Modelo electrocardiográfico de la enfermedad de Chagas crónica en ratón para la evaluación de nuevos fármacos

El tratamiento de la enfermedad de Chagas es actualmente insatisfactorio. Los compuestos empleados (nifurtimox y benznidazol) tienen actividad solo en la fase aguda siendo ineficaces en la fase crónica por presentar serios efectos adversos. Nuevos compuestos son necesarios. La manifestación clínica más importante es la miocarditis crónica tardía, siendo menos frecuente la miocarditis aguda. Debido a que la afección se disemina por todo el corazón (miocitos y sistema especializado de conducción) los trastornos electrocardiográficos (TECG) son representativos de la patología como arritmias y trastornos de conducción y repolarización ventricular. Nuestro objetivo fue obtener un modelo electrocardiográfico de la enfermedad de Chagas crónica en ratón para la evaluación de nuevos fármacos.Trabajo en modalidad posters que recibió premio en las "Cuartas Jornadas de Actualización en Clínica Pediátrica" 200

Feasibility, drug safety, and effectiveness of etiological treatment programs for Chagas disease in Honduras, Guatemala, and Bolivia: 10-year experience of Médecins Sans Frontières

BACKGROUND: Chagas disease (American trypanosomiasis) is a zoonotic or anthropozoonotic disease caused by the parasite Trypanosoma cruzi. Predominantly affecting populations in poor areas of Latin America, medical care for this neglected disease is often lacking. Médecins Sans Frontières/Doctors Without Borders (MSF) has provided diagnostic and treatment services for Chagas disease since 1999. This report describes 10 years of field experience in four MSF programs in Honduras, Guatemala, and Bolivia, focusing on feasibility protocols, safety of drug therapy, and treatment effectiveness. METHODOLOGY: From 1999 to 2008, MSF provided free diagnosis, etiological treatment, and follow-up care for patients <18 years of age seropositive for T. cruzi in Yoro, Honduras (1999-2002); Olopa, Guatemala (2003-2006); Entre Ríos, Bolivia (2002-2006); and Sucre, Bolivia (2005-2008). Essential program components guaranteeing feasibility of implementation were information, education, and communication (IEC) at the community and family level; vector control; health staff training; screening and diagnosis; treatment and compliance, including family-based strategies for early detection of adverse events; and logistics. Chagas disease diagnosis was confirmed by testing blood samples using two different diagnostic tests. T. cruzi-positive patients were treated with benznidazole as first-line treatment, with appropriate counseling, consent, and active participation from parents or guardians for daily administration of the drug, early detection of adverse events, and treatment withdrawal, when necessary. Weekly follow-up was conducted, with adverse events recorded to assess drug safety. Evaluations of serological conversion were carried out to measure treatment effectiveness. Vector control, entomological surveillance, and health education activities were carried out in all projects with close interaction with national and regional programs. RESULTS: Total numbers of children and adolescents tested for T. cruzi in Yoro, Olopa, Entre Ríos, and Sucre were 24,471, 8,927, 7,613, and 19,400, respectively. Of these, 232 (0.9%), 124 (1.4%), 1,475 (19.4%), and 1,145 (5.9%) patients, respectively, were diagnosed as seropositive. Patients were treated with benznidazole, and early findings of seroconversion varied widely between the Central and South American programs: 87.1% and 58.1% at 18 months post-treatment in Yoro and Olopa, respectively; 5.4% by up to 60 months in Entre Ríos; and 0% at an average of 18 months in Sucre. Benznidazole-related adverse events were observed in 50.2% and 50.8% of all patients treated in Yoro and Olopa, respectively, and 25.6% and 37.9% of patients in Entre Ríos and Sucre, respectively. Most adverse events were mild and manageable. No deaths occurred in the treatment population. CONCLUSIONS: These results demonstrate the feasibility of implementing Chagas disease diagnosis and treatment programs in resource-limited settings, including remote rural areas, while addressing the limitations associated with drug-related adverse events. The variability in apparent treatment effectiveness may reflect differences in patient and parasite populations, and illustrates the limitations of current treatments and measures of efficacy. New treatments with improved safety profiles, pediatric formulations of existing and new drugs, and a faster, reliable test of cure are all urgently needed

Bifurcation of critical points along gap-continuous families of subspaces

We consider the restriction of twice differentiable functionals on a Hilbert space to families of subspaces that vary continuously with respect to the gap metric. We study bifurcation of branches of critical points along these families, and apply our results to semilinear systems of ordinary differential equations

The Index Bundle and Multiparameter Bifurcation for Discrete Dynamical Systems

We develop a K-theoretic approach to multiparameter bifurcation theory of homoclinic solutions of discrete non-autonomous dynamical systems from a branch of stationary solutions. As a byproduct we obtain a family index theorem for asymptotically hyperbolic linear dynamical systems which is of independent interest. In the special case of a single parameter, our bifurcation theorem weakens the assumptions in previous work by Pejsachowicz and the first author

Cost-Effectiveness of Chagas Disease Vector Control Strategies in Northwestern Argentina

Despite decreasing rates of prevalence and incidence, Chagas disease remains a serious problem in Latin America, especially for the rural poor. Without vaccines, control and prevention rely mostly on residual spraying of insecticides. Under the aegis of the Southern Cone Initiative, and in agreement with global trends in decentralization of the health systems, in 1992 the Argentinean vector control launched a new vector control program based on community participation. The present study represents the first thorough evaluation of the overall performance of such vector control program and the first comparative assessment of the cost-effectiveness of different vector control strategies in a highly endemic rural area of northwestern Argentina. Supported by results of independent studies, the present work shows that in rural, poor and dispersed areas of the Gran Chaco region, the implementation of a mixed (i.e., vertical attack phase followed by horizontal surveillance) strategy constantly supervised and supported by national or local vector control programs would be the most cost-effective option to interrupt vector-borne transmission of Chagas disease

GROUPES FONDAMENTAUX D'UNE FAMILLE DE COURBES RATIONNELLES CUSPIDALES

GRENOBLE1-BU Sciences (384212103) / SudocSudocFranceF

Psychophysiological detection of concealed information shared by groups: an empirical study of the searching CIT

This study focused on the application of the Concealed Information Test (CIT) to situations in which the crime-related information is shared by a group of suspects but is not available to the investigators (a method known as the "searching CIT," or SCIT). Twenty-two groups, each comprising 4 to 7 participants (115 in total), planned 1 of 2 mock crimes (kidnapping or bank robbery). While planning the crime, each group decided on 5 crime-related critical items (e.g., the city in which the bank was located). Each critical item was chosen from a predefined set of 4 alternatives. At a second stage, the SCIT was administered individually and each participant was tested on the 2 crimes-the actual planned crime, in which the participant was "guilty," and the unplanned crime, in which the participant was "innocent." Two algorithms, adopted from Breska, Ben-Shakhar, and Gronau (2012), were applied to detect the critical items and to differentiate between "guilty" and "innocent" participants. Findings revealed that differentiation efficiency based on electrodermal and respiration measures was identical to that obtained with the standard CIT when applied to large groups, but lower, although significantly greater than chance, when applied to differentiate between small groups