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Resumen: Objetivo: Evaluar el nivel de exposición a plaguicidas y su correlación con indicadores de salud percibida y biomarcadores de daño (alteraciones genotóxicas y de actividad enzimática de la butirilcolinesterasa), en la población de agroaplicadores de cultivos extensivos (ACE) de la Provincia de Córdoba, Argentina. Método: Estudio transversal, en ACE (n = 47) seleccionados aleatoriamente de una muestra de 2000, y sujetos no expuestos controles (n = 52). Se relevaron variables sociodemográficas, condicionantes de exposición y de salud percibida, mediante cuestionario autoadministrado; indicadores biológicos de genotoxicidad: micronúcleos, aberraciones cromosómicas y ensayo cometa, y actividad de butirilcolinesterasa. Resultados: El 40% de los ACE tiene una antigüedad mayor de 10 años y casi el 50% reside a menos de 500 m de campos asperjados; reportan bajas tasas de uso de equipo de protección personal durante la mezcla, aplicación o reparación de equipos. Los síntomas generales, cardiorrespiratorios y dermatológicos fueron mayores entre los ACE (p

Cestode parasites cause neglected diseases, such as echinococcosis and cysticercosis, which represent a significant problem in human and animal health. Benzimidazoles and praziquantel are the only available drugs for chemotherapy and it is therefore important to identify new alternative drugs against cestode parasites. Histone deacetylases (HDACs) are validated drug targets for the treatment of cancer and other diseases, including neglected diseases. However, knowledge of HDACs in cestodes is very scarce. In this work, we investigated cestode HDACs as potential drug targets to develop new therapies against neglected diseases caused by cestodes. Here we showed the full repertoire of HDAC coding genes in several members of the class Cestoda. Between 6 and 7 zinc-dependent HDAC coding genes were identified in the genomes of species from Echinococcus, Taenia, Mesocestoides and Hymenolepis genera. We classified them as Class I and II HDACs and analyzed their transcriptional expression levels throughout developmental stages of Echinococcus spp. We confirmed for the first time the complete HDAC8 nucleotide sequences from Echinococcus canadensis G7 and Mesocestoides corti. Homology models for these proteins showed particular structural features which differentiate them from HDAC8 from Homo sapiens. Furthermore, we showed that Trichostatin A (TSA), a pan-HDAC inhibitor, decreases the viability of M. corti, alters its tegument and morphology and produces an increment of the total amount of acetylated proteins, including acetylated histone H4. These results suggest that HDAC from cestodes are functional and might play important roles on survival and development. The particular structural features observed in cestode HDAC8 proteins suggest that these enzymes could be selectively targeted. This report provides the basis for further studies on cestode HDAC enzymes and for discovery of new HDAC inhibitors for the treatment of neglected diseases caused by cestode parasites., Graphical abstract Image 1, Highlights • Cestode genomes contain six or seven histone deacetylase (HDAC) genes. • HDAC genes are expressed in several developmental stages of Echinococcus spp. • Trichostatin A decreases viability and causes histone hyperacethylation on Mesocestoides corti. • HDAC8 from cestodes show particular structural features and are potential drug targets.

An efficacious topical treatment for cutaneous leishmaniasis (CL) is highly desirable but still an ongoing challenge. Systemic risedronate (Ris) has been reported to have anti-leishmanial properties and Eudragit EPO (EuE) has shown in vitro activity against L. (L.) amazonensis. The aim of this work was to investigate the in vivo efficacy of topical Ris and EuE-Ris complexes on CL. Surface charge and Ris release kinetics from the different dispersions were analyzed. BALB/c mice were infected intradermally with promastigotes of L. (L.) amazonensis. Ulcers were treated with Ris or EuE-Ris hydrogels. All the lesions that received topical Ris or EuE-Ris showed an improvement with respect to control: reduction of ulcer average size, cicatrization, flattened edges and no signs of necrosis. In addition, a marked parasitic inhibition of 69.5 and 73.7% was observed in the groups treated with Ris and EuE-Ris, respectively, with the IgG2a levels indicating a tendency towards cure. The results are promising and the system should now be enhanced to achieve total parasite elimination., Cutaneous leishmaniasis; Risedronate; Eudragit; Topical treatment; Leishmania amazonensis.

Flavivirus infections have increased dramatically in the last decades in tropical and subtropical regions of the world. Antibody-dependent enhancement of dengue virus infections has been one of the main hypotheses to explain severity of disease and one of the major challenges to safe and effective vaccine development. In the presence of cross-reactive sub-neutralizing concentrations of anti-dengue antibodies, immune complexes can amplify viral infection in mononuclear phagocytic cells, triggering a cytokine cascade and activating the complement system that leads to severe disease. The complement system comprises a family of plasma and cellular surface proteins that recognize pathogen associated molecular patterns, modified ligands and immune complexes, interacting in a regulated manner and forming an enzymatic cascade. Pathogenic as well as protective effects of complement have been reported in flavivirus infections. This review provides updated knowledge on complement activation during flavivirus infection, including antiviral effects of complement and its regulation, as well as mechanisms of complement evasion and dysregulation of complement activity during viral infection leading to pathogenesis. Particularly, insights into classical pathway activation and its protective role on antibody-dependent enhancement of flavivirus infections are highlighted. Fil: Byrne, Alana Brooke. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Talarico, Laura Beatriz. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina

SARS-CoV-2 utilizes the IMPα/β1 heterodimer to enter host cell nuclei after gaining cellular access through the ACE2 receptor. Ivermectin has shown antiviral activity by inhibiting the formation of the importin-α (IMPα) and IMPβ1 subunits as well as dissociating the IMPα/β1 heterodimer and has in vitro efficacy against SARS-CoV-2. Plasma and lung ivermectin concentrations vs. time profiles in cattle were used to determine the apparent plasma to lung tissue partition coefficient of ivermectin. This coefficient, together with a simulated geometric mean plasma profile of ivermectin from a published population pharmacokinetic model, was utilized to develop a minimal physiologically-based pharmacokinetic (mPBPK) model. The mPBPK model accurately described the simulated ivermectin plasma concentration profile in humans. The mPBPK model was also used to simulate human lung exposure to ivermectin after 12, 30, and 120 mg oral doses. The simulated ivermectin lung exposures reached a maximum concentration of 772 ng/mL, far less than the estimated 1750 ng/mL IC50 reported for ivermectin against SARS-CoV-2 in vitro. Further studies of ivermectin either reformulated for inhaled delivery or in combination with other antivirals with differing mechanisms of action is needed to assess its therapeutic potential. Fil: Jermain, Brian. University of North Carolina; Estados Unidos Fil: Hanafin, Patrick O.. University of North Carolina; Estados Unidos Fil: Cao, Yanguang. University of North Carolina; Estados Unidos Fil: Lifschitz, Adrian Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina Fil: Lanusse, Carlos Edmundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina Fil: Rao, Gauri G.. University of North Carolina; Estados Unidos

A 68-year-old male presented with flu-like symptoms, fatigue, history of obesity, hypertension, type 2 diabetes and chronic smoking. Chest radiography revealed right basal opacity consisting of infiltrate. With respiratory failure, orotracheal intubation and mechanical ventilation were performed. Patient presented gas exchange alteration. Real-time PCR detected SARS-CoV-2. Treatment with liponavir/ritonavir and hydroxychloroquine was started. Because of poor acoustic window, speckle-tracking transoesophageal echocardiography (TEE) was performed, detecting deterioration in global longitudinal strain. Acute COVID 19 infection led us to suspect myocarditis, with no other signs or symptoms other than elevated troponin and altered strain. On day 15, the patient suffered bacteraemic sepsis at endovascular focus with Serratia marcescens and multiorgan failure. TEE-guided haemodynamic monitoring was repeated showing global longitudinal strain improvement. Acute COVID 19 infection led us to suspect myocarditis, with no other signs or symptoms beyond elevated troponin and altered strain. Un hombre de 68 años presentó síntomas similares a los de la gripe, fatiga, antecedentes de obesidad, hipertensión, diabetes de tipo 2 y tabaquismo crónico. La radiografía de tórax reveló una opacidad basal derecha consistente con infiltración. Se realizó una intubación orotraqueal y ventilación mecánica. El paciente presentó alteración del intercambio gaseoso. La PCR en tiempo real detectó SARS-CoV-2. Se inició el tratamiento con liponavir/ritonavir e hidroxicloroquina. Debido a la deficiente ventana acústica, se realizó una ecocardiografía transoesofágica (ETE) de speckle-tracking, que detectó el deterioro de la tensión longitudinal global. La infección aguda por COVID 19 nos llevó a sospechar de miocarditis, sin más signos o síntomas que la elevación de la troponina y la alteración de la cepa. El día 15, el paciente sufrió una sepsis bacteriana en el foco endovascular con Serratia marcescens y fallo multiorgánico. Se repitió la monitorización hemodinámica guiada por ETE que mostró una mejora en la tensión longitudinal global. Fil: Wehit, Jeanette M.. Hospital Alemán; Argentina Fil: Sosa, Fernando A.. Hospital Alemán; Argentina Fil: Merlo, Pablo. Hospital Bernardino Rivadavia; Argentina Fil: Roberti, Javier Eugenio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; Argentina. Hospital Alemán; Argentina Fil: Osatnik, Javier. Hospital Alemán; Argentina

Purpose Advanced triple negative breast cancer (ATNBC) is defined by a lack of expression of hormones receptors as well as HER2/neu and its high probability of visceral metastasis. This pathology is associated with a poor prognosis. Previously, we found that T2, an N4-arylsubstituted thiosemicarbazone (N4-TSC), had cytotoxic effect on human breast cancer cells lines. Hence, in this study, we investigated the anti-metastasic action of T2 on ATNBC. Methods In order to deepen T2 action mode on ATNBC, we first confirmed T2 cytotoxicity on a panel of TNBC cells and then continued studying T2 effects in vitro an in vivo on the syngeneic 4T1 mouse model. Results We found that T2 had a cytotoxic effect comparable to chemotherapeutics used in present treatment schemes for ATNBC. T2 treatment not only induced apoptosis, but it also down-modulated 4T1 invasive and metastatic-associated capacities, such as clonogenicity, migration and metallo-proteases activity. Moreover, this agent reduced the number of 4T1 cancer stem cells. Finally, T2 treatment induced a more differentiated cell phenotype and the overexpression of the metastasis suppressor gene NDRG-1. In vivo assays showed that T2 reduced tumor burden, down modulated local tumor invasion and significantly reduced the number of lung metastases in the 4T1 advanced TNBC murine model, while the compound did not exhibit intolerable toxicity. Conclusion This study provided evidence that T2 not only exerted an anti-tumor activity but it also showed anti-invasive and anti-metastatic actions on ATNBC in vivo and in vitro, suggesting that T2 could be considered as a promising therapy that deserves further analysis., Cell biology; Biochemistry; Molecular biology; Cancer research; Oncology; Triple negative breast cancer; Thiosemicarbazones; Metastasis; Invasion; Stem cells.

Background: Air pollution is a leading cause of mortality and morbidity worldwide. Short-term exposure (from one hour to days) to selected air pollutants has been associated with human mortality. This systematic review was conducted to analyse the evidence on the effects of short-term exposure to particulate matter with aerodynamic diameters less or equal than 10 and 2.5 µm (PM10, PM2.5), nitrogen dioxide (NO2), and ozone (O3), on all-cause mortality, and PM10 and PM2.5 on cardiovascular, respiratory, and cerebrovascular mortality. Methods: We included studies on human populations exposed to outdoor air pollution from any source, excluding occupational exposures. Relative risks (RRs) per 10 µg/m3 increase in air pollutants concentrations were used as the effect estimates. Heterogeneity between studies was assessed using 80% prediction intervals. Risk of bias (RoB) in individual studies was analysed using a new domain-based assessment tool, developed by a working group convened by the World Health Organization and designed specifically to evaluate RoB within eligible air pollution studies included in systematic reviews. We conducted subgroup and sensitivity analyses by age, sex, continent, study design, single or multicity studies, time lag, and RoB. The certainty of evidence was assessed for each exposure-outcome combination. The protocol for this review was registered with PROSPERO (CRD42018087749). Results: We included 196 articles in quantitative analysis. All combinations of pollutants and all-cause and cause-specific mortality were positively associated in the main analysis, and in a wide range of sensitivity analyses. The only exception was NO2, but when considering a 1-hour maximum exposure. We found positive associations between pollutants and all-cause mortality for PM10 (RR: 1.0041; 95% CI: 1.0034–1.0049), PM2.5 (RR: 1.0065; 95% CI: 1.0044–1.0086), NO2 (24-hour average) (RR: 1.0072; 95% CI: 1.0059–1.0085), and O3 (RR: 1.0043; 95% CI: 1.0034–1.0052). PM10 and PM2.5 were also positively associated with cardiovascular, respiratory, and cerebrovascular mortality. We found some degree of heterogeneity between studies in three exposure-outcome combinations, and this heterogeneity could not be explained after subgroup analysis. RoB was low or moderate in the majority of articles. The certainty of evidence was judged as high in 10 out of 11 combinations, and moderate in one combination. Conclusions: This study found evidence of a positive association between short-term exposure to PM10, PM2.5, NO2, and O3 and all-cause mortality, and between PM10 and PM2.5 and cardiovascular, respiratory and cerebrovascular mortality. These results were robust through several sensitivity analyses. In general, the level of evidence was high, meaning that we can be confident in the associations found in this study. Fil: Orellano, Pablo Wenceslao. Universidad Tecnológica Nacional. Facultad Regional San Nicolás; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Reynoso, Julieta Itati. Hospital General “San Felipe"; Argentina Fil: Quaranta, Nancy Esther. Universidad Tecnológica Nacional. Facultad Regional San Nicolás; Argentina. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; Argentina Fil: Bardach, Ariel Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; Argentina Fil: Ciapponi, Agustín. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; Argentina

The aims of this research were threefold: 1) to analyze mental health state both general (GMHS, i.e., self-perceived health and psychological distress) and specific (SMHS; i.e., depression, trait-anxiety, negative alcohol-related consequences, and suicidal risk), and impulsivity-related traits (i.e., negative urgency, positive urgency, [lack of] perseverance, [lack of] premeditation, and sensation seeking) in a sample of Argentinean adolescent college students, in function of sex (women, men) and three different altitude-latitude regions (high-north, middle-center, low-south), for identifying common and specific features; 2) to analyze relationships between impulsivity-related traits and indicators of GMHS and SMHS, in the entire sample and in each altitude-latitude region, for understanding the importance of impulsivity-related traits in these forms of mental disorders; and 3) to analyze bivariate relationships between depression, trait-anxiety, negative alcohol-related consequences, and suicidal risk, in the entire sample and considering the three altitude-latitude regions, for testing two-disorder comorbidities. Scores on impulsivity-related traits differed by sex and by altitude-latitude region. GMHS and SMHS differed by sex but not by altitude-latitude region. Several relationships were found between impulsivity-related traits, GMHS, and SMHS as well as between indicators of SMHS. Some of these relationships were dependent on altitude-latitude regions, and implications of these findings were discussed., Psychology; Depression; Anxiety; Adolescent; Suicide risk; Alcohol drinking; Sex; Altitude; Latitude

Global brain states are frequently placed within a unidimensional continuum by correlational studies, ranging from states of deep unconsciousness to ordinary wakefulness. An alternative is their multidimensional and mechanistic characterization in terms of different cognitive capacities, using computational models to reproduce the underlying neural dynamics. We explore this alternative by introducing a semi-empirical model linking regional activation and long-range functional connectivity in the different brain states visited during the natural wake-sleep cycle. Our model combines functional magnetic resonance imaging (fMRI) data, in vivo estimates of structural connectivity, and anatomically-informed priors to constrain the independent variation of regional activation. The best fit to empirical data was achieved using priors based on functionally coherent networks, with the resulting model parameters dividing the cortex into regions presenting opposite dynamical behavior. Frontoparietal regions approached a bifurcation from dynamics at a fixed point governed by noise, while sensorimotor regions approached a bifurcation from oscillatory dynamics. In agreement with human electrophysiological experiments, sleep onset induced subcortical deactivation with low correlation, which was subsequently reversed for deeper stages. Finally, we introduced periodic forcing of variable intensity to simulate external perturbations, and identified the key regions relevant for the recovery of wakefulness from deep sleep. Our model represents sleep as a state with diminished perceptual gating and the latent capacity for global accessibility that is required for rapid arousals. To the extent that the qualitative characterization of local dynamics is exhausted by the dichotomy between unstable and stable behavior, our work highlights how expanding the model parameter space can describe states of consciousness in terms of multiple dimensions with interpretations given by the choice of anatomically-informed priors. Fil: Perez Ipiña, Ignacio Martin. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Física; Argentina Fil: Donnelly Kehoe, Patricio Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Centro Internacional Franco Argentino de Ciencias de la Información y de Sistemas. Universidad Nacional de Rosario. Centro Internacional Franco Argentino de Ciencias de la Información y de Sistemas; Argentina Fil: Kringelbach, Morten. University of Oxford; Reino Unido. University Aarhus; Dinamarca Fil: Laufs, Helmut. University of Kiel; Alemania Fil: Ibañez, Agustin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; Argentina. Universidad de San Andrés; Argentina. Australian Research Council; Australia. Universidad Adolfo Ibañez; Chile. Universidad Autónoma del Caribe; Colombia Fil: Deco, Gustavo. Universitat Pompeu Fabra; España Fil: Sanz Perl Hernandez, Yonatan. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de San Andrés; Argentina Fil: Tagliazucchi, Enzo Rodolfo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Física; Argentina

Interoception (the sensing of inner-body signals) is a multi-faceted construct with major relevance for basic and clinical neuroscience research. However, the neurocognitive signatures of this domain (cutting across behavioral, electrophysiological, and fMRI connectivity levels) are rarely reported in convergent or systematic fashion. Additionally, various controversies in the field might reflect the caveats of standard interoceptive accuracy (IA) indexes, mainly based on heartbeat detection (HBD) tasks. Here we profit from a novel IA index (md) to provide a convergent multidimensional and multi-feature approach to cardiac interoception. We found that outcomes from our IA-md index are associated with –and predicted by– canonical markers of interoception, including the hd-EEG-derived heart-evoked potential (HEP), fMRI functional connectivity within interoceptive hubs (insular, somatosensory, and frontal networks), and socio-emotional skills. Importantly, these associations proved more robust than those involving current IA indexes. Furthermore, this pattern of results persisted when taking into consideration confounding variables (gender, age, years of education, and executive functioning). This work has relevant theoretical and clinical implications concerning the characterization of cardiac interoception and its assessment in heterogeneous samples, such as those composed of neuropsychiatric patients. Fil: Fittipaldi, María Sol. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt | Instituto de Neurología Cognitiva. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt | Fundación Favaloro. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt; Argentina Fil: Abrevaya, Sofia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt | Instituto de Neurología Cognitiva. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt | Fundación Favaloro. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt; Argentina Fil: de la Fuente de la Torre, Laura Alethia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; Argentina Fil: Pascariello, Guido Orlando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Centro Internacional Franco Argentino de Ciencias de la Información y de Sistemas. Universidad Nacional de Rosario. Centro Internacional Franco Argentino de Ciencias de la Información y de Sistemas; Argentina Fil: Hesse Rizzi, Eugenia Fátima. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt | Instituto de Neurología Cognitiva. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt | Fundación Favaloro. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt; Argentina Fil: Birba, Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt | Instituto de Neurología Cognitiva. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt | Fundación Favaloro. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt; Argentina Fil: Salamone, Paula Celeste. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt | Instituto de Neurología Cognitiva. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt | Fundación Favaloro. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt; Argentina Fil: Hildebrandt, Malin. Institute for Clinical Psychology and Psychotherapy; Alemania Fil: Alarco Martí, Sofía. Universidad Favaloro; Argentina Fil: Pautassi, Ricardo Marcos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina Fil: Huepe, David. Universidad Adolfo Ibañez; Chile Fil: Martorell Martorell, Miquel. Universidad Favaloro; Argentina Fil: Yoris, Adrián. Universidad Favaloro; Argentina Fil: Roca, María. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt | Instituto de Neurología Cognitiva. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt | Fundación Favaloro. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt; Argentina Fil: García, Adolfo Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt | Instituto de Neurología Cognitiva. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt | Fundación Favaloro. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt; Argentina Fil: Sedeño, Lucas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt | Instituto de Neurología Cognitiva. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt | Fundación Favaloro. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt; Argentina Fil: Ibañez, Agustin Mariano. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt | Instituto de Neurología Cognitiva. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt | Fundación Favaloro. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt; Argentina. Universidad Adolfo Ibañez; Chile. Universidad Autónoma del Caribe; Colombia

Background: Maternal infections are an important cause of maternal mortality and severe maternal morbidity. We report the main findings of the WHO Global Maternal Sepsis Study, which aimed to assess the frequency of maternal infections in health facilities, according to maternal characteristics and outcomes, and coverage of core practices for early identification and management. Methods: We did a facility-based, prospective, 1-week inception cohort study in 713 health facilities providing obstetric, midwifery, or abortion care, or where women could be admitted because of complications of pregnancy, childbirth, post-partum, or post-abortion, in 52 low-income and middle-income countries (LMICs) and high-income countries (HICs). We obtained data from hospital records for all pregnant or recently pregnant women hospitalised with suspected or confirmed infection. We calculated ratios of infection and infection-related severe maternal outcomes (ie, death or near-miss) per 1000 livebirths and the proportion of intrahospital fatalities across country income groups, as well as the distribution of demographic, obstetric, clinical characteristics and outcomes, and coverage of a set of core practices for identification and management across infection severity groups. Findings: Between Nov 28, 2017, and Dec 4, 2017, of 2965 women assessed for eligibility, 2850 pregnant or recently pregnant women with suspected or confirmed infection were included. 70·4 (95% CI 67·7–73·1) hospitalised women per 1000 livebirths had a maternal infection, and 10·9 (9·8–12·0) women per 1000 livebirths presented with infection-related (underlying or contributing cause) severe maternal outcomes. Highest ratios were observed in LMICs and the lowest in HICs. The proportion of intrahospital fatalities was 6·8% among women with severe maternal outcomes, with the highest proportion in low-income countries. Infection-related maternal deaths represented more than half of the intrahospital deaths. Around two-thirds (63·9%, n=1821) of the women had a complete set of vital signs recorded, or received antimicrobials the day of suspicion or diagnosis of the infection (70·2%, n=1875), without marked differences across severity groups. Interpretation: The frequency of maternal infections requiring management in health facilities is high. Our results suggest that contribution of direct (obstetric) and indirect (non-obstetric) infections to overall maternal deaths is greater than previously thought. Improvement of early identification is urgently needed, as well as prompt management of women with infections in health facilities by implementing effective evidence-based practices. Fil: Althabe, Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; Argentina Fil: Espinoza, Marisa Mabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; Argentina Fil: Pasquale, Julia. No especifíca; Fil: Hernández Muñoz, Rosalinda. No especifíca; Fil: Carvajal, Javier. No especifíca; Fil: Escobar, María Fernanda. No especifíca; Fil: Cecatti, José Guilherme. No especifíca; Fil: Ribeiro Do Valle, Carolina C.. No especifíca; Fil: Mereci, Wilson. No especifíca; Fil: Vélez, Paola. No especifíca; Fil: Pérez, Aquilino M.. No especifíca; Fil: Vitureira, Gerardo. No especifíca; Fil: Leroy, Charlotte. No especifíca; Fil: Roelens, Kristien. No especifíca; Fil: Vandenberghe, Griet. No especifíca; Fil: Aguemon, Christiane Tshabu. No especifíca; Fil: Cisse, Kadari. No especifíca; Fil: Ouedraogo, Henri Gautier. No especifíca; Fil: Kannitha, Cheang. No especifíca; Fil: Rathavy, Tung. No especifíca; Fil: Tebeu, Pierre Marie. No especifíca; Fil: Bustillo, Carolina. No especifíca; Fil: Bredy, Lara. No especifíca; Fil: Herrera Maldonado, Nazarea. No especifíca; Fil: Abdosh, Abdulfetah Abdulkadir. No especifíca; Fil: Teklu, Alula M.. No especifíca; Fil: Kassa, Dawit Worku. No especifíca; Fil: Kumar, Vijay. No especifíca; Fil: Suri, Vanita. No especifíca; Fil: Trikha, Sonia. No especifíca

BACKGROUND:Methicillin-resistant Staphylococcus aureus (MRSA) strains are some of the most widespread pathogens multi-resistant to antimicrobial agents (AA). The AA provoke several changes inside bacteria, which cannot be solely explained by the main mechanisms of action reported. OBJECTIVE:The role of the oxidative stress in bacteria exposed to bacteriostatic AA has not been widely studied; hence, the aim of our work was to investigate the effect of Linezolid (LZD) on S. aureus strains. METHODS:Oxidative stress markers, such as superoxide dismutase enzyme (SOD) activity, the global antioxidant response, the advanced oxidation protein products (AOPP) and the basal levels of glutathione in 28 clinical and 2 reference strains were performed. RESULTS AND CONCLUSIONS:We identified 10 of 30 strains showing a slightly increase in reactive species under LZD treatment with respect to the untreated control (between 22 to 56%). The higher generation was detected in the clinical strains compared to the reference ones, however the impact in the antioxidant response was not significant, and the oxidized protein levels were almost undetectable. The strains exposed to this oxazolidinone did not suffer acute oxidative stress. This is the first work reporting the behavior of S. aureus clinical and reference strains exposed to LZD, being the oxidative stress negligible. Fil: Martinez, Sol Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Instituto de Investigaciones en Tecnologías Energéticas y Materiales Avanzados. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Tecnologías Energéticas y Materiales Avanzados; Argentina Fil: Aiassa, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina Fil: Sola, Claudia del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina Fil: Becerra, María Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina

According to the WHO, about 3 million people die each year due to ambient air pollution. Most of the in vivo studies on the PM 2.5 effects have been done on respiratory and cardiovascular tissues. However, little is known about the effects on the tissues involved on xenobiotic removal, such as kidneys. In the present study we assess the harmful effects of sub-chronic exposure to PM 2.5 on the kidney, by investigating histologic and serum alterations in healthy and hypertensive rat models. Mean PM 2.5 concentrations during exposures were slightly above the daily WHO standard. Exposed animals showed fibrosis, mesangial expansion, decrease glomerular and tubular lumen volumes in kidneys, with an elevated BUN. Hypertensive animals also exhibited much more severe alterations than healthy animals. We conclude that PM 2.5 induces minimal or small-scale abnormalities that can be determinant for renal health preservation. Fil: Tavera Busso, Iván. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina Fil: Mateos, Ana Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina Fil: Juncos, Luis Isaias. Fundación J. Robert Cade; Argentina Fil: Canals, Norma. Oulton-inst D/diag y Tratamiento Ambulatorio; Argentina Fil: Carreras, Hebe Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina

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

Background: Worldwide, smoking tobacco causes 7 million deaths annually, and this toll is expected to increase, especially in low-income and middle-income countries. In Latin America, smoking is a leading risk factor for death and disability, contributes to poverty, and imposes an economic burden on health systems. Despite being one of the most effective measures to reduce smoking, tobacco taxation is underused and cigarettes are more affordable in Latin America than in other regions. Our aim was to estimate the tobacco-attributable burden on mortality, disease incidence, quality of life lost, and medical costs in 12 Latin American countries, and the expected health and economic effects of increasing tobacco taxes. Methods: In this modelling study, we developed a Markov probabilistic microsimulation economic model of the natural history, medical costs, and quality-of-life losses associated with the most common tobacco-related diseases in 12 countries in Latin America. Data inputs were obtained through a literature review, vital statistics, and hospital databases from each country: Argentina, Bolivia, Brazil, Chile, Colombia, Costa Rica, Ecuador, Honduras, Mexico, Paraguay, Peru, and Uruguay. The main outcomes of the model are life-years, quality-adjusted life-years, disease events, hospitalisations, disease incidence, disease cost, and healthy years of life lost. We estimated direct medical costs for each tobacco-related disease included in the model using a common costing methodology for each country. The disease burden was estimated as the difference in disease events, deaths, and associated costs between the results predicted by the model for current smoking prevalence and a hypothetical cohort of people in each country who had never smoked. The model estimates the health and financial effects of a price increase of cigarettes through taxes, in terms of disease and health-care costs averted, and increased tax revenues. Findings: In the 12 Latin American countries analysed, we estimated that smoking is responsible for approximately 345 000 (12%) of the total 2 860 921 adult deaths, 2·21 million disease events, 8·77 million healthy years of life lost, and $26·9 billion in direct medical costs annually. Health-care costs attributable to smoking were estimated to represent 6·9% of the health budgets of these countries, equivalent to 0·6% of their gross domestic product. Tax revenues from cigarette sales cover 36·0% of the estimated health expenditures caused by smoking. We estimated that a 50% increase in cigarette price through taxation would avert more than 300 000 deaths, 1·3 million disease events, gain 9 million healthy life-years, and save $26·7 billion in health-care costs in the next 10 years, with a total economic benefit of $43·7 billion. Interpretation: Smoking represents a substantial health and economic burden in these 12 countries of Latin America. Tobacco tax increases could successfully avert deaths and disability, reduce health-care spending, and increase tax revenues, resulting in large net economic benefits. Fil: Pichón-riviere, Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; Argentina Fil: Alcaraz, Andrea. Instituto de Efectividad Clínica y Sanitaria; Argentina Fil: Palacios, Alfredo. Instituto de Efectividad Clínica y Sanitaria; Argentina Fil: Rodríguez, Belén. Instituto de Efectividad Clínica y Sanitaria; Argentina Fil: Reynales Shigematsu, Luz Myriam. Instituto Nacional de Salud Pública; México Fil: Pinto, Márcia. Fundación Oswaldo Cruz; Brasil Fil: Castillo Riquelme, Marianela. Ministerio de Salud; Chile Fil: Peña Torres, Esperanza. Instituto de Evaluación Tecnológica En Salud; Colombia Fil: Osorio, Diana Isabel. Instituto de Evaluación Tecnológica en Salud; Colombia Fil: Huayanay, Leandro. Universidad Peruana Cayetano Heredia; Perú Fil: Loza Munarriz, Cesar. Universidad Peruana Cayetano Heredia; Perú Fil: Sáenz de Miera-Juárez, Belén. Universidad Autónoma de Baja California Sur; México Fil: Gallegos Rivero, Verónica. Centro Nacional de Excelencia Tecnológica en Salud; México Fil: De La Puente, Catherine. Universidad de La Frontera; Chile Fil: Navia Bueno, María del Pilar. Universidad Mayor de San Andrés; Bolivia Fil: Caporale, Joaquín. Instituto de Efectividad Clínica y Sanitaria; Argentina Fil: Roberti, Javier Eugenio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; Argentina Fil: Virgilio, Sacha Alexis. Instituto de Efectividad Clínica y Sanitaria; Argentina Fil: Augustovski, Federico Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; Argentina Fil: Bardach, Ariel Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; Argentina

BACKGROUND: Comparable global data on health and nutrition of school-aged children and adolescents are scarce. We aimed to estimate age trajectories and time trends in mean height and mean body-mass index (BMI), which measures weight gain beyond what is expected from height gain, for school-aged children and adolescents., METHODS: For this pooled analysis, we used a database of cardiometabolic risk factors collated by the Non-Communicable Disease Risk Factor Collaboration. We applied a Bayesian hierarchical model to estimate trends from 1985 to 2019 in mean height and mean BMI in 1-year age groups for ages 5–19 years. The model allowed for non-linear changes over time in mean height and mean BMI and for non-linear changes with age of children and adolescents, including periods of rapid growth during adolescence., FINDINGS: We pooled data from 2181 population-based studies, with measurements of height and weight in 65 million participants in 200 countries and territories. In 2019, we estimated a difference of 20 cm or higher in mean height of 19-year-old adolescents between countries with the tallest populations (the Netherlands, Montenegro, Estonia, and Bosnia and Herzegovina for boys; and the Netherlands, Montenegro, Denmark, and Iceland for girls) and those with the shortest populations (Timor-Leste, Laos, Solomon Islands, and Papua New Guinea for boys; and Guatemala, Bangladesh, Nepal, and Timor-Leste for girls). In the same year, the difference between the highest mean BMI (in Pacific island countries, Kuwait, Bahrain, The Bahamas, Chile, the USA, and New Zealand for both boys and girls and in South Africa for girls) and lowest mean BMI (in India, Bangladesh, Timor-Leste, Ethiopia, and Chad for boys and girls; and in Japan and Romania for girls) was approximately 9–10 kg/m2. In some countries, children aged 5 years started with healthier height or BMI than the global median and, in some cases, as healthy as the best performing countries, but they became progressively less healthy compared with their comparators as they grew older by not growing as tall (eg, boys in Austria and Barbados, and girls in Belgium and Puerto Rico) or gaining too much weight for their height (eg, girls and boys in Kuwait, Bahrain, Fiji, Jamaica, and Mexico; and girls in South Africa and New Zealand). In other countries, growing children overtook the height of their comparators (eg, Latvia, Czech Republic, Morocco, and Iran) or curbed their weight gain (eg, Italy, France, and Croatia) in late childhood and adolescence. When changes in both height and BMI were considered, girls in South Korea, Vietnam, Saudi Arabia, Turkey, and some central Asian countries (eg, Armenia and Azerbaijan), and boys in central and western Europe (eg, Portugal, Denmark, Poland, and Montenegro) had the healthiest changes in anthropometric status over the past 3·5 decades because, compared with children and adolescents in other countries, they had a much larger gain in height than they did in BMI. The unhealthiest changes—gaining too little height, too much weight for their height compared with children in other countries, or both—occurred in many countries in sub-Saharan Africa, New Zealand, and the USA for boys and girls; in Malaysia and some Pacific island nations for boys; and in Mexico for girls., INTERPRETATION: The height and BMI trajectories over age and time of school-aged children and adolescents are highly variable across countries, which indicates heterogeneous nutritional quality and lifelong health advantages and risks., Wellcome Trust, AstraZeneca Young Health Programme, EU., peer-reviewed

Hereby we communicate the first autochthon isolation of Cryptococcus gattii VGIII in Chile, which was obtained from a nasal injury in a domestic cat in the Valparaíso region in Chile. The strain was identified using morphophysiological tests, MALDI-TOF, and URA5 gene PCR-RFLP analysis. Fil: Vieille, Peggy. Universidad de Valparaiso; Chile Fil: Cruz, Rodrigo. Universidad de Valparaiso; Chile Fil: León, Paula. Clinica Veterinaria Leon; Chile Fil: Cáceres, Nicolás. Laboratorio de Estudios Diagnosticos Veterinarios Histocell; Chile Fil: Giusiano, Gustavo Emilio. Universidad Nacional del Nordeste. Facultad de Medicina; Argentina. Universidad Nacional del Nordeste. Instituto de Medicina Regional; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; Argentina

Background: Acute kidney injury (AKI) is a public health problem that affects millions of hospitalized patients worldwide. In Argentina, evidence suggests that its incidence has risen in recent years. When severe, AKI may require a renal replacement therapy (RRT) where continuous RRT (CRRT) and intermittent RRT (IRRT) are plausible options for patients in the intensive care unit. Objective: To evaluate the cost utility of CRRT versus IRRT for the National Institute of Social Services for Retirees and Pensioners, the largest social security health insurance for elders in Argentina. Methods: This was a model-based cost-utility analysis. Long-term costs and health outcomes were estimated for a hypothetical cohort with a Markov model. Parameters used were obtained from published literature and validated with local experts. Local costs were estimated and expressed in $AR of 2016. Several sensitivity analyses were run to analyze the impact of uncertainty on results. Results: Continuous RRT dominated IRRT by cumulating over the model more quality-adjusted life years and less costs. Total discounted quality-adjusted life years for both cohorts were 1049 and 1034, respectively, and total costs were $95 362 and $103 871. Cost-effectiveness (CE) results reflect these differences in favor of CRRT with a deterministic cost-saving incremental CE ratio and a probability of CRRT being CE of 65.4%, considering a CE threshold of 1 gross domestic product per capita. Conclusions: Continuous RRT for patients with AKI eligible for CRRT or IRRT would probably be a cost-effective intervention for the National Institute of Social Services for Retirees and Pensioners’ view. Nevertheless, there is considerable uncertainty around results, mainly due to the lack of adequate controlled studies and local data on the prognosis of these patients in Argentina. Fil: Garay, Osvaldo Ulises. Instituto de Efectividad Clínica y Sanitaria; Argentina Fil: Palacios, Alfredo. Instituto de Efectividad Clínica y Sanitaria; Argentina Fil: Pichón-riviere, Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; Argentina Fil: Augustovski, Federico Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; Argentina Fil: García Martí, Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; Argentina Fil: Hernández Vásquez, Akram. Instituto de Efectividad Clínica y Sanitaria; Argentina Fil: López, Elena Tapia. Instituto de Efectividad Clínica y Sanitaria; Argentina Fil: Rosa Diez, Guillermo Javier. Instituto de Efectividad Clínica y Sanitaria; Argentina Fil: Bardach, Ariel Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; Argentina

Dioctophymosis is caused by Dioctophyme renale, nematode with indirect life cycle. Its intermediate host is a freshwater oligochaete and its definitive host is a wild or household carnivore. The adult nematode develops in the definite host, generally locating itself in the kidney. This article was meant to describe the first nephrectomy performed in a domestic cat due to renal dioctophymosis in Argentina. The subject showed a non-specific appearance of generally feeling ill, hematuria and mild diarrhea. It was diagnosed through abdominal ultrasound, followed by exploratory celiotomy and nephrectomy. After verifying absence of free specimens, the right kidney was removed. This organ was found to be enlarged in a spheroidal manner in contrast to the left kidney, with significant thickening of the renal capsule, excessive congestion of vessels and adhesions involving the caudal vena cava. An adult nematode was removed from the right kidney and identified as Dioctophyme renale. Reports of feline dioctophymosis are scarce being most of them necropsy findings. In this we are presenting a confirmed case of D. renale removed by surgery from a live cat. The results presented here reinforces the fact that cats are also appropriate definitive hosts for this parasite. Fil: Butti, M.J.. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Departamento de Microbiología. Laboratorio de Parasitosis Humanas y Zoonosis Parasitarias; Argentina Fil: Gamboa, María Inés. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Departamento de Microbiología. Laboratorio de Parasitosis Humanas y Zoonosis Parasitarias; Argentina. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; Argentina Fil: Terminiello, J.D.. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina Fil: Franchini, Gisela Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina Fil: Giorello, Alejandra Nahili. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina Fil: Maldonado, Lucas Luciano. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentina Fil: Kamenetzky, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentina Fil: Luna, M.F.. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina Fil: López Merlo, Mariana Lucía. Universidad Nacional de la Plata. Facultad de Cs.veterinarias. Centro de Fisiologia Reproductiva y Metodos Complementarios de Diagnostico.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Radman, Nilda Ester. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Departamento de Microbiología. Laboratorio de Parasitosis Humanas y Zoonosis Parasitarias; Argentina

A chronic-positive energetic balance has been directly correlated with infertility in men, but the involved mechanisms remain unknown. Herein we investigated weather in a mouse model a chronic feeding with a diet supplemented with chicken fat affects sperm head morphology. To accomplish this, we fed mice for 16 weeks with either control food (low-fat diet, LFD) or control food supplemented with 22% chicken fat (high-fat diet, HFD). At the end of the feeding regimen, we measured: redox and inflammatory changes, cholesterol accumulation in testis and analyzed testicular morphological structure and ultra-structure and liver morphology. We found that the mice fed HFD resembled some features of the human metabolic syndrome, including systemic oxidative stress and inflammation, this group showed an increment in the following parameters; central adiposity (adiposity index: 1.07 ± 0.10 vs 2.26 ± 0.17), dyslipidemia (total cholesterol: 153.3 ± 2.6 vs 175.1 ± 8.08 mg/dL), insulin resistance (indirect Insulin resistance index, TG/HDL-c: 2.94 ± 0.33 vs 3.68 ± 0.15) and fatty liver. Increased cholesterol content measured by filipin was found in the testicles from HFD (fluorescence intensity increase to 50%), as well as an alteration of spermiogenesis. Most remarkably, a disorganized manchette-perinuclear ring complex and an altered morphology of the sperm head were observed in the spermatozoa of HFD-fed mice. These results add new information to our understanding about the mechanisms by which systemic oxidative stress and inflammation may influence sperm-head morphology and indirectly male fertility., Cell biology; Immunology; Molecular biology; Proteins; Diet; Male fertility; Mouse model; Inflammation; Sperm-head morphology; Dietary fat; Oxidative stress

Background: Despite international recommendations, coverage of syphilis testing in pregnant women and treatment of those found seropositive remains limited in sub-Saharan Africa. We assessed whether combining the provision of supplies with a behavioural intervention was more effective than providing supplies only, to improve syphilis screening and treatment during antenatal care. Methods: In this 18-month, cluster randomised controlled trial, we randomly assigned (1:1) 26 urban antenatal care clinics in Kinshasa, Democratic Republic of the Congo, and Lusaka, Zambia, to receive a behavioural intervention (opinion leader selection, academic detailing visits, reminders, audits and feedback, and supportive supervision) plus supplies for syphilis testing and treatment (intervention group) or to receive supplies only (control group). The primary outcomes were proportion of pregnant women who had syphilis screening out of the total who attended the clinic; and the proportion of women who had treatment with benzathine benzylpenicillin out of those who tested positive for syphilis at their first antenatal care visit. This trial is registered at ClinicalTrials.gov, number NCT02353117. Findings: The 18-month study period was Feb 1, 2016, to July 14, 2017. 18 357 women were enrolled at the 13 intervention clinics and 17 679 women were enrolled at the 13 control clinics at their first antenatal care visit. Syphilis screening was done in a median of 99·9% (IQR 99·0–100·0) of women in the intervention clinics and 93·8% (85·0–98·9) in the control clinics (absolute difference 6·1% [95% CI 1·1–14·1]; p=0·00092). Syphilis treatment at the first visit was done in a median of 100% (IQR 99·7–100·0) of seropositive women in intervention clinics and 43·2% (2·6–83·2) of seropositive women in control clinics (absolute difference 56·8% [12·8–99·0]; p=0·0028). Interpretation: A behavioural intervention, together with the provision of supplies, can lead to more than 95% of women being screened and treated for syphilis. The sole provision of supplies is sufficient to reach such levels of screening coverage but is not sufficient to ensure high levels of treatment. Funding: Bill & Melinda Gates Foundation. Fil: Althabe, Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Efectividad Clínica y Sanitaria; Argentina. Organizacion Mundial de la Salud; Argentina Fil: Chomba, Elwyn. University Teaching Hospital of Lusaka; Zambia Fil: Tshefu, Antoinette K. University of Kinshasa; República Democrática del Congo Fil: Banda, Ernest. University Teaching Hospital of Lusaka; Zambia Fil: Belizán, María Melina Eleonora. Instituto de Efectividad Clínica y Sanitaria; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Bergel, Eduardo. Instituto de Efectividad Clínica y Sanitaria; Argentina Fil: Berrueta, Amanda Mabel. Instituto de Efectividad Clínica y Sanitaria; Argentina Fil: Bertrand, Jane. University of Tulane; Estados Unidos Fil: Bose, Carl. University of North Carolina; Estados Unidos Fil: Cafferata, Maria Luisa. Instituto de Efectividad Clínica y Sanitaria; Argentina Fil: Carlo, Waldemar A. University of Alabama at Birmingahm; Estados Unidos Fil: Ciganda, Alvaro. Instituto de Efectividad Clínica y Sanitaria; Argentina Fil: Donnay, France. University of Tulane; Estados Unidos Fil: Garcia Elorrio, Ezequiel. Instituto de Efectividad Clínica y Sanitaria; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Gibbons, Luz. Instituto de Efectividad Clínica y Sanitaria; Argentina Fil: Klein, Karen. Instituto de Efectividad Clínica y Sanitaria; Argentina Fil: Liljestrand, Jerker. Bill And Melinda Gates Foundation; Estados Unidos Fil: Lusamba, Paul D. University of Kinshasa; República Democrática del Congo Fil: Mavila, Arlette K. University of Kinshasa; República Democrática del Congo Fil: Mazzoni, Agustina. Instituto de Efectividad Clínica y Sanitaria; Argentina Fil: Nkamba, Dalau M. University of Kinshasa; República Democrática del Congo Fil: Mwanakalanga, Friday H. University Teaching Hospital Lusaka; Zambia Fil: Mwapule Tembo, Abigail. University Teaching Hospital Lusaka; Zambia Fil: Mwenechanya, Musaku. University Teaching Hospital Lusaka; Zambia Fil: Pyne Mercier, Lee. Bill And Melinda Gates Foundation; Estados Unidos Fil: Spira, Cintia. Instituto de Efectividad Clínica y Sanitaria; Argentina Fil: Wetshikoy, Jean D. University of Kinshasa; República Democrática del Congo Fil: Xiong, Xu. University of Tulane; Estados Unidos Fil: Buekens, Pierre. University of Tulane; Estados Unidos

Background: Cardiovascular prognostic models guide treatment allocation and support clinical decisions. Whether there are valid models for Latin American and Caribbean (LAC) populations is unknown. Objective: This study sought to identify and critically appraise cardiovascular prognostic models developed, tested, or recalibrated in LAC populations. Methods: The systematic review followed the CHARMS (CHecklist for critical Appraisal and data extraction for systematic Reviews of prediction Modelling Studies) framework (PROSPERO [International Prospective Register of Systemic Reviews]: CRD42018096553). Reports were included if they followed a prospective design and presented a multivariable prognostic model; reports were excluded if they studied symptomatic individuals or patients. The following search engines were used: EMBASE, MEDLINE, Scopus, SciELO, and LILACS. Risk of bias assessment was conducted with PROBAST (Prediction model Risk Of Bias ASsessment Tool). No quantitative summary was conducted due to large heterogeneity. Results: From 2,506 search results, 8 studies (N = 130,482 participants) were included for qualitative synthesis. We could not identify any cardiovascular prognostic model developed for LAC populations; reviewed reports evaluated available models or conducted a recalibration analysis. Only 1 study included a Caribbean population (Puerto Rico); 3 studies were retrieved from Chile; 2 from Argentina, Brazil, Colombia, and Uruguay; and 1 from Mexico. Four studies included population-based samples, and the other 4 included people affiliated to a health facility (e.g., prevention clinics). Most studied participants were older than 50 years, and there were more women in 5 reports. The Framingham model was assessed 6 times, and the American College of Cardiology/American Heart Association pooled equation was assessed twice. Across the prognostic models assessed, calibration varied widely from one population to another, showing great overestimation particularly in some subgroups (e.g., highest risk). Discrimination (e.g., C-statistic) was acceptable for most models; for Framingham it ranged from 0.66 to 0.76. The American College of Cardiology/American Heart Association pooled equation showed the best discrimination (0.78). That there were few outcome events was the most important methodological limitation of the identified studies. Conclusions: No cardiovascular prognostic models have been developed in LAC, hampering key evidence to inform public health and clinical practice. Validation studies need to improve methodological issues. Fil: Carrillo Larco, Rodrigo M.. Imperial College London; Reino Unido Fil: Altez Fernandez, Carlos. Universidad Peruana Cayetano Heredia; Perú Fil: Pacheco Barrios, Niels. Universidad Peruana Cayetano Heredia; Perú Fil: Bambs, Claudia. Pontificia Universidad Católica de Chile; Chile Fil: Irazola, Vilma. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; Argentina Fil: Miranda, J. Jaime. Universidad Peruana Cayetano Heredia; Perú Fil: Miranda, J. Jaime. Universidad Peruana Cayetano Heredia; Perú Fil: Danaei, Goodarz. Harvard University. Harvard School of Public Health; Estados Unidos Fil: Perel, Pablo Roberto. No especifíca

Background: A recent cluster randomized trial evaluating a multicomponent intervention showed significant reductions in blood pressure in low-income hypertensive subjects in Argentina. Objectives: To assess the cost-effectiveness of this intervention. Methods: A total of 1432 hypertensive participants were recruited from 18 primary health care centers. The intervention included home visits led by community health workers, physician education, and text messaging. Resource use and quality of life data using the three-level EuroQol five-dimensional questionnaire were prospectively collected. The study perspective was that of the public health care system, and the time horizon was 18 months. Intention-to-treat analysis was used to analyze cost and health outcomes (systolic blood pressure [SBP] change and quality-adjusted life-years [QALYs]). A 1 time gross domestic product per capita per QALY was used as the cost-effectiveness threshold (US $14,062). Results: Baseline characteristics were similar in the two arms. QALYs significantly increased by 0.06 (95% confidence interval [CI] 0.04–0.09) in the intervention group, and SBP net difference favored the intervention group: 5.3 mm Hg (95% CI 0.27–10.34). Mean total costs per participant were higher in the intervention arm: US $304 in the intervention group and US $154 in the control group (adjusted difference of US $140.18; 95% CI US $75.41–US $204.94). The incremental cost-effectiveness ratio was $3299 per QALY (95% credible interval 1635–6099) and US $26 per mm Hg of SBP (95% credible interval 13–46). Subgroup analysis showed that the intervention was cost-effective in all prespecified subgroups (age, sex, cardiovascular risk, and body mass index). Conclusions: The multicomponent intervention was cost-effective for blood pressure control among low-income hypertensive patients. Fil: Augustovski, Federico Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Efectividad Clínica y Sanitaria; Argentina Fil: Chaparro, Martin. Instituto de Efectividad Clínica y Sanitaria; Argentina Fil: Palacios, Alfredo. Instituto de Efectividad Clínica y Sanitaria; Argentina Fil: Shi, Lizheng. University of Tulane; Estados Unidos Fil: Beratarrechea, Andrea Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Efectividad Clínica y Sanitaria; Argentina Fil: Irazola, Vilma. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Efectividad Clínica y Sanitaria; Argentina Fil: Rubinstein, Adolfo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Efectividad Clínica y Sanitaria; Argentina Fil: Mills, Katherine. University of Tulane; Estados Unidos Fil: He, Jiang. University of Tulane; Estados Unidos Fil: Pichón-Riviere, Andrés. Instituto de Efectividad Clínica y Sanitaria; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina

Objectives: Trypanosoma cruzi reactivation in HIV patients is considered an opportunistic infection, usually with a fatal outcome. The aim of this study was to describe the epidemiological and clinical features of T. cruzi infection in HIV patients and to compare these findings between patients with and without Chagas disease reactivation. Methods: The medical records of T. cruzi–HIV co-infected patients treated at the Muñiz Infectious Diseases Hospital from January 2005 to December 2014 were reviewed retrospectively. Epidemiological and clinical features were assessed and compared between patients with and without Chagas disease reactivation. Results: The medical records of 80 T. cruzi–HIV co-infected patients were reviewed. The most likely route of T. cruzi infection was vector-borne (32/80 patients), followed by intravenous drug use (12/80). Nine of 80 patients had reactivation. Patients without reactivation had a significantly higher CD4 T-cell count at diagnosis of T. cruzi infection (144 cells/μl vs. 30 cells/μl, p = 0.026). Chagas disease serology was negative in two of nine patients with reactivation. Conclusions: Serological assays for T. cruzi infection may be negative in severely immunocompromised patients. Direct parasitological techniques should be performed in the diagnosis of patients for whom there is a suspicion of T. cruzi reactivation. HIV patients with a lower CD4 count are at higher risk of reactivation. Fil: Benchetrit, Andres Guillermo. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina Fil: Fernández, Marisa. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina Fil: Bava, Amadeo Javier. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina Fil: Corti, Marcelo. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina Fil: Porteiro, Norma. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina Fil: Martinez Peralta, Liliana A.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentina

Thyroid dyshormonogenesis due to thyroglobulin (TG) gene mutations have an estimated incidence of approximately 1 in 100,000 newborns. The clinical spectrum ranges from euthyroid to mild or severe hypothyroidism. Up to now, one hundred seventeen deleterious mutations in the TG gene have been identified and characterized. The purpose of the present study was to identify and characterize new mutations in the TG gene. We report eight patients from seven unrelated families with goiter, hypothyroidism and low levels of serum TG. All patients underwent clinical, biochemical and image evaluation. Sequencing of DNA, genotyping, as well as bioinformatics analysis were performed. Molecular analyses revealed three novel inactivating TG mutations: c.5560G>T [p.E1835*], c.7084G>C [p.A2343P] and c.7093T>C [p.W2346R], and four previously reported mutations: c.378C>A [p.Y107*], c.886C>T [p.R277*], c.1351C>T [p.R432*] and c.7007G>A [p.R2317Q]. Two patients carried homozygous mutations (p.R277*/p.R277*, p.W2346R/p.W2346R), four were compound heterozygous mutations (p.Y107*/p.R277* (two unrelated patients), p.R432*/p.A2343P, p.Y107*/p.R2317Q) and two siblings from another family had a single p.E1835* mutated allele. Additionally, we include the analysis of 48 patients from 31 unrelated families with TG mutations identified in our present and previous studies. Our observation shows that mutations in both TG alleles were found in 27 families (9 as homozygote and 18 as heterozygote compound), whereas in the remaining four families only one mutated allele was detected. The majority of the detected mutations occur in exons 4, 7, 38 and 40. 28 different mutations were identified, 33 of the 96 TG alleles encoded the change p.R277*. In conclusion, our results confirm the genetic heterogeneity of TG defects and the pathophysiological importance of the predicted TG misfolding and therefore thyroid hormone formation as a consequence of truncated TG proteins and/or missense mutations located within its ACHE-like domain., This study was funded by grants from the FONCyT-ANPCyT-MINCyT (PICT 2014-1193 to CMR, PICT 2012-1090 and PICT 2015–1811 to HMT), CONICET (PIP 2015-11220150100499 to CMR) and Universidad de Buenos Aires (UBACyT 2016-20020150100099BA to CMR).

Uptake of low-density lipoprotein (LDL) particles by macrophages represents a key step in the development of atherosclerotic plaques, leading to the foam cell formation. Chemical modification of LDL is however necessary to induce this process. Proatherogenic LDL modifications include aggregation, enzymatic digestion and oxidation. LDL oxidation by one-electron (free radicals) and two-electron oxidants dramatically increases LDL affinity to macrophage scavenger receptors, leading to rapid LDL uptake and fatty streak formation. Circulating high-density lipoprotein (HDL) particles, primarily small, dense, protein-rich HDL3, provide potent protection of LDL from oxidative damage by free radicals, resulting in the inhibition of the generation of pro-inflammatory oxidized lipids. HDL-mediated inactivation of lipid hydroperoxides involves their initial transfer from LDL to HDL and subsequent reduction to inactive hydroxides by redox-active Met residues of apolipoprotein A-I. Several HDL-associated enzymes are present at elevated concentrations in HDL3 relative to large, light HDL2 and can be involved in the inactivation of short-chain oxidized phospholipids. Therefore, HDL represents a multimolecular complex capable of acquiring and inactivating proatherogenic lipids. Antioxidative function of HDL can be impaired in several metabolic and inflammatory diseases. Structural and compositional anomalies in the HDL proteome and lipidome underlie such functional deficiency. Concomitant normalization of the metabolism, circulating levels, composition and biological activities of HDL particles, primarily those of small, dense HDL3, can constitute future therapeutic target., Highlights • LDL oxidation dramatically increases LDL affinity to macrophage scavenger receptors, leading fatty streak formation. • HDL particles, primarily small, dense HDL3, provide potent protection to LDL from oxidative damage by free radicals. • HDL represents a multimolecular complex capable of acquiring and inactivating of proatherogenic oxidized lipids. • Antioxidative function of HDL is impaired in metabolic diseases; normalization of HDL functions can be a therapeutic target.

Resumen Objetivo: Identificar determinantes sociodemográficos asociados a la distribución espacial de la incidencia de cáncer de mama en la provincia de Córdoba, Argentina, a fin de develar inequidades sociales en salud. Método: Se desarrolló un estudio ecológico en Córdoba (26 departamentos como unidades geográficas de análisis). Mediante el índice de Moran se estimó la autocorrelación espacial de las tasas de incidencia de cáncer de mama, brutas y estandarizadas, y de indicadores sociodemográficos de urbanización, fecundidad y envejecimiento poblacional. Estas variables fueron incorporadas a a un Sistema de Información Geográfica para su mapeo. Se ajustaron modelos de regresión de Poisson multinivel, para la tasa de incidencia de cáncer de mama como variable respuesta, indicadores sociodemográficos seleccionados como covariables, y porcentaje de hogares con necesidades básicas insatisfechas como variable de ajuste. Resultados: En Córdoba, Argentina, existe un patrón no aleatorio en las distribuciones espaciales de las tasas de incidencia de cáncer de mama y de ciertos indicadores sociodemográficos. El incremento medio anual de la población urbana fue inversamente asociado a la ocurrencia de cáncer de mama, mientras que la proporción de hogares con necesidades básicas insatisfechas presentó una asociación directa. Conclusiones: Nuestros resultados definen escenarios de inequidad social que explican, en parte, los diferenciales geográficos de la carga del cáncer de mama en Córdoba, Argentina. Las mujeres residentes en hogares socioeconómicamente desfavorecidos y en áreas menos urbanizadas requieren especial atención en futuros estudios e intervenciones de salud pública en cáncer de mama. Abstract Objective: To identify sociodemographic determinants associated with the spatial distribution of the breast cancer incidence in the province of Córdoba, Argentina, in order to reveal underlying social inequities. Method: An ecological study was developed in Córdoba (26 counties as geographical units of analysis). The spatial autocorrelation of the crude and standardised incidence rates of breast cancer, and the sociodemographic indicators of urbanization, fertility and population ageing were estimated using Moran's index. These variables were entered into a Geographic Information System for mapping. Poisson multilevel regression models were adjusted, establishing the breast cancer incidence rates as the response variable, and by selecting sociodemographic indicators as covariables and the percentage of households with unmet basic needs as adjustment variables. Results: In Córdoba, Argentina, a non-random pattern in the spatial distribution of breast cancer incidence rates and in certain sociodemographic indicators was found. The mean increase in annual urban population was inversely associated with breast cancer, whereas the proportion of households with unmet basic needs was directly associated with this cancer. Conclusions: Our results define social inequity scenarios that partially explain the geographical differentials in the breast cancer burden in Córdoba, Argentina. Women residing in socioeconomically disadvantaged households and in less urbanized areas merit special attention in future studies and in breast cancer public health activities.

Objectives: Oxidative stress and inflammation are important processes in development of atherosclerosis. Paraoxonase 1 (PON1) is a bioscavenger enzyme associated with inflammation and oxidative stress. We evaluate the association of two single nucleotide polymorphisms in PON1 gene, and enzyme activities with lipid profile and glycemia. Methods: This case-control study consisted of 126 patients with coronary artery disease (CAD) and 203 healthy controls. PON Q192R and L55M polymorphisms were detected by real-time PCR. Paraoxonase and arylesterase activities were determined spectrophotometrically. Blood glucose, cholesterol, triglycerides, HDL, and LDL were measured. Results: PON1 QR192 polymorphism had a major effect on paraoxonase but no effect on arylesterase serum activities. Paraoxonase activity was higher in RR genotype and lowest in QQ genotype. Paraoxonase and arylesterase activities were higher in LL and lower in MM genotypes of PON1 LM55 polymorphism. RQ and LM variants showed intermediate activities between respective homozygous. Elevated concentrations of triglycerides in cases correlate with QQ variant or the presence of M allele. Glucose levels were elevated in cases with QQ variant or with the presence of M allele. Cholesterol and LDL did not show variations in control and cases with any variant of both polymorphisms. HDL is lower in cases with respect to controls independently of genotypes. All differences were significant with p < 0.05. Fil: Fridman, Osvaldo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Abierta Interamericana; Argentina Fil: Gariglio Zappellini, Luis Osvaldo. Universidad Abierta Interamericana; Argentina Fil: Riviere, Stephanie. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Abierta Interamericana; Argentina Fil: Porcile, Rafael. Universidad Abierta Interamericana; Argentina Fil: Fuchs, Alicia Graciela. Universidad Abierta Interamericana; Argentina Fil: Potenzoni, Miguel. Universidad Abierta Interamericana; Argentina

The transmission of Trypanosoma cruzi by vectors is confined to the Americas, and the infection circulates in at least two broadly defined transmission cycles occurring in domestic and sylvatic habitats. This study sought to detect and characterize infection by T. cruzi and other trypanosomes using PCR strategies in blood samples from free-ranging howler monkeys, Alouatta caraya, in the northeastern Argentina. Blood samples were collected at four sites with variable levels of habitat modification by human activity. PCR was conducted using primers for kinetoplast DNA, satellite DNA and ribosomal DNA of the trypanosomatid parasites. Ribosomal and satellite DNA fragments were sequenced to identify the trypanosomatid species and to characterize the discrete typing units (DTUs) of T. cruzi. Overall, 46% (50/109) of the howlers were positive according to the kDNA-PCR assay, but only 7 of the howlers were positive according to the SatDNA-PCR protocol. We sequenced the amplicons of the satellite DNA obtained from five specimens, and the sequences were 99% and 100% similar to T. cruzi. A sequence typical of DTU T. cruzi I was found in one howler monkey from the “remote” site, while sequences compatible with DTUs II, V, and VI were found in howlers from the “remote”, “rural” and “village” sites. We detected 96% positive samples for RibDNA-PCR, 9 of which were sequenced and displayed 99% identity with Trypanosoma minasense, while none showed identity with T. cruzi. The results demonstrated the presence of T. cruzi and a species closely related to T. minasense in blood samples from free-ranging A. caraya, belonging to different T. cruzi DTUs circulating in these howler monkey populations. The results obtained in this study could help evaluate the role of A. caraya as a reservoir of T. cruzi in regions where Chagas disease is hyper-endemic and where the human-wildlife interface is increasing., Graphical abstract, Highlights • Trypanosome infection was assessed in wild howler monkeys from northern Argentina. • Seven out of 109 individuals were positive for Trypanosoma cruzi. • Satellite DNA sequencing were typical of T. cruzi I and II/V/VI. • Trypanosoma minasense was detected for first time in free-ranging Alouatta caraya. • Mixed infections by T. cruzi and T. minasense were observed in a group of animals.

Background Diabetes mellitus is one of the leading causes of death and disability worldwide. Approximately three-quarters of people with diabetes live in low- and middle-income countries, and these countries are projected to experience the greatest increase in diabetes burden. Objectives We sought to compare the prevalence, awareness, treatment, and control of diabetes in 3 urban and periurban regions: the Southern Cone of Latin America and Peru, South Asia, and South Africa. In addition, we examined the relationship between diabetes and pre-diabetes with known cardiovascular and metabolic risk factors. Methods A total of 26,680 participants (mean age, 47.7 ± 14.0 years; 45.9% male) were enrolled in 4 sites (Southern Cone of Latin America = 7,524; Peru = 3,601; South Asia = 11,907; South Africa = 1,099). Detailed demographic, anthropometric, and biochemical data were collected. Diabetes and pre-diabetes were defined as a fasting plasma glucose ≥126 mg/dl and 100 to 125 mg/dl, respectively. Diabetes control was defined as fasting plasma glucose

Background: Community-led total sanitation (CLTS) uses participatory approaches to mobilise communities to build their own toilets and stop open defecation. Our aim was to undertake the first randomised trial of CLTS to assess its effect on child health in Koulikoro, Mali. Methods: We did a cluster-randomised trial to assess a CLTS programme implemented by the Government of Mali. The study population included households in rural villages (clusters) from the Koulikoro district of Mali; every household had to have at least one child aged younger than 10 years. Villages were randomly assigned (1:1) with a computer-generated sequence by a study investigator to receive CLTS or no programme. Health outcomes included diarrhoea (primary outcome), height for age, weight for age, stunting, and underweight. Outcomes were measured 1·5 years after intervention delivery (2 years after enrolment) among children younger than 5 years. Participants were not masked to intervention assignment. The trial is registered with ClinicalTrials.gov, number NCT01900912. Findings: We recruited participants between April 12, and June 23, 2011. We assigned 60 villages (2365 households) to receive the CLTS intervention and 61 villages (2167 households) to the control group. No differences were observed in terms of diarrhoeal prevalence among children in CLTS and control villages (706 [22%] of 3140 CLTS children vs 693 [24%] of 2872 control children; prevalence ratio [PR] 0·93, 95% CI 0·76-1·14). Access to private latrines was almost twice as high in intervention villages (1373 [65%] of 2120 vs 661 [35%] of 1911 households) and reported open defecation was reduced in female (198 [9%] of 2086 vs 608 [33%] of 1869 households) and in male (195 [10%] of 2004 vs 602 [33%] of 1813 households) adults. Children in CLTS villages were taller (0·18 increase in height-for-age Z score, 95% CI 0·03-0·32; 2415 children) and less likely to be stunted (35% vs 41%, PR 0·86, 95% CI 0·74-1·0) than children in control villages. 22% of children were underweight in CLTS compared with 26% in control villages (PR 0·88, 95% CI 0·71-1·08), and the difference in mean weight-for-age Z score was 0·09 (95% CI -0·04 to 0·22) between groups. In CLTS villages, younger children at enrolment (, Facultad de Ciencias Económicas, Centro de Estudios Distributivos, Laborales y Sociales

Epidemiological investigations regarding temperature influence on human health have focused on mortality rather than morbidity. In addition, most information comes from developed countries despite the increasing evidence that climate change will have devastating impacts on disadvantaged populations living in developing countries. In the present study, we assessed the impact of daily temperature range on upper and lower respiratory infections in Cordoba, Argentina, and explored the effect modification of socio-economic factors and influence of airborne particles We found that temperature range is a strong risk factor for admissions due to both upper and lower respiratory infections, particularly in elderly individuals, and that these effects are more pronounced in sub-populations with low education level or in poor living conditions. These results indicate that socio-economic factors are strong modifiers of the association between temperature variability and respiratory morbidity, thus they should be considered in risk assessments. Fil: Carreras, Hebe Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina Fil: Zanobetti, Antonella. Harvard University. Harvard School Of Public Health; Estados Unidos Fil: Koutrakis, Petros. Harvard University. Harvard School Of Public Health; Estados Unidos

Objetivos: Evaluar la bioaccesibilidad y aporte potencial (AP) de Fe y Zn de fideos comerciales fortificados (FCF), y la relación entre el tiempo de cocción y la pérdida de sólidos, Fe y Zn de dichos fideos. Materiales y métodos: se analizaron cuatro diferentes marcas de FCF. Se evaluó la pérdida de sólidos, Fe y Zn a dos tiempos de cocción (tiempo óptimo indicado por el fabricante y una sobrecocción de 10 minutos). La bioaccesibilidad de Fe y Zn se estimó a través del porcentaje del mineral dializado. El AP de minerales se determinó como el producto de la concentración y la dializabilidad de cada mineral. Resultados: Las pérdidas de sólidos resultaron inferiores al 7%, aún con sobrecocción. Tres de los cuatro FCF no cumplían con los valores declarados de contenido de Fe. Se produjeron grandes pérdidas de Fe y Zn durante la cocción, las cuales aumentaron al prolongarse el tiempo de cocción (de 43,7% a 64,7% para Fe; y de 7,7% a 15,2% para el Zn), siendo mayores las pérdidas de Fe (mineral de fortificación), que de Zn (mineral endógeno). La bioaccesibilidad de Fe y Zn resultó baja (0,82±0,27% y 0,90±0,45%, respectivamente) y el AP de una porción de 80g de FCF sólo cubriría en promedio 0,646% de los requerimientos de Fe y 0,708% de los requerimientos de Zn. Conclusiones: Los resultados muestran que la fortificación de fideos contribuye muy poco a cubrir los requerimientos de los minerales analizados ya que gran parte se pierde en el agua de cocción. Fil: Galan, Maria Gimena. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Litoral. Facultad de Ingeniería Química. Instituto de Tecnología de los Alimentos; Argentina Fil: Llopart, Emilce Elina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad del Centro Educativo Latinoamericano. Facultad de Química; Argentina Fil: Tissera, Emilia. Universidad del Centro Educativo Latinoamericano. Facultad de Química; Argentina Fil: Alladio, Anabella. Universidad del Centro Educativo Latinoamericano. Facultad de Química; Argentina Fil: Drago, Silvina Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Litoral. Facultad de Ingeniería Química. Instituto de Tecnología de los Alimentos; Argentina

The incidence of the highly infectious respiratory disease named pertussis or whooping cough has been increasing for the past two decades in different countries, as in much of the highly vaccinated world. A decrease in vaccine effectiveness over time, especially when acellular vaccines were used for primary doses and boosters, and pathogen adaptation to the immunity conferred by vaccines have been proposed as possible causes of the resurgence. The contributions of these factors are not expected to be the same in different communities, and this could lead to different epidemiological trends. In fact, differences in the magnitude and dynamics of pertussis outbreaks as well as in the distribution of notified cases by age have been reported in various regions. Using an age-structured mathematical model designed by us, we evaluated how the changes in some of the parameters that could be related to the above proposed causes of disease resurgence - vaccine effectiveness and effective transmission rates - may impact on pertussis transmission. When a linear decrease in vaccine effectiveness (VE) was assayed, a sustained increase in pertussis incidence was detected mainly in infants and children. On the other hand, when changes in effective transmission rates (βij) were made, a dynamic effect evidenced by the presence of large peaks followed by deep valleys was detected. In this case, greater incidence in adolescents than in children was observed. These different trends in the disease dynamics due to modifications in VE or βij were verified in 18 possible scenarios that represent different epidemiological situations. Interestingly we found that both incidence trends produced by the model and their age distribution resemble the profiles obtained from data reported in several regions. The implications of these correlations are discussed., Facultad de Ciencias Exactas, Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas, Instituto de Biotecnologia y Biologia Molecular

The effect of Lactobacillus rhamnosus CRL1505 on blood and bone marrow (BM) myeloid cells and their correlation with resistance against Streptococcus pneumoniae infection was evaluated in protein-malnourished mice. Repletion of malnourished mice with supplemental L. rhamnosus improved recovery of BM responsiveness against the infectious challenge through increase in myeloid progenitors and mobilisation of granulocytes. The CRL1505 strain normalised the number of Gr1+ cells and Gr1low/Gr1high cells balance in BM. These changes in BM correlated with improved neutrophils recruitment, higher phagocytic activity and increased resistance against pneumococcal infection in probiotic-treated mice. This research provides strong evidence of the importance of dietary supplementation with probiotic bacteria to reverse alterations in myeloid progenitors in malnourished mice. The present results strongly suggest that the CRL1505 strain could be used in the development of probiotic foods, which would be especially useful for the recovery of immunocompromised hosts. Fil: Herrera, Héctor Matías. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Centro de Referencia Para Lactobacilos (i); Argentina Fil: Salva, Maria Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Centro de Referencia Para Lactobacilos (i); Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia; Argentina Fil: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Centro de Referencia Para Lactobacilos (i); Argentina Fil: Barbieri, Natalia Paola del Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Centro de Referencia Para Lactobacilos (i); Argentina Fil: Alvarez, Gladis Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Centro de Referencia Para Lactobacilos (i); Argentina. Universidad Nacional de Tucumán; Argentina

This study was aimed at assessing the potential use of soybean protein concentrate (SPC) - based film as vehicle for the delivery of Duddingtonia flagrans chlamydospores for the biological control of gastric nematodes in ruminals. Glycerol and dialdehyde starch (DAS) were used as plasticizer and cross-linking agent, respectively. Films were obtained by casting and characterized in terms of their physico-mechanical properties. The impact of cross-linking extent on moisture absorption, swelling and tensile properties of the resultant films was evaluated. The adequate tensile properties and stability in wet environment of SPC films cross-linked with 10wt.%DAS was counterbalanced with the two-phase morphologies developed, irrespective of glycerol content, limiting their potential application as delivery devices. SPC films cross-linked with 5wt.%DAS and plasticized with 30wt.% glycerol exhibited the best compromise between solubility (only 29%), homogeneous morphology and adequate tensile strength (2.50 ± 0.43MPa) and elongation at break (18.72 ± 2.34 %) and swelling profile. The preliminary results of the release of D. flagrans chlamydospores in ruminal fluid revealed a slow release profile attaining 4.9% in a period of 24 h. Overall, these results substantiated the potential use of DAS-cross-linked SPC films as viable carrier matrix for D.flagrans release applications. Fil: Ciannamea, Emiliano Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Bahía Blanca. Planta Piloto de Ingeniería Química (i); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mar del Plata. Instituto de Investigación en Ciencia y Tecnología de Materiales (i); Argentina Fil: Sagüés, María Federica. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Sanidad Animal y Medicina Preventiva; Argentina Fil: Saumell, Carlos Alfredo. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Sanidad Animal y Medicina Preventiva; Argentina Fil: Stefani, Pablo Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mar del Plata. Instituto de Investigación en Ciencia y Tecnología de Materiales (i); Argentina Fil: Ruseckaite, Roxana Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mar del Plata. Instituto de Investigación en Ciencia y Tecnología de Materiales (i); Argentina

Recently (Roca et al. (2010), we used the relationship with general intelligence (Spearman’s g) to define two sets of frontal lobe or “executive” tests. For one group, including Wisconsin card sorting and verbal fluency, reduction in g entirely explained the deficits found in frontal patients. For another group, including tests of social cognition and multitasking, frontal deficits remained even after correction for g. Preliminary evidence suggested a link of the latter tasks to more anterior frontal regions. Here we develop this distinction in the context of behavioural-variant frontotemporal dementia (bvFTD), a disorder which progressively affects frontal lobe cortices. In bvFTD, some executive tests, including tests of social cognition and multitasking, decline from the early stage of the disease, while others, including classical executive tests such as Wisconsin card sorting, verbal fluency or Trail Making Test part B, show deficits only later on. Here we show that, while deficits in the classical executive tests are entirely explained by g, deficits in the social cognition and multitasking tests are not. The results suggest a relatively selective cognitive deficit at mild stages of the disease, followed by more widespread cognitive decline well predicted by g., Highlights ► A progressive loss of general intelligence (g) can be found in patients with FTD. ► Advanced FTD classical executive deficits can be entirely explained by loss of g. ► Early social cognition and multitasking deficits exceed the ones predicted from g. ► Assessment in FTD should encompass g, multitasking and social cognition.

Objective To obtain versions of the Primary Care Assessment Tools (PCAT)-Facility version to evaluate primary care (PC) in the Spanish context, and to analyze its feasibility, reliability and validity. Methods Cultural adaptation was performed through the use of forward and backward translations into Spanish and Catalan, observations and opinions of a panel of experts, and cognitive interviews with target users (PC team managers). A pilot phase was carried out in a sample of 130 managers of PC teams in Catalonia. A post-test questionnaire was sent 4-5 months later to all 194 managers of PC teams in the Barcelona health region. Analysis of metric properties included: 1) description of items and verification of Likert assumptions, since domain scores are obtained by summing item scores; 2) reliability analysis (Cronbach's alpha coefficient, Pearson's correlation coefficient, test-retest analysis); and 3) validity analysis (expert panel, cognitive interviews, and convergent and discriminant validity). Results Substantial adaptation was required for the accessory section of the questionnaire, but less was required in PC domain measurements. Items were added to the comprehensiveness domain to reflect services usually available in Spain. The lowest Cronbach's alpha scores were found for Access (0.62) and Coordination (0.59 and 0.65), while values were >0.70 for the remaining domains. Conclusion The Spanish version of the PCAT-Facility questionnaire is now available and shows adequate reliability and validity. The Spanish PCAT version will facilitate national and international comparisons of PC and analysis of the determinants of quality of service provision. Objetivo Obtener versiones del Primary Care Assessment Tools–Facility version como herramienta de evaluación de la atención primaria (AP) para la aplicación en el contexto español, y analizar su fiabilidad y validez. Métodos Se realizó una adaptación cultural con traducciones y retrotraducciones al español y al catalán, observaciones y opiniones de un panel de expertos y entrevistas cognitivas con usuarios finales (directivos del equipo de AP). Se realizó una fase piloto con una muestra de 130 directivos de AP de Cataluña. Una versión final se envió 4-5 meses después a los 194 directivos de los equipos de la región sanitaria de Barcelona. El análisis de las propiedades métricas incluyó: 1) descripción de ítems y verificación de las asunciones de la escala Likert, porque las puntuaciones de los dominios se obtienen sumando los ítems; 2) análisis de fiabilidad (alfa de Cronbach, coeficiente de correlación de Pearson, análisis test-retest); y 3) análisis de validez (panel de expertos, entrevistas cognitivas, validez convergente y discriminante). Resultados Se requirió una importante adaptación de las secciones accesorias del cuestionario, pero no en las de los dominios de AP. Se añadieron ítems en la dimensión de globalidad. Las menores puntuaciones del alfa de Cronbach se encontraron en acceso (0,62) y coordinación (0,59 y 0,65); el resto de los dominios tuvieron valores > 0,70. Conclusión Disponemos de una versión española del PCAT - Equipo de Atención Primaria con unas adecuadas fiabilidad y validez, que facilitará comparaciones nacionales e internacionales, y el análisis de los determinantes de una provisión de servicios de calidad. Fil: Pasarín, M. Isabel. Agencia de Salud Pública de Barcelona; España. CIBER de Epidemiología y Salud Pública; España. Sociedad Catalana de Medicina Familiar y Comunitaria; España Fil: Berra, Silvina del Valle. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones En Ciencias de la Salud; Argentina. CIBER de Epidemiología y Salud Pública; España. Agència d’Informació, Avaluació i Qualitat en Salut; España Fil: González, Angelina. Agencia de Salud Pública de Barcelona; España Fil: Segura, Andreu. Institut d’Estudis de la Salut; España Fil: Tebé, Cristian. Agència d’Informació, Avaluació i Qualitat en Salut; España Fil: García Altés, Anna. Agencia de Salud Pública de Barcelona; España. CIBER de Epidemiología y Salud Pública; España Fil: Vallverdú, Inma. Consorci Sanitari de Barcelona; España Fil: Starfield, Barbara. Johns Hopkins University; Estados Unidos

Background/Purpose: Oral immunization with Lactococcus lactis PppA (LPA+), a recombinant strain that is able to express the pneumococcal protective protein A, can improve the resistance to respiratory challenge with Streptococcus pneumoniae in adult mice. In this study, we investigated whether oral immunization protocols using LPA+ are able to protect young mice against pneumococcal respiratory infection. Methods: Young mice (aged, 3 weeks) were immunized orally with LPA+ for 5 consecutive days. Vaccination was performed once (non-boosted group), or twice with a 2-week interval between each immunization (boosted group). At the end of treatment, the specific immune responses and the resistance to pneumococcal infection were studied. Results: We found that the oral immunization with LPA+ was able to induce the production of specific antibodies in the respiratory and intestinal tracts as well as systemically. Analysis of IgG subtypes showed that LPA+ immunization stimulated a mixed Th1 and Th2 response. To assess whether the production of mucosal and systemic antibodies was able to afford protection against respiratory pneumococcal infection, challenge experiments with the pathogenic serotypes 3, 6B, 14, and 23F were carried out. Vaccination with LPA+ was able to increase resistance to infection with the four serotypes of S. pneumoniae, although the protective capacity of the experimental vaccine was different for each of them. Immunization decreased colonization in the lung, prevented bacteremia of serotypes 6B, 14, and 23F, and decreased colony counts of serotype 3. Conclusion: We have shown that the oral immunization of young mice with LPA+ effectively induces the production of specific antibodies against the antigen PppA, both in mucosae and at the systemic level. The antibodies produced may play an important role in the protection against pneumococcal disease, since the young mice immunized with the experimental vaccine showed an increased resistance to infection with different serotypes of the pathogen. Fil: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Bioquímica Aplicada; Argentina Fil: Medina, Marcela Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Bioquímica Aplicada; Argentina Fil: Racedo, Silvia María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina Fil: Alvarez, Gladis Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Bioquímica Aplicada; Argentina