Mutation of EpCAM leads to intestinal barrier and ion transport dysfunction

UnlabelledCongenital tufting enteropathy (CTE) is a devastating diarrheal disease seen in infancy that is typically associated with villous changes and the appearance of epithelial tufts. We previously found mutations in epithelial cell adhesion molecule (EpCAM) to be causative in CTE. We developed a knock-down cell model of CTE through transfection of an EpCAM shRNA construct into T84 colonic epithelial cells to elucidate the in vitro role of EpCAM in barrier function and ion transport. Cells with EpCAM deficiency exhibited decreased electrical resistance, increased permeability, and decreased ion transport. Based on mutations in CTE patients, an in vivo mouse model was developed, with tamoxifen-inducible deletion of exon 4 in Epcam resulting in mutant protein with decreased expression. Tamoxifen treatment of Epcam (Δ4/Δ4) mice resulted in pathological features of villous atrophy and epithelial tufts, similar to those in human CTE patients, within 4 days post induction. Epcam (Δ4/Δ4) mice also showed decreased expression of tight junctional proteins, increased permeability, and decreased ion transport in the intestines. Taken together, these findings reveal mechanisms that may underlie disease in CTE.Key messagesKnock-down EpCAM cell model of congenital tufting enteropathy was developed. In vivo inducible mouse model was developed resulting in mutant EpCAM protein. Cells with EpCAM deficiency demonstrated barrier and ion transport dysfunction. Tamoxifen-treated Epcam (Δ4/Δ4) mice demonstrated pathological features. Epcam (Δ4/Δ4) mice showed improper barrier function and ion transport

Moir\'e Engineering in 2D Heterostructures with Process-Induced Strain

We report deterministic control over moir\'e superlattice geometry in twisted bilayer graphene by implementing designable device-level heterostrain with process-induced strain engineering. We quantify strain and moir\'e interference with Raman spectroscopy through in-plane and moir\'e-activated phonon mode shifts. Results support systematic C$_{3}$ rotational symmetry breaking and tunable periodicity in moir\'e superlattices under the application of uniaxial or biaxial heterostrain, confirmed with density functional theory based first principles calculations. This provides a method to not only tune moir\'e interference without additional twisting, but also allows for a systematic pathway to explore new van der Waals based moir\'e superlattice symmetries by deterministic design

NLRP3 inflammasome activation is required for fibrosis development in NAFLD

NLR inflammasomes, caspase 1 activation platforms critical for processing key pro-inflammatory cytokines, have been implicated in the development of nonalcoholic fatty liver disease (NAFLD). As the direct role of the NLRP3 inflammasome remains unclear, we tested effects of persistent NLRP3 activation as a contributor to NAFLD development and, in particular, as a modulator of progression from benign hepatic steatosis to steatohepatitis during diet-induced NAFLD. Gain of function tamoxifen-inducible Nlrp3 knock-in mice allowing for in vivo temporal control of NLRP3 activation and loss of function Nlrp3 knockout mice were placed on short-term choline-deficient amino acid-defined (CDAA) diet, to induce isolated hepatic steatosis or long-term CDAA exposure, to induce severe steatohepatitis and fibrosis, respectively. Expression of NLRP3 associated proteins was assessed in liver biopsies of a well-characterized group of patients with the full spectrum of NAFLD. Nlrp3−/− mice were protected from long-term feeding CDAA-induced hepatomegaly, liver injury, and infiltration of activated macrophages. More importantly, Nlrp3−/− mice showed marked protection from CDAA-induced liver fibrosis. After 4 weeks on CDAA diet, wild-type (WT) animals showed isolated hepatic steatosis while Nlrp3 knock-in mice showed severe liver inflammation, with increased infiltration of activated macrophages and early signs of liver fibrosis. In the liver samples of patients with NAFLD, inflammasome components were significantly increased in those patients with nonalcoholic steatohepatitis (NASH) when compared to those with non-NASH NAFLD with mRNA levels of pro-IL1 beta correlated to levels of COL1A1. Our study uncovers a crucial role for the NLRP3 inflammasome in the development of NAFLD. These findings may lead to novel therapeutic strategies aimed at halting the progression of hepatic steatosis to the more severe forms of this disease.Fil: Wree, Alexander. University of California at San Diego; Estados Unidos. University Hospital Essen; AlemaniaFil: McGeough, Matthew D.. University of California at San Diego; Estados UnidosFil: Peña, Carla A.. University of California at San Diego; Estados UnidosFil: Schlattjan, Martin. University Hospital Essen; AlemaniaFil: Li, Hongying. University of California at San Diego; Estados UnidosFil: Inzaugarat, Maria Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Messer, Karen. University of California at San Diego; Estados UnidosFil: Canbay, Ali. University Hospital Essen; AlemaniaFil: Hoffman, Hal M.. University of California at San Diego; Estados Unidos. Ludwig Institute of Cancer Research; Estados UnidosFil: Feldstein, Ariel E.. University of California at San Diego; Estados Unido

Laparoscopic versus open colectomy for acute complicated diverticulitis: a comparative study of outcomes - a systematic review

Acute complicated diverticulitis presents a more severe form of diverticular illness frequently needing urgent medical intervention and possibly surgical therapy. The aim of this review is to gather conclusive evidence from the literature comparing laparoscopic techniques to open and conservative ones in order to determine the most effective treatment plan for complicated diverticulitis. Online databases like PubMed, Google Scholar, Cochrane, Elsevier and many others were systematically searched according to an inclusion criterion to obtain a total of 13 studies to be included in the review. 8/13 studies presented short term outcomes while 5/13 studies concluded with long term outcomes following index surgeries. Based on the end results, it can be concluded that laparoscopic surgery, in particular laparoscopic colon resection is superior to other techniques in treating complicated diverticulitis in terms of fewer short-term complications, low mortality rate better quality of life with few recurrence rates. However, other approaches have their own advantages and can be given priority based on the unique presentation of each case. The clinicians are advised to make informed decisions keeping in view all the patient and disease associated aspects

Mitochondrial peptide humanin facilitates chemoresistance in glioblastoma cells

Humanin (HN) is a mitochondrial-derived peptide with robust cytoprotective effects in many cell types. Although the administration of HN analogs has been proposed to treat degenerative diseases, its role in the pathogenesis of cancer is poorly understood. Here, we evaluated whether HN affects the chemosensitivity of glioblastoma (GBM) cells. We found that chemotherapy upregulated HN expression in GBM cell lines and primary cultures derived from GBM biopsies. An HN analog (HNGF6A) boosted chemoresistance, increased the migration of GBM cells and improved their capacity to induce endothelial cell migration and proliferation. Chemotherapy also upregulated FPR2 expression, an HN membrane-bound receptor, and the HNGF6A cytoprotective effects were inhibited by an FPR2 receptor antagonist (WRW4). These effects were observed in glioma cells with heterogeneous genetic backgrounds, i.e., glioma cells with wild-type (wtIDH) and mutated (mIDH) isocitrate dehydrogenase. HN silencing using a baculoviral vector that encodes for a specific shRNA for HN (BV.shHN) reduced chemoresistance, and impaired the migration and proangiogenic capacity of GBM cells. Taken together, our findings suggest that HN boosts the hallmark characteristics of GBM, i.e., chemoresistance, migration and endothelial cell proliferation. Thus, strategies that inhibit the HN/FPR2 pathway may improve the response of GBM to standard therapyInstituto de Biotecnología y Biología Molecula

Evaluation of baculoviruses as gene therapy vectors for brain cancer

We aimed to assess the potential of baculoviral vectors (BV) for brain cancer gene therapy. We compared them with adenoviral vectors (AdV), which are used in neuro-oncology, but for which there is pre-existing immunity. We constructed BVs and AdVs encoding fluorescent reporter proteins and evaluated their transduction efficiency in glioma cells and astrocytes. Naïve and glioma-bearing mice were intracranially injected with BVs to assess transduction and neuropathology. Transgene expression was also assessed in the brain of BV-preimmunized mice. While the expression of BVs was weaker than AdVs in murine and human glioma cell lines, BV-mediated transgene expression in patient-derived glioma cells was similar to AdV-mediated transduction and showed strong correlation with clathrin expression, a protein that interacts with the baculovirus glycoprotein GP64, mediating BV endocytosis. BVs efficiently transduced normal and neoplastic astrocytes in vivo, without apparent neurotoxicity. BV-mediated transgene expression was stable for at least 21 days in the brain of naïve mice, but it was significantly reduced after 7 days in mice systemically preimmunized with BVs. Our findings indicate that BVs efficiently transduce glioma cells and astrocytes without apparent neurotoxicity. Since humans do not present pre-existing immunity against BVs, these vectors may constitute a valuable tool for the delivery of therapeutic genes into the brain.Instituto de Biotecnología y Biología Molecula

Therapeutic communication between health workers and patients concerning diabetes mellitus care

The objective of this cross-sectional study was to analyze therapeutic communication techniques used by health workers with patients under care for diabetes mellitus. Data were collected in 2010 in a public facility in the interior of Ceará, Brazil using video camera equipment and direct observation. Results showed that the most frequently used techniques within the "expression" group were: asking questions, voicing interest, and using descriptive phrases. The most frequently used technique within the "clarification" group was: asking the patient to specify the agent of action. Finally, in regard to the "validation" group, only the technique "summarizing content of the interaction" was employed. The conclusion is that despite the use of communication techniques on the part of professionals, there is still an alarming gap concerning communication skills. Such skills should be allied with technical expertise to enable the delivery of qualified care to individuals with diabetes mellitus.Este estudio transversal tuvo como objetivo analizar las técnicas de comunicación terapéutica entre profesionales y pacientes en la atención en diabetes mellitus. Los datos se recogieron en una institución pública de Ceará-Brasil, en 2010, con equipos de video y observación directa. Los resultados mostraron que las técnicas del grupo de expresión más utilizadas fueron: hacer preguntas, expresar interés y usar frases descriptivas. Con relación a las del grupo de clarificación sobresalió solicitar al paciente que necesite el agente de la acción. Con relación a las de validación, apenas se utilizó las de organizar el contenido de la interacción. Se concluye que a pesar del uso de técnicas de comunicación por los profesionales, aun es preocupante la laguna con relación a la habilidad en comunicación, que debe ser aliada a la capacidad técnica, para así propiciar el cuidado calificado a las personas con diabetes mellitus.Objetivou-se, por este estudo transversal, analisar as técnicas de comunicação terapêutica entre profissionais e pacientes na atenção em diabetes mellitus. Os dados foram coletados em uma instituição pública de um município no interior do Ceará, Brasil, em 2010, por meio de equipamentos de vídeo e observação direta. Os resultados mostraram que as técnicas do grupo de expressão mais utilizadas foram: fazer perguntas, verbalizar interesse e usar frases descritivas. Quanto às do grupo de clarificação, sobressaiu solicitar ao paciente que precise o agente da ação. Em relação às de validação, apenas foi utilizada a técnica de sumarizar o conteúdo da interação. Conclui-se que, apesar do emprego de técnicas comunicacionais pelos profissionais, ainda é preocupante a lacuna referente à habilidade em comunicação, a qual deve ser aliada à competência técnica, para assim propiciar o cuidado qualificado às pessoas com diabetes mellitus

Mitochondrial peptide humanin facilitates chemoresistance in glioblastoma cells

Humanin (HN) is a mitochondrial-derived peptide with robust cytoprotective effects in many cell types. Although the administration of HN analogs has been proposed to treat degenerative diseases, its role in the pathogenesis of cancer is poorly understood. Here, we evaluated whether HN affects the chemosensitivity of glioblastoma (GBM) cells. We found that chemotherapy upregulated HN expression in GBM cell lines and primary cultures derived from GBM biopsies. An HN analog (HNGF6A) boosted chemoresistance, increased the migration of GBM cells and improved their capacity to induce endothelial cell migration and proliferation. Chemotherapy also upregulated FPR2 expression, an HN membrane-bound receptor, and the HNGF6A cytoprotective effects were inhibited by an FPR2 receptor antagonist (WRW4). These effects were observed in glioma cells with heterogeneous genetic backgrounds, i.e., glioma cells with wild-type (wtIDH) and mutated (mIDH) isocitrate dehydrogenase. HN silencing using a baculoviral vector that encodes for a specific shRNA for HN (BV.shHN) reduced chemoresistance, and impaired the migration and proangiogenic capacity of GBM cells. Taken together, our findings suggest that HN boosts the hallmark characteristics of GBM, i.e., chemoresistance, migration and endothelial cell proliferation. Thus, strategies that inhibit the HN/FPR2 pathway may improve the response of GBM to standard therapyInstituto de Biotecnología y Biología Molecula

Evaluation of baculoviruses as gene therapy vectors for brain cancer

We aimed to assess the potential of baculoviral vectors (BV) for brain cancer gene therapy. We compared them with adenoviral vectors (AdV), which are used in neuro-oncology, but for which there is pre-existing immunity. We constructed BVs and AdVs encoding fluorescent reporter proteins and evaluated their transduction efficiency in glioma cells and astrocytes. Naïve and glioma-bearing mice were intracranially injected with BVs to assess transduction and neuropathology. Transgene expression was also assessed in the brain of BV-preimmunized mice. While the expression of BVs was weaker than AdVs in murine and human glioma cell lines, BV-mediated transgene expression in patient-derived glioma cells was similar to AdV-mediated transduction and showed strong correlation with clathrin expression, a protein that interacts with the baculovirus glycoprotein GP64, mediating BV endocytosis. BVs efficiently transduced normal and neoplastic astrocytes in vivo, without apparent neurotoxicity. BV-mediated transgene expression was stable for at least 21 days in the brain of naïve mice, but it was significantly reduced after 7 days in mice systemically preimmunized with BVs. Our findings indicate that BVs efficiently transduce glioma cells and astrocytes without apparent neurotoxicity. Since humans do not present pre-existing immunity against BVs, these vectors may constitute a valuable tool for the delivery of therapeutic genes into the brain.Instituto de Biotecnología y Biología Molecula

First Latin American clinical practice guidelines for the treatment of systemic lupus erythematosus: Latin American Group for the Study of Lupus (GLADEL, Grupo Latino Americano de Estudio del Lupus)-Pan-American League of Associations of Rheumatology (PANLAR)

Systemic lupus erythematosus (SLE), a complex and heterogeneous autoimmune disease, represents a significant challenge for both diagnosis and treatment. Patients with SLE in Latin America face special problems that should be considered when therapeutic guidelines are developed. The objective of the study is to develop clinical practice guidelines for Latin American patients with lupus. Two independent teams (rheumatologists with experience in lupus management and methodologists) had an initial meeting in Panama City, Panama, in April 2016. They selected a list of questions for the clinical problems most commonly seen in Latin American patients with SLE. These were addressed with the best available evidence and summarised in a standardised format following the Grading of Recommendations Assessment, Development and Evaluation approach. All preliminary findings were discussed in a second face-to-face meeting in Washington, DC, in November 2016. As a result, nine organ/system sections are presented with the main findings; an 'overarching' treatment approach was added. Special emphasis was made on regional implementation issues. Best pharmacologic options were examined for musculoskeletal, mucocutaneous, kidney, cardiac, pulmonary, neuropsychiatric, haematological manifestations and the antiphospholipid syndrome. The roles of main therapeutic options (ie, glucocorticoids, antimalarials, immunosuppressant agents, therapeutic plasma exchange, belimumab, rituximab, abatacept, low-dose aspirin and anticoagulants) were summarised in each section. In all cases, benefits and harms, certainty of the evidence, values and preferences, feasibility, acceptability and equity issues were considered to produce a recommendation with special focus on ethnic and socioeconomic aspects. Guidelines for Latin American patients with lupus have been developed and could be used in similar settings.Fil: Pons Estel, Bernardo A.. Centro Regional de Enfermedades Autoinmunes y Reumáticas; ArgentinaFil: Bonfa, Eloisa. Universidade de Sao Paulo; BrasilFil: Soriano, Enrique R.. Instituto Universitario Hospital Italiano de Buenos Aires. Rectorado.; ArgentinaFil: Cardiel, Mario H.. Centro de Investigación Clínica de Morelia; MéxicoFil: Izcovich, Ariel. Hospital Alemán; ArgentinaFil: Popoff, Federico. Hospital Aleman; ArgentinaFil: Criniti, Juan M.. Hospital Alemán; ArgentinaFil: Vásquez, Gloria. Universidad de Antioquia; ColombiaFil: Massardo, Loreto. Universidad San Sebastián; ChileFil: Duarte, Margarita. Hospital de Clínicas; ParaguayFil: Barile Fabris, Leonor A.. Hospital Angeles del Pedregal; MéxicoFil: García, Mercedes A.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Amigo, Mary Carmen. Centro Médico Abc; MéxicoFil: Espada, Graciela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Catoggio, Luis J.. Hospital Italiano. Instituto Universitario. Escuela de Medicina; ArgentinaFil: Sato, Emilia Inoue. Universidade Federal de Sao Paulo; BrasilFil: Levy, Roger A.. Universidade do Estado de Rio do Janeiro; BrasilFil: Acevedo Vásquez, Eduardo M.. Universidad Nacional Mayor de San Marcos; PerúFil: Chacón Díaz, Rosa. Policlínica Méndez Gimón; VenezuelaFil: Galarza Maldonado, Claudio M.. Corporación Médica Monte Sinaí; EcuadorFil: Iglesias Gamarra, Antonio J.. Universidad Nacional de Colombia; ColombiaFil: Molina, José Fernando. Centro Integral de Reumatología; ColombiaFil: Neira, Oscar. Universidad de Chile; ChileFil: Silva, Clóvis A.. Universidade de Sao Paulo; BrasilFil: Vargas Peña, Andrea. Hospital Pasteur Montevideo; UruguayFil: Gómez Puerta, José A.. Hospital Clinic Barcelona; EspañaFil: Scolnik, Marina. Instituto Universitario Hospital Italiano de Buenos Aires. Rectorado.; ArgentinaFil: Pons Estel, Guillermo J.. Centro Regional de Enfermedades Autoinmunes y Reumáticas; Argentina. Hospital Provincial de Rosario; ArgentinaFil: Ugolini Lopes, Michelle R.. Universidade de Sao Paulo; BrasilFil: Savio, Verónica. Instituto Universitario Hospital Italiano de Buenos Aires. Rectorado.; ArgentinaFil: Drenkard, Cristina. University of Emory; Estados UnidosFil: Alvarellos, Alejandro J.. Hospital Privado Universitario de Córdoba; ArgentinaFil: Ugarte Gil, Manuel F.. Universidad Cientifica del Sur; Perú. Hospital Nacional Guillermo Almenara Irigoyen; PerúFil: Babini, Alejandra. Instituto Universitario Hospital Italiano de Buenos Aires. Rectorado.; ArgentinaFil: Cavalcanti, André. Universidade Federal de Pernambuco; BrasilFil: Cardoso Linhares, Fernanda Athayde. Hospital Pasteur Montevideo; UruguayFil: Haye Salinas, Maria Jezabel. Hospital Privado Universitario de Córdoba; ArgentinaFil: Fuentes Silva, Yurilis J.. Universidad de Oriente - Núcleo Bolívar; VenezuelaFil: Montandon De Oliveira E Silva, Ana Carolina. Universidade Federal de Goiás; BrasilFil: Eraso Garnica, Ruth M.. Universidad de Antioquia; ColombiaFil: Herrera Uribe, Sebastián. Hospital General de Medellin Luz Castro de Gutiérrez; ColombiaFil: Gómez Martín, DIana. Instituto Nacional de la Nutrición Salvador Zubiran; MéxicoFil: Robaina Sevrini, Ricardo. Universidad de la República; UruguayFil: Quintana, Rosana M.. Hospital Provincial de Rosario; Argentina. Centro Regional de Enfermedades Autoinmunes y Reumáticas; ArgentinaFil: Gordon, Sergio. Hospital Interzonal General de Agudos Dr Oscar Alende. Unidad de Reumatología y Enfermedades Autoinmunes Sistémicas; ArgentinaFil: Fragoso Loyo, Hilda. Instituto Nacional de la Nutrición Salvador Zubiran; MéxicoFil: Rosario, Violeta. Hospital Docente Padre Billini; República DominicanaFil: Saurit, Verónica. Hospital Privado Universitario de Córdoba; ArgentinaFil: Appenzeller, Simone. Universidade Estadual de Campinas; BrasilFil: Dos Reis Neto, Edgard Torres. Universidade Federal de Sao Paulo; BrasilFil: Cieza, Jorge. Hospital Nacional Edgardo Rebagliati Martins; PerúFil: González Naranjo, Luis A.. Universidad de Antioquia; ColombiaFil: González Bello, Yelitza C.. Ceibac; MéxicoFil: Collado, María Victoria. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Sarano, Judith. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Retamozo, Maria Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: Sattler, María E.. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Gamboa Cárdenas, Rocio V.. Hospital Nacional Guillermo Almenara Irigoyen; PerúFil: Cairoli, Ernesto. Universidad de la República; UruguayFil: Conti, Silvana M.. Hospital Provincial de Rosario; ArgentinaFil: Amezcua Guerra, Luis M.. Instituto Nacional de Cardiologia Ignacio Chavez; MéxicoFil: Silveira, Luis H.. Instituto Nacional de Cardiologia Ignacio Chavez; MéxicoFil: Borba, Eduardo F.. Universidade de Sao Paulo; BrasilFil: Pera, Mariana A.. Hospital Interzonal General de Agudos General San Martín; ArgentinaFil: Alba Moreyra, Paula B.. Universidad Nacional de Córdoba. Facultad de Medicina; ArgentinaFil: Arturi, Valeria. Hospital Interzonal General de Agudos General San Martín; ArgentinaFil: Berbotto, Guillermo A.. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Gerling, Cristian. Hospital Interzonal General de Agudos Dr Oscar Alende. Unidad de Reumatología y Enfermedades Autoinmunes Sistémicas; ArgentinaFil: Gobbi, Carla Andrea. Universidad Nacional de Córdoba. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gervasoni, Viviana L.. Hospital Provincial de Rosario; ArgentinaFil: Scherbarth, Hugo R.. Hospital Interzonal General de Agudos Dr Oscar Alende. Unidad de Reumatología y Enfermedades Autoinmunes Sistémicas; ArgentinaFil: Brenol, João C. Tavares. Hospital de Clinicas de Porto Alegre; BrasilFil: Cavalcanti, Fernando. Universidade Federal de Pernambuco; BrasilFil: Costallat, Lilian T. Lavras. Universidade Estadual de Campinas; BrasilFil: Da Silva, Nilzio A.. Universidade Federal de Goiás; BrasilFil: Monticielo, Odirlei A.. Hospital de Clinicas de Porto Alegre; BrasilFil: Seguro, Luciana Parente Costa. Universidade de Sao Paulo; BrasilFil: Xavier, Ricardo M.. Hospital de Clinicas de Porto Alegre; BrasilFil: Llanos, Carolina. Universidad Católica de Chile; ChileFil: Montúfar Guardado, Rubén A.. Instituto Salvadoreño de la Seguridad Social; El SalvadorFil: Garcia De La Torre, Ignacio. Hospital General de Occidente; MéxicoFil: Pineda, Carlos. Instituto Nacional de Rehabilitación; MéxicoFil: Portela Hernández, Margarita. Umae Hospital de Especialidades Centro Medico Nacional Siglo Xxi; MéxicoFil: Danza, Alvaro. Hospital Pasteur Montevideo; UruguayFil: Guibert Toledano, Marlene. Medical-surgical Research Center; CubaFil: Reyes, Gil Llerena. Medical-surgical Research Center; CubaFil: Acosta Colman, Maria Isabel. Hospital de Clínicas; ParaguayFil: Aquino, Alicia M.. Hospital de Clínicas; ParaguayFil: Mora Trujillo, Claudia S.. Hospital Nacional Edgardo Rebagliati Martins; PerúFil: Muñoz Louis, Roberto. Hospital Docente Padre Billini; República DominicanaFil: García Valladares, Ignacio. Centro de Estudios de Investigación Básica y Clínica; MéxicoFil: Orozco, María Celeste. Instituto de Rehabilitación Psicofísica; ArgentinaFil: Burgos, Paula I.. Pontificia Universidad Católica de Chile; ChileFil: Betancur, Graciela V.. Instituto de Rehabilitación Psicofísica; ArgentinaFil: Alarcón, Graciela S.. Universidad Peruana Cayetano Heredia; Perú. University of Alabama at Birmingahm; Estados Unido