Is the long-term mortality similar in COVID-19 and community-acquired pneumonia?

Introduction: There are no data on the association of type of pneumonia and long-term mortality by the type of pneumonia (COVID-19 or community-acquired pneumonia [CAP]) on long-term mortality after an adjustment for potential confounding variables. We aimed to assess the type of pneumonia and risk factors for long-term mortality in patients who were hospitalized in conventional ward and later discharged. Methods: Retrospective analysis of two prospective and multicentre cohorts of hospitalized patients with COVID-19 and CAP. The main outcome under study was 1-year mortality in hospitalized patients in conventional ward and later discharged. We adjusted a Bayesian logistic regression model to assess associations between the type of pneumonia and 1-year mortality controlling for confounders. Results: The study included a total of 1,693 and 2,374 discharged patients in the COVID-19 and CAP cohorts, respectively. Of these, 1,525 (90.1%) and 2,249 (95%) patients underwent analysis. Until 1-year follow-up, 69 (4.5%) and 148 (6.6%) patients from the COVID-19 and CAP cohorts, respectively, died (p = 0.008). However, the Bayesian model showed a low probability of effect (PE) of finding relevant differences in long-term mortality between CAP and COVID-19 (odds ratio 1.127, 95% credibility interval 0.862-1.591; PE = 0.774). Conclusion: COVID-19 and CAP have similar long-term mortality after adjusting for potential confounders.

Eficacia y seguridad de la combinación de fexofenadina con montelukast en el tratamiento de la rinitis alérgica / Efficacy and safety of combined therapy of fexofenadine and montelukast for the treatment of allergic rhinitis

El propósito de este trabajo fue revisar la literatura científica que evalúa la eficacia y seguridad de las monoterapias de fexofenadina y montelukast, la terapia combinada (fija o en asociación) de montelukast - fexofenadina, así como de montelukast con otros antihistamínicos de segunda generación en el tratamiento de la rinitis alérgica. Se realizó una estrategia de búsqueda bibliográfica de múltiples etapas, en donde se identificaron estudios basados en ensayos clínicos y estudios no aleatorizados (ensayo controlado no aleatorizado, controlado antes-después, de series de tiempo interrumpidas, con controles históricos, de cohorte, de casos y controles, estudio transversal, y series de casos) en pacientes con rinitis alérgica, en las bases de datos MEDLINE/ PubMed, Scopus, Web of Science, Biblioteca Cochrane, Redalyc y Colección BVS y debido a la cantidad de resultados obtenidos se incluyó la búsqueda en Hinari. Con base en esta revisión se concluye que las combinaciones de antihistamínicos de segunda generación y antagonistas de leucotrienos y, en particular, la combinación fija de fexofenadina ­ montelukast es eficaz, segura y favorece la adherencia al tratamiento, y a largo plazo también ayuda a alcanzar el objetivo terapéutico.

The purpose of this work was to review the scientific literature that evaluates the efficacy and safety of monotherapies of fexofenadine and montelukast, the combined therapy (fixed-dose or separate drug combinations) of montelukast-fexofenadine, as well as the use of montelukast together with other second-generation antihistamines in the treatment of allergic rhinitis. A multistage literature search strategy was designed, including clinical trials and non-randomized studies (non-randomized controlled trial, controlled before-after study, interrupted time series study, historical control study, cohort study, case-control study, crosssectional study, and case series) evaluating patients with allergic rhinitis. The databases MEDLINE/PubMed, Scopus, Web of Science, Cochrane Library, Redalyc, BVS Collection, and, due to the number of results obtained, Hinari were included. Based on this review, the conclusion is that the combinations of secondgeneration antihistamines with leukotriene antagonists and, in particular, the fixed combination of fexofenadine-montelukast are effective, safe and promote treatment adherence. In the long term, they also help achieve therapeutic goals.

A novel RGB-trichrome staining method for routine histological analysis of musculoskeletal tissues.

Morphometry and histology are essential approaches for investigation and diagnosis of musculo-skeletal disorders. Despite the advent of revolutionary methods of image analysis and high resolution three-dimensional imaging technology, basic conventional light microscopy still provides an incisive overview of the structure and tissue dynamics of the musculoskeletal system. This is crucial to both preclinical and clinical research, since several clinically relevant processes, such as bone repair, osteoarthritis, and metabolic bone diseases, display distinct, if not pathognomonic, histological features. Due to the particular characteristics of the skeletal tissues (i.e., the existence of mineralized extracellular matrices), a large number of staining methods applicable to either decalcified or undecalcified tissues are available. However, it is usually the case that several staining methods need to be sequentially applied in order to achieve the different endpoints required to fully assess skeletal tissue structure and dynamics, and to allow morphometric quantification. We describe herein a novel staining method, the RGB trichrome, amenable for application to decalcified, paraffin embedded human musculoskeletal tissues. The acronym RGB corresponds to the three primary dyes used: picrosirius Red, fast Green, and alcian Blue. Although these individual pigments are commonly used either isolated, in binary combinations, or as part of more complex polychrome staining methods, when merged in the RGB trichrome staining produce high-quality/high-contrast images, permitting not only clear identification of different tissues (i.e., the different types of cartilage, bone and fibrous connective tissue), but also discrimination between calcified and uncalcified bone and cartilage, as well as an unexpected diversity of shades of color, while displaying singular properties among polychrome staining methods, such as the unveiling of the bone osteocyte dendritic/canalicular network. Hence, we propose the RGB trichrome as simple but highly-reliable tool for the preclinical and clinical study of the musculoskeletal system.

[Municipal malnutrition in Mexican preschool children population and coverage of the Programa Nacional México Sin Hambre.] / Mala nutrición a nivel municipal en población preescolar mexicana y cobertura del Programa Nacional México Sin Hambre.

OBJECTIVE: To estimate malnutrition prevalence of preschool children at the level of municipality in Mexico, describe prevalence heterogeneity and its relationship with the Programa Nacional México Sin Hambre´s coverage. MATERIALS AND METHODS: Using the 2012 Mexican National Survey of Health and Nutrition, municipal income inequality and marginality, we applied a generalized normal model to obtain municipal distributions of nutrition status indicators from which we estimated malnutrition prevalence. RESULTS: Stunting prevalence ranged from 7.8% (95%CI: 5.9-8.9) to 64.2% (49.2-72.5), low weight prevalence ranged from 0.6% (0.005- 1.7) to 22.2% (13.5-34.9) and overweight-obesity prevalencem ranged from 2.6% (0.2-3.9) to 14.4% (11.9-27.7). A total of 275 out of 554 municipalities with stunting prevalence above 25% were covered by the Programa Nacional México Sin Hambre. CONCLUSIONS: Municipal malnutrition prevalence estimation showed wide differences within Mexico; this knowledge could assist public policy.

OBJETIVO: Estimar las prevalencias municipales de mala nutrición en población preescolar en México, y describir su variabilidad y su relación con la cobertura del Programa Nacional México Sin Hambre. MATERIAL Y MÉTODOS: A partir de datos de la Encuesta Nacional de Salud y Nutrición de 2012, la desigualdad del ingreso y marginación municipal se aplicó un modelo normal generalizado para obtener las distribuciones municipales de los indicadores de nutrición y estimar las prevalencias de mala nutrición. RESULTADOS: Las prevalencias de talla baja variaron de 7.8% (IC95%: 5.9-8.9) a 64.2% (49.2-72.5), las de bajo peso de 0.6% (0.005-1.7) a 22.2% (13.5-34.9) y de sobrepeso u obesidad de 2.6% (0.2- 3.9) a 14.4% (11.9-27.7). De los 554 municipios con prevalencias de talla baja mayor que 25%, 275 fueron cubiertos por el programa México Sin Hambre. CONCLUSIONES: La estimación de prevalencias municipales de mala nutrición evidenció grandes diferencias al interior del país, mismas que podrían asistir la política pública.

Mala nutrición a nivel municipal en población preescolar mexicana y cobertura del Programa Nacional México Sin Hambre / Municipal malnutrition in Mexican preschool children population and coverage of the Programa Nacional México Sin Hambre

Resumen: Objetivo: Estimar las prevalencias municipales de mala nutrición en población preescolar en México, y describir su variabilidad y su relación con la cobertura del Programa Nacional México Sin Hambre. Material y métodos: A partir de datos de la Encuesta Nacional de Salud y Nutrición de 2012, la desigualdad del ingreso y marginación municipal se aplicó un modelo normal generalizado para obtener las distribuciones municipales de los indicadores de nutrición y estimar las prevalencias de mala nutrición. Resultados: Las prevalencias de talla baja variaron de 7.8% (IC95%: 5.9-8.9) a 64.2% (49.2-72.5), las de bajo peso de 0.6% (0.005-1.7) a 22.2% (13.5-34.9) y de sobrepeso u obesidad de 2.6% (0.2-3.9) a 14.4% (11.9-27.7). De los 554 municipios con prevalencias de talla baja mayor que 25%, 275 fueron cubiertos por el programa México Sin Hambre. Conclusiones: La estimación de prevalencias municipales de mala nutrición evidenció grandes diferencias al interior del país, mismas que podrían asistir la política pública.

Abstract: Objective: To estimate malnutrition prevalence of preschool children at the level of municipality in Mexico, describe prevalence heterogeneity and its relationship with the Programa Nacional México Sin Hambre´s coverage. Materials and methods: Using the 2012 Mexican National Survey of Health and Nutrition, municipal income inequality and marginality, we applied a generalized normal model to obtain municipal distributions of nutrition status indicators from which we estimated malnutrition prevalence. Results: Stunting prevalence ranged from 7.8% (95%CI: 5.9-8.9) to 64.2% (49.2-72.5), low weight prevalence ranged from 0.6% (0.005-1.7) to 22.2% (13.5-34.9) and overweight-obesity prevalence ranged from 2.6% (0.2-3.9) to 14.4% (11.9-27.7). A total of 275 out of 554 municipalities with stunting prevalence above 25% were covered by the Programa Nacional México Sin Hambre. Conclusions: Municipal malnutrition prevalence estimation showed wide differences within Mexico; this knowledge could assist public policy.

Overview of acute diarrheal disease at the dawn of the 21st century: The case of Mexico.

OBJECTIVE: To provide an overview of morbidity and mortality due to acute diarrheal disease in Mexico in order to understand its magnitude, distribution, and evolution from 2000 to 2016. MATERIALS AND METHODS: We carried out a longitudinal ecological study with secondary sources of information. We used data from epidemiological surveillance, health services, and vital statistics. We calculated and mapped measures of utilization of health services rates and mortality due to diarrheal diseases. RESULTS: Diarrhea morbidity decreased by 42.1% across the period. However, emergency department attendances increased by 50.7% in the Ministry of Health. The hospitalization rate and mortality among the general population decreased by 37.6 and 39.7%, respectively, and the infant mortality rate decreased by 72.3% among children under five years of age. Chiapas and Oaxaca had the highest mortality among the states of Mexico. CONCLUSIONS: Cases of diarrhea, including rotavirus, have decreased in Mexico. However, in 2016, 3.4 per 100 000 people died due to diarrhea, which could have been avoided with health promotion.

OBJETIVO: Ofrecer un panorama de la morbimortalidad por enfermedad diarreica aguda (EDA) entre 2000 y 2016 en México, para entender su magnitud, distribución y evolución. MATERIAL Y MÉTODOS: Estudio ecológico longitudinal, con fuentes de información secundarias. Se analizaron datos de vigilancia epidemiológica, prestación de servicios y estadísticas vitales. Se calcularon tasas de utilización de servicios y mortalidad. RESULTADOS: La morbilidad por EDA disminuyó 42.1% en el periodo, sin embargo, la atención por urgencias aumentó 50.7% en SS. La tasa de hospitalización descendió 37.6% y la mortalidad 39.7% en población general y 72.3% en menores de cinco años. Chiapas y Oaxaca fueron los estados con mayor tasa de mortalidad. CONCLUSIONES: Los casos de diarrea, incluyendo los de rotavirus, han disminuido en el país. Sin embargo, en 2016 se encontró una tasa de 3.4 por 100 000 personas que mueren por EDA, lo cual podría evitarse con promoción de la salud.

[Is there a risk of adverse health effects from the consumption of fortified foods in Mexico?] / ¿Hay riesgo de efectos adversos por el consumo de nutrimentos a partir de productos alimenticios adicionados en México?

INTRODUCTION: according to the nutriment addition scheme from the current Mexican legislation, there is no data about overdose or adverse effects caused by a nutriment, or any information showing the risk for the population in Mexico. This work is classified as descriptive and observational. AIM: to assess the risk of consuming fortified food products (FFP) in Mexico. METHODS: the study was done in three phases: a) selection of the FFP and acquisition of the information from the nutritional facts label; b) elaboration of six diets according to the socioeconomic status, both in rural and urban areas, based on the ENIGH and ENSANUT surveys; and c) comparison of these diets with regimes containing FFP, calculated for an adult-equivalent (2,828 kcal). RESULTS: the FFP represent 10% of all the products in the market, being milk, corn and wheat flour, and their byproducts the most abundant. The six diets containing FFP were deficient in calcium, ascorbic acid and vitamins D and E. However, vitamins from the B complex were over the recommendation values. In general, any added nutriment was over the tolerable upper intake levels (UL). CONCLUSIONS: we demonstrated that the nutriment concentrations in the FFP do not reach the UL values and are not a risk for the Mexican population; however, they improve the nutritional contribution of the FFP.

INTRODUCCIÓN: en México no existen datos de sobredosis o reacciones adversas causadas por algún nutrimento o dato alguno que indique riesgo a la población de acuerdo al esquema de adición de nutrimentos de la legislación mexicana vigente. Este trabajo se clasifica como descriptivo y observacional. OBJETIVO: valorar el riesgo por consumo de productos alimenticios adicionados (PAA) en México. MÉTODOS: se realizó en tres fases: a) selección de PAA y obtención de la información nutrimental de las etiquetas; b) elaboración de seis dietas de acuerdo al estrato socioeconómico, tanto en el ámbito rural como en el urbano con base a las encuestas ENIGH y ENSANUT; y c) comparación de estas dietas con dietas que incluyen PAA, calculadas para un adulto equivalente (2.828 kcal). RESULTADOS: los PAA representan el 10% del total de productos presentes en el mercado. Los más frecuentes son: leche, harinas de maíz y trigo y sus derivados. Las seis dietas con PAA presentaron deficiencias en calcio, ácido ascórbico, vitamina D y E. Sin embargo, las vitaminas del complejo B superaron la recomendación. En general, ningún nutrimento adicionado se encontró por arriba del nivel de ingestión tolerable superior (UL). CONCLUSIONES: se demostró que las concentraciones de los nutrimentos en los PAA no alcanzan los UL y no representan un riesgo para la población mexicana, sin embargo, mejoran su aporte nutrimental.

¿Hay riesgo de efectos adversos por el consumo de nutrimentos a partir de productos alimenticios adicionados en México? / Is there a risk of adverse health effects from the consumption of fortified foods in Mexico?

Introducción: en México no existen datos de sobredosis o reacciones adversas causadas por algún nutrimento o dato alguno que indique riesgo a la población de acuerdo al esquema de adición de nutrimentos de la legislación mexicana vigente. Este trabajo se clasifica como descriptivo y observacional. Objetivo: valorar el riesgo por consumo de productos alimenticios adicionados (PAA) en México. Métodos: se realizó en tres fases: a) selección de PAA y obtención de la información nutrimental de las etiquetas; b) elaboración de seis dietas de acuerdo al estrato socioeconómico, tanto en el ámbito rural como en el urbano con base a las encuestas ENIGH y ENSANUT; y c) comparación de estas dietas con dietas que incluyen PAA, calculadas para un adulto equivalente (2.828 kcal). Resultados: los PAA representan el 10% del total de productos presentes en el mercado. Los más frecuentes son: leche, harinas de maíz y trigo y sus derivados. Las seis dietas con PAA presentaron deficiencias en calcio, ácido ascórbico, vitamina D y E. Sin embargo, las vitaminas del complejo B superaron la recomendación. En general, ningún nutrimento adicionado se encontró por arriba del nivel de ingestión tolerable superior (UL). Conclusiones: se demostró que las concentraciones de los nutrimentos en los PAA no alcanzan los UL y no representan un riesgo para la población mexicana, sin embargo, mejoran su aporte nutrimental

Introduction: according to the nutriment addition scheme from the current Mexican legislation, there is no data about overdose or adverse effects caused by a nutriment, or any information showing the risk for the population in Mexico. This work is classified as descriptive and observational. Aim: to assess the risk of consuming fortified food products (FFP) in Mexico. Methods: the study was done in three phases: a) selection of the FFP and acquisition of the information from the nutritional facts label; b) elaboration of six diets according to the socioeconomic status, both in rural and urban areas, based on the ENIGH and ENSANUT surveys; and c) comparison of these diets with regimes containing FFP, calculated for an adult-equivalent (2,828 kcal). Results: the FFP represent 10% of all the products in the market, being milk, corn and wheat flour, and their byproducts the most abundant. The six diets containing FFP were deficient in calcium, ascorbic acid and vitamins D and E. However, vitamins from the B complex were over the recommendation values. In general, any added nutriment was over the tolerable upper intake levels (UL). Conclusions: we demonstrated that the nutriment concentrations in the FFP do not reach the UL values and are not a risk for the Mexican population; however, they improve the nutritional contribution of the FFP

Development and validation of a method for precise dating of female puberty in laboratory rodents: The puberty ovarian maturation score (Pub-Score).

Puberty is a key developmental event whose primary regulatory mechanisms remain poorly understood. Precise dating of puberty is crucial for experimental (preclinical) studies on its complex neuroendocrine controlling networks. In female laboratory rodents, external signs of puberty, such as vaginal opening (VO) and epithelial cell cornification (i.e., first vaginal estrus, FE), are indirectly related to the maturational state of the ovary and first ovulation, which is the unequivocal marker of puberty. Whereas in rats, VO and FE are almost simultaneous with the first ovulation, these events are not so closely associated in mice. Moreover, external signs of puberty can be uncoupled with first ovulation in both species under certain experimental conditions. We propose herein the Pubertal Ovarian Maturation Score (Pub-score), as novel, reliable method to assess peripubertal ovarian maturation in rats and mice. This method is founded on histological evaluation of pre-pubertal ovarian maturation, based on antral follicle development, and the precise timing of first ovulation, by retrospective dating of maturational and regressive changes in corpora lutea. This approach allows exact timing of puberty within a time-window of at least two weeks after VO in both species, thus facilitating the identification and precise dating of advanced or delayed puberty under various experimental conditions.

[Aggressions towards Primary Health Care Workers in Madrid, Spain, 2011-2012]. / Agresiones sufridas por las personas que trabajan en atención primaria de la Comunidad de Madrid, 2011-2012.

OBJECTIVE: The number of aggressions towards health care professionals has risen over the past few years. There are no previous studies in primary care covering an entire region and to all professional categories. The aim of this study was to characterize aggressions in Primary Care in the Community of Madrid. METHODS: Multicenter cross-sectional study. Analysis of a Registration System that reports any type of aggression suffered by Primary Care workers, in the Community of Madrid. The study variables included sociodemographic characteristics of the aggressor and the victim, the type of aggression (verbal or physical abuse), its causes and consequences. We described median, intercuartilic range and frequencies. Logistic regression was performed calculating odds ratio and their 95% confidence intervals. RESULTS: 1,157 assaults were reported, 53.07% suffered by doctors. Physical assault occurred in 4.7% of the cases. The main reason was dissatisfaction with the care (36.1%). The non-medical staff showed less risk of being physically assaulted (OR: 0.38; CI95%: 0.17-0.86). The perpetrator profile was male (56.8%), aged between 31-40 (26.8%) years. Health care victim profile was female (84%), aged between 45-60 years. 10% of professionals reported some form of aggression, 5,9% of aggression were submitted to court. CONCLUSIONS: The risk of assault is higher in health personnel, particularly physicians. There were significant differences by gender and age, both in the profile of the aggressor and the victim.

Agresiones sufridas por las personas que trabajan en atención primaria de la Comunidad de Madrid, 2011-2012 / Aggressions towards primary health care workers in MAdrid, Spain, 2011-2012

Fundamentos: Las agresiones de usuarios a los profesionales de Atención Primaria se han incrementado en los últimos años. No existen estudios previos en atención primaria que abarquen toda una Comunidad Autónoma y todas las categorías profesionales. El objetivo del estudio fue caracterizar la violencia en atención primaria de la Comunidad de Madrid. Métodos: Estudio descriptivo multicéntrico de las notificaciones de agresiones sufridas por los profesionales de Atención Primaria de la Comunidad de Madrid. Las variables del estudio incluyeron características sociodemográficas de las personas agresoras y de las agredidas, el tipo de agresión, sus causas y consecuencias. Se calcularon la mediana, el rango intercuartílico y las frecuencias. Se realizó un análisis de regresión logística calculando las OR y sus IC95%. Resultados: En el periodo de estudio se notificaron 1.157 agresiones, el 53,07% las notificaron médicos. En el 4,7% de los casos hubo agresión física. El principal motivo fue la disconformidad con la atención recibida (36,1%). El personal no sanitario mostró menos riesgo de ser agredido físicamente que el personal sanitario (OR: 0,38; IC95%: 0,17-0,86). La agresión fue cometida por un hombre en el 56,8% de los casos y del grupo de edad entre 31-40 años en el 26,8%. La persona agredida fue mujer en el 84% de los casos, con una edad comprendida entre 45-60 años. El 10% de los profesionales notificaron las agresiones y el 5,9% la denunció. Conclusiones: El riesgo de sufrir agresión es mayor en el personal sanitario, especialmente médicos. Tanto en el perfil de las personas agresoras como de las agredidas se detectaron diferencias significativas por sexo y edad (AU)

Background: The number of aggressions towards health care professionals has risen over the past few years. There are no previous studies in primary care covering an entire region and to all professional categories. The aim of this study was to characterize aggressions in Primary Care in the Community of Madrid. Methods: Multicenter cross-sectional study. Analysis of a Registration System that reports any type of aggression suffered by Primary Care workers, in the Community of Madrid. The study variables included sociodemographic characteristics of the aggressor and the victim, the type of aggression (verbal or physical abuse), its causes and consequences. We described median, intercuartilic range and frequencies. Logistic regression was performed calculating odds ratio and their 95% confidence intervals. Results: 1,157 assaults were reported, 53.07% suffered by doctors. Physical assault occurred in 4.7% of the cases. The main reason was dissatisfaction with the care (36.1%). The non-medical staff showed less risk of being physically assaulted (OR: 0.38; CI95%: 0.17-0.86). The perpetrator profile is male (56.8%), aged between 31-40 (26.8%) years. Health care victim profile was female (84%), aged between 45-60 years. 10% of professionals reported some form of aggression, 5,9% of aggression were submitted to court. Conclusions. The risk of assault is higher in health personnel, particularly physicians. There are significant differences by gender and age, both in the profile of the aggressor and the victim (AU)

Crowding and Follicular Fate: Spatial Determinants of Follicular Reserve and Activation of Follicular Growth in the Mammalian Ovary.

Initiation of growth of resting ovarian follicles is a key phenomenon for providing an adequate number of mature oocytes in each ovulation, while preventing premature exhaustion of primordial follicle reserve during the reproductive lifespan. Resting follicle dynamics strongly suggest that primordial follicles are under constant inhibitory influences, by mechanisms and factors whose nature remains ill defined. In this work, we aimed to assess the influence of spatial determinants, with special attention to clustering patterns and crowding, on the fate of early follicles in the adult mouse and human ovary. To this end, detailed histological and morphometric analyses, targeting resting and early growing follicles, were conducted in ovaries from mice, either wild type (WT) or genetically modified to lack kisspeptin receptor expression (Kiss1r KO), and healthy adult women. Kiss1r KO mice were studied as model of persistent hypogonadotropism and anovulation. Different qualitative and quantitative indices of the patterns of spatial distribution of resting and early growing follicles in the mouse and human ovary, including the Morisita's index of clustering, were obtained. Our results show that resting primordial follicles display a clear-cut clustered pattern of spatial distribution in adult mouse and human ovaries, and that resting follicle aggrupation is inversely correlated with the proportion of follicles initiating growth and entering into the growing pool. As a whole, our data suggest that resting follicle crowding, defined by changes in density and clustered pattern of distribution, is a major determinant of follicular activation and the fate of ovarian reserve. Uneven follicle crowding would constitute the structural counterpart of the major humoral regulators of early follicular growth, with potential implications in ovarian ageing and pathophysiology.

Dopamine receptor 2 activation inhibits ovarian vascular endothelial growth factor secretion in an ovarian hyperstimulation syndrome (OHSS) animal model: implications for treatment of OHSS with dopamine receptor 2 agonists.

OBJECTIVE: To explore whether a dopamine receptor 2 agonist (D2-ag) can prevent ovarian hyperstimulation syndrome (OHSS) in a rat model by decreasing ovarian vascular endothelial growth factor (VEGF) production. DESIGN: Experimental study in an OHSS animal model. SETTING: University-affiliated infertility center. PATIENT(S): Immature Wistar rats. INTERVENTION(S): Immature rats were stimulated with gonadotropins to mimic OHSS and treated with a D2-ag and/or D2-antagonists (D2-ant). Vascular permeability (VP) was measured at the endpoint, and ovaries were collected to assess the effects of these drugs on VEGF production. MAIN OUTCOME MEASURE(S): VP was estimated by measuring the peritoneal extravasation of a previously injected dye. Ovarian VEGF mRNA expression and VEGF protein levels were assessed by quantitative real-time PCR and Western blots, respectively. RESULT(S): The D2-ag exerted a reduction in VP that was associated with a drastic decrease in VEGF protein production in OHSS rat ovaries. The effects of this D2-ag on VP and VEGF protein levels were partially reversed by concomitant administration of a D2-ant. Ovarian VEGF mRNA expression levels were unaffected by these drugs in OHSS rats. CONCLUSION(S): D2-ags prevent increased VP in OHSS rats by decreasing ovarian VEGF production, very likely through a D2-mediated post-transcriptional mechanism. Given the dose-dependent inhibitory effect of D2-ags on ovarian VEGF production reported herein, we infer that current OHSS therapies used in humans may be improved by increasing the intraovarian concentration of D2-ags in these patients.

Generation of multi-oocyte follicles in the peripubertal rat ovary: link to the invasive capacity of granulosa cells?

OBJECTIVE: To assess the presence and numbers of multi-oocyte follicles (MOFs) in the rat ovary at different stages of postnatal maturation. DESIGN: Animal (rat) study. SETTING: Research laboratory. ANIMAL(S): Female Wistar rats. INTERVENTION(S): Histologic/morphometric analyses in ovaries from infantile, juvenile, pubertal, and adult female rats. MAIN OUTCOME MEASURE(S): Numbers and characteristics of MOFs in rat ovaries at different stages of postnatal maturation. RESULT(S): Female rats displayed low numbers (<5/ovary) of MOFs in the infantile period (postnatal day [PND] 15). The occurrence of MOFs increased sharply by PND-21 and remained at high values (>15/ovary) up to PND-60, to decline thereafter by PND-90. The presence of irregularly shaped and connected adjacent follicles, together with the identification of ruptures at the follicle surface and the occasional invasion of the ovarian stroma by granulosa cells, strongly suggests that the majority of MOFs in peripubertal rats are generated by fusion of adjacent growing follicles. CONCLUSION(S): A new mechanism for the generation of MOFs linked to the potential invasive capacity of granulosa cells is proposed. The basis for the upsurge in the generation of MOFs during the peripubertal period and whether, as predictable, this phenomenon is applicable to other mammalian species warrant further investigation.

Distinct expression patterns predict differential roles of the miRNA-binding proteins, Lin28 and Lin28b, in the mouse testis: studies during postnatal development and in a model of hypogonadotropic hypogonadism.

Lin28 (also termed Lin28a) and Lin28b are related RNA-binding proteins, involved in the control of microRNA synthesis, especially of the let-7 family, with putative functions in early (embryo) development. However, their roles during postnatal maturation remain ill defined. Despite the general assumption that Lin28 and Lin28b share similar targets and functions, conclusive demonstration of such redundancy is still missing. In addition, recent observations suggest a role of Lin28 proteins in mammalian reproduction, which is yet to be defined. We document herein the patterns of RNA expression and protein distribution of Lin28 and Lin28b in mouse testis during postnatal development and in a model of hypogonadotropic hypogonadism as a result of inactivation of the kisspeptin receptor, Gpr54. Lin28 and Lin28b mRNAs were expressed in mouse testis across postnatal maturation, but their levels disparately varied between neonatal and pubertal periods, with peak Lin28 levels in infantile testes and sustained elevation of Lin28b mRNA in young adult male gonads, where relative levels of let-7a and let-7b miRNAs were significantly suppressed. In addition, Lin28 peptides displayed totally different patterns of cellular distribution in mouse testis: Lin28 was located in undifferentiated and type-A1 spermatogonia, whereas Lin28b was confined to spermatids and interstitial Leydig cells. These profiles were perturbed in Gpr54 null mouse testis, which showed preserved but irregular Lin28 signal and absence of Lin28b peptide, which was rescued by administration of gonadotropins, mainly hCG (as super-agonist of LH). In addition, increased relative levels of Lin28, but not Lin28b, mRNA and of let-7a/let-7b miRNAs were observed in Gpr54 KO mouse testes. Altogether, our data are the first to document the divergent patterns of cellular distribution and mRNA expression of Lin28 and Lin28b in the mouse testis along postnatal maturation and their alteration in a model of congenital hypogonadotropic hypogonadism. Our findings suggest distinct functional roles of these two related, but not overlapping, miRNA-binding proteins in the male gonad.

Evidences for the existence of a low dopaminergic tone in polycystic ovarian syndrome: implications for OHSS development and treatment.

CONTEXT: The dopamine/dopamine receptor 2 (D2/Drd2) pathway modulates vascular endothelial growth factor (VEGF)-dependent vascular permeability and angiogenesis in the ovary. Deregulation of the VEGF/VEGF receptor (VEGFR)-2 pathway leading to increased risk of ovarian hyperstimulation syndrome has been described in the ovary of patients suffering from polycystic ovarian syndrome (PCOS). OBJECTIVE: The objective of the study was to ascertain whether deregulation of the VEGF/VEGFR-2 might a least be partially due to abnormalities of the D2/Drd2 pathway in PCOS women. DESIGN: Dated, archived ovaries from PCOs and control group patients as well as human chorionic gonadotropin-stimulated luteinized granulosa cells form PCOS and non-PCOS oocyte patients were used. SETTING: The study was conducted at a private research center. PATIENTS OR OTHER PARTICIPANTS: PCOS and nonpolycystic ovarian patients and oocyte patients participated in the study. INTERVENTION(S): Human ovarian sections were stained against the Drd2 antibody. Human chorionic gonadotropin-stimulated luteinized granulosa cells (LGC) were cultured in the presence/absence and the Drd2 agonist cabergoline. MAIN OUTCOME MEASURE(S): Drd2 and vascularized stained area in the theca layer of antral (< 8 mm) and luteinized follicles was quantified. VEGF, D2, and its related metabolites were measured in the supernatant of cultured LGC by ELISA and HPLC, respectively. VEGFR-2 and Drd2 expressed by LGC was quantified through an In-Cell ELISA. RESULTS: Decreased Drd2 expression and increased vascularization in the theca layer of antral and luteinized follicles of PCOS ovaries was observed. A lower dopamine production and reduced efficacy of cabergoline in inhibiting VEGF secretion was uncovered in LGC from PCOS. CONCLUSIONS: Decreased dopaminergic tone as well as deregulated Drd2 signaling might explain higher VEGF and vascularization leading to increased ovarian hyperstimulation syndrome risk in PCOS.

El entorno virtual: un espacio para el aprendizaje colaborativo

Material cuyos autores MARTÍN, A.M.;DOMÍNGUEZ,M.; PARALERA,C.(2011) «El entorno virtual: un espacio para el aprendizaje colaborativo» [artículo en línea].EDUTEC,Revista Electrónica de Tecnología Educativa. Núm.35/Marzo 2011, analizan y describen el aprendizaje colaborativo como una metodología que trata de fomentar la competencia de “trabajar en grupo”. En este trabajo se aborda el estudio del aprendizaje en grupo dentro del contexto de las asignaturas virtuales y define al aprendizaje colaborativo como un entorno virtual que permite la interacción entre el alumnado y la interconexión y el desarrollo de habilidades relacionadas con la docencia on-line.

Necesidad de circuncisión o dilatación del prepucio. Estudio de 1.200 casos / The need of circumcision or prepuce dilation. A study with 1200 boys

Objetivos: Demostrar el incremento de la retractilidad del prepucio con la edad. Señalar la poca utilidad de la circuncisión y la dilatación forzada del prepucio en la infancia. Métodos: El desarrollo del prepucio y su retractilidad, a medida que avanza la edad, fueron evaluados en 1200 niños de 0 a 16 años. El prepucio fue catalogado en tipos I a V según fue de menor a mayor su retractilidad en todos los casos que habían sido o no dilatados previamente. Resultados: La retractilidad del prepucio en los niños menores de un año en el tipo I (no retráctil) fue 63,4 %, mientras en el tipo V (completamente retráctil) fue tan solo 3,7 %. Lo contrario se observó en los adolescentes (11 a 16 años) en los que el tipo I fue 0,9 %, mientras el tipo V se observó en 80,9 %. También se encontró que 309 niños (43,1%) de los 717 niños que habían sido dilatados forzadamente su prepucio, cuando eran mas pequeños, tenían prepucios tipos I al IV, es decir, habían adquirido nuevamente adherencias balano-prepuciales en el momento del examen para nuestra investigación. Se observó que 17 niños de los examinados (0,4%) estaban necesitados de que se les realizara circuncisión. Ningún niño sufrió infección del tractus urinario superior. Conclusiones: Todos los niños nacen con el prepucio cubriéndole el glande, si no tienen una anomalía congénita del pene, manteniendo unas adherencias entre ambas estructuras, las que van desapareciendo con la edad, siendo total la separación en la pubertad, en la mayoría de los niños. Por ello consideramos la circuncisión o la dilatación forzada del prepucio innecesaria en la mayoría de los niños (AU)

Objectives: To demonstrate the increase of preputial retractability with age. To point out the small usefulness of circumcision and preputial forced dilation during childhood. Methods: The development of the prepuce and its retractability were evaluated in 1200 boys between 0 and 16 years. The prepuce was classified as type I to V depending on its lower or higher retractability in all cases having been dilated previously or not. Results: Prepuce retractability in boys under one year was type I (not retractile} in 63.4%, whereas it was type V (completely retractile) in only 3.7%. The contrary was observed in adolescents (11 to 16 years), in which type I was 0.9% and type V was observed in 80.9%. It was also observed that 309 boys (43.1%) among the 717 with previous prepuce forced dilation, had types I to IV prepuces, so, they had acquired new balanopreputial adherences by the time of examination for our study. Seventeen boys (0.4%) required circumcision. No children suffered upper urinary tract infections. Conclusions: All boys are born with the prepuce covering the glans penis, keeping adherences between both structures, which disappear with age, being the detachment complete at the time of puberty in most boys. So, we consider circumcision or forced dilation of the prepuce unnecessary in most boys (AU)

Immunolocalization of beclin 1, a bcl-2-binding, autophagy-related protein, in the human ovary: possible relation to life span of corpus luteum.

Ovarian tissue homeostasis is maintained by highly regulated cyclic phases of cell proliferation/differentiation and programmed cell death. Compelling evidence indicates that both apoptotic and autophagic types of programmed cell death are involved in the regression of the corpus luteum (CL) in primate species. Beclin 1 is an autophagy-related protein that is involved in the inter-relationships between apoptosis and autophagy, through interaction with the anti-apoptotic protein bcl-2. We studied the presence and expression pattern of beclin 1 in the adult human ovary. In ovarian follicles, beclin 1 immunostaining was found in the theca layer, whereas granulosa cells were negative. After ovulation, beclin 1 immunostaining was present in both theca-lutein and granulosa-lutein areas. The expression of beclin 1 in granulosa-lutein cells was related to the functional and structural status of the CL, being strong at the early and mid luteal phases, barely detectable at the late luteal phase, and absent in granulosa-lutein cells in subsequent cycles. Our results indicated that beclin 1 expression was related to luteal cell survival rather than to cell death. Accordingly, persistent beclin 1 expression was found in granulosa-lutein cells under either physiological (i.e., CL of pregnancy) or pathological (irregularly regressing CL in climacteric women) conditions involving prolonged CL life span. Strong beclin 1 immunostaining was also found in ovarian androgen-producing cells (i.e., secondary interstitial and hilus cells). Our data thus suggest that beclin 1 plays important roles in the regulation of the life span of human CL and ovarian androgen-secreting cells, by maintaining autophagy at levels promoting cell survival rather than cell death.