Evaluación de la mejora de conocimientos de los participantes del taller de tapón de oído, durante las jornadas SEFAC 2021 / Evaluation of the improvement of the knowledge of the participants of the earplug workshop during the SEFAC 2021 conference

JUSTIFICACIÓN: SEFAC ha retomado la celebración de las jornadas SEFAC 21, en las 15 delegaciones, de manera presencial, en sesiones de mañana y de tarde para facilitar la asistencia. Uno de los talleres del programa ha sido: “Indicación farmacéutica en tapón de oído: prevención, tratamiento y disolución”.OBJETIVO: el objetivo principal del trabajo es evaluar la mejora de conocimiento de los farmacéuticos tras la asistencia al taller. Como objetivo general, queremos conocer la utilidad y eficacia del taller en las jornadas de SEFAC tras la asistencia al mismo.MÉTODO: para conseguir los objetivos propuestos, el grupo que elaboró el taller preparó un cuestionario tipo test, que posteriormente aprobó el comité científico, con cinco preguntas y cuatro respuestas posibles en cada una de ellas. A través de la descarga de una APP, los participantes debían contestar el cuestionario antes del inicio del taller e inmediatamente después de finalizarlo, teniendo el cuestionario las mismas preguntas en ambos casos.RESULTADOS: participantes que cubrieron el cuestionario: 278, en la mañana 175 y en la tarde 103.La primera pregunta no presenta cambios porcentuales grandes, ya que los aciertos eran muy elevados inicialmente. La segunda muestra una mejora significativa en todas las ciudades. En la tercera pregunta, el porcentaje de aciertos es similar al de la pregunta dos. La cuarta presenta una diferencia amplia entre antes y después. En la quinta pregunta se obtienen resultados de mejora próximos al 25 %.Los talleres con mejoras significativas en la formación tras la realización del cuestionario son: Barcelona, Badajoz, Alicante, Madrid y Santander. (AU)

Servicio profesional farmacéutico de indicación farmacéutica en sequedad ocular utilizando el programa 'I-VALOR' / Minor ailment service for dry eye syndromes: I-VALOR programme

INTRODUCCIÓN: la labor del farmacéutico comunitario en el Servicio de Indicación Farmacéutica (SIF) es muy importante como primera línea de asistencia a la población, aunque no está suficientemente documentada. OBJETIVOS: evaluar la intervención del farmacéutico comunitario en el SIF ante una consulta sobre enfermedad de ojo seco (EOS) con el uso de protocolos. MATERIAL Y MÉTODOS: estudio descriptivo, observacional realizado dentro del programa I-VALOR (enero-junio 2015). Los participantes fueron farmacéuticos voluntarios y pacientes que solicitaron algún remedio para aliviar la EOS. Se utilizó el protocolo del SIF del Foro de Atención Farmacéutica en Farmacia Comunitaria, un consenso para EOS realizado entre sociedades científicas, una hoja de derivación, un informe para el paciente y una hoja de recomendaciones. RESULTADOS: participaron 6.350 pacientes. 62,7 % consultas fueron realizadas por mujeres (24,3 % 46-65 años). El 60 % de los pacientes no presentaba ningún criterio de derivación. Se detectaron 3.887 criterios de derivación en 2.537 pacientes. Se decidió no derivar al 15,4 %, y del resto, 87,3 % aceptó la derivación. La dispensación de algún tratamiento tuvo lugar en el 80 % de los pacientes: 3.157 con tratamiento farmacológico (89,2 % un único medicamento) y 2.403 con tratamiento no farmacológico. El 35 % recibió consejos higiénico-dietéticos y consejo farmacéutico. Se detectaron 25 reacciones adversas a medicamentos (0,4 %). El 70,5 % de todas las consultas realizadas fueron resueltas sin necesidad de derivar al médico. CONCLUSIONES: el programa I-VALOR para EOS ha permitido evaluar la intervención protocolizada del farmacéutico en EOS mediante el registro de las actuaciones farmacéuticas para demostrar la labor desarrollada desde la farmacia comunitaria

BACKGROUND: Minor ailment service offered in community pharmacist is a key element in patient care. Thought in Spain the service is not properly documented. AIMS: The main objective was to evaluate community pharmacists' interventions through an agreed minor ailment service for dry eye syndromes (DES). METHOD: Descriptive study undertaken alongside I-VALOR programme (January-June 2015). Participants were pharmacists from SEFAC who voluntarily decided to do, and patients were those who consulted about DES in community pharmacy. Pharmacists used the Pharmaceutical Care Forum guideline for the Minor Ailment Service and an agreed consensus between pharmaceutical and medical societies. A patient's form and a referral's form were designed. RESULTS: There were 6,350 patients involved. 62.7% consultations were made by women 24.3% of 46-65 years old). No referral criteria were detected in 60% of patients. The pharmacist detected 3,887 referral criteria in 2,537 patients. Pharmacists decided not to refer 15.4% of those patients. 87.3% of the patients referred accepted the referral. Treatments were dispensed in 80% of patients: 3,157 pharmacological treatment (89.2% a single medication) and 2,403 non-pharmacological treatment (medical device, food supplement or eye cleaning product). 35% received hygienic-dietary advice and pharmaceutical advice. Twenty-five adverse drug reactions were detected (0.4%). 70.5% of all consultations made were managed with no referral to a general practitioner (GP). CONCLUSIONS: I-VALOR programme allowed to evaluate an agreed intervention for DES in community pharmacy through the record of MAS to demonstrate CP contribution to manage minor ailments

Pyrocarbon versus cobalt-chromium in the context of spherical interposition implants: an in vitro study on cultured chondrocytes.

In the context of shoulder surgical replacement, a new generation of spherical interposition implants has been developed, with the implant being a mobile spacer rubbing against the glenoid cartilage and humeral bone cavity. The aim of the present study was to compare pyrocarbon (PyC) versus cobalt-chromium (CoCr) implants, regarding preservation and regeneration of the surrounding tissues. The effect of the biomaterials on chondrocytes was analysed in vitro. Murine primary chondrocytes were grown on discs made of PyC or CoCr using two culture media to mimic either cartilage-like or bone-like conditions (CLC or BLC). Chondrocytes did grow on PyC and CoCr without alteration in cell viability or manifestation of cytotoxicity. The tissue-like cell membranes grown under BLC were examined for the chondrocyte's ability to mineralise (by alizarin red matrix staining, calcium deposit and alkaline phosphatase activity) and for their mechanical properties (by rheological tests). For the chondrocytes grown under CLC and BLC, extracellular matrix components were analysed by histological staining and immunolabelling. Under CLC, PyC promoted type II collagen expression in chondrocytes, suggesting that they may generate a more cartilage-like matrix than samples grown on both CoCr and plastic control. In BLC, the tissue-like cell membranes grown on PyC were more mineralised and homogenous. The mechanical results corroborated the biological data, since the elastic modulus of the tissue-like cell membranes developed on the PyC surface was higher, indicating more stiffness. Overall, the results suggested that PyC might be a suitable biomaterial for spherical interposition implants.

Desarrollo y evaluación de una estrategia de fortalecimiento de la calidad de atención de personas con riesgo cardiovascular global diabetes y HTA / Development implementation and assessment of a strategy to strengthen quality of care of people with global cardiovascular risk type 2 diabetes and hypertension

La apropiada estratificación de riesgo cardiovascular en el primer nivel deatención (PNA) y el seguimiento de pacientes de acuerdo con prácticasajustadas al riesgo constituyen una estrategia efectiva para la prevención deeventos cardiovasculares. El desarrollo de sistemáticas de estratificación deriesgo cardiovascular en PNA del subsistema público es de reciente aplicacióny se lleva a cabo a través del Programa Redes en el marco de los ProyectosProvinciales de Fortalecimiento de Redes de Salud (PPFRS).ObjetivosConocer el estado actual y evaluar el efecto de la aplicación de una estrategiade fortalecimiento de redes de servicios de salud en la práctica clínica y en lacalidad de atención de personas adultas con diabetes tipo 2 (DBT2), hipertensiónarterial (HTA) y riesgo cardiovascular global (RCVG) moderado, alto y muy alto.MétodosEl estudio se llevó adelante en las siguientes etapas: 1) identificación de lascaracterísticas de acceso, cobertura y práctica clínica en los efectores del PNA parael abordaje del RCVG en personas con DBT2 y HTA; 2) implementación de unaestrategia de fortalecimiento de redes de servicio de salud y de cuidado integralde las personas adultas con RCVG moderado, alto y muy alto; 3) evaluación delefecto de la estrategia desarrollada en la práctica clínica y el cuidado integral de laspersonas adultas con DBT2 y HTA, y personas con RCVG moderado, alto y muy alto.ResultadosLos resultados constituyen una evaluación de la primera experiencia deaplicación de una sistemática de atención en enfermedades crónicas(hipertensión y diabetes), que se orienta a una estrategia de prevencióncardiovascular basada en la evaluación del RCVG.ConclusionesLa información generada por esta investigación puede ser útil para mejorarel diseño de las estrategias de implementación de guías o pautas de prácticaclínica de prevención cardiovascular, llevadas adelante por el Ministerio deSalud de la Nación con el fin de mejorar la calidad de atención.

Multi-scale mechanical characterization of prostate cancer cell lines: Relevant biological markers to evaluate the cell metastatic potential.

BACKGROUND: Considering the importance of cellular mechanics in the birth and evolution of cancer towards increasingly aggressive stages, we compared nano-mechanical properties of non-tumoral (WPMY-1) and highly aggressive metastatic (PC-3) prostate cell lines both on cell aggregates, single cells, and membrane lipids. METHODS: Cell aggregate rheological properties were analyzed during dynamic compression stress performed on a homemade rheometer. Single cell visco-elasticity measurements were performed by Atomic Force Microscopy using a cantilever with round tip on surface-attached cells. At a molecular level, the lateral diffusion coefficient of total extracted lipids deposited as a Langmuir monolayer on an air-water interface was measured by the FRAP technique. RESULTS: At cellular pellet scale, and at single cell scale, PC-3 cells were less stiff, less viscous, and thus more prone to deformation than the WPMY-1 control. Interestingly, stress-relaxation curves indicated a two-step response, which we attributed to a differential response coming from two cell elements, successively stressed. Both responses are faster for PC-3 cells. At a molecular scale, the dynamics of the PC-3 lipid extracts are also faster than that of WPMY-1 lipid extracts. CONCLUSIONS: As the evolution of cancer towards increasingly aggressive stages is accompanied by alterations both in membrane composition and in cytoskeleton dynamical properties, we attribute differences in viscoelasticity between PC-3 and WPMY-1 cells to modifications of both elements. GENERAL SIGNIFICANCE: A decrease in stiffness and a less viscous behavior may be one of the diverse mechanisms that cancer cells adopt to cope with the various physiological conditions that they encounter.

Essential role for SphK1/S1P signaling to regulate hypoxia-inducible factor 2α expression and activity in cancer.

The sphingosine kinase-1/sphingosine 1-phosphate (SphK1/S1P) signaling pathway has been reported to modulate the expression of the canonical transcription factor hypoxia-inducible HIF-1α in multiple cell lineages. HIF-2α is also frequently overexpressed in solid tumors but its role has been mostly studied in clear cell renal cell carcinoma (ccRCC), the most common form of kidney cancer, where HIF-2α has been established as a driver of a more aggressive disease. In this study, the role of SphK1/S1P signaling with regard to HIF-2α was investigated in various cancer cell models including ccRCC cells. Under hypoxic conditions or in ccRCC lacking a functional von Hippel-Lindau (VHL) gene and expressing high levels of HIF-2α, SphK1 activity controls HIF-2α expression and transcriptional activity through a phospholipase D (PLD)-driven mechanism. SphK1 silencing promotes a VHL-independent HIF-2α loss of expression and activity and reduces cell proliferation in ccRCC. Importantly, downregulation of SphK1 is associated with impaired Akt and mTOR signaling in ccRCC. Taking advantage of a monoclonal antibody neutralizing extracellular S1P, we show that inhibition of S1P extracellular signaling blocks HIF-2α accumulation in ccRCC cell lines, an effect mimicked when the S1P transporter Spns2 or the S1P receptor 1 (S1P1) is silenced. Here, we report the first evidence that the SphK1/S1P signaling pathway regulates the transcription factor hypoxia-inducible HIF-2α in diverse cancer cell lineages notably ccRCC, where HIF-2α has been established as a driver of a more aggressive disease. These findings demonstrate that SphK1/S1P signaling may act as a canonical regulator of HIF-2α expression in ccRCC, giving support to its inhibition as a therapeutic strategy that could contribute to reduce HIF-2 activity in ccRCC.

Targeted resequencing of a genomic region influencing tameness and aggression reveals multiple signals of positive selection.

The identification of the causative genetic variants in quantitative trait loci (QTL) influencing phenotypic traits is challenging, especially in crosses between outbred strains. We have previously identified several QTL influencing tameness and aggression in a cross between two lines of wild-derived, outbred rats (Rattus norvegicus) selected for their behavior towards humans. Here, we use targeted sequence capture and massively parallel sequencing of all genes in the strongest QTL in the founder animals of the cross. We identify many novel sequence variants, several of which are potentially functionally relevant. The QTL contains several regions where either the tame or the aggressive founders contain no sequence variation, and two regions where alternative haplotypes are fixed between the founders. A re-analysis of the QTL signal showed that the causative site is likely to be fixed among the tame founder animals, but that several causative alleles may segregate among the aggressive founder animals. Using a formal test for the detection of positive selection, we find 10 putative positively selected regions, some of which are close to genes known to influence behavior. Together, these results show that the QTL is probably not caused by a single selected site, but may instead represent the joint effects of several sites that were targets of polygenic selection.

Consumo de tabaco y alcohol en pacientes con cáncer esofágico en el Hospital Vargas de Caracas durante el período 2004-2009 / Tobacco and alcohol consumption in patients with esophageal cancer at

El Cáncer de Esófago ocupa el noveno lugar entre las neoplasias malignas a nivel mundial y está asociado al hábito tabáquico y alcohólico. En el Hospital Vargas de Caracas ocupa el lugar número 11 entre las primeras 15 (2.5%) causas de egresos por cáncer al año. Determinar el consumo de tabaco y alcohol en pacientes ingresados por Cáncer de esófago en el Hospital Vargas de Caracas durante el período 2004 - 2009. Se realizó estudio retrospectivo y descriptivo, luego de la revisión de historias de 24 pacientes ingresados por cáncer de esófago con diagnóstico de cáncer de esófago. Se utilizaron medidas de tendencia central para interpretación de resultados. 21(87.5%) de los pacientes fueron masculinos y 3(12.5%), femeninos. La edad promedio fue de 61 años. El 83.3%(20) refirieron hábito tabáquico de más de 24 paquetes/año y hábito alcohólico mayor a 120 gr/día. Histológicamente 87.5% (21) correspondió a Carcinoma Epidermoide localizados en 1/3 medio de esófago en 58.3% (14). Adenocarcinoma fue diagnosticado en 3 pacientes (12.5%) El hallazgo histopatológico más frecuente fue el carcinoma epidermoide en el 87.5% de las historias revisadas. El 83% de los pacientes tenían una asociación importante al hábito tabáquico y alcohólico, por lo que recomendamos implementación de Programa conjunto de promoción y prevención en salud entre la Sociedad Venezolana de Gastroenterología y la Sociedad Anticancerosa de Venezuela, de lucha contra los factores de riesgo de esta enfermedad...

Esophageal cancer ranks ninth among malignancies worldwide and is associated with smoking and alcoholism. In Hospital Vargas de Caracas is ranked number 11 among the top 15 (2.5%) causes of cancer discharges per year. To determine the consumption of tobacco and alcohol in patients admitted due to esophageal cancer in Hospital Vargas de Caracas during 2004-2009. A retrospective descriptive study was performed after reviewing the charts of 24 patients admitted with esophageal cancer. We used central tendency measures for interpretation of results. 21 (87.5%) patients were male and three (12.5%) female. The average age was 61 years-old. 83.3% (20) reported smoking over 24 pack/years and become an alcoholic greater than 120 g/day. Histologically, 87.5% (21) corresponded to epidermoid carcinoma located in 1/3 of the esophagus in 58.3% (14). Adenocarcinoma was diagnosed in 3 patients (12.5%). The most common histopathological fi nding was squamous cell carcinoma in 87.5% of the charts reviewed. 83% of patients had a signifi cant association with smoking and alcoholism, that’s why, we recommend the implementation of a joint program in health promotion and disease prevention among the Venezuelan Society of Gastroenterology and Cancer Society of Venezuela, to fight against the risk factors of this disease...

Lesiones gástricas premalignas en familiares en primer grado de pacientes con cáncer gástrico evaluados en la consulta de gastroenterología de dos hospitales universitarios de Caracas / Premalignant gastric lesions in first-degree relatives of gastric cancer patients evaluated in the gastroenterology at two university hospitals in Caracas

Las alteraciones morfológicas de la mucosa gástrica que predisponen al desarrollo de cáncer gástrico son atrofia, metaplasia y displasia. Diversos factores etiológicos han sido estudiados, destacándose el parentesco en primer grado con una probabilidad de presentar cáncer gástrico 2 veces más que la población general. Diagnosticar lesiones gástricas premalignas en familiares de pacientes con cáncer gástrico, evaluados en las consultas de Gastroenterología del Hospital Vargas de Caracas y Hospital Militar "Dr. Carlos Arvelo". Se realizó un estudio descriptivo, prospectivo, longitudinal, desde Octubre 2008 a Mayo 2009. Se incluyeron 75 individuos con edades comprendidas entre 18 y 80 años, familiares en primer grado de pacientes con cáncer gástrico, a los cuales se les practicó endoscopia digestiva superior con toma de biopsia. En 51 pacientes femeninos (68%) y 24 (32%) masculinos, se encontraron los siguientes hallazgos endoscópicos: endoscopia normal 52%, gastropatía crónica 33%, úlcera gástrica 5,33%, pólipos gástricos 3,33% y úlcera duodenal 1,33%. El estudio histológico determinó que la atrofia estuvo presente en 25 pacientes (33,3%), metaplasia intestinal en 17 pacientes (22,67%), displasia en 4 pacientes (5,33%), la mitad de ellas de alto grado y 1 (1,33%) indefinido para displasia. Conclusión y recomendación: En el grupo estudiado se encontró un 42,6% de lesiones gástricas premalignas, de las cuales el 5,33% correspondió a displasia, ninguno de estos con lesiones endoscópicas de malignidad; lo que nos hace recomendar de rutina en todos los servicios de gastroenterología del país un programa de pesquisa en familiares en primer grado de pacientes de cáncer gástrico...

Morphological alterations of the gastric mucosa that predispose to the development of gastric cancer are atrophy, metaplasia and dysplasia. Various etiologic factors have been studied, especially in first degree relatives,with a probability of gastric cancer double than that of the general population. To diagnose premalignant gastric lesions in relatives of patients with gastric cancer evaluated in the Gastroenterology consultation of "Hospital Vargas de Caracas", and "Hospital Militar Dr. Carlos Arvelo". A descriptive, prospective, longitudinal study was made, from October 2008 to May 2009. We included 75 individuals aged 18 to 80 years in first degree relatives of patients with gastric cancer, who underwent upper gastrointestinal endoscopy with biopsy guided. We found 51 (68%) female and 24 (32%) male, with these endoscopic findings: normal in 52% of the patients, with chronic gastropathy 37, 33%, gastric ulcer in 5,3%, gastric polyps in 3,33% and duodenal ulcer in 1,33%. The histological study found that atrophy was present in 25 (33.3%) patients, intestinal metaplasia in 17 (22, 67%) and dysplasia in 4(5, 33%) and 1(1,33%) indefinite to dysplasia. In this group of patients it was found a 42.6% of premalignant gastric lesions, of which 5.33% corresponded to dysplasia. Neither one had endoscopic malignant lesions. We recommend as a routine in all Gastroenterology Divisions in the country a program of screening in first degree families of patients of gastric cancer...

Consumo de tabaco y alcohol en pacientes con cáncer esofágico y su relación con el tipo histológico: Hospital Vargas de Caracas período 2004 - 2009 / Consumption of snuff and alcohol use in patients with esophageal cancer and its relation to histological type: Hospital Vargas de Caracas period 2004 - 2009

El Cáncer de Esófago ocupa el noveno lugar entre las neoplasias malignas a nivel mundial y está asociado al hábito tabáquico y alcohólico. En el Hospital Vargas de Caracas ocupa el lugar número 11 entre las primeras 15 (2.5%) causas de egresos por cáncer al año. Determinar el consumo de tabaco y alcohol en pacientes ingresados por Cáncer de esófago en el "Hospital Vargas de Caracas" durante el período 2004 - 2009. Se realizó estudio retrospectivo y descriptivo, luego de la revisión de historias de 24 pacientes ingresados con diagnóstico de cáncer de esófago. Se utilizaron medidas de tendencia central para interpretación de resultados. 21 (87.5%) de los pacientes fueron masculinos y 3 (12.5%) femeninos. La edad promedio fue de 61 años. El 83.3% (20) refirieron hábito tabáquico de más de 24 paquetes/año y hábito alcohólico mayor a 120 gr/día. Histológicamente 87.5% (21) correspondió a Carcinoma Epidermoide localizado en 1/3 medio de esófago en 58.3% (14). Adenocarcinoma fue diagnosticado en 3 pacientes (12.5%). El hallazgo histopatológico más frecuente fue el carcinoma epidermoide en el 87.5% de las historias revisadas. El 83% de los pacientes tenía una asociación importante al hábito tabáquico y alcohólico, por lo que recomendamos implementación de Programa conjunto de promocióny prevención en salud entre la Sociedad Venezolana de Gastroenterología y la Sociedad Anticancerosa de Venezuela, de lucha contra los factores de riesgo de esta enfermedad...

Esophageal Cancer ranks ninth among malignant neoplasias worldwide and is associated to smoking and alcohol consumption. In "HospitalVargas de Caracas" its ranked number 11 among the top 15 (2.5%) cases of cancer annually discharged. Determine the tobacco and alcohol consumption in patients admitted for esophageal cancer in "Hospital Vargas de Caracas" during the period 2004 to 2009. We performeda retrospective, descriptive study, after reviewing the charts of 24 patients admitted for esophageal cancer diagnosis. We used central tendency measures for interpretation of results. 21 (87.5%) patients were male and 3 (12.5%) female. The average age was 61 years. 83.3% (20) reported smoking over 24 packs-years and alcohol consumption greater than 120 g / day. Histologically, 87.5% (21) corresponded to squamous cell carcinoma located in 1 / 3 of the esophagus in 58.3% (14). 3 patients (12.5%) were diagnosed with Adenocarcinoma. Squamous cell carcinoma in 87.5% was the most common histopathological finding among the reviewed charts. 83% of patients had a significant association to smoking and alcohol, thus, we recommend the implementation of a joint prevention and health promotion program about the management of risk factors of this disease between the Venezuelan Society of Gastroenterology and Venezuela's Anti-Cancer Society, the control of risk factors of this disease...

Prevalencia de enfermedad por reflujo gastroesofágico en la población adulta Venezolana

La enfermedad por reflujo gastroesofágico (ERGE) es una enfermedad crónica recurrente, que constituye uno de los trastornos gastrointestinales que afecta con mayor frecuencia a población mundial. Objetivo: Determinar la prevalencia de enfermedad por reflujo gastroesofágico en la población adulta venezolana. Pacientes y Métodos: Se realiza un estudio descriptivo, de corte transversal, multicéntrico durante los meses de abril y mayo de 2008. Se entrevistaron a individuos en edades comprendidas entre 15 - 65 años de diferentes estados del país (Aragua, Anzoátegui, Barinas, Carabobo, Delta Amacuro, Distrito Capital, Mérida, Miranda, Sucre, Zulia) escogidos a través del azar simple, realizándose un muestreo por conglomerados, de donde, en cada estado se seleccionó un Municipio y de éste, lugares como iglesias, centro comerciales, cines y paradas de autobuses. Se tomó en consideración la población de cada municipio según el Censo Nacional 2001. Resultados: Un total de 1318 individuos fueron encuestados en los estados incluidos, 814 mujeres (61,76%) y 504 Hombres (38,24%). En cuanto a la distribución por categoría de edad, el grupo de 25-35 años constituyó el de mayor predominio. Se obtuvo una Prevalencia Nacional de 11,54%, donde los síntomas cardinales pirosis y regurgitación ácida representaron 16,62% y 12,75% respectivamente. Conclusión: La prevalencia nacional de enfermedad por reflujo gastroesofágico en la población venezolana es del 11,54%.

The gastroesophageal reflux disease (GERD) is a chronic recurrent illness that represents one of the most common gastrointestinal disorders that affects worldwide population. Aim: To determine the prevalence of gastroesophageal reflux disease in the Venezuelan adult population. Patients and Methods: A Descriptive, cross section, multicentric study was made. A survey was done to people in ages between 15 - 65 years of different states of the country (Aragua, Anzoátegui, Barinas, Carabobo, Delta Amacuro, Distrito Capital, Mérida, Miranda, Sucre, Zulia) chosen randomly. Cluster sampling was performed, where in each State was selected a municipality and, of which one places like churches, malls, cinemas and bus stops. To calculate de amount of people The National Census 2001 was taken in account in each municipality. Results: A total of 1318 individuals were surveyed in the mentioned States including, 814 women (61.76%) and 504 men (38.24%). The predominant distribution by age was the group of 25-35 years old. A National Prevalence of 11.54% was obtained, where the cardinal symptoms were heartburn and acid regurgitation represented 16.62% and 12.75% respectively. Conclusion: The national prevalence of gastroesophageal reflux disease in the Venezuelan adult population is 11.54%.

Consumo de alcohol en los pacientes que acudieron por consulta externa del Hospital Vargas de Caracas durante el período Marzo - Mayo 2008

El consumo de alcohol en nuestro país constituye un problema de salud pública relacionado con el desarrollo de eventos que afectan la esfera biopsicosocial del individuo. Objetivo: Caracterizar los patrones de consumo de alcohol en personas de 14 años y más que consultaron a los servicios de gastroenterología, Medicina Interna, Endocrinología y Cirugía del Hospital Vargas de Caracas. Pacientes y Métodos: El levantamiento de los datos se realizó durante el trimestre marzo-mayo 2008, en horario matutino y vespertino, de lunes a viernes. Se entrevistó una muestra intencional, heterogénea de 450 pacientes. Se aplicó una encuesta de preguntas abiertas en la cual se incluyeron los datos de identificación (nombre, apellido, sexo, edad, teléfono), consumo de alcohol (edad de inicio, número de tragos, frecuencia) y las preguntas del Test de Cage. Para medir el consumo de alcohol se utilizó una clasificación que permitió conocer el riesgo de Alcoholismo. Resultados: Se realizaron un total de 450 encuestas, en 149 pacientes masculinos y 301 femeninos. Del total de la muestra se identificaron 186 pacientes que consumen alcohol y 264 que no consumen, con un 41,55% y 58,45% respectivamente. El riesgo alto de consumo de alcohol estuvo presente en 16 pacientes y el consumo perjudicial en 50 pacientes, con un 8,60% y 26,88% respectivamente. Cabe destacar, que el riesgo alto de consumo fue mas elevado en el sexo femenino 10,34%, mientras que el consumo perjudicial en el sexo masculino con 43,87%. Conclusiones: El consumo de alcohol en los pacientes que acudieron a las Consultas Externas del Hospital Vargas de Caracas es alto, en un 41,55 % de los encuestados, con un riesgo de consumo de alcohol de 35,48 %.

Alcohol intake in our country is a public health problem related with the development of many events that affect the bio - psychosocial area of the patients. Objective: Characterize the patterns of alcohol intake in people from 14 years old on; that attended the gastroenterology, Internal Medicine, Endocrinology and Surgery Divisions at the Hospital Vargas in Caracas. Patients and Methods: the data was collected during March-May 2008, in the morning and afternoon, from Monday through Friday. Interviews were done in an intentional, heterogeneous sample of 450 patients. An opened questions survey was applied, in which the identification data (name, last name, sex, age, telephone), alcohol intake were included (age of beginning, number of drinks, frequency), as well as the Cage Test questions. In order to measure alcohol intake, we used a classification that allowed knowing the risk of Alcoholism. Results: A total of 450 surveys were made, in 149 male patients and 301 females. Of the total of the sample, 186 patients consume alcohol and 264 do not, 41.55% and 58.45% respectively. 16 patients, presented with high risk of alcohol intake and 50 patients with severe intake, 8.60% and 26.88% respectively. It is important to stress out that females presented a high risk of intake (10.34%), whereas the detrimental intake in males was 43.87%. Conclusions: Alcohol intake in patients who attended "Hospital Vargas de Caracas" outpatient clinic is high, with a 41.55% of the patients, and an alcohol intake risk of 35.48 %.

Screens using RNAi and cDNA expression as surrogates for genetics in mammalian tissue culture cells.

We have developed methods for the automation of transfection-grade DNA preparation, high-throughput retroviral preparation, and highly parallel phenotypic screens to establish approaches that will allow investigators to examine in an unbiased manner the roles of proteins in mammalian cells. These methods have been used to raise or lower the levels of individual kinases in individual micro-well cultures either by cDNA or short hairpin RNA expression and will allow investigators to treat mammalian cells in culture in manners that are analogous to genetic screens in yeast. Our proof-of-principle experiments have been performed in human cells using repositories that represent over 75% of the protein, nucleotide, carbohydrate, lipid, and amino acid kinases in the human genome. These initial experiments have demonstrated the feasibility of two general types of screens. We have performed phenotypic screens to identify proteins with specific roles in a chosen function and genetic interaction screens to establish epistatic relations between different proteins. The results suggest that any phenotype that can be scored by a robust assay in tissue culture is amenable to these types of screens and that interactions between mammalian proteins can be established. These results point to the near-term goal of establishing comprehensive, unbiased screens that will allow queries on the roles of all human proteins.

FLEXGene repository: from sequenced genomes to gene repositories for high-throughput functional biology and proteomics.

The vast amount of information generated by the human genome sequencing project and related projects has given rise to a new paradigm in experimental biology. This new paradigm invokes the experimentation and data analysis at genome-wide scales, as well as the generation of new technologies and resources that take full advantage of the available sequence information. The Institute of Proteomics at Harvard Medical School is building a comprehensive, characterized, arrayed and flexible gene repository that will allow full exploitation of the genomic information by enabling functional genomics as well as protein expression, purification and analysis at genome wide scale. The FLEXGene repository (Full Length EXpression-ready) will contain clones representing the complete set of open reading frames (ORFs) of different organisms including H. sapiens and several pathogens and model organisms. The clones are constructed using recombination-based cloning technology so that hundreds or thousands of coding regions can be transferred into any expression vector in a parallel and timely mode, allowing the broadest variety of experiments to be carried out.

Identification of selective inhibitors of cyclin dependent kinase 4.

A new structural type of kinase inhibitor, containing a benzocarbazole nucleus, has been identified. Members of the series are selective for inhibition of the cyclin dependent kinase family of enzymes. Although the cdks are highly homologous, representatives of the series showed intra-cdk selectivities, especially for cdk4. SAR studies elucidated the important features of the molecules for inhibition.

SCF(beta-TRCP) and phosphorylation dependent ubiquitinationof I kappa B alpha catalyzed by Ubc3 and Ubc4.

NF kappa B is an important transcriptional regulator of multiple pro-inflammatory genes. In non-stimulated cells NF kappa B is anchored in the cytoplasm via the inhibitory protein I kappa B alpha. Following exposure to diverse pro-inflammatory signals (e.g. TNF alpha, IL1, LPS) various signal transduction cascades are initiated converging on the I kappa B kinase (IKK). IKK phosphorylates I kappa B alpha on serines 32 and 36 signaling the inhibitory protein for ubiquitin-mediated degradation. The SCF beta-TRCP complex is the ubiquitin ligase responsible for mediating phosphorylation dependent ubiquitination of I kappa B alpha. Here we reconstitute phosphorylation dependent ubiquitination of I kappa B alpha using recombinant components. Our results suggest that the cullin specificity of the SCF complex may reflect its ability to associate with Rbx1. We demonstrate specific ubiquitination of I kappa B alpha by Ubc3 and Ubc4 in a phosphorylation and SCF beta-TRCP dependent manner and that both are capable of associating with the SCF beta-TRCP complex isolated from human cells. Finally, we show that Ubc4 is in excess to Ubc3 in THP.1 cells and 19 times more efficient in catalyzing the reaction, suggesting that Ubc4 is the preferentially used Ubc in this reaction in vivo. Our results also suggest that ubiquitin is transferred directly from the Ubc to phospho-I kappa B alpha in a SCF beta-TRCP dependent reaction. Oncogene (2000) 19, 3529 - 3536

Structure-activity relationship studies of flavopiridol analogues.

Cyclin dependent kinases (CDKs) along with the complementary cyclins form key regulatory checkpoint controls on the cell cycle. Flavopiridol is a synthetic flavone that shows potent and selective cyclin-dependent kinase inhibitory activity. In this paper, we report modifications of the 3-hydroxy-1-methylpiperidinyl (D ring) of flavopiridol and their effect on CDK inhibitory activity.

Comparison between isosorbide dinitrate in aerosol and in tablet form for the treatment of hypertensive emergencies in the elderly.

BACKGROUND: Isosorbide dinitrate in spray form is an effective and safe option for the treatment of hypertensive emergencies. The aim of this study was to evaluate whether isosorbide dinitrate spray is as effective and safe as treatment in tablet form for the management of hypertensive emergencies in the elderly. METHODS: Forty patients with hypertensive emergencies were randomly divided into two groups of 20 patients each. Group A received 1.25 mg isosorbide dinitrate aerosol upon arrival and a second dose 15 min later when mean systemic arterial pressure (MAP) reduction was <15% . Group B patients received a single 5 mg tablet of sublingual isosorbide dinitrate. RESULTS: Blood pressure in Group A patients decreased from 193 +/- 13/123 +/- 6.6 mmHg to 154 +/- 15/92.5 +/- 7.6 mmHg (p < 0.005), the reduction beginning 10 min after drug administration; no adverse effects were found. Two patients in Group B did not respond but for the other patients in this group blood pressure decreased from 197 +/- 10/121 +/- 7 to 154 +/- 11/90 +/- 4 mmHg, (p < 0.005), the reduction beginning 45 min after receiving the medication; 8 patients suffered headache. CONCLUSION: Our results indicate that isosorbide dinitrate aerosol is more effective than tablets for the treatment of elderly patients with hypertensive emergencies.

Mechanism of Cdk2/Cyclin E inhibition by p27 and p27 phosphorylation.

The biochemical interactions between the Cdk2/Cyclin E kinase and its inhibitor p27, were investigated using purified, recombinant p27 and CAK-phosphorylated Cdk2/Cyclin E. From kcat/Km determinations using either histone H1 or pRb as substrates, we found that Cdk2/Cyclin E has 60-fold higher specificity for pRb than for histone H1. The IC50 value of p27 increased with increasing Cdk2/Cyclin E concentrations while it remained constant at various ATP and histone H1 concentrations, suggesting that p27 acts as a tight binding inhibitor of Cdk2/Cyclin E. We also found that p27 could be phosphorylated by Cdk2/Cyclin E only at high enzyme concentrations, and that p27 forms a stable interaction with Cdk2/Cyclin E regardless of its phosphorylation state. Our results further indicate that the Cdk2/Cyclin E/p27 ternary complex is kinetically inactive as an enzyme; instead it serves as a substrate for Cdk2/Cyclin E. These results suggest that if phosphorylation of p27 by Cdk2/Cyclin E is involved in its ubiquitin-dependent degradation, as previously suggested, then the target for such event is the phosphorylated p27 bound to Cdk2/Cyclin E and not free p27.

Crystal structure of the complex of the cyclin D-dependent kinase Cdk6 bound to the cell-cycle inhibitor p19INK4d.

The crystal structure of the cyclin D-dependent kinase Cdk6 bound to the p19 INK4d protein has been determined at 1.9 A resolution. The results provide the first structural information for a cyclin D-dependent protein kinase and show how the INK4 family of CDK inhibitors bind. The structure indicates that the conformational changes induced by p19INK4d inhibit both productive binding of ATP and the cyclin-induced rearrangement of the kinase from an inactive to an active conformation. The structure also shows how binding of an INK4 inhibitor would prevent binding of p27Kip1, resulting in its redistribution to other CDKs. Identification of the critical residues involved in the interaction explains how mutations in Cdk4 and p16INK4a result in loss of kinase inhibition and cancer.