Identification and management of prediabetes: results of the Latin America Strategic Prediabetes Meeting.

To understand the status of prediabetes diagnosis and treatment in Latin America and to evaluate the use of metformin for diabetes prevention in this context. A panel of 15 diabetes experts from seven countries in Latin America met on 14 - 15 August 2014 in Lima, Peru, to review the available literature, discuss the role of prediabetes in type 2 diabetes mellitus and cardiovascular disease, analyze collected information, and make conclusions for prediabetes diagnosis and treatment in Latin America. Prediabetes diagnosis, screening, and treatment, including lifestyle changes, pharmacological treatment, and cost-effectiveness were discussed. Five resulting statements were issued for Latin America: prediabetes is a clinical and public health problem; health care systems do not currently diagnose/treat prediabetes; use of prediabetes risk detection tools are needed region-wide; treatment includes lifestyle changes, multidisciplinary education, and metformin; and registries of patient records and further studies should be supported. The expert panel concluded that in Latin America, preventive treatment through lifestyle changes and metformin are cost-effective interventions. It is important to improve prediabetes identification and management at the primary care level.

Comprender el estado del diagnóstico y el tratamiento de la prediabetes en América Latina y evaluar el uso de la metformina para la prevención de la diabetes en este contexto.Un panel de 15 expertos en diabetes de siete países de América Latina se reunió del 14 al 15 de agosto de 2014 en Lima, Perú, para revisar la literatura disponible, discutir el papel de la prediabetes en la diabetes mellitus tipo 2 y la enfermedad cardiovascular, analizar la información recolectada y formular conclusiones para el diagnóstico y el tratamiento de la prediabetes en América Latina.Se analizaron el diagnóstico, el tamizaje y el tratamiento de la prediabetes, inclusive los cambios en el estilo de vida, el tratamiento farmacológico y la relación costo-eficacia. Se emitieron cinco conclusiones para América Latina: la prediabetes es un problema clínico y de salud pública; los sistemas de atención de la salud actualmente no diagnostican o no tratan la prediabetes; el uso de herramientas de detección del riesgo de prediabetes es necesario en toda la región; el tratamiento incluye cambios en el estilo de vida, educación multidisciplinaria y metformina; y se debe brindar apoyo para llevar registros de historias clínicas y realizar estudios adicionales.El panel de expertos concluyó que en América Latina el tratamiento preventivo basado en cambios en el estilo de vida y administración de metformina son intervenciones eficaces en relación al costo. Es importante mejorar la identificación y el manejo de la prediabetes en el nivel de atención primaria.

Entender o estado do diagnóstico e tratamento do prediabetes na América Latina e avaliar o uso de metformina para prevenção de diabetes neste contexto.Um painel de 15 especialistas em diabetes de sete países da América Latina reuniu-se de 14 a 15 de agosto de 2014 em Lima, Peru, para analisar a literatura disponível, discutir o papel do prediabetes em diabetes mellitus tipo 2 e doenças cardiovasculares, analisar informações coletadas e fazer conclusões para o diagnóstico e tratamento do prediabetes na América Latina.O diagnóstico, rastreio e tratamento pré-diabetes, incluindo mudanças de estilo de vida, tratamento farmacológico e custo-efetividade foram discutidos. Foram emitidas cinco conclusões resultantes para a América Latina: o prediabetes é um problema clínico e de saúde pública; os sistemas de saúde atualmente não diagnosticam/tratam prediabetes; o uso de ferramentas de detecção de risco de prediabetes é necessário em toda a região; o tratamento inclui mudanças de estilo de vida, educação multidisciplinar e metformina; e devem ser suportados registros de pacientes e outros estudos.O painel de especialistas concluiu que na América Latina, o tratamento preventivo através de mudanças de estilo de vida e metformina são intervenções efetivas em relação ao custo. É importante melhorar a identificação e gestão do prediabetes no nível de atenção primária.

A mitochondria-K+ channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth.

The unique metabolic profile of cancer (aerobic glycolysis) might confer apoptosis resistance and be therapeutically targeted. Compared to normal cells, several human cancers have high mitochondrial membrane potential (DeltaPsim) and low expression of the K+ channel Kv1.5, both contributing to apoptosis resistance. Dichloroacetate (DCA) inhibits mitochondrial pyruvate dehydrogenase kinase (PDK), shifts metabolism from glycolysis to glucose oxidation, decreases DeltaPsim, increases mitochondrial H2O2, and activates Kv channels in all cancer, but not normal, cells; DCA upregulates Kv1.5 by an NFAT1-dependent mechanism. DCA induces apoptosis, decreases proliferation, and inhibits tumor growth, without apparent toxicity. Molecular inhibition of PDK2 by siRNA mimics DCA. The mitochondria-NFAT-Kv axis and PDK are important therapeutic targets in cancer; the orally available DCA is a promising selective anticancer agent.

Association of genes to genetically inherited diseases using data mining.

Although approximately one-quarter of the roughly 4,000 genetically inherited diseases currently recorded in respective databases (LocusLink, OMIM) are already linked to a region of the human genome, about 450 have no known associated gene. Finding disease-related genes requires laborious examination of hundreds of possible candidate genes (sometimes, these are not even annotated; see, for example, refs 3,4). The public availability of the human genome draft sequence has fostered new strategies to map molecular functional features of gene products to complex phenotypic descriptions, such as those of genetically inherited diseases. Owing to recent progress in the systematic annotation of genes using controlled vocabularies, we have developed a scoring system for the possible functional relationships of human genes to 455 genetically inherited diseases that have been mapped to chromosomal regions without assignment of a particular gene. In a benchmark of the system with 100 known disease-associated genes, the disease-associated gene was among the 8 best-scoring genes with a 25% chance, and among the best 30 genes with a 50% chance, showing that there is a relationship between the score of a gene and its likelihood of being associated with a particular disease. The scoring also indicates that for some diseases, the chance of identifying the underlying gene is higher.

[Effectiveness and safety of the surgical closure of permeable arteriosus conduct by the general pediatric surgeon: clinical trial]. / Eficacia y seguridad del cierre quirúrgico del conducto arterioso permeable por el cirujano pediatra general: ensayo clínico.

Antecedentes: El conducto arterioso permeable (CAP) es un defecto cardiaco congénito y se considera un problema de salud pública. Se presenta en un alto porcentaje de recién nacidos y en algunos mayores de 1 mes. El cierre farmacológico es el tratamiento inicial preferido, ya que ha tenido excelentes resultados; sin embargo, en aquellos casos en los que no es posible, está indicado el cierre quirúrgico. Objetivo: Evaluar la eficacia y la seguridad del cierre quirúrgico del CAP por cirujanos pediatras sin especialidad en cirugía cardiovascular. Método: Ensayo clínico realizado en pacientes del Hospital General de Occidente, centro hospitalario público de segundo nivel, con diagnóstico de CAP, que requirieron corrección quirúrgica. Se revisaron en forma retrospectiva los expedientes de enero de 2001 a diciembre de 2018. Resultados: Se incluyeron 224 pacientes divididos en dos grupos: grupo I, con 184 (82%) recién nacidos, y grupo II, con 40 (18%) niños grandes de 2 meses a 8 años de edad. A todos se les realizó cierre quirúrgico: 3 por toracoscopía y 221 por toracotomía posterolateral izquierda. Presentaron complicaciones 36 pacientes, lo que representa el 16% del total; solo el 5.3% fueron complicaciones mayores. Fallecieron 24 pacientes en el posoperatorio, lo que representa una mortalidad del 10.7%; ninguno falleció por complicaciones transquirúrgicas. El CAP es un defecto cardíaco congénito que se presenta en alto porcentaje en pacientes prematuros. El cierre farmacológico es el principal tratamiento por tener excelentes resultados en recién nacidos; sin embargo, en aquellos casos en los que no sea posible está indicado el cierre quirúrgico. Todos los pacientes fueron operados por cirujanos pediatras generales, con una sobrevida global del 92%. Conclusiones: En los hospitales donde no hay cirujano cardiovascular pediátrico ni cardiólogo intervencionista, la corrección quirúrgica del CAP puede ser llevada a cabo por un cirujano pediatra. La técnica es reproducible, fácil de realizar y con mínimas complicaciones. Background: The Patent Ductus Arteriosus (PDA) is congenital heart defect and is considered a public health problem. It occurs in a high percentage of newborns and in some older than 1 month. Pharmacological closure is the preferred initial treatment, as it has had excellent results; however, in those cases where it is not possible, surgical closure is indicated. Objective: The objective is to evaluate the efficacy and safety of the surgical closure of the patent PDA when it is carried out by pediatric surgeons without specialization in cardiovascular surgery. Methods: This study was conducted at the West General Hospital, a 2nd level public hospital, with the diagnosis of patent ductus arteriosus that required surgical correction. For the collection of the information, the files from January 2001 to December 2018 were retrospectively reviewed. Results: 224 patients were included; divided into two groups: Group I: 184 (82%) "newborns" and Group II: 40 (18%) "big children" with ages from 2 months to 8 years. All had a surgical closure; 3 by thoracoscopy and 221 by left posterolateral thoracotomy. 36 patients presented complications representing 16% of the total of patients, only 5.3% were major complications. 24 patients died in the postoperative period, representing a mortality of 10.7%, none died due to trans-surgical complications. PDA is a congenital heart defect that occurs in a high percentage of premature patients. The pharmacological closure is the principal treatment because it has had excellent results in newborns; however, in those cases where it is not possible, surgical closure it´s indicated. All patients were operated by general pediatric surgeons, with a global survival of 92%. Conclusions: We conclude that in hospitals where there is no pediatric cardiovascular surgeon or interventional cardiologist, the surgical correction of the PDA can be carried out by a general pediatric surgeon. The technique is reproducible, easy to perform and with minimal complications.

Current situation of congenital heart diseases in two public hospitals in the state of Jalisco.

Introduction: Congenital heart disease represents a public health issue worldwide. Objective: To know the number of patients with heart disease treated in two public hospitals of the State of Jalisco, as well as the mortality and resources available to participating hospitals for the care of these patients in the period from 2015 to 2018; the information was requested to the -National Transparency Platform, and the database of pediatric cardiology services and pediatric cardiovascular surgery of the participating hospitals were also reviewed. Results: The second level hospital has human resources, but not the material to attend to these patients; so it is not possible to offer any type of palliative or corrective treatment. A total of 624 patients were evaluated, of which 92.2% corresponded to non-critical heart disease; overall mortality was 12% but in critical heart disease it was 79.5%. The third level hospital has human and material resources to care for these patients. During the study period, 289 operations were performed and the overall mortality was 20.4%. Conclusion: Congenital heart disease in the State of Jalisco is an important cause of mortality, with a high incidence and a very limited resolution capacity since the health services in the State of Jalisco for the care of these patients are insufficient and inadequate. It is essential to strengthen the health system for the care for these patients.

Introducción: Las cardiopatías congénitas representan un problema de salud pública a nivel mundial. Objetivo: Conocer la cantidad de pacientes cardiópatas atendidos en dos hospitales públicos del estado de Jalisco, así como la mortalidad y los recursos con que cuentan los hospitales participantes para la atención de estos pacientes en el período del 2015 al 2018. Se solicitó la información a la Plataforma Nacional de Transparencia y además se revisaron las bases de datos de los servicios de cardiología pediátrica y cirugía cardiovascular pediátrica de los hospitales participantes. Resultados: El hospital de segundo nivel cuenta con los recursos humanos, pero no con el material para atender a estos pacientes, por lo que no es posible ofrecer ningún tipo de tratamiento paliativo o correctivo (sólo se cierran algunos conductos arteriosos en la etapa neonatal). Se valoró a un total de 624 pacientes, de los cuales el 92.2% correspondió a cardiopatías no críticas; la mortalidad global fue del 12% pero en las cardiopatías críticas fue del 79.5%. El hospital de tercer nivel cuenta con recursos humanos y material para atender a estos pacientes; en el período de estudio se realizaron 289 operaciones y la mortalidad global fue del 20.4%. Conclusión: Las cardiopatías congénitas en el estado de Jalisco son una causa importante de mortalidad, con una incidencia elevada y una capacidad de resolución sumamente limitada, ya que los servicios de salud de Jalisco para la atención de estos pacientes son insuficientes e inadecuados. Es esencial fortalecer el sistema de salud para atender a estos pacientes.

Current situation of congenital heart diseases in two public hospitals in the state of Jalisco.

Introduction: Congenital heart disease represents a public health issue worldwide. Objective: To know the number of patients with heart disease treated in two public hospitals of the State of Jalisco, as well as the mortality and resources available to participating hospitals for the care of these patients in the period from 2015 to 2018; the information was requested to the -National Transparency Platform, and the database of pediatric cardiology services and pediatric cardiovascular surgery of the participating hospitals were also reviewed. Results: The second level hospital has human resources, but not the material to attend to these patients; so it is not possible to offer any type of palliative or corrective treatment. A total of 624 patients were evaluated, of which 92.2% corresponded to non-critical heart disease; overall mortality was 12% but in critical heart disease it was 79.5%. The third level hospital has human and material resources to care for these patients. During the study period, 289 operations were performed and the overall mortality was 20.4%. Conclusion: Congenital heart disease in the State of Jalisco is an important cause of mortality, with a high incidence and a very limited resolution capacity since the health services in the State of Jalisco for the care of these patients are insufficient and inadequate. It is essential to strengthen the health system for the care for these patients.

Introducción: Las cardiopatías congénitas representan un problema de salud pública a nivel mundial. Objetivo: Conocer la cantidad de pacientes cardiópatas atendidos en dos hospitales públicos del estado de Jalisco, así como la mortalidad y los recursos con que cuentan los hospitales participantes para la atención de estos pacientes en el período del 2015 al 2018. Se solicitó la información a la Plataforma Nacional de Transparencia y además se revisaron las bases de datos de los servicios de cardiología pediátrica y cirugía cardiovascular pediátrica de los hospitales participantes. Resultados: El hospital de segundo nivel cuenta con los recursos humanos, pero no con el material para atender a estos pacientes, por lo que no es posible ofrecer ningún tipo de tratamiento paliativo o correctivo (sólo se cierran algunos conductos arteriosos en la etapa neonatal). Se valoró a un total de 624 pacientes, de los cuales el 92.2% correspondió a cardiopatías no críticas; la mortalidad global fue del 12% pero en las cardiopatías críticas fue del 79.5%. El hospital de tercer nivel cuenta con recursos humanos y material para atender a estos pacientes; en el período de estudio se realizaron 289 operaciones y la mortalidad global fue del 20.4%. Conclusión: Las cardiopatías congénitas en el estado de Jalisco son una causa importante de mortalidad, con una incidencia elevada y una capacidad de resolución sumamente limitada, ya que los servicios de salud de Jalisco para la atención de estos pacientes son insuficientes e inadecuados. Es esencial fortalecer el sistema de salud para atender a estos pacientes.

Inequity of congenital heart disease care in the public hospitals of Mexico. The false right to health.

La cardiología pediátrica y la cirugía cardiovascular han tenido avances importantes en los últimos años; las cardiopatías congénitas (CC) son una de las principales causas de mortalidad en niños. Muchos de los factores que determinan la evolución final de estos pacientes incluyen el tipo de cardiopatía y el tiempo del diagnóstico y tratamiento; infortunadamente, dos de los que presentan mayores efectos son el estado socioeconómico y el área geográfica de atención en México. El objetivo de este estudio es conocer el tipo de atención para los pacientes con CC en hospitales públicos del país.Pediatric cardiology and cardiovascular surgery have made significant advances in recent years, congenital heart diseases (CHD) are one of the leading causes of mortality in children. Many of the factors that determine the final evolution of these patients include the type of heart disease, the time of diagnosis and treatment; unfortunately, in our country, two of those greatest impact area the socioeconomic status and the geographic area of attention. The objective of this study is to know the type of care for patients with CHD in public hospitals in the country.

Comparación de oxímetros para detección de cardiopatías congénitas críticas.

Introduction and objectives: In some centers the pulse oximetry is not performed with the justification of lack of the adequate oximeter. We compared the effectiveness of two brands of oximeters to perform it. Methods: In neonates a term of the joint housing service of a Hospital General de Occidente in Zapopan Jalisco Mexico from May-November 2018, an examination of the characteristics of the American Academy of Pediatrics with both oximeters (ChoiceMMed® and Masimo SET®) was carried out, comparing the detection of critical congenital heart disease (CCC), time of intake and false positives. Results: In each group 1,022 patients were analyzed; with the Masimo SET® oximeter 83 positive tests were obtained (8.12%), of which 22 cases had some heart disease (26.5%), which represents a sensitivity of 100%, specificity of 93.9%, positive predictive value of 26.5% and negative predictive value of 100% (OR: 0.73; 95% CI: 0.6-0.8). With the ChoiceMMed® oximeter, 168 positive tests were obtained (16.4%), of which 22 cases had some heart disease (13.09%), with a sensitivity of 100%, specificity of 85.4%, positive predictive value of 13.09% and negative predictive value 100% (OR: 0.86; 95% CI: 0.8-0.92). Regarding the time to perform the cardiac sieve, the mean in minutes of the Masimo SET® oximeter was 5.38 and the ChoiceMMed® oximeter was 9.7 minutes. Conclusions: The ChoiceMMed® oximeter contains a large number of false positives and a greater number of echocardiograms and comparatively longer cardiac screen printing with Masimo SET®, however, both with a negative predictive value of 100% eliminating such excuses.

Introducción y objetivos: En algunos centros el tamiz cardíaco no se realiza con la justificación de no tener el oxímetro adecuado. Comparamos la efectividad de dos marcas de oxímetros para realizarlo. Métodos: En los neonatos a término del Servicio de alojamiento conjunto del Hospital General de Occidente en Zapopan Jalisco México de mayo a noviembre del 2018 se realizó tamiz cardíaco según las guías de la Academia Americana de Pediatría con dos oxímetros, el Masimo SET® (aprobado por la FDA) y el ChoiceMMed®, comparando su efectividad para la detección de cardiopatías congénitas críticas, el tiempo de toma y los falsos positivos. Resultados: En cada grupo se analizaron 1,022 pacientes; con el oxímetro Massimo SET® se obtuvieron 83 pruebas positivas (8.12%) de las cuales 22 casos presentaron alguna cardiopatía (26.5%), lo que representa una sensibilidad del 100%, una especificidad del 93.9%, un valor predictivo positivo del 26.5% y un valor predictivo negativo del 100% (Odd Ratio [OR]: 0.73; IC 95%: 0.6-0.8). Con el oxímetro ChoiceMMed® se obtuvieron 168 pruebas positivas (16.4%), de las cuales 22 casos presentaron alguna cardiopatía (13.09%), con una sensibilidad del 100%, una especificidad del 85.4%, un valor predictivo positivo del 13.09% y un valor predictivo negativo del 100% (OR: 0.86; IC 95%: 0.8-0.92). En cuanto al tiempo para realizar el tamiz cardíaco, la media en minutos del oxímetro Masimo SET® fue 5.38 y del oxímetro ChoiceMMed® fue 9.7 minutos. Conclusiones: El oxímetro ChoiceMMed® presentó mayor cantidad de falsos positivos y mayor tiempo de realización del tamiz cardíaco en comparación al Masimo SET®, sin embargo, ambos presentan un valor predictivo negativo del 100%, siendo igualmente útiles como método de detección de cardiopatías críticas.

Comparison of oximeters for the detection of critical congenital heart diseases.

Introduction and objectives: In some centers, the pulse oximetry is not performed with the justification of lack of the adequate oximeter. We compared the effectiveness of two brands of oximeters to perform it. Methods: In neonates, a term of the joint housing service of the Hospital General de Occidente in Zapopan, Jalisco, Mexico, from May to November 2018, an examination of the characteristics of the American Academy of Pediatrics with both oximeters (ChoiceMMed® and Masimo SET®) was carried out, comparing the detection of critical congenital heart disease, time of intake, and false positives. Results: In each group, 1022 patients were analyzed; with the Masimo SET® oximeter, 83 positive tests were obtained (8.12%), of which 22 cases had some heart disease (26.5%), which represents a sensitivity of 100%, specificity of 93.9%, positive predictive value of 26.5%, and negative predictive value of 100% (odds ratio [OR]: 0.73; 95% confidence interval [CI] 0.6-0.8). With the ChoiceMMed® oximeter, 168 positive tests were obtained (16.4%), of which 22 cases had some heart disease (13.09%), with a sensitivity of 100%, specificity of 85.4%, positive predictive value of 13.09%, and negative predictive value 100% (OR: 0.86; 95%CI: 0.8-0.92). Regarding the time to perform the cardiac sieve, the mean in minutes of the Masimo SET® oximeter was 5.38 and the ChoiceMMed® oximeter was 9.7 min. Conclusions: The ChoiceMMed® oximeter contains a large number of false positives and a greater number of echocardiograms and comparatively longer cardiac screen printing with Masimo SET®, however, both with a negative predictive value of 100% eliminating such excuses.

Introducción y objetivos: En algunos centros el tamiz cardíaco no se realiza con la justificación de no tener el oxímetro adecuado. Comparamos la efectividad de dos marcas de oxímetros para realizarlo. Métodos: En los neonatos a término del Servicio de alojamiento conjunto del Hospital General de Occidente en Zapopan Jalisco México de mayo a noviembre del 2018 se realizó tamiz cardíaco según las guías de la Academia Americana de Pediatría con dos oxímetros, el Masimo SET® (aprobado por la FDA) y el ChoiceMMed®, comparando su efectividad para la detección de cardiopatías congénitas críticas, el tiempo de toma y los falsos positivos. Resultados: En cada grupo se analizaron 1,022 pacientes; con el oxímetro Massimo SET® se obtuvieron 83 pruebas positivas (8.12%) de las cuales 22 casos presentaron alguna cardiopatía (26.5%), lo que representa una sensibilidad del 100%, una especificidad del 93.9%, un valor predictivo positivo del 26.5% y un valor predictivo negativo del 100% (Odd Ratio [OR]: 0.73; IC 95%: 0.6-0.8). Con el oxímetro ChoiceMMed® se obtuvieron 168 pruebas positivas (16.4%), de las cuales 22 casos presentaron alguna cardiopatía (13.09%), con una sensibilidad del 100%, una especificidad del 85.4%, un valor predictivo positivo del 13.09% y un valor predictivo negativo del 100% (OR: 0.86; IC 95%: 0.8-0.92). En cuanto al tiempo para realizar el tamiz cardíaco, la media en minutos del oxímetro Masimo SET® fue 5.38 y del oxímetro ChoiceMMed® fue 9.7 minutos. Conclusiones: El oxímetro ChoiceMMed® presentó mayor cantidad de falsos positivos y mayor tiempo de realización del tamiz cardíaco en comparación al Masimo SET®, sin embargo, ambos presentan un valor predictivo negativo del 100%, siendo igualmente útiles como método de detección de cardiopatías críticas.

Systematic association of genes to phenotypes by genome and literature mining.

One of the major challenges of functional genomics is to unravel the connection between genotype and phenotype. So far no global analysis has attempted to explore those connections in the light of the large phenotypic variability seen in nature. Here, we use an unsupervised, systematic approach for associating genes and phenotypic characteristics that combines literature mining with comparative genome analysis. We first mine the MEDLINE literature database for terms that reflect phenotypic similarities of species. Subsequently we predict the likely genomic determinants: genes specifically present in the respective genomes. In a global analysis involving 92 prokaryotic genomes we retrieve 323 clusters containing a total of 2,700 significant gene-phenotype associations. Some clusters contain mostly known relationships, such as genes involved in motility or plant degradation, often with additional hypothetical proteins associated with those phenotypes. Other clusters comprise unexpected associations; for example, a group of terms related to food and spoilage is linked to genes predicted to be involved in bacterial food poisoning. Among the clusters, we observe an enrichment of pathogenicity-related associations, suggesting that the approach reveals many novel genes likely to play a role in infectious diseases.

Global analysis of bacterial transcription factors to predict cellular target processes.

Whole-genome sequences are now available for >100 bacterial species, giving unprecedented power to comparative genomics approaches. We have applied genome-context methods to predict target processes that are regulated by transcription factors (TFs). Of 128 orthologous groups of proteins annotated as TFs, to date, 36 are functionally uncharacterized; in our analysis we predict a probable cellular target process or biochemical pathway for half of these functionally uncharacterized TFs.

Update on XplorMed: A web server for exploring scientific literature.

As scientific literature databases like MEDLINE increase in size, so does the time required to search them. Scientists must frequently inspect long lists of references manually, often just reading the titles. XplorMed is a web tool that aids MEDLINE searching by summarizing the subjects contained in the results, thus allowing users to focus on subjects of interest. Here we describe new features added to XplorMed during the last 2 years (http://www.bork.embl-heidelberg.de/xplormed/).

Human Lsg1 defines a family of essential GTPases that correlates with the evolution of compartmentalization.

BACKGROUND: Compartmentalization is a key feature of eukaryotic cells, but its evolution remains poorly understood. GTPases are the oldest enzymes that use nucleotides as substrates and they participate in a wide range of cellular processes. Therefore, they are ideal tools for comparative genomic studies aimed at understanding how aspects of biological complexity such as cellular compartmentalization evolved. RESULTS: We describe the identification and characterization of a unique family of circularly permuted GTPases represented by the human orthologue of yeast Lsg1p. We placed the members of this family in the phylogenetic context of the YlqF Related GTPase (YRG) family, which are present in Eukarya, Bacteria and Archea and include the stem cell regulator Nucleostemin. To extend the computational analysis, we showed that hLsg1 is an essential GTPase predominantly located in the endoplasmic reticulum and, in some cells, in Cajal bodies in the nucleus. Comparison of localization and siRNA datasets suggests that all members of the family are essential GTPases that have increased in number as the compartmentalization of the eukaryotic cell and the ribosome biogenesis pathway have evolved. CONCLUSION: We propose a scenario, consistent with our data, for the evolution of this family: cytoplasmic components were first acquired, followed by nuclear components, and finally the mitochondrial and chloroplast elements were derived from different bacterial species, in parallel with the formation of the nucleolus and the specialization of nuclear components.

Eficacia y seguridad del cierre quirúrgico del conducto arterioso permeable por el cirujano pediatra general: ensayo clínico / Effectiveness and safety of the surgical closure of permeable arteriosus conduct by the general pediatric surgeon: clinical trial

Resumen Antecedentes: El conducto arterioso permeable (CAP) es un defecto cardiaco congénito y se considera un problema de salud pública. Se presenta en un alto porcentaje de recién nacidos y en algunos mayores de 1 mes. El cierre farmacológico es el tratamiento inicial preferido, ya que ha tenido excelentes resultados; sin embargo, en aquellos casos en los que no es posible, está indicado el cierre quirúrgico. Objetivo: Evaluar la eficacia y la seguridad del cierre quirúrgico del CAP por cirujanos pediatras sin especialidad en cirugía cardiovascular. Método: Ensayo clínico realizado en pacientes del Hospital General de Occidente, centro hospitalario público de segundo nivel, con diagnóstico de CAP, que requirieron corrección quirúrgica. Se revisaron en forma retrospectiva los expedientes de enero de 2001 a diciembre de 2018. Resultados: Se incluyeron 224 pacientes divididos en dos grupos: grupo I, con 184 (82%) recién nacidos, y grupo II, con 40 (18%) niños grandes de 2 meses a 8 años de edad. A todos se les realizó cierre quirúrgico: 3 por toracoscopía y 221 por toracotomía posterolateral izquierda. Presentaron complicaciones 36 pacientes, lo que representa el 16% del total; solo el 5.3% fueron complicaciones mayores. Fallecieron 24 pacientes en el posoperatorio, lo que representa una mortalidad del 10.7%; ninguno falleció por complicaciones transquirúrgicas. El CAP es un defecto cardíaco congénito que se presenta en alto porcentaje en pacientes prematuros. El cierre farmacológico es el principal tratamiento por tener excelentes resultados en recién nacidos; sin embargo, en aquellos casos en los que no sea posible está indicado el cierre quirúrgico. Todos los pacientes fueron operados por cirujanos pediatras generales, con una sobrevida global del 92%. Conclusiones: En los hospitales donde no hay cirujano cardiovascular pediátrico ni cardiólogo intervencionista, la corrección quirúrgica del CAP puede ser llevada a cabo por un cirujano pediatra. La técnica es reproducible, fácil de realizar y con mínimas complicaciones.

Abstract Background: The Patent Ductus Arteriosus (PDA) is congenital heart defect and is considered a public health problem. It occurs in a high percentage of newborns and in some older than 1 month. Pharmacological closure is the preferred initial treatment, as it has had excellent results; however, in those cases where it is not possible, surgical closure is indicated. Objective: The objective is to evaluate the efficacy and safety of the surgical closure of the patent PDA when it is carried out by pediatric surgeons without specialization in cardiovascular surgery. Methods: This study was conducted at the West General Hospital, a 2nd level public hospital, with the diagnosis of patent ductus arteriosus that required surgical correction. For the collection of the information, the files from January 2001 to December 2018 were retrospectively reviewed. Results: 224 patients were included; divided into two groups: Group I: 184 (82%) "newborns" and Group II: 40 (18%) "big children" with ages from 2 months to 8 years. All had a surgical closure; 3 by thoracoscopy and 221 by left posterolateral thoracotomy. 36 patients presented complications representing 16% of the total of patients, only 5.3% were major complications. 24 patients died in the postoperative period, representing a mortality of 10.7%, none died due to trans-surgical complications. PDA is a congenital heart defect that occurs in a high percentage of premature patients. The pharmacological closure is the principal treatment because it has had excellent results in newborns; however, in those cases where it is not possible, surgical closure it´s indicated. All patients were operated by general pediatric surgeons, with a global survival of 92%. Conclusions: We conclude that in hospitals where there is no pediatric cardiovascular surgeon or interventional cardiologist, the surgical correction of the PDA can be carried out by a general pediatric surgeon. The technique is reproducible, easy to perform and with minimal complications.

Ranking the whole MEDLINE database according to a large training set using text indexing.

BACKGROUND: The MEDLINE database contains over 12 million references to scientific literature, with about 3/4 of recent articles including an abstract of the publication. Retrieval of entries using queries with keywords is useful for human users that need to obtain small selections. However, particular analyses of the literature or database developments may need the complete ranking of all the references in the MEDLINE database as to their relevance to a topic of interest. This report describes a method that does this ranking using the differences in word content between MEDLINE entries related to a topic and the whole of MEDLINE, in a computational time appropriate for an article search query engine. RESULTS: We tested the capabilities of our system to retrieve MEDLINE references which are relevant to the subject of stem cells. We took advantage of the existing annotation of references with terms from the MeSH hierarchical vocabulary (Medical Subject Headings, developed at the National Library of Medicine). A training set of 81,416 references was constructed by selecting entries annotated with the MeSH term stem cells or some child in its sub tree. Frequencies of all nouns, verbs, and adjectives in the training set were computed and the ratios of word frequencies in the training set to those in the entire MEDLINE were used to score references. Self-consistency of the algorithm, benchmarked with a test set containing the training set and an equal number of references randomly selected from MEDLINE was better using nouns (79%) than adjectives (73%) or verbs (70%). The evaluation of the system with 6,923 references not used for training, containing 204 articles relevant to stem cells according to a human expert, indicated a recall of 65% for a precision of 65%. CONCLUSION: This strategy appears to be useful for predicting the relevance of MEDLINE references to a given concept. The method is simple and can be used with any user-defined training set. Choice of the part of speech of the words used for classification has important effects on performance. Lists of words, scripts, and additional information are available from the web address http://www.ogic.ca/projects/ks2004/.

Inconsistencies over time in 5% of NetAffx probe-to-gene annotations.

BACKGROUND: DNA microarray probes are designed to match particular mRNA transcripts, often based on expressed sequences like ESTs, or cDNAs, many times incomplete. As a result, the relations between probes and genes can change as the sequence data are updated. However, it is frequent that the reported results of microarray analyses are given just as lists of genes without any reference to the underlying probes. RESULTS: We show for a particular commercial microarray design that the number of probes associated to some genes change with time. These changes concern approximately 5% of the probe sets across the history of annotation releases over a two year span. CONCLUSION: We recommend to report probe set identifiers when publishing microarray results, and to submit those analyses to microarray public databases to ensure that the interpretation of the data is updated with the latest set of annotations.

Study of stem cell function using microarray experiments.

DNA Microarrays are used to simultaneously measure the levels of thousands of mRNAs in a sample. We illustrate here that a collection of such measurements in different cell types and states is a sound source of functional predictions, provided the microarray experiments are analogous and the cell samples are appropriately diverse. We have used this approach to study stem cells, whose identity and mechanisms of control are not well understood, generating Affymetrix microarray data from more than 200 samples, including stem cells and their derivatives, from human and mouse. The data can be accessed online (StemBase; http://www.scgp.ca:8080/StemBase/).