Advanced non-squamous NSCLC with no actionable oncogenic driver in Spain: a cross-sectional descriptive analysis of data from the Thoracic Tumor Registry.

BACKGROUND: Non-small cell lung cancer (NSCLC) accounts for the vast majority of all diagnosed lung cancers. According to their histology, most NSCLCs are considered non-squamous cell carcinoma (NSCC), and up to 85% of the latter may lack either one of the two main actionable oncogenic drivers (i.e., EGFR mutations and ALK rearrangements). OBJECTIVE: Our analysis aimed to describe the clinical and epidemiological characteristics of Spanish patients suffering from NSCC with no actionable oncogenic driver in daily clinical practice. DESIGN: A retrospective, cross-sectional, descriptive analysis. METHODS: We analyzed the records of all Spanish patients with advanced NSCC diagnosed between January 2011 and January 2020 and included in the Spanish Thoracic Tumor Registry database. We evaluated the presence of metastasis and molecular profiling at the time of diagnosis and treatments received. We also assessed overall survival (OS) and progression-free survival (PFS) according to first-line treatment. RESULTS: One thousand seven hundred ninety-seven Spanish patients with NSCC were included. They were mainly men (73.2%), smokers (current [44.4%] and former [44.4%]) and presented adenocarcinoma histology (97.6%). Most patients had at least one comorbidity (80.4%) and one metastatic site (96.8%), and a non-negligible number of those tested were PD-L1 positive (35.2%). Notably, the presence of liver metastasis indicated a shorter median OS and PFS than metastasis in other locations (p < 0.001). Chemotherapy was more often prescribed than immunotherapy as first-, second-, and third-line treatment in that period. In first-line, the OS rates were similar in patients receiving either regimen, but PFS rates significantly better in patients treated with immunotherapy (p = 0.026). Also, a high number of patients did not reach second- and third-line treatment, suggesting the failure of current early diagnostic measures and therapies. CONCLUSIONS: This analysis of the most lethal tumor in Spain could highlight the strengths and the weaknesses of its clinical management and set the ground for further advances and research.

Evaluación de la estabilidad de parámetros hematológicos en muestras pediátricas bajo diferentes condiciones de almacenamiento determinados en un analizador Sysmex XN / Stability of hematological parameters in pediatric samples under different storage conditions using the Sysmex XN analyser / Avaliação de estabilidade de parâmetros hematológicos em amostras pediátricas sob diferentes condições de armazenamento determinados em um analisador Sysmex XN

Resumen Conocer la estabilidad de las muestras biológicas es esencial para obtener resultados confiables en el laboratorio de análisis clínicos. La Norma IRAM-ISO 15189:2023 establece que cada laboratorio debe estandarizar las condiciones de almacenamiento de las muestras. El objetivo de este trabajo fue determinar el tiempo y la temperatura óptimos para conservar muestras sanguíneas para la determinación de parámetros hematológicos en un analizador Sysmex XN 1000. Se procesaron muestras de sangre entera conservadas hasta 48 horas a temperatura ambiente y hasta 72 horas en heladera. De acuerdo a los resultados, para la determinación del hemograma, las muestras almacenadas a temperatura ambiente deben procesarse dentro de las 6-8 horas posextracción; los parámetros limitantes son aquellos influenciados por cambios en el volumen eritrocitario. En las muestras conservadas en heladera el análisis puede retrasarse hasta 48 horas y el recuento de plaquetas es el parámetro menos estable.

Abstract Knowing sample stability is essential to obtain reliable results in the clinical laboratory. The IRAM-ISO 15189:2023 Standard establishes that each laboratory must standardise the storage conditions of biological samples. This study was conducted to investigate the stability of haematological parameters using a Sysmex XN 1000 in samples stored for up to 48-72 hours at different temperatures. According to these results, the hematologic analytes should be processed in this laboratory within 6-8 hours after extraction if they are stored at room temperature. The limiting parameters are those influenced by changes in the erythrocyte volume. If storage is in a refrigerator, the analysis can be delayed up to 48 hours, being platelet count the limiting parameter.

Resumo Conhecer a estabilidade das amostras biológicas é essencial para obter resultados confiáveis no laboratório de exames clínicas. A Norma IRAM-ISO 15189:2023 estabelece que cada laboratório deve padronizar as condições de armazenamento das amostras. O objetivo deste trabalho foi determinar o tempo e a temperatura ideais para preservar amostras de sangue para a determinação de parâmetros hematológicos em um analisador em um Sysmex XN 1000. Para isso, foram processadas amostras de sangue total armazenadas por até 48 horas em temperatura ambiente e por até 72 horas em geladeira. De acordo com os resultados obtidos, para a determinação do hemograma, as amostras armazenadas em temperatura ambiente devem ser processadas dentro de 6-8 horas após a extração, sendo os parâmetros limitantes aqueles influenciados por alterações no volume eritrocitário. Nas amostras armazenadas em geladeira, a análise pode demorar até 48 horas, sendo a contagem de plaquetas o parâmetro menos estável.

SEOM-GEIS clinical guideline for gastrointestinal stromal tumors (2022).

Gastrointestinal stromal tumor (GIST) is the most common malignant neoplasm of mesenchymal origin, and a paradigmatic model for a successful rational development of targeted therapies in cancer. The introduction of tyrosine kinase inhibitors with activity against KIT/PDGFRA in both localized and advanced stages has remarkably improved the survival in a disease formerly deemed resistant to all systemic therapies. These guidelines are elaborated by the conjoint effort of the Spanish Society of Medical Oncology (SEOM) and the Spanish Sarcoma Research Group (GEIS) and provide a multidisciplinary and updated consensus for the diagnosis and treatment of GIST patients. We strongly encourage that the managing of these patients should be performed within multidisciplinary teams in reference centers.

Viral-Mediated Microbe Mortality Modulated by Ocean Acidification and Eutrophication: Consequences for the Carbon Fluxes Through the Microbial Food Web.

Anthropogenic carbon emissions are causing changes in seawater carbonate chemistry including a decline in the pH of the oceans. While its aftermath for calcifying microbes has been widely studied, the effect of ocean acidification (OA) on marine viruses and their microbial hosts is controversial, and even more in combination with another anthropogenic stressor, i.e., human-induced nutrient loads. In this study, two mesocosm acidification experiments with Mediterranean waters from different seasons revealed distinct effects of OA on viruses and viral-mediated prokaryotic mortality depending on the trophic state and the successional stage of the plankton community. In the winter bloom situation, low fluorescence viruses, the most abundant virus-like particle (VLP) subpopulation comprising mostly bacteriophages, were negatively affected by lowered pH with nutrient addition, while the bacterial host abundance was stimulated. High fluorescence viruses, containing cyanophages, were stimulated by OA regardless of the nutrient conditions, while cyanobacteria of the genus Synechococcus were negatively affected by OA. Moreover, the abundance of very high fluorescence viruses infecting small haptophytes tended to be lower under acidification while their putative hosts' abundance was enhanced, suggesting a direct and negative effect of OA on viral-host interactions. In the oligotrophic summer situation, we found a stimulating effect of OA on total viral abundance and the viral populations, suggesting a cascading effect of the elevated pCO2 stimulating autotrophic and heterotrophic production. In winter, viral lysis accounted for 30 ± 16% of the loss of bacterial standing stock per day (VMMBSS) under increased pCO2 compared to 53 ± 35% in the control treatments, without effects of nutrient additions while in summer, OA had no significant effects on VMMBSS (35 ± 20% and 38 ± 5% per day in the OA and control treatments, respectively). We found that phage production and resulting organic carbon release rates significantly reduced under OA in the nutrient replete winter situation, but it was also observed that high nutrient loads lowered the negative effect of OA on viral lysis, suggesting an antagonistic interplay between these two major global ocean stressors in the Anthropocene. In summer, however, viral-mediated carbon release rates were lower and not affected by lowered pH. Eutrophication consistently stimulated viral production regardless of the season or initial conditions. Given the relevant role of viruses for marine carbon cycling and the biological carbon pump, these two anthropogenic stressors may modulate carbon fluxes through their effect on viruses at the base of the pelagic food web in a future global change scenario.

Impacto económico en el medio odontológico durante la pandemia del COVID-19: revisión integradora / Economic impact in the dental field during COVID-19 pandemic: integrative review

La pandemia por COVID-19 no sólo ha generado un impacto negativo en la salud, sino que la economía global también se ha visto mermada, afectando más a los países subdesarrollados. Con relación a estos daños en las finanzas de los profesionales de la salud, existen algunos efectos que derivan de la pandemia COVID-19, los cuales tienen una fuerte repercusión en la economía de todos los trabajadores a nivel mundial y el ámbito odontológico no es la excepción. Esta revisión se obtuvo mediante la búsqueda de la información en una exploración electrónica en las bases de datos PubMed, Cochrane Library, LILACS, SciELO y Latindex. El impacto económico derivado de esta pandemia, sin lugar a dudas, ha afectado la economía de los odontólogos de práctica pública y privada, por lo que la toma de decisiones en la odontología debe contemplar un uso equilibrado de los recursos financieros (AU)

The COVID-19 pandemic has not only generated a negative impact on health, but the global economy has also been reduced, being the underdeveloped countries the most affected ones. In relation to these damages in the finances of health professionals, there are some effects that derive from the COVID-19 pandemic, having a strong impact on the economy of all workers worldwide and the dental field is no exception. This review was obtained by searching the information through an electronic examination in databases like PubMed, Cochrane Library, LILACS, SciELO and Latindex databases. The economic impact derived from this pandemic has undoubtedly affected the economy of dentists in public and private practice, so that decision-making in dentistry must consider a balanced use of financial resources (AU)

Combination of gefitinib and olaparib versus gefitinib alone in EGFR mutant non-small-cell lung cancer (NSCLC): A multicenter, randomized phase II study (GOAL).

OBJECTIVES: Progression-free survival (PFS) and response rate to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) varies in patients with non-small-cell lung cancer (NSCLC) driven byEGFR mutations, suggesting that other genetic alterations may influence oncogene addiction. Low BRCA1 mRNA levels correlate with longer PFS in erlotinib-treated EGFR-mutant NSCLC patients. Since the poly (ADP-ribose) polymerase (PARP) inhibitor, olaparib, may attenuate and/or prevent BRCA1 expression, the addition of olaparib to gefitinib could improve outcome in EGFR-mutant advanced NSCLC. MATERIALS AND METHODS: GOAL was a multicenter, randomized phase IB/II study performed in two countries, Spain and Mexico. Eligible patients were 18 years or older, treatment-naïve, pathologically confirmed stage IV NSCLC, with centrally confirmed EGFR mutations and measurable disease. Patients were randomly allocated (1:1) to receive gefitinib 250 mg daily or gefitinib 250 mg daily plus olaparib 200 mg three times daily in 28-day cycles. The primary endpoint was PFS. Secondary endpoints included overall survival (OS), response rate, safety and tolerability. RESULTS: Between September 2013, and July 2016, 182 patients underwent randomization, 91 received gefitinib and 91 received gefitinib plus olaparib. There were no differences in gender, age, smoking status, performance status, presence of bone and brain metastases or type ofEGFR mutation. Median PFS was 10.9 months (95 % CI 9.3-13.3) in the gefitinib arm and 12.8 months (95 % CI 9.1-14.7) in the gefitinib plus olaparib arm (HR 1.38, 95 % CI 1.00-1.92; p = 0.124). The most common adverse events were anemia, 78 % in gefitinib plus olaparib group, 38 % in gefitinib arm, diarrhea, 65 % and 60 %, and fatigue, 40 % and 32 %, respectively. CONCLUSIONS: The gefitinib plus olaparib combination did not provide significant benefit over gefitinib alone. The combination's safety profile showed an increase in hematological and gastrointestinal toxicity, compared to gefitinib alone, however, no relevant adverse events were noted.

Influencia de los anticoagulantes EDTAK² y EDTAK³ en los resultados del hemograma / Influence of the EDTAK² and EDTAK³ anticoagulants on hematology testing results / Influência dos anticoagulantes EDTAK² e EDTAK³ nos resultados do hemograma

El International Council for Standardization in Haematology (ICSH) recomienda el uso de ácido etilendiaminotretaacético dipotásico (EDTAK2) como anticoagulante para el hemograma, mientras que el Clinical and Laboratory Standards Institute (CLSI) EDTAK2 o ácido etilendiaminotetraacético tripotásico (EDTAK3). El objetivo de este trabajo fue evaluar la influencia del tipo de sal de EDTA utilizado en la variación de los resultados de los parámetros hematológicos. Se recolectaron 24 muestras por venopunción, de cada una se cargó una alícuota en EDTAK3 y otra en EDTAK2. De los 23 parámetros evaluados en el autoanalizador Sysmex XN1000 (Roche Diagnostics), sólo los de la serie roja presentaron diferencias estadísticamente significativas en las muestras pareadas (p<0,05). El sesgo superó las especificaciones de calidad de Variabilidad Biológica Mínima para hematocrito (2,9%) y concentración de hemoglobina corpuscular media (1,7%), de Variabilidad Biológica Deseable para el volumen corpuscular medio (1,7%) y Variabilidad Biológica Óptima para hemoglobina (1,2%) y recuento de eritrocitos (1,2%). No se hallaron diferencias significativas en los parámetros de la serie blanca, ni en los plaquetarios y tampoco en los reticulocitarios. Para disminuir el error preanalítico, cada laboratorio debe estandarizar la extracción de los hemogramas empleando un único tipo de anticoagulante.

The International Council for Standardization in Haematology (ICSH) currently supports de use of ethylenediaminetetraacetic acid dipotassium (EDTAK2) anticoagulant for hematology testing, while the Clinical and Laboratory Standards Institute (CLSI) recommends EDTAK2 or ethylenediaminetetraacetic acid tripotassium (EDTAK3). The objective of this study was to evaluate the influence of the EDTA formulations in the results of hematologic parameters. A total of 24 samples were collected by venous puncture and two aliquots were loaded: one in EDTAK3 and another in EDTAK2. Of the 23 hematologic parameters tested with the use of Sysmex XN1000 (Roche diagnostics) hematologic analyser, only those in the red series showed statistically significant differences in the paired samples (p < 0.05). The bias exceeded the quality specifications of Minimum Biological Variability for hematocrit (2.9%) and mean corpuscular hemoglobin concentration (1.7%), Desirable Biological Variability for the mean corpuscular volume (1.7%) and Biological Variability Optimal for hemoglobin (1.2%) and erythrocyte count (1.2%). No significant differences were found in the parameters of white series, neither platelets, nor reticulocytes. To reduce the preanalytical error, each laboratory should standardize the extraction for complete blood cell count using a single type of anticoagulant.

A International Council for Standardization in Haematology (ICSH) recomenda a utilização do ácido etileno diamino treta-acético dipotássico (EDTAK2) como anticoagulante para hemograma, enquanto que a Clinical and Laboratory Standards Institute (CLSI) EDTAK2 ou ácido etileno diamino treta-acético tripotássico (EDTAK3). O objetivo deste trabalho foi avaliar a influência do tipo de sal de EDTA utilizado na variação dos resultados dos parâmetros hematológicos. Foram recolhidas 24 amostras por venopunção, de cada uma se carregou uma alíquota de EDTAK3 e outra de EDTAK2. Dos 23 parâmetros avaliados no autoanalisador Sysmex XN1000 (Roche Diagnostics), apenas aqueles da série vermelha apresentaram diferenças estatisticamente significativas nas amostras emparelhadas (p<0,05). O viés superou as especificações de qualidade da Variabilidade Biológica Mínima para o hematócrito (2,9%) e concentração de hemoglobina corpuscular média (1,7%), de Variabilidade Biológica Desejável para o volume corpuscular médio (1,7%) e Variabilidade Biológica Ótima para a hemoglobina (1,2%) e contagem de eritrócitos (1,2%). Não foram encontradas diferenças significativas nos parâmetros da série branca, nem nos plaquetários, nem nos reticulocitários. Para reduzir o erro pré-analítico, cada laboratório deve padronizar a extração dos hemogramas usando um único tipo de anticoagulante.

Multifocal Lymphangioendotheliomatosis with Thrombocytopenia: Presentation of Two Cases Treated with Sirolimus.

Multifocal lymphangioendotheliomatosis with thrombocytopenia (MLT) is a rare disease characterized by congenital and progressive vascular lesions of the skin and gastrointestinal tract that may be associated with thrombocytopenia and possibly life-threatening gastrointestinal bleeding. Reports published on the disease and treatment strategies are scarce. We present two cases of MLT treated with sirolimus.

[Topographical-medical study on the Virgin of Guadalupe's ayate. Unpublished paper from a New Spanish sage]. / Estudio topográfico-médico sobre el ayate de la virgen de Guadalupe. Escrito inédito de un sabio novohispano.

In the context of medical studies, the topographic aspect (a study about the special circumstances that contributes to the beginning, develop, and ending of diseases belonging to a country) acquired particular significance in New Spain through the work of Diego Cisneros (1618). Juan de Melgarejo, professor, protophysician, priest, and author of two medical writings, continued with the work of Cisneros. The one that concerns us in this paper is called Parecer que ejecutó el Dr. D. Juan de Melgarejo por mandato de su Santidad y orden del Proto Medicato sobre la incorrupción del Ayate de María Santísima de Guadalupe, por los años de 1666. This text remained unpublished and it is closely related to the line of Melgarejo's works on the Virgin of Guadalupe. In this work he analyzes the ayate (cloak) of Juan Diego from a topographic perspective inserted in theoretical and experimental aspects of the hippocratical-galenic slope that prevailed in the medicine perspective of the Baroque New Spain. This research includes aspects on the university education of the author and regarding his tasks as protophysician, one of which was, precisely, the development of the Guadalupean manuscript. All the sources we have used are original. They come from México's General Archive of the Nation, and they all were interpreted by the author. They show the training given by doctors at the Royal and Pontifical University of Mexico and the link between this and the tasks of the Royal Protomedicato Tribunal.

En el marco de los estudios médicos, la vertiente topográfica (estudio detenido de las circunstancias especiales que contribuyen al desarrollo, curso y desenlace de las enfermedades propias de un país) adquirió especial relevancia en la Nueva España a partir de la obra de Diego Cisneros (1618). Un continuador de ella fue el doctor Juan de Melgarejo, catedrático, protomédico, sacerdote y autor de dos escritos médicos. El texto al que se hace referencia en este artículo, denominado Parecer que ejecutó el Dr. D. Juan de Melgarejo por mandato de su Santidad y orden del Proto Medicato sobre la incorrupción del Ayate de María Santísima de Guadalupe, por los años de 1666, había permanecido inédito y está estrechamente relacionado con la línea de trabajos guadalupanos de Juan de Melgarejo. En él analiza el ayate de la imagen guadalupana desde una perspectiva médico-topográfica inserta en aspectos teóricos y experimentales, en la vertiente hipocrática-galénica que prevalecía en la medicina novohispana del barroco. La presente investigación incluye los aspectos de la formación universitaria del autor y de sus tareas como protomédico, una de las cuales fue la elaboración del escrito guadalupano. Las fuentes a las que se recurrió son todas originales, proceden de los fondos del Archivo General de la Nación de México, y fueron interpretadas por la autora. En esas fuentes se describe cómo se llevaba a cabo la formación de los médicos en la Real y Pontificia Universidad de México y la vinculación entre ella y las tareas del Real Tribunal del Protomedicato.

[A New Spain medication: magisterial oil and salutiferous liquor]. / Un medicamento novohispano: aceite magistral y licor salutífero.

During the 16th century, physicians who lived and cured New Spain's population, attended their profession privately and institutionally; few of them were authors of medical works, and it is not easy to discover one who invented and used successfully medicament of his own development. We have found one, Joan Martel, a Spaniard, who came to New Spain and here cured and served. He invented and used a salutiferous oil and liquor widely accepted by other physicians, but mainly by the neighbors of Mexico City. In reward for his successfully medicament, he received the appointment of physician at the Royal Court Prison. This article is dedicated to him, and his until now unknown life, his work and the relation between his oil with a similar product in Spain. This study forms part of larger social-historical research that deals with "Physicians in New Spain, their social and professional roles (16 to 19 centuries)."

Pandemic A/H1N1 influenza: transmission of the first cases in Spain.

INTRODUCTION: Pandemic A/H1N1 influenza emerged in Mexico at the end of March 2009. Since then, it is still important to provide evidences that contributed to the international spread of the virus and to ascertain the attack rate of this new strain of influenza among the first cases in Spain that led to identify the first transmission in Europe. METHODS: Three pandemic A/H1N1 influenza groups related to an overseas flight were studied: 71 student group, 94 remaining passengers, and 68 contacts of confirmed cases. The attack rate with their 95% confidence interval (CI) among the student group and contacts was calculated. On April 26th, when the first cases were notified, strong preventive measures were implemented among the student group and the contacts of the confirmed cases. RESULTS: On 27th April, the first pandemic A/H1N1 influenza cases confirmed in Spain were three students that came back from Mexico by airplane. A student generated the first native case in Spain and one of the first cases in Europe. Similar attack rates were found between the student group (14.1%; CI: 12.1-16.1) and their contacts (13.2%; CI: 4.4-22.0), but no cases among remaining passengers were detected, suggesting low transmission risk during air travel. CONCLUSION: The first cases of pandemic A/H1N1 influenza in Spain were imported by airplane from Mexico. Preventive efforts to reduce the impact of the influenza influenced that primary and secondary rates were lower than first estimations by WHO.

Un cirujano en las Cárceles del Santo Oficio, Juan Antonio Xarillo, representante de asceno socio-económico en la sociedad novohispana del siglo XVIII / A surgeon in the prisons of the Inquisition, Juan Antonio Xarillo, representing the socioeconomic progress in the colonial society of the XVIII century

En el siglo XVIII, las cárceles del Tribunal del Santo Oficio de la Inquisición disponían de cirujanos para atender a sus reos. Juan Antonio Xarillo destacó en ese grupo por su alto nivel socio-económico. Dicha posición fue producto de actividades distintas a la cirugía. Gracias a los inventarios de la época sabemos que poseyó casas, terrenos, numerosos libros, instrumentos quirúrgicos y utensilios de uso cotidiano. (AU)

Convento real de Nuestra Señora de la Concepción, la atención médico-quirúrgica de su población femenin / Convent of Nuestra Señora de la Concepción: Medical-surgical care for the female population

The monasteries in New Spain dedicated to women were the result of the ideals of conquerors and religious people, but also of the rest of the population of the large cities, mainly, Mexico City. Here the first institution of nuns was founded as the Monastery of [quot ]Nuestra Señora de la Concepción,[quot ] thanks to the archbishop Juan de Zumárraga. From it, the expansion of new and different foundations was constant and, to give support and refuge to the female population in need of housing due to poverty or abandonment, were their main tasks. Inside the monasteries and behind their tall walls, all persons received spiritual and medical attention. The latter was in the hands of physicians, apothecaries and surgeon who cured all [quot ]external[quot ] disorders and, during the first years of existence of all the monasteries, they were mainly barbers. The purpose of this article is to discover who the surgeons were who served the first female monastery and this study constitutes part of a larger research study that not only studied all monasteries both for men and women, but also the large number of surgeons who lived and worked in New Spain. The number of surgeons serving in this monastery were all those that we were able to find.

[Convent of "Nuestra Señora de la Concepción": Medical-surgical care for the female population]. / Convento real de Nuestra Señora de la Concepción, la atención médico-quirúrgica de su población femenin.

The monasteries in New Spain dedicated to women were the result of the ideals of conquerors and religious people, but also of the rest of the population of the large cities, mainly, Mexico City. Here the first institution of nuns was founded as the Monastery of "Nuestra Señora de la Concepción," thanks to the archbishop Juan de Zumárraga. From it, the expansion of new and different foundations was constant and, to give support and refuge to the female population in need of housing due to poverty or abandonment, were their main tasks. Inside the monasteries and behind their tall walls, all persons received spiritual and medical attention. The latter was in the hands of physicians, apothecaries and surgeon who cured all "external" disorders and, during the first years of existence of all the monasteries, they were mainly barbers. The purpose of this article is to discover who the surgeons were who served the first female monastery and this study constitutes part of a larger research study that not only studied all monasteries both for men and women, but also the large number of surgeons who lived and worked in New Spain. The number of surgeons serving in this monastery were all those that we were able to find.

ER-bound PTP1B is targeted to newly forming cell-matrix adhesions.

Here, we define the mechanism through which protein tyrosine phosphatase 1B (PTP1B) is targeted to cell-matrix adhesion sites. Green fluorescent protein (GFP)-labeled PTP1B bearing the substrate-trapping mutation D181A was found in punctate structures in lamellae. The puncta co-localized with focal adhesion kinase (FAK) and Src, and defined the distal tips of cell-matrix adhesion sites identified with paxillin and vinculin. PTP1B is largely associated with the external face of the endoplasmic reticulum (ER) and the puncta develop from ER projections over cell-matrix adhesion sites, a process dependent on microtubules. Deletion of the ER-targeting sequence resulted in cytosolic localization and altered the distribution of PTP1B at cell-matrix foci, whereas mutations disrupting interactions with Src homology 3 (SH3) domains, and the insulin and cadherin receptors had no effect. PTP1B recognizes substrates within forming adhesion foci as revealed by its preferential association with paxillin as opposed to zyxin-containing foci. Our results suggest that PTP1B targets to immature cell-matrix foci in newly forming lamellae by dynamic extensions of the ER and contributes to the maturation of these sites.

Uso da bromocriptina associado a hiperestimulação ovariana controlada em pacientes más respondedoras / Bromocriptine method associated with ovarian stimulation in poor responder patients

OBJETIVO: avaliar a resposta ovariana de pacientes más respondedoras submetidas ao método da bromocriptina. MÉTODOS: foi realizado estudo prospectivo com 10 pacientes más respondedoras em programa de fertilização in vitro. Pacientes endocrinologicamente normais com menos de 38 anos de idade, que apresentaram ciclos anteriores de má resposta a hiperestimulação ovariana controlada, foram submetidas a 12 ciclos com o método da bromocriptina. O referido método utilizou a bromocriptina, um agonista dopaminérgico, no ciclo precedente com a finalidade de bloquear a produção da prolactina. Ao interromper a medicação no início do ciclo de hiperestimulação ovariana conseguiu-se um efeito rebote da prolactina que otimizou a sua concentração sérica, melhorando a qualidade dos oócitos e embriões. Foram analisadas as concentrações séricas de prolactina e estradiol, o número de folículos produzidos, o número e a qualidade dos oócitos captados e embriões clivados e as taxas de fertilização e gravidez. RESULTADOS: foi observada redução na quantidade de ampolas de gonadotrofinas utilizadas, nos dias de indução, melhora no recrutamento folicular, na captação de oócitos, na morfologia dos embriões e nas taxas de fertilização e gravidez. A taxa de fertilização foi de 77,7 por cento, a taxa de gravidez 44,4 por cento e a taxa de bebê em casa de 25 por cento. CONCLUSÕES: este estudo sugere que o método da bromocriptina melhora o recrutamento folicular e o desenvolvimento embrionário, resultando em aumento da taxa de fertilização e gravidez em pacientes más respondedoras quando comparado com o esquema tradicional de hiperestimulação ovariana. Estudos com maior casuística controlada são necessários para se confirmarem os dados aqui encontrados.

[The venerable Varón Gregorio López, impact of his life and work throughout 400 years, 1562-2000]. / El venerable Varón Gregorio López, repercusiones de su vida y obra a lo largo de cuatrocientos años, 1562-2000.

During the second half of the 16th century in New Spain, there was a peculiar but versatile man named Gregorio López whose ascetic lifestyle, remarkable erudition and talent granted him an important place in history to date. The aim of this work was to focus attention on two aspects that have been ignored by contemporary historians. On the one hand, we will refer to Lopez's medical works, known as Tesoro de Medicinas (A Treasure of Medicines), a piece that although it is still immersed within the hypocraticgalenic tradition, continues to be highly valued. On the other hand, we found a vast amount of historiographic works that support the case for his beautification that began just 24 years after his death in 1596. The contribution we now make is divided into two parts for better understanding of the subject. We must emphasize, however, that both the exciting life this "Venerable Man" (Venerable Varón) led and the repercussions his deeds had, demonstrate an extraordinary coherence between the learned and the mystical man that he was. Gregorio López always maintained a remarkable social and religious presence, not only throughout the three centuries of colonial rule in Mexico, but also during the subsequent two hundred years that followed the struggle for Independence.

Social context for workplace health promotion: feasibility considerations in Costa Rica, Finland, Germany, Spain and Sweden.

We constructed a simple, flexible procedure that facilitates the pre-assessment of feasibility of workplace health promotion (WHP) programmes. It evaluates cancer hazards, workers' need for hazard reduction, acceptability of WHP, and social context. It was tested and applied in 16 workplace communities and among 1085 employees in industry, construction, transport, services, teaching and municipal works in Costa Rica, Finland, Germany, Spain and Sweden. Social context is inseparable from WHP. It covers workers' organizations and representatives, management, safety committees, occupational health services, health and safety enforcement agencies, general health services, non-government organizations, insurance systems, academic and other institutions, regulatory stipulations pertaining WHP, and material resources. Priorities, risk definitions, attitudes, hazard profiles, motivations and assessment methods were highly contextual. Management preferred passive interventions, helping cover expert costs, participating in planning and granting time. Trade unions, workers' representatives, safety committees and occupational health services appeared to be important operational partners. Occupational health services may however be loaded with curative and screening functions or be non-existent. We advocate participatory, multifaceted WHP based on the needs and empowerment of the workers themselves, integrating occupational and lifestyle hazards. Workforce in irregular and shift work, in agriculture, in small enterprises, in the informal sector, and immigrant, seasonal and temporary workers represent groups in need of particular strategies such as community health promotion. In a more general framework, social context itself may become a target for intervention.

Comparaçäo entre três escores embrionários como fator prognóstico do sucesso em fertilizaçäo in vitro / Comparison between three embryo scoring systems as predictive of the outcome of in vitro fertilization

OBJETIVO: avaliar três sistemas de escore embrionário para embriöes de 3º dia e correlacioná-los com resultados positivos da técnica de fertilizaçäo in vitro. MÉTODO: estudo retrospectivo desenvolvido pelo programa de fertilizaçäo in vitro do Hospital das Clínicas da Faculdade de Medicina de Ribeiräo Preto - USP. Foram incluídas 137 pacientes submetidas a fertilizaçäo in vitro e transferência de 439 embriöes. Os principais resultados avaliados foram taxa de gravidez e taxa de implantaçäo. RESULTADOS: nos três métodos observou-se diferença significativa no escore embrionário entre o grupo de grávidas (n=53) e näo grávidas (n=84) (p<0,0001). No escore 1, avaliando-se apenas o número de células, observou-se maior taxa de gravidez (70 por cento) e taxa de implantaçäo (42 por cento) nas transferências de embriöes com média dos blastômeros acima de 8. O escore 2, baseado num escore total de quatro pontos (clivagem, número de blastômeros, fragmentaçäo e simetria), mostrou aumento nas taxas de gravidez (52,8 por cento) e implantaçäo (31 por cento) nos escores acima de 2. No escore 3, baseado no número de células e no grau morfológico, também as taxas de gravidez e de implantaçäo elevaram-se de acordo com o aumento do escore médio dos embriöes transferidos. CONCLUSÄO: Os três sistemas de escore avaliados em embriöes de 3º dia, correlacionaram-se positivamente com taxa de gravidez e taxa de implantaçäo