Genetic and Epigenetic Regulation in Nonalcoholic Fatty Liver Disease (NAFLD)

Genetics and epigenetics play a key role in the development of several diseases, including nonalcoholic fatty liver disease (NAFLD). Family studies demonstrate that first degree relatives of patients with NAFLD are at a much higher risk of the disease than the general population. The development of the Genome Wide Association Study (GWAS) technology has allowed the identification of numerous genetic polymorphisms involved in the evolution of diseases (e.g., PNPLA3, MBOAT7). On the other hand, epigenetic changes interact with inherited risk factors to determine an individual’s susceptibility to NAFLD. Modifications of the histones amino-terminal ends are key factors in the maintenance of chromatin structure and gene expression (cAMP-responsive element binding protein H (CREBH) or SIRT1). Activation of SIRT1 showed potential against the physiological mechanisms related to NAFLD. Abnormal DNA methylation represents a starting point for cancer development in NAFLD patients. Besides, the evaluation of circulating miRNA profiles represents a promising approach to assess and non-invasively monitor liver disease severity. To date, there is no approved pharmacologic therapy for NAFLD and the current treatment remains weight loss with lifestyle modification and exercise. In this review, the status of research into relevant genetic and epigenetic modifiers of NAFLD progression will be discusse

Radiofrequency-induced heating versus mechanical stapler for pancreatic stump closure: in vivo comparative study

Purpose: To assess the capacity of two methods of surgical pancreatic stump closure in terms of reducing the risk of pancreatic fistula formation (POPF): radiofrequencyinduced heating versus mechanical stapler. Materials and Methods: Sixteen pigs underwent a laparoscopic transection of the neck of the pancreas. Pancreatic anastomosis was always avoided in order to work with an experimental model prone to pancreatic fistula formation (POPF). Pancreatic stump closure was conducted either by stapler (ST Group, n=8) or radiofrequency energy (RF Group, n=8). Both groups were compared for incidence of POPF and histopathologic alterations of the pancreatic remnant. Results: Six animals (75%) in the ST Group and one (14%) in the RF Group were diagnosed of POPF (p=0.019). One animal in the RF Group and three animals in the ST Group had a pseudocyst in close contact with both pancreas stumps. On day 30 postoperative, almost complete atrophy of the exocrine distal pancreas was observed when the main pancreatic duct was efficiently sealed. Conclusions: Our findings suggest that RF-induced heating is more effective at closing the pancreatic stump than mechanical stapler and leads to the complete atrophy of the distal remnant pancreas.This work was supported by the Spanish 'Programa Estatal de Investigacion, Desarrollo e Innovacion Orientada a los Retos de la Sociedad' under grant TEC2014-52383-C3-R (TEC2014-52383-C3-3-R). F.B., R.Q. and E.B. declare stock ownership in Apeiron Medical S.L., a company that has a license for the patent US 8.303.584.B2, on which the device tested in this study is based. The other authors report no conflict of interests or financial ties to disclose. The authors alone are responsible for the content and writing of the paper.Burdío Pinilla, F.; Dorcaratto, D.; Hernandez, L.; Andaluz, A.; Moll, X.; Quesada-Diez, R.; Poves, I.... (2016). Radiofrequency-induced heating versus mechanical stapler for pancreatic stump closure: in vivo comparative study. International Journal of Hyperthermia. 32(3):272-280. https://doi.org/10.3109/02656736.2015.113684527228032

Research funding: What do I need before I start looking for a funding source? Part 1

Esta es la primera parte de un artículo sobre la búsqueda de financiamiento para un proyecto de investigación. Esta entrega resume los principales ítems para tener en consideración a la hora de postularse a una convocatoria. Requerimientos del proceso: 1. Tiempo protegido. 2. Propuesta de investigación sólida. 3. Equipo calificado y con experiencia. 4. Definición y organización de actividades. 5. Cronograma de actividades. 6. Estimación de costosThis is the first part of an article about finding funding for a research project. This delivery summarizes the main ítems to take into consideration when applying for a call. Process requirements: 1. Protected time. 2. Strong research proposal. 3. Qualified and experienced team. 4. Definition and organization of activities. 5. Schedule of activities. 6. Cost estimateFil: Posadas Martinez, Maria Lourdes. Hospital Italiano; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Grande Ratti, Maria Florencia. Hospital Italiano; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Burgos, Mariana. Hospital Italiano; ArgentinaFil: Herrera, Víctor. Hospital Italiano; Argentin

Diagnosis of pulmonary embolism in patients with acute exacerbations of chronic obstructive pulmonary disease: a cross-sectional study

Introduction: Pulmonary embolism (PE) remains a frequent complication in patients with chronic obstructive pulmonary disease (COPD). It is unclear that the extent to which the traditional risk stratifying scores for PE are accurate in this population. Methods: Cross-sectional study of adult patients with COPD and suspected PE included in an Institutional Registry of Thromboembolic Disease at a tertiary teaching hospital in the city of Buenos Aires, Argentina. We estimated the area under the receiver operating characteristic curves (AU-ROC), sensitivity and specificity of the Wells and Geneva scores using a positive computed tomography angiography as the gold standard for PE. We also estimated the sensitivity and specificity for the presence of isolated worsening of dyspnea at presentation, without other cardinal symptoms of acute exacerbation of COPD. Results: A total of 168 patients were included, of which 22% had confirmed PE. The AUC was 0.66 (95% CI 0.56-0.76) and 0.56 (95% CI 0.45-0.67) for the Wells and Geneva, respectively. Considering the most widely used cutoff points, the sensitivity and specificity were 24% and 90% for the Wells and 59% and 43% for the Geneva score, respectively. Isolated worsening of dyspnea on presentation had a sensitivity of 92% and specificity of 37%. Conclusions: Both Wells and Geneva scores exhibit poor diagnostic accuracy for the diagnosis of PE in patients with COPD. The presence of isolated worsening of dyspnea on presentation could be an easy to identify criteria for the initial triage in this population. Further validation of our findings remains warranted.Fil: Maritano Furcada, Joaquín. Hospital Italiano; ArgentinaFil: Castro, Horacio Matías. Hospital Italiano; ArgentinaFil: de Vito, Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Grande Ratti, María Florencia. Hospital Italiano; ArgentinaFil: Posadas Martinez, Maria Lourdes. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Italiano; ArgentinaFil: Giunta, Diego Hernan. Hospital Italiano; ArgentinaFil: Vazquez, Fernando Javier. Hospital Italiano; ArgentinaFil: Ferreyro, Bruno Leonel. Hospital Italiano; Argentina. University of Toronto; Canad

Influence of TiO2-Coating Layer on Nanoporous Alumina Membranes by ALD Technique

Geometrical, chemical, optical and ionic transport changes associated with ALD of TiO2-coating on the porous structure of two nanoporous alumina membranes (NPAMs), which were obtained by the two-step aluminum anodization method but with different pore size and porosity, are presented. Chemical and morphological changes were determined by analyzing XPS spectra and SEM images, showing practically total coverage of the NPAMs surface and leading to a reduction in the geometrical parameters of both samples, while SAED and high resolution TEM measurements allowed us to determine the crystalline structure and thickness of the TiO2-coating, with the latter confirmed by depth-profile XPS analysis. Spectroscopic ellipsometry measurements were also carried out in order to detect changes in characteristic optical parameters (refractive index, n, and extinction coefficient, k), due to the TiO2-coating of NPAMs. Considering the common application of NPAMs in solute/ion diffusion processes, the effect of the TiO2-coverage on electrochemical parameters was analyzed by measuring the concentration potential with a typical model electrolyte (KCl solutions), leading to an increase of the electropositive character for both kinds of samples

Endocannabinoid regulation of amyloid-induced neuroinflammation

The modulation of endocannabinoid (EC) levels and the activation of cannabinoid receptors are seen as promising therapeutic strategies in a variety of diseases, including Alzheimer’s disease (AD). We aimed to evaluate the effect of the pharmacological and genetic inhibiton of anandamide (AEA)-degrading enzyme in a mouse model of AD (5xFAD). Pharmacological inhibition of the fatty acid amide hydrolase (FAAH) had little impact on the expression of key enzymes and cytokines as well as on the cognitive impairment and plaque deposition and gliosis in 5xFAD mice. CB1 blockade exacerbated inflammation in this transgenic mouse model of AD. The genetic inactivation of FAAH led to increases in the expression of inflammatory cytokines. At the same time, FAAH-null 5xFAD mice exhibited a behavioral improvement in spatial memory that was independent of the level of anxiety and was not CB1-mediated. Finally, mice lacking FAAH showed diminished soluble amyloid levels, neuritic plaques and gliosis. These data reinforce the notion of a role for the endocannabinoid system in neuroinflammation and open new perspectives on the relevance of modulating endocannabinoid levels in the inflammed brain.pre-print687 K

Concordance between circulating tumor cells and clinical status during follow-up in anaplastic lymphoma kinase (ALK) non-small-cell lung cancer patients

Background: The identification of anaplastic lymphoma kinase (ALK) rearrangements is found in approximately 5% of non-small-cell lung cancers (NSCLCs). However, the development of liquid biopsies as a diagnostic tool is less developed in these cases. This study investigates the use of CTCs during treatment, together with an extended follow-up to correlate with clinical evolution. Patients and Methods: A total of 13 patients out of a cohort of 212 patients with lung adenocarcinoma, presented ALK rearrangements (6%) confirmed by tumor biopsy. A total of 60 serial blood samples were collected from these patients who were prospectively enrolled in the study. Results: All patients had a positive CTC count at baseline (mean = 3). The median follow-up was 9 months (range 1-17 months). Three patients underwent surgery and their CTC counts decreased after the procedure but still remained detectable. After radiotherapy, 3 cases showed an average decrease of 5 CTCs. A total of 6 patients were treated with ALK inhibitors and a partial response was observed in 3 of them, who also presented decreased CTC counts. The other 3 patients presented primary resistance, and their CTC counts were higher than those obtained prior to progression. Conclusion: We believe that the use of CTCs for dynamic monitoring of NSCLC with ALK rearrangement and to detect disease persistence or recurrence may be a reliable technique. CTC counts may also have potential use to monitor the efficacy of ALK inhibitors, facilitating detection of resistance to treatmentThis study was supported by Carlos III Institute of Health, Spanish Ministry of Science and Innovation, and European Regional Development Fund (grant number: PI16/01818 and PIE14/00064), D. Pérez-Callejo is supported by SEOM-Río-Hortega contract, A Romero is supported by Joan Rodés fellowship (grant number: JR14/00017) and M Sánchez-Beato is supported by Miguel Servet contract (CP11/00018 and CPII16/00024

Phylogeny of Polycladida (Platyhelminthes) based on mtDNA data

A phylogenetic analysis of Polycladida based on two partial mitochondrial genes (cox1 and 16S) is provided. The analysis includes 30 polyclad terminals that represent species from the two taxa which traditionally divide the groups Cotylea and Acotylea. Our phylogenetic analyses produced a well-supported hypothesis that confirms the monophyly of Polycladida, as well as Acotylea and Cotylea. Within Acotylea, there are two lineages not highly supported: on one hand, Leptoplanoidea (excluding Hoploplana elisabelloi) and one Stylochoidea member (Pseudostylochus intermedius) (classification sensu Faubel, 1983, 1984), and on the other hand, Stylochoidea members together with Discocelis tigrina and H. elisabelloi. The genera Stylochus and Imogine are not monophyletic. Within Cotylea, Pseudocerotidae and Euryleptidae are monophyletic, though not highly supported, while Prosthiostomidae is not. Euryleptoidea is paraphyletic. The genera Pseudobiceros and Pseudoceros are monophyletic and highly supported. Our results suggest that, within Acotylea, the prostatoid organs of Discocelis may have been derived from a prostatic vesicle. The genus Hoploplana could be included in Stylochoidea. Within Cotylea, the common ancestor of Euryleptidae and Pseudocerotidae might have been an aposematic animal with tentacles.Facultad de Ciencias Naturales y Muse

Incidence of hospital-acquired venous thromboembolic disease.

Background: There is limited knowledge of the incidence of venous thromboembolic disease (VTE) during hospitalization, since most of these are community-based data.Purpose: To estimate the incidence rate (IR) of VTE developed during hospitalization.Methods: Prospective cohort of all inpatients admitted in a university tertiary hospital, in Argentina. The inclusion criteria were defined as: adult patients consecutively admitted from July/2006 to August/2013, for any cause. Patients admitted for VTE were excluded; all patients at the time of admission were free of event. Each person was followed contributing time at risk, from admission to event, discharge or death. VTE incident cases were captured from the Institutional Registry of Thromboembolic Disease (ClinicalTrials.gov Identifier NCT01372514). Incidence rate was calculated with 95% confidence intervals.Results: The crude incidence rate of VTE for clinical patients was 0.49 (95%CI 0.45-0.55) per 1,000 cases person-days, and IR adjusted for WHO was 0.23 (95%CI 0.19-0.26). The crude IR of VTE for surgical patients was 0.25 (95%CI 0.23-0.27), and IR adjusted for WHO was 0.13 (95%CI 0.10-0.17). The incidence rate ratio (IRR) for VTE shows that surgical admission reduces the IRR and age categories increases the thrombosis rate risk, after adjustment for age category, sex and surgical admission.Conclusions: This study suggests that there is a high risk of VTE in hospitalized patients and is still a frequent problem.</p