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Fractal geometry has provided a new range of concepts that could explain the non-linear behaviour of seemingly unpredictable natural systems. The aim of this work is to apply nonlinear analysis to study the . in vitro erythrocyte aggregation produced by incubation of human red blood cells (RBCs) with . Ascaris lumbricoides and also . Trichinella spirallis larvae extracts. The approach used was based on calculating the fractal slope (D), through image processing of control and treated RBCs at different incubation times (200 images). The results showed a decrease in the fractal dimension value of . Ascaris lumbricoides treated RBCs (up to 10%) and a constant value of D in the case of . Thichinella spiralis treated RBCs, in contrast to a more disperse value showed in normal controls. This modification in the D might be correlated with the different actions of each parasite over the erythrocyte membrane leading to abnormal RBCs aggregation. Fil: Lupo, Maela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Médicas; Argentina Fil: Leguto, Alcides José. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina Fil: Bortolato, Santiago Andres. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina Fil: Korol, Ana María. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Física de Rosario. Universidad Nacional de Rosario. Instituto de Física de Rosario; Argentina

Invasive micropapillary carcinoma of the breast (IMPC) is a histological tumor variant that occurs with low frequency characterized by an inside-out formation of tumor clusters with a pseudopapillary arrangement. IMPC is an aggressive tumor with poor clinical outcome. In addition, this histological subtype usually expresses human epidermal growth factor receptor 2 (HER2) which also correlates with a more aggressive tumor. In this work we studied the clinical significance of IMPC in HER2-positive breast cancer patients treated with adjuvant trastuzumab. We also analyzed mucin 4 (MUC4) expression as a novel biomarker to identify IMPC. Fil: Mercogliano, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Inurrigarro, Gloria. Sanatorio Mater Dei Hermanas de María de Schoenstatt; Argentina Fil: de Martino, Mara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Venturutti, Leandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Rivas, Martin Alfredo. Cornell University; Estados Unidos Fil: Cordo Russo, Rosalia Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Proietti Anastasi, Cecilia Jazmín. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Fernandez, Elmer Andres. Universidad Católica de Córdoba; Argentina Fil: Frahm, Isabel. Sanatorio Mater Dei Hermanas de María de Schoenstatt; Argentina Fil: Barchuk, Sabrina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos ; Argentina Fil: Allemand, Daniel H.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos ; Argentina Fil: Figurelli, Silvina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos ; Argentina Fil: Gil Deza, Ernesto. Instituto Oncológico Henry Moore; Argentina Fil: Ares, Sandra. Instituto Oncológico Henry Moore; Argentina Fil: Gercovich, Felipe G.. Instituto Oncológico Henry Moore; Argentina Fil: Cortese, Eduardo. Ministerio de Defensa. Fuerza Aérea Argentina. Hospital Aeronáutico Central ; Argentina Fil: Amasino, Matías. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Guzmán, Pablo. Universidad de La Frontera; Chile Fil: Roa, Juan C.. Universidad de La Frontera; Chile Fil: Elizalde, Patricia Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Schillaci, Roxana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina

Microsatellite instability (MSI) is a hallmark tool for Lynch syndrome (LS) screening and a prognostic marker for sporadic colorectal cancer (CRC). In regions with limited resources and scarce CRC molecular characterization as South America, the implementation of universal MSI screening is under debate for both its purposes. We sought to estimate the frequency of BAT26 in colorectal adenocarcinomas and to determine associated clinical and histological features. Consecutive patients from a CRC registry were included. BAT26 determination was performed in all cases; if instability was found, immunohistochemistry (IHC) and BRAF mutation analyses were done, as appropriate. Differences were assessed by chi-squared or Fisher’s exact test, or by T test or Mann–Whitney. Multiple logistic regression was used to identify factors independently associated with BAT26-unstable tumors. We included 155 patients; mean age was 65.6 (SD 14.4) and 56.1% were male. The frequency of BAT26-unstable tumors was 22% (95% CI 15.7–29.3). Factors independently associated with BAT26-unstable tumors were right colon localization (OR 3.4, 95% CI 1.3–8.7), histological MSI features (OR 5.1, 95% CI 1.9–13.6) and Amsterdam criteria (OR 23.2, 95% CI 1.9–286.7). IHC was altered in 85.3% BAT26-unstable tumors and 70.6% lacked MLH1 expression; 47.8% of these harbored BRAF V600E mutation. We provide evidence to link the frequency of BAT26 to an increased diagnostic yield (up to 1.4-folds) of suspected LS cases in comparison to the revised Bethesda guidelines alone. In regions with limited resources, clinical and histological features associated with BAT26-unstable status could be useful to direct MSI screening in sporadic CRCs and may help guide clinical care and future research. Fil: González, María Laura. Hospital Italiano; Argentina Fil: Causada Calo, Natalia. Hospital Italiano; Argentina. McMaster University; Canadá Fil: Santino, Juan Pablo. Hospital Italiano; Argentina Fil: Dominguez Valentin, Mev. The Norwegian Radium Hospital; Noruega Fil: Ferro, Fabiana Alejandra. Hospital Italiano; Argentina Fil: Sammartino, Inés. Hospital Italiano; Argentina Fil: Kalfayan, Pablo Germán. Hospital Italiano; Argentina Fil: Verzura, Maria Alicia. Hospital Italiano; Argentina Fil: Piñero, Tamara Lejandra. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Italiano; Argentina Fil: Cajal, Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Italiano; Argentina Fil: Pavicic, Walter Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Italiano; Argentina Fil: Vaccaro, Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Italiano; Argentina

Background: Intravitreal injection of chemotherapy in retinoblastoma eyes with vitreous seeds may lead to a risk of extraocular tumour dissemination that has not been assessed so far. Aims: To develop a sensitive and clinically feasible technique to assess for potential retinoblastoma cell reflux after intravitreal injection of melphalan. Methods: Filter papers were cut in 6 mm diameter circles and sterilised before use. Eyes with retinoblastoma vitreous seeds (group D, International Classification) received weekly intravitreal melphalan injections (20 µg or 30 µg/dose) followed by cryotherapy as part of local treatment. Immediately after finishing the injection and cryotherapy, filter papers were placed on the injection site and on the cryoprobe tip to assess for the expression of the cone-rod homeobox gene (CRX) by real-time qPCR as a surrogate of retinoblastoma RNA. The assay was developed and validated to determine sensitivity, linearity, recovery, repeatability and reproducibility. Results: The assay for quantitation of CRX expression was linear in the range of 1 to 1000 cells. The lowest limit of detection was one retinoblastoma cell and allowed to recover 100% of the cell load in external supplementation. A total of 14 eyes received 22 cycles of intravitreal melphalan and were evaluated for potential extraocular tumour cell dissemination using the developed technique. None of the cycles were positive for CRX in samples from the scar or from the cryoprobe tip. Conclusions: A sensitive and simple method of tumour cell assessment has been developed that can be used in the clinics to assess for potential extraocular dissemination after intravitreal injections to assure its performance. Fil: Winter, Ursula Andrea. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Unidad de Farmacocinética Clínica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Nicolas, Michael. Université de Lausanne. Faculté de Biologie et de Médecine; Suiza Fil: Sgroi, Mariana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; Argentina Fil: Sampor, Claudia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Servicio de Hemato-Oncología; Argentina Fil: Torbidoni, Ana Vanesa. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Fandiño, Adriana Cristina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría ; Argentina Fil: Chantada, Guillermo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Servicio de Hemato-Oncología; Argentina Fil: Munier, Francis L.. Université de Lausanne. Faculté de Biologie et de Médecine; Suiza Fil: Schaiquevich, Paula Susana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Unidad de Farmacocinética Clínica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina

Langerhans cell histiocytosis (LCH) is a rare disease with an unknown etiology characterized by heterogeneous lesions containing CD207+CD1a+ cells that can arise in almost any tissue and cause significant morbidity and mortality. Precursors of pathological Langerhans cells have yet to be defined. Our aim was to identify circulating CD207+CD1a+ cells and their inducers in LCH. Expression of CD207 and CD1a in the blood myeloid compartment as well as thymic stromal lymphopoietin (TSLP) and transforming growth factor β (TGF-β) plasma levels were measured in 22 pediatric patients with active disease (AD) or nonactive disease (NAD). In patients with AD vs those with NAD, the myeloid compartment showed an increased CD11b (CD11bhigh plus CD11b+) fraction (39.7 ± 3.6 vs 18.6 ± 1.9), a higher percentage of circulating CD11bhighCD11c+CD207+ cells (44.5 ± 11.3 vs 3.2 ± 0.5), and the presence of CD11chighCD207+CD1a+ cells (25.0 ± 9.1 vs 2.3 ± 0.5). Blood CD207+CD1a+ cells were not observed in adult controls or umbilical cord. Increased TSLP and TGF-β levels were detected in patients with AD. Interestingly, plasma from patients with AD induces CD207 expression on CD14+ monocytes. We conclude that CD207+CD1a+ cells are circulating in patients with active LCH, and TSLP and TGF-β are potential drivers of Langerhans-like cells in vivo. Fil: Carrera Silva, Eugenio Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: Nowak, Wanda. Universidad de Buenos Aires. Facultad de Medicina; Argentina Fil: Tessone, Licina. Universidad de Buenos Aires. Facultad de Medicina; Argentina Fil: Olexen, Cinthia Mariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina Fil: Ortiz Wilczyñski, Juan Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: Estecho, Ivana Gisele. Universidad de Buenos Aires. Facultad de Medicina; Argentina Fil: Elena, Graciela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); Argentina Fil: Errasti, Andrea Emilse. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina Fil: Rosso, Diego. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); Argentina

Background and purpose: Studies assessing the correlations between L-DOPA-induced dyskinesias (LIDs) and motor fluctuations with health-related quality of life (HRQoL) in Parkinson's disease (PD) have yielded conflicting results. This study aimed to assess the relationship between LIDs and motor fluctuations with HRQoL in patients with PD, and to assess the relative contribution of their severity and duration in a large sample of patients with PD. Methods: A total of 683 patients with PD from the COPARK survey were evaluated. HRQoL was assessed using the 39-Item Parkinson's Disease Questionnaire (PDQ-39) (primary outcome) and 36-Item Short Form Survey (SF-36). The daily duration and severity of LIDs were obtained from Unified Parkinson's Disease Rating Scale (UPDRS) IV items 32 and 33, respectively. The daily duration of motor fluctuations was obtained from UPDRS IV item 36 and severity was estimated as the difference between the UPDRS 2 (Activities of Daily Living) score in ‘OFF’ versus ‘ON’ condition. Results: A total of 235 patients with PD (35%) experienced motor fluctuations and 182 (27%) experienced LIDs. The PDQ-39 total and SF-36 physical scores were significantly worse in patients with LIDs, after adjusting for the presence of motor fluctuations. The PDQ-39 total score and SF-36 physical and mental score were significantly worse in patients with motor fluctuations, after adjusting for the presence of LIDs. The severity of LIDs and the duration of motor fluctuations significantly and independently affected PDQ-39 scores. The SF-36 physical score was affected only by the severity of motor fluctuations, whereas the mental score was not affected by any of the aforementioned variables. Conclusion: Our findings suggest that LIDs (mainly their severity) and motor fluctuations (mainly their duration) correlate independently with HRQoL in patients with PD. Fil: Pérez Lloret, Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; Argentina Fil: Negre Pages, Laurence. LN Pharma; Francia. Hôpital la Colombière; Francia Fil: Damier, Philippe. Universite de Nantes; Francia Fil: Delval, Arnaud. Universite Lille 3; Francia Fil: Derkinderen, Paul. Universite de Nantes; Francia Fil: Destée, Alain. Universite Lille 3; Francia Fil: Meissner, Wassilios G.. Universite de Bordeaux; Francia Fil: Tison, F.. Universite de Bordeaux; Francia Fil: Rascol, Olivier. Université de Toulouse; Francia

Introduction: Biological drugs are therapies designed to target a specific molecule of the immune system that have been linked with the development of autoimmune diseases. Areas covered: The BIOGEAS Registry currently collects information about nearly 13,000 reported cases of autoimmune diseases developed in patients exposed to biologics, including more than 50 different systemic and organ-specific autoimmune disorders, of which psoriasis (n=6375), inflammatory bowel disease (n=845), demyelinating CNS disease (n=803), interstitial lung disease (n=519) and lupus (n=369) were the most frequently reported. The main biologics involved were anti-TNF agents in 9133 cases (adalimumab in 4154, infliximab in 3078 and etanercept in 1681), immune checkpoint inhibitors in 913 (ipilimumab in 524 and nivolumab in 225), B-cell targeted therapies in 741 (rituximab in 678), and growth factor inhibitors in 549 cases (bevacizumab in 544). Even though targeting a particular immune molecule may be associated with an excellent clinical response in most patients, an unexpected autoimmune disease may arise in around 8 out of 10,000 exposed patients. Expert opinion: Following the increased use of biologics, the number and diversity of induced autoimmune diseases is increasing exponentially. Management of these disorders will be an increasing clinical challenge in the daily practice in the next years. Fil: Pérez De Lis, Marta. Hospitalario Universitario de la Coruña; España Fil: Retamozo, Maria Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina. Hospital Clínic; España. Hospital Privado Universitario de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina Fil: Flores Chávez, Alejandra. Hospital Clínic; España. Hospital de Especialidades; México. Universidad de Colima; México Fil: Kostov, Belchin. Primary Care Research Group; España Fil: Perez Alvarez, Roberto. Hospital Alvaro Cunqueiro; España Fil: Brito Zerón, Pilar. Hospital Clínic; España. Hospital CIMA; España Fil: Ramos Casals, Manuel. Hospital Clínic; España. Universidad de Barcelona; España

Introducción y objetivos: El tratamiento quirúrgico de la enfermedad renal vascular sigue teniendo resultados favorables cuando se realiza con criterio. El objetivo de este trabajo consiste en presentar 10 casos con distinta afección vascular renal y sus resultados a corto y a largo plazo. Métodos: Estudio retrospectivo de todos los pacientes con diagnóstico de aneurisma y/o estenosis de las arterias renales (AR) cuya enfermedad requirió resolución quirúrgica desde junio de 2000 a julio de 2015 en nuestro centro. Resultados: De 10 pacientes el 90% eran mujeres, edad media de 52±17 años. El 90% tenía hipertensión arterial, 2 insuficiencia renal crónica y un paciente insuficiencia renal aguda. Cinco pacientes tenían un diagnóstico previo de fibrodisplasia muscular. El 30% había sido intervenido previamente con stents en las AR, y uno de ellos tenía como antecedente una cirugía de bypass aortorrenal. En 6 casos se realizó bypass a las AR con autoinjerto de safena, en otro paciente se colocó un tubo protésico de politetrafluoroetileno expandido, además se realizó una plastia de arteria renal y, en 2 casos, se llevó a cabo una nefrectomía para poder resolver la enfermedad que luego se autotrasplantó. La estancia hospitalaria fue de 9,2±3,3 días y el tiempo de seguimiento fue de 5,8±4,5 años. No se registró ninguna muerte intra ni perioperatoria. Conclusiones: A pesar de que en la actualidad el tratamiento no invasivo está indicado en un gran número de escenarios, la resolución quirúrgica sigue siendo la terapéutica de elección en pacientes seleccionados, teniendo buenos resultados. Introduction and objectives: Surgical treatment of renal vascular pathology is still having favorable results when it is performed in selected patients. The aim of this study is to analyze 10 cases with renovascular disease and its short and long-term outcomes. Methods: We conducted a retrospective study with all the patients who had a diagnosis of aneurysm and/or stenosis of the renal arteries (RA) that required surgical treatment from June 2000 to July 2015 in our centre. Results: From 10 patients, 90% were female, mean age 52±17 years. Ninety percent had hypertension, 2 patients had history of chronic renal failure, and one case was admitted with acute renal failure. Five patients had muscular fibrodysplasia. Thirty percent were previously treated with stents in the RA, and another one had a history of an aortic-renal bypass. In 6 cases surgery was performed using the saphenous vein as a graft for the bypass, and in one, the bypass was made with an expanded polytetrafluoroethylene prosthesis. One patient had a RA plasty, and in 2 cases a nephrectomy was performed in order to resolve the pathology, and after that, the kidney was autotransplanted. Hospital stay was 9.2±3.3 days and mean follow up time was 5.8±4.5 years. There were no deaths during or after surgery. Conclusions: Even though endovascular treatment for renal artery disease is indicated in some scenarios, surgical treatment is still an option in selected patients with excellent results. Fil: Zuñiga, Juan J.. Fundación Favaloro; Argentina Fil: Gilbert, Mónica D.. Fundación Favaloro; Argentina Fil: Candioti, Mariano M.. Fundación Favaloro; Argentina Fil: Kalbermatten, Marcos M.. Fundación Favaloro; Argentina Fil: Cotti, Carlos F.. Fundación Favaloro; Argentina Fil: Dosso, Nicolás. Fundación Favaloro; Argentina Fil: Hernandez, Mario G.. Fundación Favaloro; Argentina Fil: Cari, Alfredo. Fundación Favaloro; Argentina Fil: Zambrano, Alejandro. Fundación Favaloro; Argentina Fil: Vigliano, Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Fundación Favaloro; Argentina

Introduction: Currently, available therapies for Parkinson’s disease (PD) are symptomatic. Therefore, the search for neuroprotective drugs remains a top priority. Areas covered: In this review, the potential symptomatic or disease-modifying effect of drugs targeting the Renin-Angiotensin System (RAS) in PD will be explored. Expert opinion: The importance of nigrostriatal local RAS has only begun to be unraveled in the last decades. On one hand, there is a complex feedback cycle between RAS and dopamine (DA). On the other hand, RAS affects dopaminergic neurons vulnerability. Neuroprotective effects in animal PD models have been shown for the angiotensin-converting enzyme (ACE) inhibitors captopril and perindopril, and the AT1 receptor antagonists losartan, candesartan and telmisartan. These effects appear to be mediated by a reduction in the overproduction of reactive oxygen species. In a proof-of-concept, randomized, double-blind, crossover study in PD patients, perindopril enhanced the effect of levodopa without inducing dyskinesias. There has not been any clinical trial exploring the neuroprotective effect of RAS drugs, but one cohort study in hypertensive patients suggested a protective effect of ACE inhibitors on PD risk. RAS is a promising target for symptomatic and neuroprotective therapies in PD. Further studies in PD animal models and patients are warranted. Fil: Pérez Lloret, Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; Argentina Fil: Otero-Losada, Matilde Estela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; Argentina Fil: Toblli, Jorge Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; Argentina Fil: Capani, Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; Argentina

Incorporation of direct acting antivirals (DAA) in the treatment of Hepatitis C Virus (HCV) significantly increases sustained virologic response rates. However, despite the greater potency offered by these antivirals, drug resistance plays a key role in patients with failure to DAA. Nevertheless, there is no information about the prevalence of resistance-associated substitutions (RASs) in Argentina. The aim of this study was to analyze HCV variants resistant to protease inhibitors (PI) in naïve patients infected with HCV genotype 1 from Argentina. In this retrospective cross-sectional study, 103 patients infected with HCV-1 were included. Eighteen positions related with RASs were analyzed by Sanger at baseline and phylogenetic analysis was performed to determine the diversification of this samples. The analyzed RASs were present in 38 out of 103 patients (36.9%) infected with HCV-1. Patients infected with subtype HCV-1b had higher prevalence of baseline RASs than patients infected with HCV-1a [51.6% vs. 12.8%, respectively (p < 0.001)]. The Q80K polymorphism was not found in HCV-1a samples, even when 51% of them belonged to cluster 1, which is associated with a high frequency of Q80K. Phylogenetic analysis showed that Argentinean samples were intermingled with sequences from other geographic regions. RASs to PI were highly prevalent and subtype dependent in treatment-naïve Argentinean patients. Surprisingly, Q80K polymorphism was not detected in our study population. The phylogenetic analysis showed no relationship between our samples and other samples from Brazil which also present a low prevalence of Q80K. This study supports the need for surveillance of resistance in patients who will be treated with DAA in each particular country since the observed RASs have very different prevalence worldwide. Fil: Martínez, Alfredo P.. Centro de Educaciones Médicas e Investigación Clínica "Norberto Quirno"; Argentina Fil: Culasso, Andrés Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina Fil: Pérez, Paula Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina Fil: Romano, Vanesa. Centro de Educaciones Médicas e Investigación Clínica "Norberto Quirno"; Argentina Fil: Campos, Rodolfo Hector. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina Fil: Ridruejo, Ezequiel. Centro de Educaciones Médicas e Investigación Clínica "Norberto Quirno"; Argentina Fil: García, Gabriel. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina Fil: Di Lello, Federico Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina

As there is no precise laboratory test or imaging study for detection of pancreas allograft rejection, there is increasing interest in obtaining pancreas tissue for diagnosis. Pancreas allograft biopsies are most commonly performed percutaneously, transcystoscopically, or endoscopically, yet pancreas transplant surgeons often lack the skills to perform these types of biopsies. We have performed 160 laparoscopic pancreas biopsies in 95 patients. There were 146 simultaneous kidney-pancreas biopsies and 14 pancreas-only biopsies due to pancreas alone, kidney loss, or extraperitoneal kidney. Biopsies were performed for graft dysfunction (89) or per protocol (71). In 13 cases, an additional laparoscopic procedure was performed at the same operation. The pancreas diagnostic tissue yield was 91.2%; however, the pancreas could not be visualized in eight cases (5%) and in 6 cases the tissue sample was nondiagnostic (3.8%). The kidney tissue yield was 98.6%. There were four patients with intraoperative complications requiring laparotomy (2.5%) with two additional postoperative complications. Half of all these complications were kidney related. There were no episodes of pancreatic enzyme leak and there were no graft losses related to the procedure. We conclude that laparoscopic kidney and pancreas allograft biopsies can be safely performed with very high tissue yields. Fil: Uva, Pablo Daniel. Instituto de Nefrología de Buenos Aires; Argentina. Provincia de Formosa. Hospital de Alta Complejidad “Pte J. D. Peron”; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina Fil: Odorico, J. S.. University of Wisconsin; Estados Unidos Fil: Giunippero, Alejandro. Instituto de Nefrología de Buenos Aires; Argentina Fil: Cabrera, I. C.. Instituto de Nefrología de Buenos Aires; Argentina Fil: Gallo, A.. Instituto de Nefrología de Buenos Aires; Argentina Fil: Leon, L. R.. Instituto de Nefrología de Buenos Aires; Argentina Fil: Minué, Elena. Instituto de Nefrología de Buenos Aires; Argentina Fil: Toniolo, Fernanda. Instituto de Nefrología de Buenos Aires; Argentina Fil: Gonzalez, I.. Provincia de Formosa. Hospital de Alta Complejidad “Pte J. D. Peron”; Argentina Fil: Chuluyan, Hector Eduardo. Instituto de Nefrología de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina Fil: Casadei, D. H.. Instituto de Nefrología de Buenos Aires; Argentina

Background: The pathogenesis of non‐alcoholic fatty liver disease (NAFLD) is closely associated with the co‐occurrence of multiple pathological conditions characterising the metabolic syndrome (MetS), obesity in particular. However, NAFLD also develops in lean subjects, whose risk factors remain poorly defined. Methods: We performed a meta‐analysis of 15 studies, along with the data pertaining to our own population (n=336 patients). Data from lean (n=1966) and obese (n=5938) patients with NAFLD were analysed; lean (n=9946) and obese (n=6027) subjects without NAFLD served as controls. Results: Relative to the lean non‐NAFLD controls, lean patients with NAFLD were older (3.79±0.72 years, P=1.36×10−6) and exhibited the entire spectrum of the MetS risk factors. Specifically, they had a significant (P=10−10) increase in plasma glucose levels (6.44±1.12 mg/dL) and HOMA‐IR (0.52±0.094‐unit increment), blood lipids (triglycerides: 48.37±3.6, P=10−10 and total cholesterol: 7.04±3.8, mg/dL, P=4.2×10−7), systolic (5.64±0.7) and diastolic (3.37±0.9) blood pressure (mm Hg), P=10−10, and waist circumference (5.88±0.4 cm, P=10−10); values denote difference in means±SE. Nevertheless, the overall alterations in the obese group were much more severe when compared to lean subjects, regardless of the presence of NAFLD. Meta‐regression suggested that NAFLD is a modifier of the level of blood lipids. Conclusion: Lean and obese patients with NAFLD share a common altered metabolic and cardiovascular profile. The former, while having normal body weight, showed excess of abdominal adipose tissue as well as other MetS features. Fil: Sookoian, Silvia Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina Fil: Pirola, Carlos José. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina

Background Early detection of neurodegenerative diseases is essential for treatment and proper care of these patients. Screening tools available today are effective for several types of dementia. However, there is no one specific for Lewy Body Dementia (LBD). Objectives The aim of this paper is to present a tool for early detection of LBD, accessible even for non-medical staff. Methods We stratified subjects (MMSE > 20) into four groups: health controls (HC), Mild Cognitive Impairment (MCI), LBD and other dementias (Alzheimer and vascular). All subjects (age range 50–90) were examined with a comprehensive neuropsychological and neuropsychiatric evaluation, as well as neuroimaging to differentiate diagnosis between groups, fulfilling corresponding criteria. Both neurologists and neuropsychologists were blind to the performance on clinical evaluations and ASI, respectively. The sensitivity and specificity of the instrument were determined to differentiate LBD from other groups. Results We evaluated 427 subjects, 91 HC, 140 with MCI and 196 with dementia. In the dementia group, 75 were diagnosed with LBD and 121 with other dementias. ASI total score was 12.7 ± 0.4 for LBD, 2.9 ± 0.2 for HC, 5 ± 0.7 for MCI, and 5.4 ± 2.6 for other causes of dementia. ROC curve analysis showed a sensitivity of 90.7% and a specificity of 93.6% stands, with 9 as the cutoff with better test performance compared against other groups. Conclusion ASI is a brief screening tool for LBD with high sensitivity and specificity and useful even for non-medical staff. Fil: Garcia Basalo, M. M.. Hospital Italiano; Argentina Fil: Fernandez, M. C.. Hospital Italiano; Argentina. Asociacion Lewy Body Argentina; Argentina Fil: Ojea Quintana, M.. Hospital Italiano; Argentina. Asociacion Lewy Body Argentina; Argentina Fil: Rojas, J. I.. Hospital Italiano; Argentina Fil: Garcia Basalo, M. J.. Hospital Italiano; Argentina. Asociacion Lewy Body Argentina; Argentina Fil: Bogliotti, E.. Hospital Italiano; Argentina Fil: Cámpora, Nuria Elide. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Italiano; Argentina Fil: Fernandez, M.. Hospital Italiano; Argentina Fil: Berrios, W.. Hospital Italiano; Argentina Fil: Cristiano, E.. Hospital Italiano; Argentina Fil: Golimstok, Angel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Italiano; Argentina. Asociacion Lewy Body Argentina; Argentina

Identifying tumor biomarkers associated with clinical behavior in breast cancer patients may allow higher accuracy in the selection of treatment. Different types of cells were determined in the primary tumors of stage I, II, and III of breast cancer patients, who were assigned to one of the two groups: (1) disease-free or (2) relapsed/progressed, at 5 years after primary treatment. We studied 32 tumor samples. CD4+ lymphocytes and CD44+CD24−/low cells (cancer stem cells) showed a significant association with clinical outcome at 5 years of primary treatment, while CD8+, Foxp3+, CD34+, and myeloid-derived suppressor cells did not show any association. Coincident with the results of individual analysis, we identified CD4+ cells and CD44+CD24−/low cells as good predictors of long-term clinical outcome in a logistic regression. Fil: Rico, Maria Jose. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; Argentina Fil: Perroud, Herman Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; Argentina Fil: Herrera, Cintia. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; Argentina Fil: Alasino, Carlos M.. Instituto de Oncología de Rosario; Argentina Fil: Roggero, Eduardo Angel. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; Argentina Fil: Pezzotto, Stella Maris. Universidad Nacional de Rosario. Facultad de Ciencias Médicas; Argentina. Universidad Nacional de Rosario. Consejo de Investigación; Argentina Fil: Nocito, Ana Lía. Universidad Nacional de Rosario. Facultad de Ciencias Médicas; Argentina Fil: Rozados, Viviana Rosa. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; Argentina Fil: Scharovsky, Olga Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; Argentina. Universidad Nacional de Rosario. Consejo de Investigación; Argentina

Uric acid (UA) has been associated with renal fibrosis and progression of chronic kidney disease. However, the underlying mechanisms of this process have still not been identified. Here, we studied the role of the innate imunity receptor NLRP3/ASC in UA induced epithelial-mesenchymal transition (EMT) in kidney. Wistar rats were fed with oxonic acid 2% and UA 2% (OXA + U), OXA + U plus allopurinol (ALL) or regular chow (C) for 7 weeks. We analyzed the presence of EMT markers, the expression of NLRP3, ASC, Caspase-1 and Smad 2/3 molecules and the mitochondrial morphological and functional characteristics. High UA induced renal fibrosis, mild chronic inflammation, as well as morphological and biochemical evidence of EMT. High UA also increased the expression of NLRP3/ASC with activation of both inflammasome related caspase-1 and inflammasome unrelated Smad 2/3 pathways. Ultrastructural co-localization of NLRP3 and Smad 2/3 indicated physical interaction between the two molecules. No morphological or functional changes were found between mitochondria exposed to high UA. In conclusion, kidney epithelial NLRP3/ASC expression was increased in high UA state in rats and both inflammasome related caspase-1 and non-inflammasome related P-Smad 2/3 pathways were associated with the observed EMT, inflammation and fibrosis induced by UA in the kidney. Fil: Romero, Cesar Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina Fil: Remor, Aline. Universidade Federal de Santa Catarina; Brasil Fil: Latini, Alexandra. Universidade Federal de Santa Catarina; Brasil Fil: de Paul, Ana Lucia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina Fil: Torres, Alicia Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina Fil: Mukdsi, Jorge Humberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina

OBJECTIVE. We sought to explore whether patients with pectus excavatum have exaggerated interventricular dependence and to evaluate the impact of the malformation severity (assessed on CT) on both anatomic and functional cardiac parameters (assessed on cardiac MRI). SUBJECTS AND METHODS. The current study involved consecutive patients with a diagnosis of pectus excavatum who were referred to undergo cardiac MRI and chest CT to establish surgical candidacy or to define treatment strategies. RESULTS. Sixty-two patients with pectus excavatum underwent cardiac MRI and chest CT. Fifty (81%) patients were male, and the median age was 17.5 years (range, 14.0-23.0 years). Forty-seven (76%) patients had evidence of right ventricular compression. The left ventricle showed a significantly decreased end-diastolic volume (inspiration vs expiration: 70.4 ± 11.6 vs 76.1 ± 13.7 mL/m2, respectively; p = 0.01) and a significantly higher eccentricity index (1.52 ± 0.2 vs 1.20 ± 0.1, p < 0.0001) during inspiration than during expiration. The median respiratory-related septal excursion was 8.1% (interquartile range, 5.1-11.7%). Patients with pericardial effusion showed a significantly higher pectus excavatum severity index than patients without pericardial effusion (6.3 ± 3.4 vs 4.4 ± 1.3, respectively; p = 0.003). Patients with a relative septal excursion equal to or larger than 11.8% showed a significantly higher pectus excavatum severity index than patients with a relative septal excursion of less than 11.8% (6.3 ± 2.6 vs 4.7 ± 2.4, respectively; p = 0.05). CONCLUSION. In this study, patients with pectus excavatum showed significant alterations of cardiac morphology and function that were related to the deformation severity and that manifest as an exaggerated interventricular dependence. Fil: Deviggiano, Alejandro. Diagnostico Maipu; Argentina Fil: Vallejos, Javier. Diagnostico Maipu; Argentina Fil: Vina, Natalia. Diagnostico Maipu; Argentina Fil: Martinez Ferro, Marcelo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); Argentina Fil: Bellia Munzon, Gaston. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); Argentina Fil: Carrascosa, Patricia. Diagnostico Maipu; Argentina Fil: Rodriguez Granillo, Gaston Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Diagnostico Maipu; Argentina

Traditional approaches for risk assessment of ischemic heart disease (IHD) are based on the physiological consequences of an epicardial coronary stenosis. Of note, normal coronary arteries or nonobstructive coronary artery disease (CAD) is a common finding in women with signs and symptoms of ischemia. Therefore, assessment of risk based on a coronary stenosis approach may fail in women. Positron emission tomography (PET) quantifies absolute myocardial blood flow (MBF) which may help to elucidate other mechanisms involved such as endothelial dysfunction and alterations in the smooth muscle cell relaxation responsible for IHD in women. The objective of the present review is to describe the current state of the art of PET imaging in assessing IHD in women with nonobstructive CAD. Fil: Campisi, Roxana. Instituto Argentino de Diagnostico y Tratamiento; Argentina. Diagnostico Maipu; Argentina Fil: Marengo, Fernando Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina

Purpose of review: One of the most important challenges in the intestinal (ITx) and multivisceral transplant (MVTx) is to achieve a successful abdominal wall closure. Recent findings: A tension-free primary closure should be our aim. In most of the cases, we need to perform a component separation technique, alone or combined, to the use of a synthetic mesh. If those options are not feasible, the abdominal wall composite vascularized allograft transplant (AW-CVA) utilizing direct orthotopic vascularization can be considered. The nonvascularized abdominal rectus fascia has also become an alternative method used worldwide, proving to be simple and well tolerated procedure. Furthermore, the use of the AW has been recently proposed as a new tool for a sentinel monitoring of the intestinal or pancreas allograft. Summary: There are different validated options for abdominal wall closure following intestinal transplantation. The long-term benefits of transplanting the abdominal wall, full or partial thickness and vascularized or nonvascularised, were shown. New developments might help to expand their applications in different areas such as reconstructive surgery and immunology. Fil: Gondolesi, Gabriel Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Favaloro; Argentina Fil: Aguirre, Nicolas. Fundación Favaloro; Argentina

Purpose The use of traditional complementary/alternative medicine (TCAM) among children with cancer has been well documented. South America has a rich history of traditional healers and medicinal resources; however, little is known about the use of TCAM among children with cancer. We sought to investigate patterns, beliefs, and determinants of TCAM use among South American children with cancer. Methods A cross-sectional survey was administered to 199 children treated for cancer at institutions located in Buenos Aires, Argentina, and Montevideo, Uruguay. Participants were queried about the type of TCAM and strength of beliefs associated with its use. Logistic regression analysis was used to estimate the odds ratios with 95% CIs. Results We found that the use of TCAM was common in both Argentina (47%) and Uruguay (76%). Variations in the forms of TCAM used were observed between the countries; however, both countries used TCAM primarily for supportive care. Mother's education, wealth index, and TCAM belief system were significant predictors of TCAM. Conclusion To our knowledge, this study is the first to report on the use of TCAM in pediatric oncology in South America. The study identifies several predictors of TCAM use, which may serve as target variables for educational and research initiatives. The finding that most families use TCAM for supportive care suggests that future efforts could evaluate the role of TCAM to enhance existing supportive care regimens, particularly in settings where access to conventional medications are limited. Fil: Rocha, Valeria. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina Fil: Ladas, Elena J.. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina Fil: Lin, Meiko. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina Fil: Cacciavillano, Walter. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina Fil: Ginn, Elizabeth. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina Fil: Kelly, Kara M.. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina Fil: Chantada, Guillermo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina Fil: Castillo, Luis. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina

We hypothesized that DNA methylation is involved in human adrenal functional zonation. mRNAsexpression and methylation pattern of RARB, NR4A1 and HSD3B2 genes in human adrenal tissues (HAT)and in pediatric virilizing adrenocortical tumors (VAT) were analyzed. For analysis of the results sampleswere divided into 3 age groups according to FeZ involution, pre and post-adrenarche ages. In all HAT,similar RARB mRNA was found including microdissected zona reticularis (ZR) and zona fasciculata, butHSD3B2 and NR4A1 mRNAs were lower in ZR (p < 0.05). NR4A1 and RARB promoters remainedunmethylated in HAT and VAT. No adrenal zone-specific differences in NR4A1 methylation wereobserved.In summary, RARB was not associated with ZR-specific downregulation of HSD3B2 in postnatal humanadrenocotical zonation. DNA methylation would not be involved in NR4A1 adrenocortical cell-typespecific downregulation. Lack of CpG islands in HSD3B2 suggested that HSD3B2 ZR-specific downregulationwould not be directly mediated by DNA methylation. Fil: Baquedano, María Sonia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina Fil: Perez Garrido, Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Goñi, Javier. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina Fil: Saraco, Nora Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina Fil: Aliberti, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina Fil: Berensztein, Esperanza Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Rivarola, Marco Aurelio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina Fil: Belgorosky, Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina

Objective To explore the relationship between ventricular filling curves and the extent of late enhancement on cardiac magnetic resonance imaging (MRI) in patients with hypertrophic cardiomyopathy. Material and methods We retrospectively included consecutive patients with suspected and/or confirmed hypertrophic cardiomyopathy and a control group of patients matched for age and sex who underwent cardiac MRI with evaluation of late enhancement. Among other determinations, we evaluated the following parameters on cine sequences: peak filling rate, time to the first peak filling rate, and filling rate normalized to the filling volume. Results Late enhancement was observed in 29 (73%) of the 40 patients with hypertrophic cardiomyopathy. The normalized peak filling rate was significantly lower in patients with late enhancement (4.9 ± 1.6 in those with hypertrophic cardiomyopathy positive for late enhancement vs. 5.8 ± 2.2 in those with hypertrophic cardiomyopathy negative for late enhancement vs. 6.3 ± 1.5 in controls, p = 0.008) and the time to peak filling was longer in patients with late enhancement (540.6 ± 89.7 ms vs. 505.5 ± 99.3 ms in those with hypertrophic cardiomyopathy negative for late enhancement vs. 486.9 ± 86.3 ms in controls, p = 0.02). When the population was stratified into three groups in function of the normalized peak filling rate, significant differences were observed among groups for age (p = 0.002), mean wall thickness (p = 0.036), and myocardial mass (p = 0.046) and atrial dimensions, whereas no significant differences with respect to late enhancement were seen. Conclusions In patients with hypertrophic cardiomyopathy, we found a significant association between ventricular filling patterns and age, wall thicknesses, and atrial dimensions, but not with the extent of late enhancement. Objetivo Explorar mediante resonancia magnética cardíaca la relación entre las curvas de llenado ventricular y la extensión del realce tardío (RT) en pacientes con miocardiopatía hipertrófica. Material y métodos Se incluyeron de forma retrospectiva pacientes consecutivos con sospecha y/o diagnóstico de miocardiopatía hipertrófica, y un grupo control de pacientes pareados según sexo y edad en quienes se realizó una resonancia magnética cardíaca con valoración de RT. Entre otras determinaciones, se evaluaron mediante secuencias cine: tasa de llenado pico, tiempo a la primera tasa de llenado pico y tasa de llenado pico normalizada al volumen de llenado. Resultados De los 40 pacientes con miocardiopatía hipertrófica, 29 (73%) presentaron RT. Se evidenciaron diferencias significativas respecto a la tasa de llenado pico normalizada (RT positivo 4,9 ± 1,6, vs. RT negativo 5,8 ± 2,2, vs. control 6,3 ± 1,5, p = 0,008) y al tiempo a la tasa de llenado pico (540,6 ± 89,7 ms, vs. 505,5 ± 99,3 ms, vs. 486,9 ± 86,3 ms, p = 0,02). Al estratificar la población en tercios según la tasa de llenado pico normalizada al volumen de llenado se registraron diferencias significativas entre los grupos respecto a la edad (p = 0,002), espesor parietal medio (p = 0,036), masa miocárdica (p = 0,046) y dimensiones auriculares, mientras que no se observaron diferencias significativas respecto al RT. Conclusiones En pacientes con miocardiopatía hipertrófica encontramos una asociación significativa entre patrones de llenado ventricular y edad, espesores parietales y dimensiones auriculares, mientras que no se identificó una relación significativa con la extensión del RT. Fil: De Zan, M.. Departamento de Estudios Cardiovasculares no Invasivos de Diagnóstico; Argentina Fil: Carrascosa, P.. Departamento de Estudios Cardiovasculares no Invasivos de Diagnóstico; Argentina Fil: Deviggiano, A.. Departamento de Estudios Cardiovasculares no Invasivos de Diagnóstico; Argentina Fil: Capunay, C.. Departamento de Estudios Cardiovasculares no Invasivos de Diagnóstico; Argentina Fil: Rodriguez Granillo, Gaston Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Departamento de Estudios Cardiovasculares no Invasivos de Diagnóstico; Argentina

Background/Aim: Congenital hypothyroidism (CH) is a heterogeneous entity. Neonatal screening programs based on thyrotropin (TSH) determination allow primary CH diagnosis but miss central CH (CCH). CCH causes morbidity, alerts to other pituitary deficiencies, and is more prevalent than previously thought. We aimed at developing a pilot neonatal screening program for CCH detection. Patients and Methods: A prospective 2-year pilot neonatal screening study based on simultaneous dried blood specimen TSH and thyroxine (T4) measurements was implemented in term newborns aged 2-7 days. Those with T4 ≤4.5 μg/dL (-2.3 SDS) and TSH

Antecedentes Desde fines del siglo xix las mujeres están irrumpiendo global y vigorosamente en las profesiones científicas, de tal manera que en los albores del xxi, en medicina y neurología, ya equiparan a los hombres. Sin embargo, continúan subrepresentadas en cargos de liderazgo asistencial y académico. El objetivo de este trabajo es analizar la magnitud, la evolución y las características de la feminización de la neurología en Argentina. Método Se analizó la información obtenida en organismos oficiales, asociaciones y publicaciones médicas y neurológicas de Argentina, y en las bases de datos internacionales empleando las palabras «mujeres en medicina», «mujeres en neurología», «feminización en medicina», «feminización en neurología», «liderazgo en medicina» y «liderazgo en neurología». Resultados Existe una marcada desproporción entre el incremento demográfico de las mujeres y su reducida participación en cargos de liderazgo. Asimismo, el creciente aumento en publicaciones de trabajos neurológicos justifica aún más la demanda de reparo del desequilibrio, incluso siendo inferior a la tasa de publicación de las médicas clínicas en Argentina o al de las neurólogas en revistas internacionales. Conclusiones La feminización de la neurología y la subrepresentación en cargos jerárquicos en Argentina forman parte de un cambio cultural global. Los indicadores actuales sugieren que lentamente se está corrigiendo el desequilibrio. Las neurólogas líderes constituyen un valioso recurso para estimular la productividad de las jóvenes y denunciar la existencia de barreras arbitrarias. Background Since the beginning of the 19th century, women have firmly pervaded the scientific field resulting in a present one-on-one relationship with men in Medicine in general and Neurology in particular. Nevertheless, they remain underrepresented in hierarchical positions, both in clinical and research areas. The objective of this study is to analyze the characteristics, evolution and magnitude of the process of feminization of Neurology in Argentina. Method We analyzed the information gathered from governmental institutions, medical associations and international and national medical and neurological publications using the words “women in Medicine”, “women in Neurology”, “feminization in Medicine”, “feminization in Neurology”, “leadership in Medicine” and “leadership in Neurology”. Results There is a clear asymmetry between the proportion of working women in Medicine and Neurology and their number in senior positions. In addition, their production of neurological publications grows at a steady rate, although at a slower pace in comparison with clinical articles or international neurological papers. Conclusions The feminization of Neurology in Argentina and the underrepresentation of women in hierarchical positions are the local expressions of a worldwide social and cultural process. Extant estimations suggest that this discrepancy is being slowly rectified. Current female neurologist leaders are key in opening pathways to younger peers and in breaking the arbitrary barriers that they have encountered or will encounter in the future. Fil: Somoza, Manuel J.. Fundación Para la Investigación En Neuroepidemiologia; Argentina Fil: Quarracino, Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; Argentina

Background: Langerhans cell histiocytosis (LCH) is a rare histiocytic disorder of unknown etiopathogenesis. Central diabetes insipidus (CDI) is the most frequent endocrine manifestation and is a known risk factor for the development of further anterior pituitary hormone deficiencies (APD). However, not all CDI patients develop APD, as observed during prolonged periods of follow-up. Aim: To find predictors of developing APD in LCH children with CDI followed in our institution. Methods: We retrospectively analysed 44 patients over a median period (quartiles) of 12.3 years (8.79-14.24). Patients were subdivided into group 1 and group 2, according to absence or presence of APD, respectively. The main variables studied were: (1) chronological age (CA) at LCH diagnosis, (2) the primary site of LCH at diagnosis: low risk (LR) and multisystemic risk organs, and (3) the presence of reactivation. Results: Multivariate Cox regression analysis showed that APD was positively associated with CA at LCH diagnosis [relative risk (RR) 1.14, p < 0.01], the LR clinical form (RR 8.6, p < 0.03), and negatively associated with the presence of reactivations (RR 0.3, p < 0.01). Conclusions: Patients with older CA at LCH diagnosis, LR clinical forms, and fewer reactivation episodes might represent a subgroup of paediatric LCH CDI patients with a higher risk of developing APD. Fil: Vaiani, Elisa. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina Fil: Malossetti, Carmen. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina Fil: Vega, Lina Margarita. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina Fil: Zubizarreta, Pedro. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina Fil: Braier, Jorge. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina Fil: Belgorosky, Alicia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina

Las úlceras venosas crónicas (UVC) de miembros inferiores son una consecuencia severa de la Insuficiencia Venosa Crónica. Es una patología recurrente de alta prevalencia que afecta calidad de vida de los pacientes que las padecen, representando una grave problemática social y económica en el mundo. La ausencia de una caracterización completa de las mismas con un número de muestras estadísticamente significativo y un método estandarizado de seguimiento terapéutico son la causa por la cual los esquemas de tratamiento utilizados son inefectivos y no pueden lidiar con la cronicidad. Por ello, el principal objetivo de la presente tesis fue realizar una caracterización integral de UVC y sus pacientes y correlacionarla con espectros FT-IR de sus exudados, de manera de hallar perfiles espectrales característicos que permitan ofrecer un método rápido de diagnóstico, pronóstico y el diseño personalizado de tratamientos.Este trabajo se realizó en colaboración entre el Servicio de Dermatología del Hospital de Clínicas Nicolás Avellaneda y el Laboratorio de Estudios Farmacéuticos y Biotecnología Farmacéutica (LEFyBiFa-INBIOFAL-CONICET-UNT). El protocolo de trabajo fue aprobado y monitoreado por el Comité Independiente de Ética Médica del Noroeste Argentino (CIEMNOA) y por el Comité de Docencia e Investigación del mencionado Nosocomio. Utilizando criterios de inclusión preestablecidos, se seleccionaron 93 pacientes, reclutados bajo firma de consentimiento informado. Dicho protocolo permitió la caracterización de los pacientes y sus úlceras: a) Microbiológicamente en biopsias y exudados. b) Histológicamente en biopsias. c) Bioquímicamente (pH, ácido láctico, glucosa) en exudados. d) Fisicoquímicamente a través del estudio de los exudados por espectroscopia infrarroja con Transformadas de Fourier (FT-IR). e) Macroscópicamente mediante fotografías y estudios por planimetría. f) Clínicamente a través del estudio de historias clínicas y anamnesis de los pacientes afectados.La caracterización clínica permitió determinar que la mayoría de los pacientes afectados son mayores de 60 años sin distinción de género, encontrándose una alta correlación con comorbilidades que típicamente llevan al edema de miembros inferiores.Se encontraron parámetros clínicos que permiten el seguimiento y caracterización de estado de una UVC: a) Δ = [Tºcorporal-Tºúlcera]>3ºC; b) Un abundante volumen de exudado con un pH ≥ 8. c) La ausencia de dolord) Planimetría: Tejido de granulación < 80% e) Biopsias: Un % de fibrosis 105 UFC/gtejido, Estos podrían considerarse como marcadores clínicos de baja efectividad terapéutica.Se caracterizó microbiológicamente a las UVC identificando los patógenos más frecuentemente aislados en nuestro medio y su resistencia a diferentes antibióticos. Además, se determinó la biocarga característica en muestras de biopsia. A partir de un complejo análisis en muestras de exudado mediante espectrosopia FTIR, se encontraron diversos parámetros celulares (células inflamatorias y carga bacteriana) y moleculares (Fibrina, proteínas pro-inflamatorias, exopolisacáridos) como potenciales indicadores de cicatrización. Por esto, la caracterización de UVC propuesta en este plan no solo aportará al conocimiento de la fisiopatogenia sino que permitirá el desarrollo de un método rápido de diagnóstico y pronóstico clínico de las mismas. Esto a su vez, ayudará al diseño de tratamientos específicos para cada herida (personalizados), aumentando en gran medida la probabilidad de éxito terapéutico Chronic venous leg ulcers (CVLU) are a Chronic Venous Insufficiency severe consequence. It is a recurrent pathology of high prevalence that affects the patient’s quality of life who suffer from them, representing a serious social and economic world problem. The lack of a complete CVLU characterization statistically significant and the absence of a therapeutic follow-up standardized method are the reasons why the employed treatment schemes fail and cannot deal with the chronicity. Therefore, the thesis main aim was to perform an integral CVLU characterizatio and then correlate it with patient exudates FT-IR spectra, in order to find spectral profiles that offer a quick diagnosis and prognosis method and a custom treatments design. This work was carried out in collaboration between the Dermatology Service of the Nicolas Avellaneda Hospital and the Laboratory of Pharmaceutical Studies and Pharmaceutical Biotechnology (LEFyBiFa-INBIOFAL-CONICET-UNT). The protocol was approved and monitored by the Independent Committee of Medical Ethics of the Argentine Northwest (CIEMNOA) and by the Teaching and Research Committee of the mentioned Nosocomium. Using pre-established inclusion criteria, 93 patients were selected, recruited under informed consent signature. This protocol allowed the patient and ulcers characterization: a) Microbiologically in biopsies and exudates. b) Histologically in biopsies. c) Biochemically (pH, lactic acid, glucose) in exudates. d) Physicochemically through the exudate study by Fourier Transforms Infrared spectroscopy (FT-IR). e) Macroscopically by palnimetric study of photographs. f) Clinically, by clinical records study and patient anamnesis. From clinical characterization was determined that the majority of affected patients are older than 60 years without gender distinction, finding a high correlation with comorbidities that typically lead to lower limbs edema. Other clinical parameters that allow monitoring and characterization of CVLU state were found: a) Δ = [ToBody-ToUlcer]> 3oC; b) A large exudate volume with a pH ≥ 8. c) Pain absence. d) Planimetry: Granulation tissue 10 5 CFU/gtissue. These parameters could be considered as low therapeutic effectiveness clinical markers. The CVLU was microbiologically characterized, identifying the most frequently isolated pathogens in the region and their antibiotics resistance. In addition, the characteristic bioburden in biopsy samples was determined. From a FTIR spectroscopy complex analysis performed on exudate samples, several cellular parameters (inflammatory cells and bacterial load) and molecular parameters (Fibrin, pro-inflammatory proteins, exopolysaccharides) as potential healing markers were found. Therefore, the proposed CVLU characterization contribute to the physiopathogenesis knowledge and also will allow the development of a diagnosis and clinical prognosis quick method. Then, it will help to design specific treatments for each wound (personalized), greatly increasing the therapeutic success probability Fil: Cerúsico, Nicolás Abel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán; Argentina

OBJECTIVE: To assess the frequency of additional care, and parents' perceptions of quality, respectful care, in pregnancies subsequent to stillbirth. DESIGN: Multi-language web-based survey. SETTING: International. POPULATION: A total of 2716 parents, from 40 high- and middle-income countries. METHODS: Data were obtained from a broader survey of parents' experiences following stillbirth. Data were analysed using descriptive statistics and stratified by geographic region. Subgroup analyses explored variation in additional care by gestational age at index stillbirth. MAIN OUTCOME MEASURES: Frequency of additional care, and perceptions of quality, respectful care. RESULTS: The majority (66%) of parents conceived their subsequent pregnancy within 1 year of stillbirth. Additional antenatal care visits and ultrasound scans were provided for 67% and 70% of all parents, respectively, although there was wide variation across geographic regions. Care addressing psychosocial needs was less frequently provided, such as additional visits to a bereavement counsellor (10%) and access to named care provider's phone number (27%). Compared with parents whose stillbirth occurred at ≤ 29 weeks of gestation, parents whose stillbirth occurred at ≥ 30 weeks of gestation were more likely to receive various forms of additional care, particularly the option for early delivery after 37 weeks. Around half (47-63%) of all parents felt that elements of quality, respectful care were consistently applied, such as spending enough time with parents and involving parents in decision-making. CONCLUSIONS: Greater attention is required to providing thoughtful, empathic and collaborative care in all pregnancies following stillbirth. Specific education and training for health professionals is needed. Fil: Wojcieszek, A.M.. The University Of Queensland; Australia Fil: Boyle, F.M.. The University Of Queensland; Australia Fil: Belizan, Jose. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. International Stillbirth Alliance; Reino Unido. Instituto de Eficacia Clínica y Política de Salud; Argentina Fil: Cassidy, J. International Stillbirth Alliance; Reino Unido. Umamanita; España Fil: Cassidy, P. International Stillbirth Alliance; Reino Unido. Umamanita; España Fil: Erwich, J.J.H.M.. International Stillbirth Alliance; Reino Unido. University of Groningen; Países Bajos Fil: Farrales, L. International Stillbirth Alliance; Reino Unido. University of British Columbia; Canadá. Research and Support Society; Canadá Fil: Gross, MM. International Stillbirth Alliance; Reino Unido. Hannover Medical School; Alemania. Universitat Zurich; Suiza Fil: Heazell, A.E.P. International Stillbirth Alliance; Reino Unido. University of Manchester; Reino Unido. Manchester Academic Health Science Centre; Reino Unido Fil: Leisher, S.H.. International Stillbirth Alliance; Reino Unido. The University Of Queensland; Australia Fil: Mills, T. University of Manchester; Reino Unido Fil: Murphy, M. International Stillbirth Alliance; Reino Unido. University College Cork; Irlanda Fil: Pettersson, K. International Stillbirth Alliance; Reino Unido. Karolinska University; Suecia Fil: Ravaldi, C. International Stillbirth Alliance; Reino Unido. Ciao Lapo Onlus; Italia Fil: Ruidiaz, J. International Stillbirth Alliance; Reino Unido. Era en Abril; Argentina Fil: Siassakos, D. International Stillbirth Alliance; Reino Unido. University of Bristol; Reino Unido Fil: Silver, R.M.. International Stillbirth Alliance; Reino Unido. University of Utah; Estados Unidos Fil: Storey, C. International Stillbirth Alliance; Reino Unido Fil: Vannacci, A. International Stillbirth Alliance; Reino Unido. Ciao Lapo Onlus; Italia. University of Florence; Italia Fil: Middleton, P. International Stillbirth Alliance; Reino Unido. South Australian Health and Medical Research Institute; Australia Fil: Ellwood, D. International Stillbirth Alliance; Reino Unido. Griffith University and Gold Coast University ; Australia Fil: Flenady, V. International Stillbirth Alliance; Reino Unido. University of Queensland; Australia

Background Evidence about the clinical course of bipolar disorder is inconsistent and limited. The aim of this study was to assess changes in morbidity in patients with bipolar disorder along a mean follow-up period of 80 months. Methods Based on a mirror-image design, the follow-up period of each patient was divided into two halves. Then, three measures of morbidity — number of affective episodes, time spent ill, and cycle length — were recorded and compared between each half of the follow-up period. Results On average, there was a trend to a smaller amount of time spent with subclinical symptomatology during the second half of the follow-up period. In contrast, there were no differences in terms of number of episodes, time spent with clinical symptoms, or cycle length between the first and second half of the follow-up period. A subgroup analysis identified 21.9% of patients with consistent data of a worsening during follow-up. Conclusions The results suggest that, on average, there is stability or slight improvement of clinical morbidity over the course of BD. Then, worsening of the clinical course may be a feature of a subgroup of patients rather than an inherent characteristic of the disorder. These subgroups or patient profiles could represent an opportunity for further studies to assess clinical, pathophysiologic, and therapeutic features associated with them. Fil: Martino, Diego Javier. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Favaloro; Argentina Fil: Samame, Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Favaloro; Argentina Fil: Marengo, E.. Universidad Favaloro; Argentina Fil: Igoa, A.. Universidad Favaloro; Argentina Fil: Scápola, M.. Universidad Favaloro; Argentina Fil: Strejilevich, S. A.. Universidad Favaloro; Argentina. Instituto de Neurología Cognitiva; Argentina

Subclinical spirometric abnormalities may be detected in patients with rhinitis without asthma, proportional to the severity established by ARIA (Allergic Rhinitis and Its Impact on Asthma) guidelines. New criteria of rhinitis classification were recently validated according to the ARIA modified (m-ARIA), which allow the discrimination between moderate to severe grades. The impact of rhinitis on lung function according to frequency and severity is unknown. Objectives To investigate subclinical spirometric impairment in children and adolescents with allergic and non-allergic rhinitis without overt symptoms of asthma, according to the frequency and severity criteria of rhinitis classified by m-ARIA. Methods An observational cross-sectional study, including children and adolescents aged 5–18 years with allergic and non-allergic rhinitis without asthma. We analysed the functional abnormalities and bronchodilator response with spirometry in relation to the grade of rhinitis established by m-ARIA using an adjusted logistic model. A value of p 0.05). Conclusions Impaired lung function was associated with persistence and severity of rhinitis and there was no significant difference between patients with moderate and severe rhinitis. The spirometric abnormality was demonstrated in patients with allergic and non-allergic rhinitis. Fil: Saranz, Ricardo José. Universidad Catolica de Córdoba. Facultad de Medicina. Clinica Universitaria Reina Fabiola; Argentina Fil: Lozano, Alejandro. Universidad Catolica de Córdoba. Facultad de Medicina. Clinica Universitaria Reina Fabiola; Argentina Fil: Valero, Antonio. Universidad Catolica de Córdoba. Facultad de Medicina. Clinica Universitaria Reina Fabiola; Argentina Fil: Lozano, Natalia A.. Universidad Catolica de Córdoba. Facultad de Medicina. Clinica Universitaria Reina Fabiola; Argentina Fil: Bovina Martijena, María P.. Universidad Catolica de Córdoba. Facultad de Medicina. Clinica Universitaria Reina Fabiola; Argentina Fil: Agresta, María F.. Universidad Catolica de Córdoba. Facultad de Medicina. Clinica Universitaria Reina Fabiola; Argentina Fil: Ianiero, Luciano. Universidad Catolica de Córdoba. Facultad de Medicina. Clinica Universitaria Reina Fabiola; Argentina Fil: Ponzio, Marina Flavia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina

Objectives: To assess, describe and compare the requirements and pathwaysof medical devices from licensing to coverage in four Latin American countries(LAC) health systems. Methods: We conducted a literature search (February 2015)on Pubmed, Lilacs and Value in Health Regional Issues journal. We also searchedspecific websites of Health Technology Assessment (HTA) and regulatory agencies,ministries of health and health agencies; and a performed generic Internet search.We included all publications describing aspects related to regulation, coverage,medical technology innovation, and HTA and Economic Evaluation (EE) guidelines.We additionally interviewed key informants from all countries to gather informationrelated to the aforementioned processes. We present here the literature searchresults. Results: We included 60 studies out of 2190. Five percent of the publicationsanalyzed the four countries jointly, 75% were from Brazil, 8.3% from Mexico, 5%from Colombia and 5.7% from LAC in general. Half of the studies described the roleof the HTA and EE in decision-making and aspects or policies related to innovation(25% and 23.3%). Regarding the description of the coverage process, it was addressedin 13.3% of the studies; 10% of the publications focused on technovigilance; and also10% on regulatory aspects. Remaining publications were methodological guidelinesand general descriptions of the health systems and the role of medical devices. Allcountries had HTA and EE guidelines, although there did not include device specificrecommendations. There is a spectrum of HTA formalization for technology incorporationafter licensing, higher in Brazil and lower in Argentina Conclusions:There is scarce information on the processes and requirements to achieve coveragefor medical devices in these countries. Processes differ, are in general not explicit,lack transparency, and usually replicate those of drugs not taking into account thespecificities of medical devices. Fil: Rey Ares, Lucila. Instituto de Efectividad Clínica y Sanitaria; Argentina Fil: Hernández Vásquez, Akram. Instituto de Efectividad Clínica y Sanitaria; Argentina Fil: Garay, Osvaldo Ulises. Instituto de Efectividad Clínica y Sanitaria; Argentina Fil: Pichón-Riviere, Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Efectividad Clínica y Sanitaria; Argentina Fil: García Martí, Sebastián. Instituto de Efectividad Clínica y Sanitaria; Argentina Fil: Gilardino, Ramiro. Johnson & Johnson Medical Companies; Argentina Fil: Cabra, Hermilio Arturo. Johnson & Johnson Medical Companies; Argentina Fil: Augustovski, Federico Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Efectividad Clínica y Sanitaria; Argentina

Introduction: The selective inhibitors of COX-2, coxibs, are nonsteroidal anti-inflammatory drugs (NSAIDs) that have much better gastrointestinal safety profile as compared with non-selective NSAIDs. In this review, we analyze both the epidemiological features of coxib-induced hepatotoxicity and the clinical impact of coxib-associated liver damage, based on literature data. Areas covered: We carried out a search of the databases MEDLINE (PubMed), LILACS and SCIELO, from December 1999 to January 2016, to retrieve studies exploring the real impact of coxibs in liver toxicity as compared to non-selective COX-2 inhibitor NSAIDs. Expert opinion: Although reliable data on the incidence of celecoxib- and etoricoxib-induced hepatotoxicity are lacking, because of cohort studies have been generally underpowered to detect hepatic events, coxibs have been scarcely related to hepatotoxicity. Hence, coxib-induced liver injury seems to be an uncommon event, yet exhibits a wide spectrum of damage. Increasing COX-2 drug selectivity, as for rofecoxib, valdecoxib, parecoxib, and lumiracoxib, has been associated with higher cardiovascular risk, as well as dermatological and serious hepatic reactions. The actual risk of liver toxicity from the currently approved coxibs compared with non-selective NSAIDs will be discussed. Finally, classical and novel molecular mechanisms of coxib-induced hepatotoxicity are also described. Fil: Bessone, Fernando. Provincia de Santa Fe. Ministerio de Salud y Medio Ambiente - Rosario. Hospital Provincial del Centenario; Argentina Fil: Hernandez, Nelia. Universidad de la República; Uruguay Fil: Roma, Marcelo Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; Argentina Fil: Ridruejo, Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno”; Argentina Fil: Mendizabal, Manuel. Hospital Universitario Austral; Argentina Fil: Medina Cáliz, Inmaculada. Universidad de Málaga; España Fil: Robles Díaz, Mercedes. Universidad de Málaga; España Fil: Lucena, M. Isabel. Universidad de Málaga; España Fil: Andrade, Raúl J.. Universidad de Málaga; España

Objetivos: El acceso temprano a la población de pacientes con artritis reumatoidea (AR) a la asistencia especializada es un predictor de buen pronóstico. Sin embargo, la demora en la consulta es una constante; fueron identificados factores tales como los vinculados al paciente, el médico generalista o al sistema de salud. El objeto del estudio fue el de explorar la percepción de la población fuera del ámbito asistencial en un escenario potencial de sintomatología compatible con AR. Material y métodos: Se realizó un muestreo aleatorio de 1073 individuos mayores de 18 años, se realizó en la vía pública de los partidos de Quilmes y Berazategui. La encuesta fue efectuada por voluntarias entrenadas a tal fin las que indagaron acerca de a qué profesional consultaría si tuviera dolor e inflamación de los nudillos y muñecas de ambas manos, si cree padecer estos síntomas y si conoce la diferencia entre artritis y artrosis. Resultados: Frente a la posibilidad de padecer síntomas que remedan AR, la población encuestada eligió a los siguientes especialistas: traumatólogo (61%), clínico (17%), reumatólogo (15%), otros (7%). Un tercio de los encuestados refirió padecer esos síntomas y la mayoría (61%) referían no conocer la diferencia entre artritis y artrosis. Quienes más eligieron al reumatólogo como opción (56%) fueron del sexo femenino de entre 51 y 80 años y que conocían la diferencia entre AR y OA. Conclusiones: La ausencia relativa del reumatólogo en la preferencia de la población encuestada, así como la confusión respecto de la presencia de sintomatología compatible con la enfermedad o de la diferencia entre artritis y artrosis señalan la necesidad de ejecutar campañas de concientización pública dirigidas a la reafirmación de la especialidad frente a la patología articular inflamatoria. Objectives: Early access to specialized care is a predictor of good prognosis in patients recently diagnosed rheumatoid arthritis (RA). However, the delay in the consultation is a constant; they were identified factors such as those related to the patient, the general practitioner or the health system. The purpose of the study was to explore the perception of the population outside the healthcare setting in a potential scenario of symptoms compatible with RA. Material and methods: A random sample of 1073 individuals aged 18 and over was conducted. It was held in public matches of Quilmes and Berazategui. The survey was conducted by volunteers trained for this purpose which were asked which professional (in terms of specialty) would consult if they had pain and swelling of the knuckles and wrists of both hands, and "if you know the difference between arthritis and osteoarthritis". Results: Facing the possibility of having symptoms that mimic RA, the population surveyed chose the following specialists: orthopedic surgeons (61%), clinicians (17%), rheumatologists (15%), others (7%). A third of respondents have referred these symptoms and most (61%) reported not knowing the difference between arthritis and osteoarthritis. People who chose rheumatologist an option (56%) were female between 51 and 80 years and knew the difference between RA and OA. Conclusions: The relative absence of rheumatologist in the preference of the surveyed population, as well as confusion about the presence of symptoms compatible with the disease or the difference between arthritis and osteoarthritis indicate the need to implement public awareness campaigns aimed at reaffirming specialty against inflammatory joint disease. Fil: Velasco Zamora, Jorge. Fundación Articular; Argentina. Instituto CER-Quilmes; Argentina Fil: Papagno, María Julia. Instituto CER-Quilmes; Argentina Fil: Benítez, Alejandro. Instituto CER-Quilmes; Argentina Fil: Estévez, Adrián. Instituto CER-Quilmes; Argentina Fil: Preisegger, Matías Adán. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina Fil: Dewey, Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina

BACKGROUND: We sought to determine whether the response of pulmonary elimination of CO2 (Vco2) to a sudden increase in positive end-expiratory pressure (PEEP) could predict fluid responsiveness and serve as a noninvasive surrogate for cardiac index (CI).METHODS: Fifty-two patients undergoing cardiovascular surgery were included in this study. By using a constant-flow ventilation mode, we performed a PEEP challenge of 1-minute increase in PEEP from 5 to 10 cm H2O. At PEEP of 5 cm H2O, patients were preloaded with 500 mL IV salinesolution after which a second PEEP challenge was performed. Patients in whom fluid administration increased CI by ≥15% from the individual baseline value were defined as volume responders.Beat-by-beat CI was derived from arterial pulse contour analysis, and breath-by-breath Vco2 data were collected during the protocol. The sensitivity and specificity of Vco2 for detecting thefluid responders according to CI was performed by the receiver operating Characteristic curves.RESULTS: Twenty-one of 52 patients were identified as fluid responders (40%). The PEEP maneuver before fluid administration decreased CI from 2.65 ± 0.34 to 2.21 ± 0.32 L/min/m2 (P = 0.0011) and Vco2 from 150 ± 23 to 123 ± 23 mL/min (P = 0.0036) in responders, whereas the changes in CI and Vco2 were not significant in nonresponders. The PEEP challenge afterfluid administration induced no significant changes in CI and Vco2, in neither responders nor nonresponders. PEEP-induced decreases in CI and Vco2 before fluid administration were well correlated (r2 = 0.75, P < 0.0001) but not thereafter. The area under the receiver operating characteristic curves for a PEEP-induced decrease in ΔCI and ΔVco2 was 0.99, with a 95% confidence interval from 0.96 to 0.99 for ΔCI and from 0.97 to 0.99 for ΔVco2. During the PEEP challenge,a decrease in Vco2 by 11% predicted fluid responsiveness with a sensitivity of 0.90 (95% confidence interval, 0.87?0.93) and a specificity of 0.95 (95% confidence interval, 0.92?0.98).CONCLUSIONS: PEEP-induced changes in Vco2 predicted fluid responsiveness with accuracy in patients undergoing cardiac surgery. (Anesth Analg 2016;122:1404?11) Fil: Tusman, Gerardo. Fundación Medica de Mar del Plata. Hospital Privado de Comunidad; Argentina Fil: Groisman, Ivan. Fundación Medica de Mar del Plata. Hospital Privado de Comunidad; Argentina Fil: Maidana, Gustavo A.. Fundación Medica de Mar del Plata. Hospital Privado de Comunidad; Argentina Fil: Scandurra, Adriana G.. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Departamento de Electronica; Argentina Fil: Martinez Arca, Jorge. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Departamento de Electronica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Ciencia y Tecnología de Materiales. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Instituto de Investigaciones en Ciencia y Tecnología de Materiales; Argentina Fil: Bohm, Stephan H.. University Hospital; Suecia Fil: Suarez-Sipmann, Fernando. Instituto de Salud Carlos III; España

Background and Objectives The first weeks of treatment with antipsychotics are important for the development of their long-term efficacy. The objective of this study was to identify factors related to early clinical effects and quality of life (QoL) improvements with quetiapine extended-release (XR). Methods Six hundred and sixty-five patients starting with quetiapine XR were followed up for 8 weeks (schizophrenia = 153, major depression = 200, bipolar depression = 252, other psychiatric conditions = 60). Clinical effects were assessed by the Clinical Global Impression of Change scale (CGI-C), QoL by the visual analog scale (VAS) of the EQ-5D (QoL-VAS), and adherence by the Moriksy scale. Adverse events were explored: movement disorders by the UKU and Simpson-Angus scales, weight gain by calibrated balances, and diurnal somnolence by the Epworth Somnolence Scale (ESS). Results The mean dose of quetiapine XR during follow-up was 195.6 ± 154.8 mg/day. CGI and QoL-VAS scores improved significantly at week 8 by 2.7 ± 0.1 points and 25.1 ± 0.9 points. Adverse events were observed in 34 and 26 % of patients at weeks 4 and 8, respectively. A significant reduction in ESS score was also observed at week 8. Factors independently associated with change in QoL-VAS ≥20 points (n = 292, 43 %) were female gender, more severe disease at baseline, higher antipsychotic dose during follow-up, and improvements in somnolence. Factors independently associated with clinically significant improvement (CGI-C ≥5, n = 610, 93 %) were greater change in QoL-VAS, less frequent movement disorders at baseline, and lack of adverse events during follow-up, especially somnolence. Conclusions Results from this real-setting, large observational study in Central America suggest that disease severity at baseline, gender, antipsychotic dose, and occurrence of adverse reactions has a significant impact on the early clinical effects of quetiapine XR. Fil: Molina, Luis. Clínica de Especialidades Altamira; Nicaragua Fil: Recinos, Byron. Universidad San Carlos de Guatemala; Guatemala Fil: Paz, Bezner. Hospital Juan de Dios de San Pedro; Honduras Fil: Rovelo, Mauricio. Instituto de Salud Mental; Honduras Fil: Elias Rodriguez, Fanny Elizabeth. Colonia Médica; El Salvador Fil: Calderón, José. Clínica de la Conducta; Panamá Fil: Arellano, Arturo. Corporación Farmacéutica Recalcine; Costa Rica Fil: Pomata, Santiago. Corporación Farmacéutica Recalcine; Costa Rica Fil: Rey, María Verónica. Etymos Consulting Group; Argentina Fil: Pérez Lloret, Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; Argentina

Objective: Compensatory hypertrophy has been classically described in patients with monorchidism. However, it remains unclear whether there is a functional compensatory activity of the different cell populations. Our aim was to assess the functional capacity of the solitary testis in monorchid males from infancy through puberty in order to determine whether the remaining gonad is capable of compensating the functional activity of Sertoli and Leydig cells of the absent gonad. Design: In a retrospective, cross-sectional, analytical study performed at a tertiary paediatric public hospital, we included 89 boys with monorchidism and 358 healthy controls, aged 6 months-18 years. Testicular volume and circulating levels of reproductive hormones were compared between patients with monorchidism and normal boys. Serum anti-Mullerian hormone (AMH) and FSH were used as biomarkers of the functional mass of prepubertal Sertoli cells, whereas serum testosterone and LH were used as biomarkers of Leydig cells. Results: In the vast majority of the cases, the testicular volume of monorchid boys was smaller than the sum of the volume of both testes of healthy controls. Serum AMH was lower and FSH was higher in patients with monorchidism than in controls aged 13 years. Serum testosterone and LH did not differ significantly between patients and controls. Conclusion: In boys and adolescents with monorchidism, there is a dissociated capacity of the remaining testis to compensate for the absence of the other gonad: while Leydig cell function is largely compensated, Sertoli cell proliferation and function was lower than in controls. Fil: Grinspon, Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas ; Argentina Fil: Habib, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas ; Argentina Fil: Bedecarras, Patricia Gladys. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas ; Argentina Fil: Gottlieb, Silvia Elisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas ; Argentina Fil: Rey, Rodolfo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas ; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina

Background The number of previous episodes in patients with BD is a variable widely used for both clinical and research purposes. The aim of this study was to compare the number of episodes retrospectively reported by euthymic BD subjects with that registered by their psychiatrists during a follow-up period. Methods Fifty euthymic patients with BD and more than 2 years of follow-up were retrospectively asked in a standardized fashion about the number of hypomanic/manic and depressive episodes suffered during that period. Patient-reported outcomes were compared with the number of episodes registered by psychiatrists in a life chart during the same period. Results The mean follow-up of patients was 66.70 months. There was a mean difference of 2.74 episodes between reports of patients´ and psychiatrists´ reports during the complete follow-up period; Intraclass correlation coefficient was 0.40 (CI95% = 0.15-0.61). This difference increased with the duration of the follow-up period (R = 0.33, p = 0.023) and with the number of episodes occurred during that (R = 0.32, p = 0.023). The difference between patient-reported and clinician-rated in the number of depressive during the follow-up period was more pronounced in BDII than in BDI (Z = -2.47, p = 0.014), and it correlated with the number of previous depressive episodes at baseline (R = 0.28, p = 0.047) and subclinical depressive symptoms (R = 0.41, p = 0.003). Conclusions The number of previous episodes referred by patients with BD is not an accurate measure of the true number of episodes suffered. The theoretical and practical implications of these findings are discussed. Fil: Martino, Diego Javier. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Favaloro; Argentina Fil: Marengo, Eliana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Favaloro; Argentina Fil: Igoa, Ana. Universidad Favaloro; Argentina Fil: Scápola, María. Universidad Favaloro; Argentina Fil: Urtueta Baamonde, Mariana. Universidad Favaloro; Argentina Fil: Strejilevich, Sergio. Universidad Favaloro; Argentina. Instituto de Neurología Cognitiva; Argentina

The aim of this study was to investigate sexual health and sexual risk behaviors for sexually transmitted infections (STI) among women with bipolar disorder (BDW). Sixty-three euthymic women diagnosed with bipolar disorder type I, II or not otherwise specified were included and matched with a control group of 63 healthy women. Demographic and clinical data, structured sexual health measures and extensive assessment of sexual risk behavior were obtained and compared between groups. BDW had casual partners, were in non-monogamous sexual partnerships and had sex with partners with unknown HIV condition more frequently than healthy control women. History of two or more STI was more frequent among BDW. Inclusion of sexual behavior risk assessment among BDW in treatment is necessary to better identify those women with higher risk for STI and to take measures to improve their sexual health. Fil: Marengo, Eliana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Favaloro. Facultad de Medicina. Instituto de Neurociencias. Programa de Trastornos Bipolares; Argentina Fil: Martino, Diego Javier. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Favaloro. Facultad de Medicina. Instituto de Neurociencias. Programa de Trastornos Bipolares; Argentina Fil: Igoa, Ana. Universidad Favaloro. Facultad de Medicina. Instituto de Neurociencias. Programa de Trastornos Bipolares; Argentina Fil: Fassi, Guillermo. Universidad Favaloro. Facultad de Medicina. Instituto de Neurociencias. Programa de Trastornos Bipolares; Argentina Fil: Scápola, María. Universidad Favaloro. Facultad de Medicina. Instituto de Neurociencias. Programa de Trastornos Bipolares; Argentina Fil: Urtueta Baamonde, Mariana. Universidad Favaloro. Facultad de Medicina. Instituto de Neurociencias. Programa de Trastornos Bipolares; Argentina Fil: Strejilevich, Sergio. Universidad Favaloro. Facultad de Medicina. Instituto de Neurociencias. Programa de Trastornos Bipolares; Argentina

Fil: Garona, Juan. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina Fil: Sobol, Natasha Tatiana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina Fil: Alonso, Daniel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina

Tinnitus is a highly prevalent condition that is associated with hearing loss in most cases. In the absence of external stimuli, phantom perceptions of sounds emerge from alterations in neuronal activity within central auditory and nonauditory structures. Pioneering studies using lidocaine revealed that tinnitus is susceptible to pharmacological interventions. However, lidocaine is not effective in all patients, and no other drug has been identified with clear efficacy for the long-term treatment of tinnitus. In this review, we present recent advances in tinnitus research, including more detailed knowledge of its pathophysiology and involved neurotransmitter systems. Moreover, we summarize results from animal and clinical treatment studies as well as from studies that identified tinnitus as a side effect of pharmacological treatments. Finally, we focus on challenges in the development of pharmacological compounds for the treatment of tinnitus, namely the limitations of available animal models and of standardized clinical research methodologies. Fil: Langguth, Berthold. Universitat Regensburg; Alemania Fil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina Fil: Cederroth, Christopher R.. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia

Chronic lymphocytic leukemia (CLL) represents the most common leukemia in the Western world, accounting for 30-40% of all adult leukemias. The disease is characterized by a highly variable clinical course, ranging from indolent cases to patients with aggressive and rapidly progressing disease. Although staging systems are reliable predictors of outcome, they do not fully explain the heterogeneity in treatment response and survival. In the last decades, several prognostic biomarkers have been identified, allowing the subdivision of this heterogeneous disease into clinical relevant subgroups. Among them, genomic alterations and the IGHV (immunoglobulin heavy chain variable region) mutational status are of significance. Particularly, recurrent cytogenetic abnormalities namely deletions of chromosomes 11q, 13q and 17p and, trisomy 12, define subgroups of patients with different clinical behavior and response to treatment while IGHV mutational status permits to distinguish two major CLL subtypes, mutated (M) associated with a good prognosis, and unmutated (UM), characterized by a poor clinical evolution. Fil: Rodríguez, Cecilia María. Universidad Nacional de Córdoba. Facultad de Medicina. Hosp.nacional de Clinicas. Laboratorio de Biología Molecular Citometría de Flujo del Servicio de Oncología y Hematología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina Fil: Stanganelli, Carmen Graciela. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas ; Argentina Fil: Bussi, Claudio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina Fil: Arroyo, Daniela Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina Fil: Sastre, Darío. Universidad Nacional de Córdoba. Facultad de Medicina. Hosp.nacional de Clinicas. Laboratorio de Biología Molecular Citometría de Flujo del Servicio de Oncología y Hematología; Argentina Fil: Heller, Viviana. Universidad Nacional de Córdoba. Facultad de Medicina. Hosp.nacional de Clinicas. Laboratorio de Biología Molecular Citometría de Flujo del Servicio de Oncología y Hematología; Argentina Fil: Iribarren, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina Fil: Slavutsky, Irma Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina

Background: The endometrium is one of the most important female reproductive organs. Polycystic ovarian syndrome (PCOS) is a reproductive and endocrine pathology that affect women of reproductive age. PCOS negatively affects the endometrium, leading to implantation failure and proliferative aberrations. Methods: We conducted a search at the http://www.ncbi.nlm.nhi.gov/pubmed/electronic database using the following key words: endometrial steroid receptors, endometrium, uterine function, endometrium and PCOS, implantation window, implantation and PCOS, implantation markers, inflammation, oxidative stress. We selected the articles based on their titles and abstracts, then we analyzed the full text and classified the articles depending on the information provided according to the sections of the present review. Results: The endocrine and metabolic abnormalities displayed in women with PCOS promote complex effects on the endometrium, leading to a low rate of implantation and even infertility. Women with PCOS show alterations in the Hypothalamic-Pituitary- Ovarian axis, which results in constant circulating levels of estrogen, similar to those at the early follicular phase, and a deficiency in the withdrawal of estrogen and progesterone. Besides this deficiency in the withdrawal of estrogen and progesterone, the insulin/ glucose pathway, adhesion molecules, cytokines and the inflammatory cascade, together with the establishment of a pro-oxidative status, lead to an imbalance in the uterine function, which in turn leads to implantation failure or even endometrial cancer. Conclusion: Women with PCOS display a dysregulation of the Hypothalamic-Pituitary- Ovarian axis, which alters the steroid pathway. In addition, the deficiency in the withdrawal of estrogen and progesterone in the endometrium results in abnormal endometrial cellular proliferation. The imbalance in adipose tissue observed in PCOS patients reinforces the increase in circulating hormones. The present review describes the role of hormones, metabolites, cytokines, adhesion molecules and the insulin/glucose pathway related to the uterine endometrium in women with PCOS and their role in implantation failure and development of endometrial cancer. Fil: Ferreira, Silvana Rocio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina Fil: Motta, Alicia Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina

Primary Sjögren syndrome (SjS) is a systemic autoimmune disease that may affect 1 in 1000 people (overwhelmingly women) and that can be a serious disease with excess mortality due to severe organ-specific involvements and the development of B cell lymphoma; systemic involvement clearly marks the disease prognosis, and strongly suggests the need for closer follow-up and more robust therapeutic management. Therapy is established according to the organ involved and severity. As a rule, the management of systemic SjS should be organ-specific, with glucocorticoids and immunosuppressive agents limited to potentially-severe involvements; unfortunately, the limited evidence available for these drugs, together with the potential development of serious adverse events, makes solid therapeutic recommendations difficult. The emergence of biological therapies has increased the therapeutic armamentarium available to treat primary SjS. Biologics currently used in SjS patients are used off-label and are overwhelmingly agents targeting B cells, but the most recent studies are moving on into the evaluation of targeting specific cytokines involved in the SjS pathogenesis. The most recent etiopathogenic advances in SjS are shedding some light in the search for new highly-selective biological therapies without the adverse effects of the standard drugs currently used (corticosteroids and immunosuppressant drugs). This review summarizes the potential pharmacotherapeutic options targeting the main cytokine families involved in the etiopathogenesis of primary SjS and analyzes potential insights for developing new therapies. Fil: Retamozo, Maria Soledad. Laboratory of Autoimmune Diseases Josep Font; España. Hospital Privado Universitario de Córdoba; Argentina. Hospital Clínic de Barcelona; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina Fil: Flores Chavez, Alejandra. Laboratory of Autoimmune Diseases Josep Font; España. Mexican Institute for Social Security; México. Universidad de la Colima; México. Hospital Clínic de Barcelona; España Fil: Consuegra Fernández, Marta. Institut D'Investigacions Biomèdiques August Pi I Sunyer; España Fil: Lozano, Francisco. Institut D'Investigacions Biomèdiques August Pi I Sunyer; España. Hospital Clínic de Barcelona; España. Universidad de Barcelona; España Fil: Ramos Casals, Manuel. Laboratory of Autoimmune Diseases Josep Font; España. Universidad de Barcelona; España. Hospital Clínic de Barcelona; España Fil: Brito Zerón, Pilar. Laboratory of Autoimmune Diseases Josep Font; España. Hospital CIMA-Sanitas; España. Hospital Clínic de Barcelona; España

Allatotropin (AT) and allatostatin-C (AST-C) are neuropeptides originally characterized by their ability to modulate the secretion of juvenile hormones in insects. Beyond the allatoregulatory function, these neuropeptides are pleiotropic acting as myoregulators not only in insects, but also in other groups of invertebrates. We have previously proposed the existence of AT and AST-C like systems in Hydra sp., a member of the phylum Cnidaria, which is a basal group of Metazoa, sharing a common ancestor with Bilateria. In the present study we analyze the regulatory effects of both peptides on the activity of the hypostome during feeding in Hydra sp. Furthermore, the importance of changes in the cytosolic Ca2+ levels involved in the response of the hypostome were analyzed. Physiological assays showed that while the presence of food or treatment with AT stimulates the extrusion of the hypostome, AST-C has an inhibitory effect on the behavior induced by both, food and AT. These facts suggest that both systems participate in the regulatory mechanisms associated with feeding and, as in insects, AST-C and AT may exert opposite effects. The use of thapsigargin (TG) and nifedipine, two compounds that modify the levels of cytosolic Ca2+, showed that changes in the levels of this ion are involved in the regulation of the activity of the hypostome. Indeed, these results suggest that the two basic mechanisms operating to increase the cytosolic levels of Ca2+ (i.e. the influx from the extracellular space and the release from endoplasmic reticulum) are relevant for the extrusion of the hypostome. Like in insects, the treatment with TG counteracted the effect of AST-C, suggesting that this peptide acts by reducing cytosolic Ca2+ levels. Furthermore, nifedipine prevented the myostimulatory effect of AT, showing that the effect of this peptide depends on the influx of Ca2+ throughout voltage-gated calcium channels. Altogether, these results suggest that the Allatotropin/Orexin and Allatostatin/Somatostatin regulatory systems could represent an ancestral mechanisms regulating hypostome activity and feeding behavior in Cnidaria. Fil: Alzugaray, Maria Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo; Argentina Fil: Ronderos, Jorge Rafael. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo; Argentina

Dietary phenolic compounds are plant metabolites with beneficial effects on the central nervous system. Thus, our aim was to identify anti-inflammatory compounds from South American plants on glia, which regulates neuro-immune response. The compounds were extracted from Lantana grisebachii (LG), Aspidosperma quebracho-blanco (AQB), and Ilex paraguariensis (IP) teas and identified by HPLC-DAD-MS. Extracts (0–200 µg/ml) were tested on human T98-G and rat C6 glioma lines. Cellular viability (by the resazurin assay), fatty acid profile (by gas chromatography) and pro-inflammatory interleukin-6 release (IL-6 by ELISA) were determined. Data were analyzed by partial least-square regression to discriminate bioactive compounds. Twenty-one compounds were determined in LG, mainly iridoids, which were linked to ω-3 and ω-6 polyunsaturated fatty acids, but not to IL-6 release. Thirty-one compounds were found in AQB, mostly hydroxybenzoic derivatives, which were positively related to IL-6 release. Twenty-three compounds were identified in IP, including caffeoylquinic derivatives and mainly chlorogenic acid. They increased the ω-7 palmitoleic fatty acid, which was related to IL-6 decrease. These results enhances phytochemical knowledge of widely available plants, and suggest the lipid-related anti-inflammatory activity of IP phenolic compounds, which give nutritional relevance to the tea. Fil: Cittadini, María Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina. Universidad Nacional de Córdoba;Facultad de Ciencias Médicas;Cátedra de Bioquímica Molecular; Argentina. Ministerio de Salud; Argentina Fil: García Estévez, Ignacio. Universidad de Salamanca; España Fil: Escribano Bailón, M. Teresa. Universidad de Salamanca; España Fil: Rivas Gonzalo, Julián C.. Universidad de Salamanca; España Fil: Valentich, Mirta Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina. Universidad Nacional de Córdoba;Facultad de Ciencias Médicas;Cátedra de Bioquímica Molecular; Argentina. Universidad Nacional de Cordoba. Facultad de Medicina. Instituto de Biologia Celular; Argentina Fil: Repossi Marquez, Pablo Gaston. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina. Universidad Nacional de Córdoba;Facultad de Ciencias Médicas;Cátedra de Bioquímica Molecular; Argentina. Universidad Nacional de Cordoba. Facultad de Medicina. Instituto de Biologia Celular; Argentina Fil: Soria, Elio Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina. Universidad Nacional de Córdoba;Facultad de Ciencias Médicas;Cátedra de Bioquímica Molecular; Argentina. Universidad Nacional de Cordoba. Facultad de Medicina. Instituto de Biologia Celular; Argentina

Commonly known for testosterone secretion, the testes also produce the protein hormones anti-müllerian hormone (AMH), inhibin B, and insulin-like factor 3 (INSL3). AMH and inhibin B are secreted by Sertoli cells, whereas INSL3 is a Leydig cell product. AMH is involved in fetal sex differentiation and induces the regression of the anlagen of the uterus and fallopian tubes. INSL3 participates in fetal testicular descent. Serum testicular protein hormone assessment can be very useful and complementary to testosterone measurements in patients with DSD. AMH and inhibin B determination is extremely helpful during childhood, when basal testosterone is normally low. Serum AMH and inhibin B above the female range are indicative of the presence of testicular tissue, and their circulating levels reflect the amount of functional Sertoli cells. In DSD patients with normal male levels of AMH and inhibin B, the diagnosis of gonadal dysgenesis can be ruled out, and isolated androgen secretion deficiency or androgen insensitivity should be suspected. In externally virilized XY patients with persistent müllerian ducts, serum AMH levels determine the diagnosis to AMH deficiency or resistance. At pubertal age, inhibin B levels serve to predict spermatogenic development. Fil: Freire, Analia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina Fil: Grinspon, Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina Fil: Rey, Rodolfo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina

Increased arterial stiffness is an important determinant of cardiovascular risk, able to predict morbidity and mortality, and closely associated with ageing and blood pressure. The aims of this study were: (1) To determine the age-dependent reference pulse wave velocity (PWV), and compare it with values from hypertensive patients, and (2) to evaluate the impact of isolated and untreated hypertension on arterial stiffness. A total of 1079 patients were enrolled and divided into a control group (NT) of asymptomatic normotensive patients and a group of asymptomatic hypertensive patients (HT). Blood pressure, carotid-femoral PWV, and body mass index were measured in each subject, whose blood was drawn for laboratory tests. Aortic mean PWV in the NT group was 6.85 ± 1.66 m/s, which increased linearly (R2 = 0.62; P

Background: To analyze the impact of the International Nosocomial Infection Control Consortium (INICC) multidimensional approach (IMA) on ventilator-associated pneumonia (VAP) rates in 11 hospitals within 5 cities of Argentina from January 2014-April 2017. Methods: A multicenter, prospective, before–after surveillance study was conducted through the use of International Nosocomial Infection Control Consortium Surveillance Online System. During baseline, we performed outcome surveillance of VAP applying the definitions of the Centers for Disease Control andPrevention's National Healthcare Safety Network. During intervention, we implemented the IMA, which included a bundle of infection prevention practice interventions, education, outcome surveillance, process surveillance, feedback on VAP rates and consequences, and performance feedback of process surveillance. Bivariate and multivariate regression analyses were performed using a logistic regression model to estimate the effect of the intervention. Results: We recorded 3,940 patients admitted to 14 intensive care units. At baseline, there were 19.9 VAPs per 1,000 mechanical ventilator (MV)-days—with 2,920 MV-days and 58 VAPs, which was reduced during intervention to 9.4 VAPs per 1,000 MV-days—with 9,261 MV-days and 103 VAPs. This accounted for a 52% rate reduction (incidence density rate, 0.48; 95% confidence interval, 0.3-0.7; P.001). Conclusions: Implementing the IMA was associated with significant reductions in VAP rates in intensive care units within Argentina. Fil: Rosenthal, Victor Daniel. International Nosocomial Infection Control Consortium; Argentina Fil: Desse, Javier. Sanatorio San Cayetano; Argentina Fil: Maurizi, Diego Marcelo. Hospital Privado del Sur; Argentina. Hospital Municipal Doctor Leónidas Lucero; Argentina Fil: Chaparro, Gustavo Jorge. No especifíca; Fil: Orellano, Pablo Wenceslao. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Tecnológica Nacional. Facultad Regional San Nicolás; Argentina Fil: Chediack, Viviana. Policlínico Central Unión Obrera Metalúrgica; Argentina Fil: Cabrera, Rafael. No especifíca; Fil: Golschmid, Daniel. Hospital Privado Raul Matera; Argentina Fil: Silva, Cristina Graciela. No especifíca; Fil: Vimercati, Julio Cesar. No especifíca; Fil: Stagnaro, Juan Pablo. Instituto Central de Medicina; Argentina Fil: Perez, Ivanna. Clínica San Cayetano; Argentina Fil: Spadaro, María Laura. Hospital Privado Raul Matera; Argentina Fil: Montanini, Adriana Miriam. Hospital Municipal Doctor Leónidas Lucero; Argentina Fil: Pedersen, Dina. Hospital Municipal Doctor Leónidas Lucero; Argentina Fil: Paniccia, Teresa Laura. Hospital Municipal Doctor Leónidas Lucero; Argentina Fil: Ríos Aguilera, Ana María. Hospital Privado del Sur; Argentina Fil: Cermesoni, Raul. Hospital Privado del Sur; Argentina Fil: Mele, Juan Ignacio. Hospital Privado del Sur; Argentina Fil: Alda, Ernesto. Hospital Privado del Sur; Argentina Fil: Paldoro, Analía Edith. No especifíca; Fil: Ortta, Agustín Román. No especifíca; Fil: Cooke, Bettina. No especifíca; Fil: García, María Cecilia. No especifíca; Fil: Obed, Mora Nair. No especifíca; Fil: Domínguez, Cecilia Verónica. Policlínico Central Unión Obrera Metalúrgica; Argentina Fil: Saúl, Pablo Alejandro. Policlínico Central Unión Obrera Metalúrgica; Argentina Fil: Rodríguez del Valle, María Cecilia. Hospital Zonal General de Agudos Dr Ricardo Gutiérrez; Argentina Fil: Bianchi, Alberto Claudio. Hospital Zonal General de Agudos Dr Ricardo Gutiérrez; Argentina Fil: Alvarez, Gustavo. Instituto Central de Medicina; Argentina Fil: Pérez, Ricardo. Instituto Central de Medicina; Argentina Fil: Oyola, Carolina. No especifíca

Background and Objective: Pain is a frequent symptom in Parkinson’s disease (PD), and the therapeutic alternatives are scarce. The goal of this trial was to measure the effects of botulinum toxin type A (BTXA) in the treatment of limb pain in advanced PD. Methods: A randomized double-blind crossover versus placebo study of BTXA for limb pain in advanced Parkinson’s disease was conducted. Subjects received individualized BTXA/placebo dosing per pain distribution in limbs. The primary outcome was a measure of change in global pain on a numeric rating scale (NRS) at 4 and 12 weeks postinjection and on a visual analogue scale 12 weeks after treatment. Secondary outcomes included the percentage of responders, physician-rated clinical global impressions, MDS–UPDRS and PDQ–39 scores, and adverse events. Results: A total of 12 subjects completed the trial. Treatment with BTXA (average dose=241.66 U) produced a significant reduction in NRS score 4 weeks after the injections (–1.75 points, range from –3 to 7, p=0.033). However, there was no significant difference compared to placebo (p=0.70). Participants with dystonic pain showed a greater reduction in NRS score after 4 weeks when treated with BTXA (2.66 points vs. 0.75 for placebo). There were no significant differences for any of the secondary outcomes or significant adverse events. Conclusions: Targeted BTXA injections were safe in patients with limb pain and advanced PD; however, the present study failed to show a significant effect when compared to placebo. Further studies may be focused on evaluating the effect of BTXA particularly in dystonic pain. Contexte et objectifs: Ressentir de la douleur demeure un symptôme fréquent de la maladie de Parkinson. Cela dit, les solutions thérapeutiques continuent à être limitées. L’objectif de cet essai clinique a donc été de mesurer les effets de la toxine botulique de type A en ce qui regarde le soulagement de la douleur aux membres chez des sujets au stade avancé de la maladie de Parkinson. Méthodes: Nous avons mené une étude randomisée et croisée à double insu, contrôlée par placebo, au sujet de l’efficacité de la toxine botulique de type A dans le soulagement de la douleur. On a ainsi administré à nos sujets une posologie individualisée de toxine botulique de type A ainsi qu’un placebo en fonction de la distribution de la douleur à leurs membres. Le principal indicateur mesuré a porté, 4 et 12 semaines après les injections, sur les changements de scores obtenus sur l’échelle numérique de la douleur et, 12 semaines plus tard, sur l’échelle visuelle analogique. D’autres indicateurs secondaires ont également été mesurés : le pourcentage d’intervenants impliqués, les impressions cliniques d’ensemble de médecins, l’échelle d’évaluation unifiée de la maladie de Parkinson de la Movement Disorder Society, les scores obtenus au PDQ–39 et la fréquence d’évènements indésirables. Résultats: Au total, 12 sujets ont complété cet essai clinique. L’administration de toxine botulique de type A (dose moyenne=241,66 U) a produit, 4 semaines après les injections, une réduction importante des scores obtenus sur l’échelle numérique d’évaluation de la douleur (-1,75 points ; écart de -3 à 7 ; p=0,033). Cela dit, aucune différence notable n’a été observée par rapport au placebo (p=0,70). Chez les sujets souffrant de douleurs d’origine dystonique, on a pu observer, 4 semaines après les injections, la plus grande réduction des scores obtenus sur l’échelle numérique d’évaluation de la douleur (2,66 points contre 0,75 pour le placebo). Fait à noter, on n’a observé aucune différence notable quant aux indicateurs secondaires énumérés ci-dessus ou en ce qui regarde des évènements indésirables. Conclusions: Les injections ciblées de toxines botuliques de type A se sont avérées sans danger dans le cas de sujets au stade avancé de la maladie de Parkinson souffrant de douleurs aux membres. La présente étude n’a toutefois pas été en mesure de révéler un effet notable des toxines botuliques de type A après comparaison avec un placebo. Cela étant, il se peut que des études ultérieures se penchent sur les effets de ces toxines, en particulier en ce qui regarde les douleurs d’origine dystonique. Fil: Bruno, Veronica Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. University Health Network; Canadá Fil: Freitas, Maria Eliza. University Health Network; Canadá Fil: Mancini, Deborah. University Health Network; Canadá Fil: Lui, Jane P.. University Health Network; Canadá Fil: Miyasaki, Janis. University of Alberta; Canadá Fil: Fox, Susan H.. University Health Network; Canadá

An established characteristic of neoplastic cells is their metabolic reprogramming, known as the Warburg effect, with greater reliance on energetically less efficient pathways (such as glycolysis and pentose phosphate shunt) compared with oxidative phosphorylation. This results in an overproduction of acidic species that must be extruded to maintain intracellular homeostasis. We recently described that blocking the proton currents in leukemic cells mediated by Hv1 ion channels triggers a marked intracellular acidification and apoptosis induction. Moreover, histamine H1-receptor antagonists were found to induce apoptosis in tumoral cells but the mechanism is still unclear. By using Jurkat T cells, we now show how diphenhydramine inhibits Hv1 mediated currents, inducing a drop in intracellular pH and cellular viability. This provides evidence of a new target structure responsible of the known pro-apoptotic action of antihistaminic drugs., Facultad de Ciencias Exactas, Instituto de Estudios Inmunológicos y Fisiopatológicos

Congenital platelet function disorders are often the result of defects in critical signal transduction pathways required for platelet adhesion and clot formation. Mutations affecting RASGRP2, the gene encoding the Rap GTPase activator, CalDAG-GEFI, give rise to a novel, and rare, group of platelet signal transduction abnormalities. We here report platelet function studies for two brothers (P1 and P2) expressing a novel variant of RASGRP2, CalDAG-GEFI(p.Gly305Asp). P1 and P2 have a lifelong history of bleeding with severe epistaxis successfully treated with platelet transfusions or rFVIIa. Other bleedings include extended hemorrhage from minor wounds. Platelet counts and plasma coagulation were normal, as was αIIbβ3 and GPIb expression on the platelet surface. Aggregation of patients’ platelets was significantly impaired in response to select agonists including ADP, epinephrine, collagen, and calcium ionophore A23187. Integrin αIIbβ3 activation and granule release were also impaired. CalDAG-GEFI protein expression was markedly reduced but not absent. Homology modeling places the Gly305Asp substitution at the GEF-Rap1 interface, suggesting that the mutant protein has very limited catalytic activity. In summary, we here describe a novel mutation in RASGRP2 that affects both expression and function of CalDAG-GEFI and that causes impaired platelet adhesive function and significant bleeding in humans. Fil: Bermejo, Emilse. Academia Nacional de Medicina de Buenos Aires; Argentina Fil: Alberto, Maria Fabiana. Academia Nacional de Medicina de Buenos Aires; Argentina Fil: Paul, David S.. University of North Carolina; Estados Unidos Fil: Cook, Aaron A.. University of North Carolina; Estados Unidos Fil: Nurden, Paquita. Hôpital Xavier Arnozan; Francia Fil: Sánchez Luceros, Analía Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina Fil: Nurden, Alan T.. Hôpital Xavier Arnozan; Francia Fil: Bergmeier, Wolfgang. University of North Carolina; Estados Unidos

Background Primary Prevention of Diabetes Program in Buenos Aires Province evaluates the effectiveness of adopting healthy lifestyle to prevent type 2 diabetes (T2D) in people at high risk of developing it. We aimed to present preliminary data analysis of FINDRISC and laboratory measurements taken during recruitment of people for the Primary Prevention of Diabetes Program in Buenos Aires Province in the cities of La Plata, Berisso, and Ensenada, Argentina. Methods People were recruited through population approach (house-to-house survey by FINDRISC in randomized areas) and opportunistic approach (FINDRISC completed by participants during consultations for nonrelated prediabetes/diabetes symptoms in public and private primary care centres of cities involved). In people with FINDRISC score ≥ 13 points, we evaluated blood concentrations of HbA1c , creatinine, lipids, and an oral glucose tolerance test (OGTT). Results Approximately 3415 individuals completed the FINDRISC populational survey and 344 the opportunistic survey; 43% of the 2 groups scored over 13 points; 2.8 and 75.4% of them, respectively, took the prescribed OGTT. Approximately 53.7% of the OGTT showed normal values and 5.2% unknown T2D. The remaining cases showed 69.5% impaired fasting glucose, 13.6% impaired glucose tolerance, and 16.9% both impairments. HbA1c values showed significant differences compared with normal glucose tolerance (4.96 ± 0.43%), prediabetes (5.28 ± 0.51%), and T2D (5.60 ± 0.51%). Participants with prediabetes and T2D showed a predominant increase in low-density lipoprotein-cholesterol values. In prediabetes, >50% showed insulin resistance. Conclusions People with prediabetes/T2D had dyslipidemia associated with insulin resistance, which promotes the development of T2D and cardiovascular disease. Thus, it merits its appropriate treatment., Centro de Endocrinología Experimental y Aplicada, Instituto de Investigaciones en Humanidades y Ciencias Sociales