Collectively, our results show that iPSC-NPCs represent an alternative source of transplantable NPCs for the treatment of a variety of disorders affecting the spinal cord, including trauma, ischemia, or amyotrophic lateral sclerosis

Reproductive life disorders in Italian celiac women. A case-control study

BACKGROUND: The aim of this study is to explore the association between celiac disease and menstrual cycle, gestation and puerperal disorders. METHODS: The association between celiac disease and menstrual cycle, gestation and puerperal disorders in a sample of 62 childbearing age women (15-49 age) was assessed within an age and town of residence matched case-control study conducted in 2008. Main outcome measures were the presence of one or more disorders in menstrual cycle and the presence of one or more complication during pregnancy. RESULTS: 62 celiac women (median age: 31.5, range: 17-49) and 186 healthy control (median age: 32.5, range: 15-49) were interviewed. A higher percentage of menstrual cycle disorders has been observed in celiac women. 19.4% frequency of amenorrhea was reported among celiac women versus 2.2% among healthy controls (OR = 33, 95% CI = 7.17-151.8;, p = 0.000). An association has been observed between celiac disease and oligomenorrhea, hypomenorrhea, dysmenorrhea and metrorrhagia (p < 0.05). The likelihood of having at least one complication during pregnancy has been estimated to be at least four times higher in celiac women than in healthy women (OR = 4.1, 95% CI = 2-8.6, p = 0.000). A significant correlation has emerged for celiac disease and threatened abortion, gestational hypertension, placenta abruption, severe anaemia, uterine hyperkinesia, intrauterine growth restriction (p < 0.001). A shorter gestation has on average been observed in celiac women together with a lower birth weight of celiac women babies (p < 0.001). CONCLUSIONS: The occurrence of a significant correlation between celiac disease and reproductive disorders could suggest to consider celiac disease diagnostic procedures (serological screening) in women affected by these disorders