Obesity is associated with increased pediatric dengue virus infection and disease: A 9-year cohort study in Managua, Nicaragua.

BACKGROUND: Obesity is on the rise globally in adults and children, including in tropical areas where diseases such as dengue have a substantial burden, particularly in children. Obesity impacts the risk of severe dengue disease; however, the impact on dengue virus (DENV) infection and dengue cases remains an open question. METHODS: We used 9 years of data from 5,940 children in the Pediatric Dengue Cohort Study in Nicaragua to examine whether pediatric obesity is associated with increased susceptibility to DENV infection and symptomatic presentation. Analysis was performed using Generalized Estimating Equations adjusted for age, sex, and pre-infection DENV antibody titers. RESULTS: From 2011 to 2019, children contributed 26,273 person-years of observation, and we observed an increase in the prevalence of overweight (from 12% to 17%) and obesity (from 7% to 13%). There were 1,682 DENV infections and 476 dengue cases in the study population. Compared to participants with normal weight, participants with obesity had higher odds of DENV infection (Adjusted Odds Ratio [aOR] 1.21, 95% confidence interval [CI] 1.03-1.42) and higher odds of dengue disease given infection (aOR 1.59, 95% CI 1.15-2.19). Children with obesity infected with DENV showed increased odds of presenting fever (aOR 1.46, 95% CI 1.05-2.02), headache (aOR 1.51, 95% CI 1.07-2.14), and rash (aOR 2.26, 95% CI 1.49-3.44) when compared with children with normal weight. CONCLUSIONS: Our results indicate that obesity is associated with increased susceptibility to DENV infection and dengue cases in children, independently of age, sex, and pre-infection DENV antibody titers.

The Effect of Plasmodium on the Outcome of Ebola Virus Infection in a Mouse Model.

Following the Ebola virus epidemic in West Africa, several studies investigated whether there was an effect of Plasmodium coinfection on survival in Ebola virus (EBOV) disease patients. Different effects of coinfection were found in different patient cohorts. To determine whether an effect of Plasmodium coinfection on EBOV survival may exist, we modeled coinfection of Plasmodium yoelii and mouse-adapted EBOV (MA-EBOV) in CD1 mice. Subsequent infection with MA-EBOV at different time points after P. yoelii infection did not have any significant effect on survival.

Obesity is associated with increased pediatric dengue virus infection and disease: A 9-year cohort study in Managua, Nicaragua.

Background: Obesity is on the rise globally in adults and children, including in tropical areas where diseases such as dengue have a substantial burden, particularly in children. Obesity impacts the risk of severe dengue disease; however, the impact on dengue virus (DENV) infection and dengue cases remains an open question. Methods: We used 9 years of data from 5,940 children in the Pediatric Dengue Cohort Study in Nicaragua to examine whether pediatric obesity is associated with increased susceptibility to DENV infection and symptomatic presentation. Analysis was performed using Generalized Estimating Equations adjusted for age, sex, and pre-infection DENV antibody titers. Results: From 2011 to 2019, children contributed 26,273 person-years of observation, and we observed an increase in the prevalence of overweight (from 12% to 17%) and obesity (from 7% to 13%). There were 1,682 DENV infections and 476 dengue cases in the study population. Compared to participants with normal weight, participants with obesity had higher odds of DENV infection (Adjusted Odds Ratio [aOR] 1.21, 95% confidence interval [CI] 1.03-1.42) and higher odds of dengue disease given infection (aOR 1.59, 95% CI 1.15-2.19). Children with obesity infected with DENV showed increased odds of presenting fever (aOR 1.46, 95% CI 1.05-2.02), headache (aOR 1.51, 95% CI 1.07-2.14), and rash (aOR 2.26, 95% CI 1.49-3.44) when compared with children with normal weight. Conclusions: Our results indicate that obesity is associated with increased susceptibility to DENV infection and dengue cases in children, independently of age, sex, and pre-infection DENV antibody titers.

Protection against symptomatic dengue infection by neutralizing antibodies varies by infection history and infecting serotype.

Dengue viruses (DENV1-4) are the most prevalent arboviruses in humans and a major public health concern. Understanding immune mechanisms that modulate DENV infection outcome is critical for vaccine development. Neutralizing antibodies (nAbs) are an essential component of the protective immune response, yet their measurement often relies on a single cellular substrate and partially mature virions, which does not capture the full breadth of neutralizing activity and may lead to biased estimations of nAb potency. Here, we analyze 125 samples collected after one or more DENV infections but prior to subsequent symptomatic or inapparent DENV1, DENV2, or DENV3 infections from a long-standing pediatric cohort study in Nicaragua. By assessing nAb responses using Vero cells with or without DC-SIGN and with mature or partially mature virions, we find that nAb potency and the protective NT50 cutoff are greatly influenced by cell substrate and virion maturation state. Additionally, the correlation between nAb titer and protection from disease depends on prior infection history and infecting serotype. Finally, we uncover variations in nAb composition that contribute to protection from symptomatic infection differently after primary and secondary prior infection. These findings have important implications for identifying antibody correlates of protection for vaccines and natural infections.

Elevated Cytokine Levels in Gingival Crevicular Fluid of Teeth with Apical Periodontitis.

INTRODUCTION: Biomarkers assayed from gingival crevicular fluid (GCF) are a potential tool for endodontic diagnosis and for monitoring treatment response. This cross-sectional study measured cytokines in GCF from teeth with apical periodontitis and evaluated their relationship with preoperative pain and other clinical findings. METHODS: Participants presenting for root-end resection surgery due to apical periodontitis diagnosis (n = 56) underwent standardized clinical testing and completed preoperative questionnaires. GCF from diseased and control teeth were collected, processed, and analyzed. Mann-Whitney U and Wilcoxon tests were used to examine the cytokine levels in diseased compared to healthy control teeth. We also assessed the relationship of cytokine levels with clinical findings. RESULTS: Interleukins (IL)-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, interferon-γ, and tumor necrosis factor-⍺ (TNF-⍺) were detected in GCF. TNF-⍺ levels were significantly higher in GCF collected from diseased versus control teeth (P = .02) and increased IL-1ß levels in diseased teeth were detected (P = .06). Lower IL-10 levels were observed in teeth with a sinus tract and/or swelling compared to teeth without a sinus tract and/or swelling (P = .08). Cytokine levels did not clearly relate to the presence of pain. CONCLUSIONS: Elevated levels of proinflammatory cytokines, including TNF-⍺ and IL1- ß, were detected in GCF from diseased teeth compared to the healthy controls. Additional studies are needed to further investigate the utility of these biomarkers for objectively evaluating periradicular pathology.

The association of neutralizing antibodies with protection against symptomatic dengue virus infection varies by serotype, prior infection history, and assay condition.

The four dengue virus serotypes (DENV1-4) are the most prevalent arboviruses in humans and a major public health concern worldwide. Understanding immune mechanisms that modulate DENV infection outcome is critical for epidemic preparedness and development of a safe and effective vaccine. Neutralizing antibodies (nAbs) are an essential component of the protective response, yet their measurement often relies on a single cellular substrate and partially mature virions, which do not capture the full breadth of neutralizing activity and may lead to biased estimations of nAb potency. Here, we investigated the characteristics of nAbs associated with protection against dengue cases using samples collected after one or more DENV infections but prior to subsequent symptomatic or inapparent DENV1, DENV2, or DENV3 infections from a long- standing pediatric cohort study in Nicaragua. By assessing nAb responses using Vero cells with or without the attachment factor DC-SIGN and with mature or partially mature virions, we found that nAb potency and the protective NT 50 cutoff were greatly influenced by cell substrate and virion maturation state. Additionally, the correlation between nAb titer and protection from disease depended on an individual's prior infection history and the subsequent infecting DENV serotype. Finally, we uncovered variations in nAbs composition that contributed to protection from symptomatic DENV infection differently after primary and secondary prior infection. These findings have important implications for identifying antibody correlates of protection in the context of vaccines and natural infections.

Distinct VSV-based Nipah virus vaccines expressing either glycoprotein G or fusion protein F provide homologous and heterologous protection in a nonhuman primate model.

BACKGROUND: Nipah virus (NiV) causes recurrent outbreaks of lethal respiratory and neurological disease in Southeast Asia. The World Health Organization considers the development of an effective vaccine against NiV a priority. METHODS: We produced two NiV vaccine candidates using the licensed VSV-EBOV vaccine as a backbone and tested its efficacy against lethal homologous and heterologous NiV challenge with Nipah virus Bangladesh and Nipah virus Malaysia, respectively, in the African green monkey model. FINDINGS: The VSV-EBOV vaccine expressing NiV glycoprotein G (VSV-NiVG) induced high neutralising antibody titers and afforded complete protection from homologous and heterologous challenge. The VSV-EBOV vaccine expressing NiV fusion protein F (VSV-NiVF) induced a lower humoral response and afforded complete homologous protection, but only partial heterologous protection. Both vaccines reduced virus shedding from the upper respiratory tract, and virus replication in the lungs and central nervous system. None of the protected animals vaccinated with VSV-NiVG or VSV-NiVF showed histological lesions in the CNS, but one VSV-NiVF-vaccinated animal that was not protected developed severe meningoencephalitis. INTERPRETATION: The VSV-NiVG vaccine offers broad protection against NiV disease. FUNDING: This study was supported by the Intramural Research Program, NIAID, NIH.

Favipiravir (T-705) Protects IFNAR-/- Mice against Lethal Zika Virus Infection in a Sex-Dependent Manner.

Zika virus (ZIKV), a member of the Flaviviridae family, is an important human pathogen that has caused epidemics in Africa, Southeast Asia, and the Americas. No licensed treatments for ZIKV disease are currently available. Favipiravir (T-705; 6-fluoro-3-hydroxy-2-pyrazinecarboxamide) and ribavirin (1-(ß-D-Ribofuranosyl)-1H-1,2,4-triazole-3-carboxamide) are nucleoside analogs that have exhibited antiviral activity against a broad spectrum of RNA viruses, including some flaviviruses. In this study, we strengthened evidence for favipiravir and ribavirin inhibition of ZIKV replication in vitro. Testing in IFNAR-/- mice revealed that daily treatments of favipiravir were sufficient to provide protection against lethal ZIKV challenge in a dose-dependent manner but did not completely abrogate disease. Ribavirin, on the other hand, had no beneficial effect against ZIKV infection in this model and under the conditions examined. Combined treatment of ribavirin and favipiravir did not show improved outcomes over ribavirin alone. Surprisingly, outcome of favipiravir treatment was sex-dependent, with 87% of female but only 25% of male mice surviving lethal ZIKV infection. Since virus mutations were not associated with outcome, a sex-specific host response likely explains the observed sex difference.

Single low-dose VSV-EBOV vaccination protects cynomolgus macaques from lethal Ebola challenge.

BACKGROUND: Ebola virus (EBOV), variant Makona, was the causative agent of the 2013-2016 West African epidemic responsible for almost 30,000 human infections and over 11,000 fatalities. During the epidemic, the development of several experimental vaccines was accelerated through human clinical trials. One of them, the vesicular stomatitis virus (VSV)-based vaccine VSV-EBOV, showed promising efficacy in a phase 3 clinical trial in Guinea and is currently used in the ongoing EBOV outbreak in the northeastern part of the Democratic Republic of the Congo (DRC). This vaccine expresses the EBOV-Kikwit glycoprotein from the 1995 outbreak as the immunogen. METHODS: Here we generated a VSV-based vaccine expressing the contemporary EBOV-Makona glycoprotein. We characterized the vaccine in tissue culture and analyzed vaccine efficacy in the cynomolgus macaque model. Subsequently, we determined the dose-dependent protective efficacy in nonhuman primates against lethal EBOV challenge. FINDINGS: We observed complete protection from disease with VSV-EBOV doses ranging from 1 × 107 to 1 × 101 plaque-forming units. Some protected animals receiving lower vaccine doses developed temporary low-level EBOV viremia. Control animals developed classical EBOV disease and reached euthanasia criteria within a week after challenge. This study demonstrates that very low doses of VSV-EBOV uniformly protect macaques against lethal EBOV challenge. INTERPRETATION: Our study provides missing pre-clinical data supporting the use of reduced VSV-EBOV vaccine doses without decreasing protective efficacy and at the same time increase vaccine safety and availability - two critical concerns in public health response. FUNDING: Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health.

Perfil de calidad de vida en municipios de mayor densidad poblacional de longevos en Villa Clara / Quality of life profile in municipalities from Villa Clara with the highest density of ageing population

RESUMEN Se realizó un estudio descriptivo transversal en los municipios de mayor densidad de longevos en Villa Clara: Camajuaní, Placetas, Ranchuelo y Santa Clara, durante el año 2018. El objetivo de la investigación fue caracterizar la calidad de vida según la escala de GENCAT, a partir de los datos emitidos por la Oficina Nacional de Estadísticas e Información, y las historias de salud familiar. El universo de estudio estuvo constituido por 9874 adultos mayores de 85 años. La muestra quedó conformada por 367 personas, las cuales fueron seleccionadas por muestreo aleatorio estratificado. Se seleccionaron: números, porcentajes y la asociación entre las variables por Kruskal-Wallis. Predominaron: el sexo femenino, el grupo de 85 a 89 años de edad, la piel blanca en el municipio Placetas, la procedencia urbana y el acceso fácil a los servicios de salud, con diferentes porcentajes entre los municipios. Camajuaní obtuvo el perfil de calidad de vida con mayor puntuación.

ABSTRACT A cross-sectional descriptive study was conducted in municipalities from Villa Clara with the highest density of ageing population during 2018: Camajuaní, Placetas, Ranchuelo and Santa Clara. The objective of the research was to characterize the quality of life according to the GENCAT Scale, based on data issued by the National Office of Statistics and Information, as well as family health histories. The study universe consisted of 9874 adults over 85 years of age. The sample was made up of 367 people, who were selected by means of stratified random sampling. Numbers, percentages and the association between variables were used by means of Kruskal-Wallis test. Female gender, age group from 85 to 89 years old, white skin in Placetas municipality, urban origin, easy access to health services, with percentage differences among municipalities were the predominant variables. Camajuaní had the highest quality of life profile.

Evaluación de formulaciones inmunoterapéuticas experimentales en el modelo hibrido murino de Reaccion del Injerto contra el Hospedador / Evaluation of experimental immunotherapeutic formulations in the hybrid murine model of Graft-versus-Host Reaction

Introducción: La Enfermedad del Injerto Contra el Hospedador es la complicación más frecuente de los Trasplantes de Células Madre Hematopoyéticas y de todos los trasplantes que contengan células inmunocompetentes alogénicas, el 100 por ciento la padecen y cerca del 30 por ciento mueren por su causa; una proporción alta de casos son esteroide-refractarios, asimismo otras medidas inmunosupresoras modernas fracasan. En los campos de la Inmunoterapia y la Vaccinología también existe una escasez preocupante de inmunomoduladores de origen biológico potentes, efectivos, seguros y de amplio espectro. Existe un modelo híbrido murino de gran utilidad metodológica para estudios experimentales. Objetivo: Evaluar dos formulaciones novedosas de origen biotecnológico, una de ellas inmunopotenciadora y otra inmunosupresora, desarrolladas como cocleatos. Material y Métodos: Mediante Microscopia Electrónica y RT-PCR se caracterizaron las formulaciones como nanopartículas y su capacidad de regular la expresión del ARNm de linfoquinas definitorias de sus perfiles, respectivamente. Empleando el modelo de Enfermedad del Injerto Contra el Hospedador en ratón híbrido F1 (CBAxC57BL), se evaluó su carácter inmunomodulador in vivo . Resultados: Partiendo de los proteoliposomas de Neisseria meningitidis, se obtuvieron dos formulaciones en forma de cocleatos, ambas con diámetros de partícula inferior a 100nm. La Formulación 1mostró un perfil proinflamatorio con potente capacidad de aumentar el IFNγ y el TNFα y potenció el Índice de Bazo hasta 2,05 en el modelo EICH con p=0,0002. La Formulación 2 mostró un perfil supresor-regulatorio con potente capacidad de aumentar la IL-10 y el TGFβ y además de suprimir la producción de TNFα. En el modelo usado, esta formulación, suprimió el Índice de Bazo de manera dosis dependiente y con alta significación estadística. Se corroboró el conocido perfil de seguridad y ausencia de reactogenicidad de ambas formulaciones. Conclusiones: Ambas formulaciones tienen potencial aplicación en los campos de la terapia de Enfermedad del Injerto Contra el Hospedador en otras patologías y en Vaccinología. Los resultados obtenidos en el presente trabajo fundamentan la conveniencia de continuar el desarrollo farmacéutico y completar la preclínica de ambas formulaciones(AU)

Introduction: Graft-versus-host disease is the most frequent complication of Hematopoietic Stem Cell Transplants and all transplants containing allogeneic immunocompetent cells; 100 percent of patients suffer from this complication and about 30 percent die for this particular cause. A high proportion of cases are steroid-refractory; likewise, other modern immunosuppressive measures fail. In the fields of Immunotherapy and Vaccinology, there is also a worrying shortage of powerful, effective, safe and broad spectrum immunomodulators of biological origin. There is a hybrid murine model of great methodological utility for experimental studies. Objective: To evaluate two novel formulations of biotechnological origin: an immunopotentiator formulation and an immunosuppressive one, which were developed as cochleates. Material and Methods: The formulations assayed by Electron Microscopy and RT-PCR were characterized as nanoparticles and for their capacity to regulate lymphokine mRNA expression profile, respectively. The immunomodulatory character was evaluated in vivo using Graft-versus-host disease in (CBAxC57BL) F1 hybrid mice. Results: Starting from the proteoliposomes derived from Neisseria meningitides, two cochleate formulations were obtained, both with particle diameters below 100 nm. Formulation 1 showed a proinflammatory profile with potent capacity to increase IFNγ and TNFα, and potentiated the Spleen Index up to 2.05 in the GVDH model with p = 0.0002. Formulation 2 showed a suppressor/regulatory profile with potent capacity to increase IL-10 and TGFβ and suppress the production of TNFα. In the model used, this formulation suppressed the Spleen Index in a dose-dependent manner with high statistical significance. The known safety profile and absence of reactogenicity of both formulations was corroborated. Conclusions: Both formulations have potential application in the fields of GVHD therapy and other pathologies as well as in Vaccinology. The results obtained in the present work suggest the usefulness to continue with the pharmaceutical development and complete the preclinical studies of both formulations(AU)

Rehabilitación cardiovascular en pacientes con infarto agudo de miocardio con elevación del segmento ST e intervencionismo coronario percutáneo / Cardiac rehabilitation in patients with ST-segment elevation acute myocardial infarction and percutaneous coronary intervention

RESUMEN Introducción: La rehabilitación cardiovascular es beneficiosa en múltiples situaciones clínicas. En pacientes que son tratados mediante intervencionismo coronario es necesario seguir profundizando su estudio. Objetivos: Determinar los efectos de la rehabilitación cardiovascular en pacientes con infarto agudo de miocardio con elevación del segmento ST a quienes se les realizó intervencionismo coronario percutáneo. Método: Estudio cuasi-experimental en 30 pacientes con infarto agudo de miocardio con elevación del ST después de ser tratados con angioplastia coronaria y que se atendieron en el Servicio de Rehabilitación Cardiovascular del Hospital Universitario Celestino Hernández Robau, en el período de septiembre de 2016 a marzo de 2018. Se recolectaron datos clínicos y epidemiológicos, y se analizaron variables ergométricas y ecocardiográficas al inicio y luego de 12 semanas de realizar un programa de rehabilitación cardiovascular. Resultados: Existió un efecto positivo en la frecuencia cardíaca en reposo (66±11 vs. 61±11 latidos/minuto; p=0,008), el tiempo de ejercicio (8,3±2,5 vs. 10,2±2,0 minutos; p<0,0001) y del máximo consumo de oxígeno (24,2±5,0 vs. 27,6±4,9 ml/kg/min; p<0,0001). Existió mejoría de la fracción de eyección y reducción del diámetro del ventrículo izquierdo en diástole, pero sin diferencia estadística significativa. Conclusiones: Existió mejoría en los parámetros ergométricos y ecocardiográficos luego del programa de rehabilitación cardiovascular, que fue más beneficioso en pacientes con hipertensión arterial, hábito de fumar e intervencionismo coronario percutáneo de dos arterias.

ABSTRACT Introduction: Cardiovascular rehabilitation is beneficial in multiple clinical situations. In patients who are treated through percutaneous coronary intervention it is necessary to continue deepening its study. Objectives: To determine the effects of cardiovascular rehabilitation in patients with ST-segment elevation acute myocardial infarction who underwent percutaneous coronary intervention. Method: Quasi-experimental study in 30 patients with ST-segment elevation acute myocardial infarction after being treated with coronary angioplasty, and who were attended at the Department of Cardiovascular Rehabilitation of the Hospital Universitario Celestino Hernández Robau, in the period from September 2016 to March 2018. Clinical and epidemiological data were collected, and ergometric and echocardiographic variables were analyzed before and after 12 weeks of developing a cardiovascular rehabilitation program. Results: There was a positive effect on heart rate at rest (66±11 vs. 61±11 beats/minute; p=0.008), exercise time (8.3±2.5 vs. 10.2±2.0 minutes; p <0.0001) and maximum oxygen consumption (24.2±5.0 vs. 27.6±4.9 ml/kg/min; p<0.0001). There was improvement of the ejection fraction and reduction of the diameter of the left ventricle in diastole left ventricular end diastolic diameter, but without significant statistical difference. Conclusions: There was improvement in the ergometric and echocardiographic parameters after the cardiovascular rehabilitation program, which was more beneficial in patients with high blood pressure, smoking habit and percutaneous coronary intervention of two arteries.

Fragmentación del QRS y muerte súbita en paciente con displasia arritmogénica del ventrículo derecho / Fragmented QRS and sudden death in a patient with arrhythmogenic right ventricular dysplasia/cardiomyopathy

RESUMEN La miocardiopatía o displasia arritmogénica del ventrículo derecho es una cardiopatía de origen genético cuyo diagnóstico supone, a menudo, un reto para el clínico. Es una de las causas más comunes de muerte súbita cardíaca en la adolescencia y en los adultos jóvenes. Se presenta el caso de un paciente con historia de arritmias ventriculares malignas y de muerte súbita cardíaca recuperada, por displasia arritmogénica del ventrículo derecho, con fragmentación del QRS en las derivaciones precordiales derechas, como marcador de la presencia de un sustrato propicio para el surgimiento de la fibrilación ventricular espontánea. Se comenta la patogenia, el diagnóstico y el tratamiento de esta enfermedad.

ABSTRACT The arrhythmogenic right ventricular dysplasia or cardiomyopathy is a genetic heart disease whose diagnosis is often a challenge for the clinician. It is one of the most common causes of sudden cardiac death in adolescence and in young adults. We present the case of a patient with a history of malignant ventricular arrhythmias and recovered sudden cardiac death due to arrhythmogenic right ventricular dysplasia, with QRS fragmentation in the right precordial leads, as a marker of the presence of a suitable substrate for the emergence of spontaneous ventricular fibrillation. The pathogenesis, diagnosis and treatment of this disease are discussed.

Comorbilidad y mortalidad en una cohorte de pacientes cubanos con artritis reumatoide / Morbidity and mortality present in a group of Cuban patients presenting with rheumatoid arthritis

La esperanza de vida en la artritis reumatoide (AR) es inferior a la de poblaciones control y existe estrecha relación con la comorbilidad. Identificar la frecuencia de la comorbilidad, mortalidad y variables relacionadas con su incremento. La muestra fue de 172 enfermos que cumplieron criterios del Colegio Americano de Reumatología, vistos en la Sección de Reumatología del Hospital Universitario Cmdte Manuel Fajardo en un período de 6 años. Se midieron 13 variables a 136 pacientes y se compararon con las de los fallecidos en dicho período, se realizaron medidas de tendencia central, dispersión, porcentajes, comorbilidad y relación con la mortalidad. El 65,1 por ciento de los casos tuvo comorbilidades (media de 1,58 por paciente), las más frecuentes fueron: hipertensión arterial (26,7 por ciento), diabetes mellitus (9,3 por ciento) y enfermedad tiroidea (8,7 por ciento). Hubo 9 fallecidos y una tasa de mortalidad de 5,2 por ciento; las causas de muerte mßs frecuentes fueron la enfermedad cardiovascular y el sangrado digestivo. En los fallecidos, las cifras más altas se hallaron en las variables: edad media (65,2 vs. 55,9), bajo nivel cultural (88,8 vs. 36,7 por ciento), velocidad de sedimentación globular (77 ± 29,9 vs. 49,8 ± 30,7) cuestionario autoaplicado para medir incapacidad (1,7 ± 0,74 vs. 0,9 ± 0,65) y comorbilidad (2,67 vs. 1,57). Más de la mitad de los pacientes tuvo comorbilidades, la mortalidad fue baja. El bajo nivel cultural, la velocidad de sedimentación globular, el cuestionario autoaplicado para medir incapacidad y el número de comorbilidades se relacionaron estrechamente con la mortalidad.

Life expectancy in rheumatoid arthritis (RA) is lower than that of control-populations, and there is a close relationship with morbidity. Objectives: to identify frequency of morbidity, mortality, and variables related to its increase. Sample included 172 sick persons fulfilled criteria of American College of Rheumatology, seen in Rheumatology Service of Comandante Manuel Fajardo University Hospital during 6 years. In 136 patients 13 variables were measured and were compared with that of deceased in such period and we applied measures of central trend, dispersion, percentages, morbidity, and relationship with mortality. The 65.1 percent of cases had morbidities (mean of 1.58 by patient), where the more frequent included: high blood pressure/26.7 percent, diabetes mellitus/9.3 percent, and thyroid disease/8.7 percent. There were 9 deceased and a mortality rate of 5.2 percent; the more frequent causes were: cardiovascular disease, and digestive bleeding. In deceased ones, higher figures were present in following variables: mean age (65.2 percent versus 55.9 percent), low cultural level (88.8 versus 36.7 percent), globular sedimentation speed (77 ± 29,9 versus 49.8 ± 40.7), self-applied questionnaire to measure inability, and the number or morbidities was closely related to mortality.

Antigenicidad e inmunogenicidad de una cepa inactivada de Vibrio cholerae O1 El Tor Inaba / Antigenicity and immunogenicity of inactivated Vibrio cholerae 01 El Tor Inaba

INTRODUCCIÓN: el cólera continúa siendo problema de salud, principalmente en las zonas más pobres. La mayoría de los aislamientos que se realizan al nivel mundial pertenecen a Vibrio cholerae O1 biotipo El Tor serotipo Ogawa, aunque se han reportado brotes causados por el serotipo Inaba, por lo que se aconseja que una vacuna efectiva contra la enfermedad deberá contener células o antígenos de ambos serotipos. OBJETIVO: describir las características de la cepa de V. cholerae O1 El Tor Inaba C6706 como posible cepa para la obtención de vacunas inactivadas contra el cólera. MÉTODOS: se elaboró un lote de siembra de trabajo crioconservado a - 70 ºC, se evaluó su identidad, pureza y viabilidad. La cepa fue cultivada en caldo triptona soya y su inactivación se realizó a 56 ºC durante 20 min. Se evaluó la capacidad antigénica del producto obtenido mediante western blot y ELISA de inhibición de lipopolisacárido. La inmunogenicidad en conejos, inoculados por vía intraduodenal, se determinó mediante la cinética de anticuerpos vibriocidas. RESULTADOS: el lote de siembra de trabajo mantuvo su identidad, pureza y viabilidad durante 18 meses de estudio. Se observó la presencia de los antígenos lipopolisacárido, hemaglutinina sensible a manosa y proteína de membrana externa U, en las suspensiones de células inactivadas de V. cholerae O1, no así de las subunidades A y B de la toxina colérica (CTA y CTB, respectivamente) o pilli corregulado con la toxina (TCP). Por otra parte, se obtuvieron títulos vibriocidas en los sueros de conejos, similares a la respuesta inducida por la cepa viva atenuada 638 de V. cholerae O1, candidata a vacuna oral. CONCLUSIONES: la cepa de V. cholerae O1 El Tor Inaba C6706 mostró características culturales, antigénicas e inmunogénicas que permiten considerarla como posible cepa para la obtención de vacunas inactivadas contra el cólera.

INTRODUCTION: cholera continues being a serius health problem, mainly in the poorest areas. Most of the isolations worldwide belong to Vibrio cholerae O1 biotype El Tor serotype Ogawa, although there have been reported outbreaks caused by serotype Inaba, that is why it is recommended that an effective vaccine against the illness should contain cells or antigens of both serotypes. OBJECTIVE: to describe the characteristics of the strain C6706 of V. cholerae O1 El Tor Inaba as a likely strain for the obtaining of inactivated vaccines for cholera. METHODS: a criopreserved working culture batch was made up at - 70 ºC to evaluate identity, purity and viability. The strain was cultured in tryptone soy broth and was inactivated at 56º C for 20 minutes. Antigenicity of this preparation was tested by Western Blot and ELISA inhibition test. Immunogenicity in adult rabbits, inoculated intraduodenally, was determined by means of kinetics of vibriocidal antibodies. RESULTS: the working culture batch kept their identity, purity and viability during 18 months of study. The results confirmed the presence of relevant antigens as lipopolysaccharide (LPS), mannose-sensitive hemagglutinin (MSHA) and outer membrane protein U (OmpU) in the suspension of inactivated V. cholerae O1 cells, but not cholera toxin subunits (CTA, CTB) or toxin-coregulated pili (TCP).On the other hand, vibriocidal titers were found in rabbit sera, which were similar to those previously reported for the live V. cholerae O1 strain 638, an attenuated oral vaccinal candidate CONCLUSIONS: the V. cholerae O1 El Tor Inaba C6706 strain showed cultural, antigenic and immunogenic characteristics that allow us to consider it as a possible strain for the obtaining of inactivated vaccines for cholera.

¿Qué puede hacer realmente un reumatólogo en la atención primaria de salud? / What can a rheumatologist do in primary health care?

Introducción: la reumatología es una especialidad eminentemente hospitalaria que ha tenido un acercamiento beneficioso a la atención primaria en varios países. Objetivo: analizar el comportamiento de las consultas de reumatología en la atención primaria y su influencia sobre la atención hospitalaria. Métodos: se realizó un estudio descriptivo prospectivo de sección transversal a 1 000 pacientes vistos en consulta externa en un período de 6 meses, a los que se recogieron sistemáticamente las variables: edad, sexo, color de la piel, casos nuevos, reconsultas y diagnóstico. Se determinaron los porcentajes, las medidas de frecuencia, de centralización, dispersión y razón reconsultas/casos nuevos. Resultados: se efectuaron 1 122 consultas, y se analizaron los primeros 1 000 registros de nuestra base de datos. El 41,9 por ciento fueron primeras visitas y 58,1 por ciento reconsultas. Las 3 enfermedades más frecuentemente consultadas fueron: la osteoartritis (22,9 por ciento), reumatismos de partes blandas (21 por ciento) y la artritis reumatoide (13,3 por ciento), con un predominio de estas sobre las conectivopatías (2,1 por ciento). La tasa de incidencia por enfermedades reumáticas fue de 2,5, y la de prevalencia de 6,2 x 1 000 hab. El promedio de edad fue de 49,4 años, DE 17,3 años, con predominio del sexo femenino en 71,6 por ciento y color de piel blanca en 83,5 por ciento. Conclusiones: las consultas de reumatología en atención primaria descongestionan los servicios hospitalarios, que deben dedicar más tiempo al seguimiento de enfermedades reumáticas sistémicas.

Introduction: rheumatology is an eminently hospital specialty that has had a beneficial approach to primary health care in various countries. Objective: to analyze the behavior of the rheumatology consultations in primary health care and their influence on hospital attention. Methods: a descriptive, prospective and cross-sectional study was conducted among 1 000 patients seen at the outpatient department during 6 months. The following variables were systematically collected: age, sex, color of the skin, new cases, reconsultations and diagnosis. The percentages, the measures of frequency, centralization, dispersion and the reconsultation/new cases rate were determined. Results: 1 222 consultations were carried out and the first 1 000 registers of our database were analyzed. 41.9 percent were first visits and 58.1 percent were reconsultations. The 3 most frequent consulted diseases were: osteoarthritis (22.9 percent), rheumatisms of soft tissues (21 percent) and rheumatoid arthritis (13.3 percent), with a predominance of them over connectivopathies (2.1 percent). The incidence rate by rheumatic diseases was 2.5 and that of prevalence was 6.2 x 1 000 inhabitants. Average age was 49.4 years old, DS 17.3 years old, with predominance of females in 71.6 percent and white color of the skin in 83.5 percent. Conclusions: the rheumatological consultations in primary health care alleviate the hospital services, which should devote more time to the follow-up of systemic rheumatic diseases.

Expresión de la neumopatía intersticial en pacientes cubanos con esclerosis sistémica / Expression of interstitial pneumopathy in Cuban patients with systemic sclerosis

La neumopatía intersticial (NI) se presenta frecuentemente en pacientes con esclerosis sistémica (ES) y ocasiona morbilidad y mortalidad significativas. Se realizó un estudio descriptivo, prospectivo con 46 pacientes, que cumplieron criterios del Colegio Americano de Reumatología, para identificar las formas de expresión y detección de la NI. Se estimó porcentajes, análisis univariable para medidas de centralización, dispersión y pruebas de significación estadística chi cuadrado (X2). Se halló una edad media de 50,4 años, predominio femenino (88 por ciento), color de piel blanco (66 por ciento), tuvieron neumopatía intersticial 20 pacientes (43,4 por ciento); disnea de esfuerzo, el 100 por ciento de los casos, lo cual fue estadísticamente significativo (p=0,02). La función respiratoria estuvo afectada en el 75 por ciento de los enfermos. Según tomografía computadorizada de alta resolución (TC) de pulmón, 50 por ciento tuvo patrón en vidrio esmerilado y 50 por ciento, patrón en panal de abejas, 66 por ciento de los pacientes con NI tuvieron lavado broncoalveolar activo y de ellos, 88 por ciento correspondió a los que tenían patrón en vidrio esmerilado. Se concluyó que la neumopatía intersticial se expresó en un alto porcentaje de pacientes, la disnea de esfuerzo fue el síntoma más frecuente, predominó el patrón restrictivo. La TC y el estudio citológico del lavado broncoalveolar constituyeron herramientas clave para el diagnóstico precoz de NI.

Interstitial pneumopathy (IP) usually appears in patients with systemic sclerosis (SS) and causes significant morbidity and mortality. A descriptive and prospective study was conducted among 46 patients that fulfilled the criteria of the American Rheumatology College to identify the forms of expression and detection of IP. Percentages were estimated, and the univariable analysis for centralization and dispersion measurements and the chi square tests (X2) of statistical significance were used. A mean age of 50.4 years old was found. A prevalence of females (88 percent) and of white individuals (66 percent) was observed. 20 patients (43.4percent) had interstitial pneumopathy, whereas 100 percent of the cases presented effort dyspnea, which was statistically significant (p=0.02). The respiratory function was affected in 75 percent of the sick. According to high resolution computerized tomography of the lung, 50 percent had ground glass pattern and 50 percent honeycomb pattern, 66 percent of the patients with IP had active bronchoalveolar lavage and of them, 88 percent corresponded to those with ground glass pattern. It was concluded that interstitial pneumopathy was expressed in a high percentage of patients. Effort dyspnea was the most frequent symptom and the restrictive pattern predominated. CAT and the cytological study of bronchoalveolar lavage were key tools for the early diagnosis of IP.

Alteración ortostática en mujeres con fibromialgia / Orthostatic alteration in women with fibromyalgia

La fibromialgia es considerada actualmente una enfermedad multisistémica con una posible patogenia disautonómica. El objetivo de este trabajo fue determinar, en las pacientes del área de salud, la relación entre la fibromialgia (FM) y las alteraciones del sistema nervioso autónomo. Se realizó un estudio prospectivo de sección transversal de casos y controles, en el período de 1 año, se estimaron porcentajes, análisis univariante para medidas de centralización y de dispersión, riesgo relativo (RR) e IC 95 %. Para estudiar la asociación entre las variables fibromialgia y disautonomía se hicieron pruebas de significación estadística Chi cuadrado X2 exacta de Fisher y la t de Student, todas para grupos independientes. Las pacientes con FM tuvieron una media de edad de 46,1 años y ± 1 DE 10,6 años, con predominio entre los 30 y los 50 años. Se presentó hipotensión ortostática en 31 de ellas (62 %), este hallazgo fue altamente significativo al compararlas con el grupo control, en el cual solamente fue apreciada en 11 de los 50 casos (22 %). Se concluyó que la hipotensión ortostática podría ser un factor de riesgo para padecer FM lo cual explicaría además el posible papel patogénico de la disautonomía planteado en esta enfermedad.

Fibromyalgia is considered at present a multisystemic disease with a possible dysautonomic pathogeny. The objective of this paper was to determine in the patients from the health area the relation between fibromyalgia (FM) and the alterations of the autonomous nervous system. A one-year prospective cross-sectional case-control study was conducted, percentages were estimated, and an univariant analysis for centralization and dispersion measures, relative risk (RR) and CI 95 %, was made. Chi square tests of statistical significance, exact test (Fisher) and Student's t test were made to study the association between fibromyalgia and dysautonomia in different groups. The mean age of the patients with FM was 46.1 years old and ± 1 aged 10.6 , with predominance between 30 and 50 years old. 31 of them (62 %) presented orthostatic hypotension. This finding was highly significant on comparing them with the control group, where it was only observed in 11of the 50 cases (22 %). It was concluded that orthostatic hypotension could be a risk factor for suffering from FM, which would explain the possible pathogenic role of dysautonomia stated in this disease.

El forceps en el Hospital de Giado, Libia. / The forceps at the Hospital of Giado, Libya

Se estudian las aplicaciones de forceps realizadas en el hospital Central de Giado Republica Arabe y Socialista de Libia, durante el ano 1979. Se analizan sus indicaciones, estado de los ninos al nacimiento, segun conteo de Apgar, asi como las complicaciones artribuibles al empleo del instrumento. Se encuentra que el 5,12% de los nacimientos durante este periodo fue mediante la aplicacion del forceps