Mutational spectrum and genotype-phenotype correlation in Mexican patients with infantile-onset and late-onset Pompe disease.

BACKGROUND: Pompe Disease (PD) is a metabolic myopathy caused by variants in the GAA gene, resulting in deficient enzymatic activity. We aimed to characterize the clinical features and related genetic variants in a series of Mexican patients. METHODS: We performed a retrospective study of clinical records of patients diagnosed with LOPD, IOPD or pseudodeficiency. RESULTS: Twenty-nine patients were included in the study, comprising these three forms. Overall, age of symptom onset was 0.1 to 43 years old. The most frequent variant identified was c.-32-13T>G, which was detected in 14 alleles. Among the 23 different variants identified in the GAA gene, 14 were classified as pathogenic, 5 were likely pathogenic, and 1 was a variant of uncertain significance. Two variants were inherited in cis arrangement and 2 were pseudodeficiency-related benign alleles. We identified two novel variants (c.1615 G>A and c.1076-20_1076-4delAAGTCGGCGTTGGCCTG). CONCLUSION: To the best of our knowledge, this series represent the largest phenotypic and genotypic characterization of patients with PD in Mexico. Patients within our series exhibited a combination of LOPD and IOPD associated variants, which may be related to genetic diversity within Mexican population. Further population-wide studies are required to better characterize the incidence of this disease in Mexican population.

Renal impairment and mortality in patients with STEMI and cardiogenic shock/cardiac arrest.

OBJECTIVES: We sought to study the association of renal impairment (RI) with mortality in ST-segment elevation myocardial infarction (STEMI) complicated by cardiogenic shock and/or cardiac arrest (CS/CA). METHODS: Patients with RI (estimated glomerular filtration rate <60 mL/min/1.73 m2 ) were identified from the Midwest STEMI consortium, a prospective registry of four large regional programs comprising consecutive patients over 17 years. Primary outcome was in-hospital and 1-year mortality stratified by RI status and presence of CS/CA among patients with STEMI referred for coronary angiography. RESULTS: In a cohort of 13,463 STEMI patients, 13% (n = 1754) had CS/CA, 30% (n = 4085) had RI. Overall, in-hospital mortality was 5% (12% RI vs. 2% no-RI, p < 0.001) and 1-year mortality 9% (21% RI vs. 4% no-RI, p < 0.001). Among uncomplicated STEMI, in-hospital mortality was 2% (4% RI vs. 1% no-RI, p < 0.001) and 1-year mortality 6% (13% RI vs. 3% no-RI, p < 0.001). In STEMI with CS/CA, in-hospital mortality was 29% (43% RI vs. 15% no-RI, p < 0.001) and 1-year mortality 33% (50% RI vs. 16% no-RI, p < 0.001). Using Cox proportional hazards, RI was an independent predictor of in-hospital mortality in STEMI with CS/CA (odds ratio [OR]: 3.86; confidence interval [CI]: 2.6, 5.8). CONCLUSIONS: The association of RI with in-hospital and 1-year mortality is disproportionately greater in those with CS/CA compared to uncomplicated STEMI presentations. Factors predisposing RI patients to higher risk STEMI presentations and pathways to promote earlier recognition in the chain of survival need further investigation.

Infantile-onset Pompe disease in seven Mexican children.

INTRODUCTION: Pompe disease (PD) is a rare form of metabolic myopathy; the classic infantile presentation is severe, with death occurring before reaching one year of life, and the non-classical form is of slower progression and survival can exceed one year. OBJECTIVE: To describe the genotype and characteristics of Mexican patients with infantile-onset PD. METHODS: Seven patients with PD confirmed by enzymatic activity determination and GAA gene molecular analysis were included. Mutations were reviewed in genomic databases. RESULTS: Median age at symptom onset was four months (1-12 months) and age at diagnosis was eight months (4-16 months). All patients had cardiomyopathy: four who died before one year of age had mutations that predicted severe disease (c.2431dup, c.2560C>T, c.655G>A, c.1987delC) and were negative for cross-reactive immunologic material (CRIM). Three patients survived after one year of age with enzyme replacement therapy; one survived almost five years, another 18 months, and one girl was almost three years of age at the time of this report; their pathogenic variants predicted potentially less severe disease (c.1979G>A, c.655G>A, c.1447G>A) and they were positive for CRIM. CONCLUSION: There was a good correlation between genotype and phenotype in children with Pompe disease.

INTRODUCCIÓN: La enfermedad de Pompe (EP) es una forma rara de miopatía metabólica; la presentación infantil clásica es severa y el fallecimiento acontece antes del año de vida, y la forma no clásica es de progresión más lenta y la sobrevivencia puede superar el año. OBJETIVO: Describir genotipo y características de pacientes mexicanos con EP de inicio infantil. MÉTODOS: Se incluyeron siete pacientes con enfermedad confirmada mediante actividad enzimática y estudio molecular del gen GAA. Se revisaron las mutaciones en bases de datos genómicas. RESULTADOS: La mediana de la edad de inicio de los síntomas fue de cuatro meses (1-12 meses) y la edad de diagnóstico fue de ocho meses (4-16 meses). Todos los pacientes tenían cardiomiopatía: cuatro que fallecieron antes del año presentaron mutaciones que predicen enfermedad severa (c.2431dup, c.2560C>T, c.655G>A, c.1987delC) y CRIM (cross-reactive immunologic material) negativo; tres sobrevivieron después del año de edad con terapia de reemplazo enzimático, uno casi cinco años, otro 18 meses y una niña tenía casi tres años al momento de este informe; sus variantes patogénicas predecían enfermedad potencialmente menos severa (c.1979G>A, c.655G>A, c.1447G>A) y CRIM positivo. CONCLUSIÓN: Existió buena correlación entre genotipo y fenotipo en niños con enfermedad de Pompe.

Enfermedad de Pompe de inicio infantil en siete niños mexicanos / Infantile-onset Pompe disease in seven Mexican children

Resumen Introducción: La enfermedad de Pompe (EP) es una forma rara de miopatía metabólica; la presentación infantil clásica es severa y el fallecimiento acontece antes del año de vida, y la forma no clásica es de progresión más lenta y la sobrevivencia puede superar el año. Objetivo: Describir genotipo y características de pacientes mexicanos con EP de inicio infantil. Métodos: Se incluyeron siete pacientes con enfermedad confirmada mediante actividad enzimática y estudio molecular del gen GAA. Se revisaron las mutaciones en bases de datos genómicas. Resultados: La mediana de la edad de inicio de los síntomas fue de cuatro meses (1-12 meses) y la edad de diagnóstico fue de ocho meses (4-16 meses). Todos los pacientes tenían cardiomiopatía: cuatro que fallecieron antes del año presentaron mutaciones que predicen enfermedad severa (c.2431dup, c.2560C>T, c.655G>A, c.1987delC) y CRIM (cross-reactive immunologic material) negativo; tres sobrevivieron después del año de edad con terapia de reemplazo enzimático, uno casi cinco años, otro 18 meses y una niña tenía casi tres años al momento de este informe; sus variantes patogénicas predecían enfermedad potencialmente menos severa (c.1979G>A, c.655G>A, c.1447G>A) y CRIM positivo. Conclusión: Existió buena correlación entre genotipo y fenotipo en niños con enfermedad de Pompe.

Abstract Introduction: Pompe disease (PD) is a rare form of metabolic myopathy; the classic infantile presentation is severe, with death occurring before reaching one year of life, and the non-classical form is of slower progression and survival can exceed one year. Objective: To describe the genotype and characteristics of Mexican patients with infantile-onset PD. Methods: Seven patients with PD confirmed by enzymatic activity determination and GAA gene molecular analysis were included. Mutations were reviewed in genomic databases. Results: Median age at symptom onset was four months (1-12 months) and age at diagnosis was eight months (4-16 months). All patients had cardiomyopathy: four who died before one year of age had mutations that predicted severe disease (c.2431dup, c.2560C>T, c.655G>A, c.1987delC) and were negative for cross-reactive immunologic material (CRIM). Three patients survived after one year of age with enzyme replacement therapy; one survived almost five years, another 18 months, and one girl was almost three years of age at the time of this report; their pathogenic variants predicted potentially less severe disease (c.1979G>A, c.655G>A, c.1447G>A) and they were positive for CRIM. Conclusion: There was a good correlation between genotype and phenotype in children with Pompe disease.

Neurological Involvement in Pediatric Patients with Acute Leukemia: A Retrospective Cohort.

Acute leukemia (AL) is an important cause of morbidity and mortality in children, and neurological manifestations (NM) are frequent. The objective of this study was to analyze neurological manifestations in children with acute leukemia from cases attended in the last five years at the Centro Médico Nacional "20 de Noviembre". METHODS: Conducting a retrospective and analytical study from 1 January 2015 to 31 December 2020 in children with AL classified according to sex, age range and AL type. Participants were grouped according the presence of NM. RESULTS: We analyzed 607 patients: 54.85% boys and 44.14% girls, with a mean age of 7.27 ± 4.54 years. When comparing groups, the NM group was significantly older (p = 0.01), and the highest prevalence was between 6 and 12 years old. ALL was predominant over the other lineages (p ≤ 0.01). The most frequent NM was CNS infiltration, seizures, headache and neuropathy. Death outcomes occurred in 18.7% of children with AML, 11.8% with ALL and 50% with MPAL (p ≤ 0.002). The NM group was associated with higher mortality during a follow-up time of 77.9 ± 49 months (44.4% vs. 8.9% deaths, NM vs. non-NM, respectively; OR = 3.3; 95% CI 2.4 to 4.6; p ≤ 0.0001). CONCLUSIONS: ALL was the most prevalent leukemia type. CNS infiltration, seizures, headache, neuropathy and PRES were the most frequent symptoms in the NM group. NM was associated with a higher mortality rate.

Diabetic Patients Who Present With ST-Elevation Myocardial Infarction.

BACKGROUND: The long-term outcomes of diabetic patients presenting with ST-segment elevation myocardial infarction (STEMI) in contemporary practice have received limited study. METHODS: We evaluated the clinical characteristics and outcomes of STEMI patients with and without diabetes in a large regional STEMI program designed to facilitate timely primary percutaneous coronary intervention (PCI) (Minneapolis Heart Institute at Abbott Northwestern Hospital, Minneapolis, MN). The primary and secondary outcome measures were in-hospital mortality, 1-year major adverse cardiovascular events (MACE) (stroke, myocardial infarction, unplanned PCI or coronary artery bypass graft [CABG] surgery, and all-cause mortality), and 5-year mortality. RESULTS: Of the 6292 patients included, 1158 (18.4%) had Diabetes Mellitus (DM) (95.3% Type II, 4.7% Type I). Patients with DM were older (mean age 66 vs. 62.8 years, p < 0.01), had more co-morbidities and were more likely to receive medical therapy without reperfusion (13% vs. 10%, p = 0.003). Patients with DM had higher in-hospital (8% vs. 5%, p = 0.001), 1-year (8% vs. 4%, p < 0.001) and 5-year mortality (16% vs. 9%, p < 0.001) compared to non-diabetics. On Cox proportional hazards analysis, DM was independently associated with worse mortality (hazard ratio: 1.70, 95% confidence interval (CI): 1.32-2.19, p < 0.001) and MACE [HR: 1.63 (95% (CI)): 1.28-2.08, p < 0.001]. CONCLUSIONS: Despite advancements in medical therapy and revascularization strategies for STEMI, DM remains independently associated with higher short- and long-term morbidity and mortality in contemporary practice.

Assessment of Gradient-Based Algorithm for Surface Determination in Multi-Material Gap Measurements by X ray Computed Tomography.

X-ray computed tomography is one of the most promising measurement techniques for the dimensional evaluation of industrial components. However, the inherent complexity of this technology also involves important challenges. One of them is to develop surface determination algorithms capable of providing measurement results with better accuracy in any situation-for example, for single and multi-material parts, inner and outer geometries, with and without image artefacts, etc.-and reducing user influence. The surface determination is particularly complex in the case of multi-material parts, especially when they are separated by small air gaps. In previous works, two gradient-based algorithms were presented, that showed less measurement variability throughout the whole part, and reduced the computational cost and operator influence compared to threshold-based algorithms. This work focuses on the evaluation of the performance of these algorithms when used in a scenario so complex that parts of it are made of one or more materials (metal-metal and polymer-metal) with gaps inside. For this purpose, a set of multi-material reference standards is used. The presented gradient-based algorithms show measurement errors comparable to commercial threshold-based algorithms, but with the capability of obtaining accurate measurements in smaller gaps, apart from reducing the user influence on the measurement process.

Geochemical anomalies for the determination of surface stream sediments pollution: case of Sierra de Cartagena-La Unión mining district, Spain.

This work explores the ability of the Spanish Geochemical Database to identify the existence of polluted stream sediments due to the presence of abandoned mine wastes. The mining district of Sierra de Cartagena-La Unión has been used as test area. A total of 18 abandoned tailings facilities were selected and samples were taken for analysis of the content in potential toxic elements. The results were contrasted with geochemical background values in order to identify which geochemical elements could entail anomalies potentially reflected in the Spanish Geochemical Database. For the study area, As, Cd, Pb, and Zn have been identified as potential toxic elements which can be used as geochemical indicators of sediment pollution processes originated in abandoned mine wastes. Furthermore, the correlation between Cd and Zn allows them to be considered as the best indicators of potential sediment contamination. The study of anomaly thresholds, through the analysis of accumulated frequencies of the contents of these elements in the sediments of the Spanish Geochemical Database, allows identifying sediments that may have been contaminated. A Mann-Whitney test contrasting the data of tailings, polluted sediments, and non-polluted sediments has been performed in order to verify differences among these types of samples. In addition, a geospatial analysis has demonstrated a very close relationship between contaminated sediments and the presence of mining wastes upstream. This methodology can be applied to any other mining region, to recognize the possible influence of pollution processes derived from the presence of abandoned mine wastes taking advantage of existing geochemical databases.

Differential Gene Expression Profile Induced by Valproic Acid (VPA) in Pediatric Epileptic Patients.

Epilepsy is a neuronal disease that affects up to 70 million people worldwide. The development of effective therapies to combat childhood epilepsy requires early biomarkers. Here, we performed a whole-genome microarray analysis in blood cells to identify genes differentially expressed between epileptic and epileptic valproic acid (VPA)-treated children versus normal children to obtain information about the gene expression to help us to understand genetic aspects of this disease. We found that the most significant differentially expressed genes were related to the transcriptional factor cAMP-response element binding protein (CREB) that is overexpressed in children with epilepsy compared with normal children, and 6 and 12 months of VPA treatment reversed several of these changes. Interestingly, leukocyte-associated immunoglobulin-like receptor 1 (LAIR1), a type I transmembrane glycoprotein that binds collagen proteins and contains CREB binding sites, was one of the more up-regulated genes in epileptic patients, and treatment with VPA strongly reversed its up-regulation. CREB up-regulates genes related to epilepsy; here, we suggest that LAIR1 could activate CREB, and together, they trigger epilepsy. After VPA treatment, LAIR1 repressed genes by disrupting the functional LAIR1⁻CREB complex, resulting in successful treatment. A functional microarray analysis offers new information that could open novel avenues of research in biomarker discovery, which may be useful for the early identification of children with a predisposition to epilepsy.

Effects of Valproate Monotherapy on the Oxidant-Antioxidant Status in Mexican Epileptic Children: A Longitudinal Study.

Epilepsy is a neurological disorder that can produce brain injury and neuronal death. Several factors such as oxidative stress have been implicated in epileptogenesis. Valproic acid (VPA) is a widely used drug for the treatment of epilepsy, but the mechanisms underlying these benefits are complex and still not fully understood. The objective of this study was to evaluate, for the first time, the effects of VPA on the oxidant-antioxidant status in Mexican epileptic children before and after 6 or 12 months of treatment with VPA by determining the activities of several plasmatic antioxidant enzymes (glutathione reductase (GR), glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT)) and oxidant marker (malondialdehyde (MDA), hydrogen peroxide (H2O2), 8-hydroxy-2-deoxyguanosine (8-OHdG), and 3-nitrotyrosine (3-NT) levels) profiles. The possible relationships between these markers and some clinicopathological factors were also evaluated. Plasma samples were obtained from the peripheral blood of 16 healthy children and 32 patients diagnosed with epilepsy, and antioxidant/oxidant markers were measured spectrometrically. Significant decreases in all antioxidant enzyme activities, with the exception of GPx, and increases in all oxidant markers in epileptic subjects versus healthy children were observed. Interestingly, all these effects reverted after VPA monotherapy, although the results were different depending on the treatment period (6 or 12 months). These changes were contingent upon brain imaging findings, type of epilepsy, etiology of epilepsy, and the efficacy of 6 months of VPA monotherapy. Significant and positive correlations of GPx and SOD activities and H2O2 and 8-OHdG levels with the age of children at the beginning of treatment were observed. H2O2 levels were also positively correlated with number of seizures before VPA monotherapy. VPA showed significant antioxidant effects decreasing seizure activity, possibly depending on the presence of cerebral structural alterations, treatment time, and age.

Long-term follow-up of patients with chronic hepatitis C treated with α-interferon and ribavirin antiviral therapy: clinical and fibrosis impact of treatment response.

BACKGROUND AND GOALS: The slow progression of chronic hepatitis C (CHC) infection requires long observation periods to detect clinical changes. We compare the incidence of clinical events, hepatocellular carcinoma (HCC), overall mortality, liver-related mortality, and fibrosis progression between patients with a sustained virological response (SVR) and nonresponders (NR) after a 13-year follow-up period. STUDY: One hundred and eighty-two CHC patients, who received interferon and ribavirin treatment between 1996 and 2000, were included. Clinical events were evaluated during follow-up. At the end of follow-up, transient elastography was used to assess fibrosis progression. RESULTS: Of the 182 patients, 46.7% (n=85) achieved an SVR. Twenty-seven patients developed hepatic decompensation (one SVR) and 15 developed HCC (three SVR). Twenty-nine patients died (eight SVR). Twelve of the 29 deaths were liver related (two SVR). Independent factors associated with hepatic decompensation were NR to treatment [hazard ratio (HR)=23.35; 95% confidence interval (CI): 2.90-189.25; P=0.003], advanced fibrosis at baseline (HR=9.11; 95% CI: 4.13-20.09), and treatment delay after diagnosis (HR=1.02; 95% CI: 1.00-1.03; P=0.012). Only the latter two were associated with HCC development and liver-related mortality. An assessment of liver fibrosis was performed on 125 patients (66 SVR). Fibrosis values were significantly lower in SVR patients, showing less progression to advanced stages of fibrosis [SVR: 6.6 (2.8); 95% CI: 5.8-7.3] than NR [NR: 14.0 (11.1); 95% CI: 11.1-16.9; P<0.001]. CONCLUSION: In patients with CHC, SVR is durable and reduces clinical events. The risk of HCC development is lower, but not eliminated. Sustained responders showed fibrosis stabilization or improved fibrosis values.

A Revista Engenharia Sanitária e Ambiental no Sistema Brasileiro de Ciência, Tecnologia e Inovação / The Sanitary and Environmental Engineering Journal in the Brazilian Science, Technology and Innovation System

A análise do histórico de revistas científicas é um dos objetos principais de pesquisas nas áreas de bibliometria, cienciometria, informetria e webometria. Geralmente, essas análises procuram identificar o perfil cronológico dos artigos, autores e contextos editoriais das publicações. Quando entendida como uma organização inserida em um sistema de ciência, tecnologia e inovação (CT & I), uma revista científica é um agente de memória organizacional, que dissemina e promove conhecimento. Assim, além de análises sobre seu contexto editorial, é relevante verificar outros fatores que posicionam a revista no sistema de CT & I ao qual se refere. Uma das formas de tratar essa questão se dá pela combinação de métricas da informetria com análises oriundas da engenharia e da gestão do conhecimento. Neste artigo, aplica-se um modelo multidisciplinar com essa natureza, para verificar a base de conhecimentos criada pela Revista Engenharia Sanitária e Ambiental (Revista ESA) no sistema brasileiro de CT & I. Foram analisados os 333 artigos publicados entre agosto de 2004 e dezembro de 2012, o perfil curricular dos 816 autores, bem como o perfil de financiamento em CT & I realizados nos fundos setoriais em temáticas afins à revista, no mesmo período das publicações. Os resultados dessas análises foram verificados por especialistas no domínio das ciências ambientais e engenharia sanitária, com experiência no histórico da revista. Os resultados indicam que o perfil de conhecimentos produzidos pela Revista ESA guarda correspondência com os critérios de financiamento federais para CT & I, evidenciando o papel que a revista representa como formadora de uma base de conhecimento científico em engenharia sanitária e ambiental.

One of the main goals of bibliometrics, scientometrics, informetrics and webometrics is to analyze the history of scientific journals. Usually these studies analyze journals history, authors' profiles and how publications have evolved over time. In a broader view, a scientific journal can be thought of as a memory agent that promotes and disseminates knowledge in a science, technology and innovation system (STI). This brings other possibilities of understanding the role of scientific journals in STI systems. We address this challenge by combining informetrics with knowledge engineering and management techniques. In this article, we apply a multidisciplinary model to verify the knowledge base created by the Brazilian Scientific Journal called "Engenharia Sanitária e Ambiental" (ESA) in the Brazilian STI system. We analyzed the 333 articles published between August 2004 and December 2012. We also studied the national database of curricula in Brazil to analyze the profiles of the 816 authors and a national database, to check for public funding in subjects published in ESA. We concluded that both the knowledge published in ESA and the areas funded by national grant in Brazil have evolved in a similar way. This indicates that ESA plays a significant role as a memory agent in environmental and sanitary engineering in Brazil.

Enxertos de tecido conjuntivo na região anterior em implantes

O estudo teve por objetivo revisar e analisar em pesquisa bibliográfica os aspectos e assuntos relacionados à otimização estética e funcional por intermédio de enxertia de tecido conjuntivo...

Calling on a million minds for community annotation in WikiProteins.

WikiProteins enables community annotation in a Wiki-based system. Extracts of major data sources have been fused into an editable environment that links out to the original sources. Data from community edits create automatic copies of the original data. Semantic technology captures concepts co-occurring in one sentence and thus potential factual statements. In addition, indirect associations between concepts have been calculated. We call on a 'million minds' to annotate a 'million concepts' and to collect facts from the literature with the reward of collaborative knowledge discovery. The system is available for beta testing at http://www.wikiprofessional.org.

Prevalancia de hipoturoidismo en pacientes mayores de 55 años en la consulta de geriatría del Hospital Central Militar / Prevalence of hypothyroidism in patients elder than 55 years, see at the outpatient geriatric care of the Military Central Hospital

Prevalencia de hipotiroidismo en pacientes mayores de 60 años, no ha sido determinada en México, nos interesa presentar su importancia clínica, el impacto diagnóstico y el tratamiento oportuno, así como su relación con otras enfermedades. Se incluyeron 119 pacientes (58 hombres y 61 mujeres) entre las edades de 60 a 85 años, en el periodo comprendido de septiembre 1997 a febrero de 1998, sin antecedentes de factores que alteran el funcionamiento de la glándula tiroides y sus hormonas (T4 y THS). Se revisaron los datos clínicos de los pacientes y se obtuvo una muestra sanguínea para determinar los valores de TSH, T4, (procesado mediante el equipo ACCESS) perfil de lípidos y glicemia. Encontramos una prevalencia de alteraciones tiroideas del 15 por ciento, de los cuales 13 pacientes (11 por ciento, 10 mujeres y 3 hombres) correspondieron a hipotiroideos y el restante 4 por ciento a pacientes hipertiroideos (3 mujeres y 2 hombres). Se concluye que la prevalencia encontrada es una cifra de interés para toda la población mayor de 60 años, y para los médicos que tienen contacto con ésta, es por ello que recomendamos integrar los datos clínicos y de laboratorio que presentaron con más frecuencia en los pacientes incluidos en este estudio