Obesity in Spanish Schoolchildren: Relationship with Lipid Profile and Insulin Resistance.

This article reports cross-sectional data from a total of 1048 children, 6 to 8 years of age, categorized by presence or absence of obesity, who participated in a voluntary survey of cardiovascular risk factors in Spain over the period of 1998 to 2000, to establish the relationship between obesity and its metabolic consequences at this age. The prevalence of obesity and overweight were 9.4% and 15.7%, respectively, in boys and 10.5% and 18.0%, respectively, in girls. We observed that, in both sexes, obese children had higher triglycerides and lower high-density lipoprotein-cholesterol levels than non-obese children. No differences were found in plasma glucose or low-density lipoprotein-cholesterol levels between normal and obese children. However, we observed that insulin levels and the homeostasis model assessment for insulin resistance were significantly (p < 0.001) higher in obese children of both sexes but that free fatty acid levels were lower in obese children than in nonobese children, with a statistical significance in girls (0.72 ± 0.30 vs. 0.61 ± 0.16 mEq/liter). In summary, our survey found some metabolic consequences of obesity similar to those found in adults (elevated triglycerides, insulin, and the homeostasis model assessment for insulin resistance, and lower high-density lipoprotein-cholesterol). However, other features (glucose, total cholesterol, low-density lipoprotein-cholesterol, and free fatty acid levels) were found to behave differently, indicating that the association of obesity with risk factors seems to change as the children age and may depend on the chronology of sexual maturation.post-print51 K

Insulin and HOMA in Spanish prepubertal children: Relationship with lipid profile.

Objective: The effects of insulin or insulin resistance on the lipid profile seem to change with age. The aim of this study was to analyze insulin levels and an insulin resistance index and to investigate the relationship between these and the lipid profile in a population-based sample of Spanish prepubertal children. Methods: 1048 (524 boys and 524 girls) randomly selected prepubertal children were studied. Children were 6 to 8 years old with a mean age of 6.7. Plasma lipid, FFA and insulin levels were measured. The homeostatic model assessment (HOMA) was calculated as an indicator of insulin resistance. Results: When analyzing percentile values of insulin, HOMA and FFA by sex, we observed that girls had significantly higher insulin concentrations than boys (except at the 10th percentile) and significantly higher FFA (except at the 90th percentile) with no significant differences between sexes for HOMA. Multivariate regression analyses showed that insulin was positively associated with glucose, triglycerides and apoB in boys but not in girls, and negatively associated with FFA in both genders. Conclusions: We report here data about the distribution of insulin in the Spanish prepubertal population. The higher levels of insulin in prepubertal girls could indicate that girls start to be more insulin resistant than boys at this age, although other manifestations of insulin resistance are not yet detectable.pre-print211 K

STIM1 deficiency is linked to Alzheimer’s disease and triggers cell death in SH-SY5Y cells by upregulation of L-type voltage-operated Ca2+ entry

La STIM1 es una proteína del retículo endoplásmico con un papel en la movilización y señalización del Ca2+. Como sensor de los niveles intraluminales de Ca2+, STIM1 modula los canales de Ca2+ de la membrana plasmática para regular la entrada de Ca2+. En las células de neuroblastoma SH-SY5Y y en los fibroblastos cutáneos familiares de pacientes con la enfermedad de Alzheimer, STIM1 se divide en el dominio transmembrana por la presenilina-1-asociada a γ-secretase, lo que lleva a una desregulación de la homeostasis del Ca2+. En este informe, investigamos los niveles de expresión de STIM1 en los tejidos cerebrales (giro frontal medio) de pacientes con enfermedad de Alzheimer confirmada patológicamente, y observamos que el nivel de expresión de la proteína STIM1 disminuyó con la progresión de la neurodegeneración. Para estudiar el papel de STIM1 en la neurodegeneración, se diseñó una estrategia para eliminar la expresión del gen STIM1 en la línea de células de neuroblastoma SH-SY5Y mediante la edición del genoma mediado por CRISPR/Cas9, como un modelo in vitro para examinar el fenotipo de las células neuronales deficientes de STIM1. Se demostró que, si bien la STIM1 no es necesaria para la diferenciación de las células SH-SY5Y, es absolutamente esencial para la supervivencia de las células en la diferenciación. Las células STIM1-KO diferenciadas mostraron una disminución significativa de la actividad del complejo I de la cadena respiratoria mitocondrial, la despolarización de la membrana interna de la mitocondria, la reducción de la concentración de Ca2+ libre en la mitocondria y mayores niveles de senescencia en comparación con las células de tipo salvaje. En paralelo, las células STIM1-KO mostraron una entrada de Ca2+ potenciada en respuesta a la despolarización, que era sensible a la nifedipina, apuntando a los canales de Ca2+ operados por voltaje de tipo L como mediadores de la entrada de Ca2+ aumentada. El derribo estable de las transcripciones de CACNA1C restauró la función mitocondrial, aumentó los niveles mitocondriales de Ca2+ y redujo la senescencia a los niveles basales, demostrando el papel esencial de la regulación de la entrada de Ca2+ operada por voltaje a través de los canales Cav1.2 en la muerte celular deficiente de STIM1 SHSY5Y.STIM1 is an endoplasmic reticulum protein with a role in Ca2+ mobilization and signaling. As a sensor of intraluminal Ca2+ levels, STIM1 modulates plasma membrane Ca2+ channels to regulate Ca2+ entry. In neuroblastoma SH-SY5Y cells and in familial Alzheimer’s disease patient skin fibroblasts, STIM1 is cleaved at the transmembrane domain by the presenilin-1-associated γ-secretase, leading to dysregulation of Ca2+ homeostasis. In this report, we investigated expression levels of STIM1 in brain tissues (medium frontal gyrus) of pathologically confirmed Alzheimer’s disease patients, and observed that STIM1 protein expression level decreased with the progression of neurodegeneration. To study the role of STIM1 in neurodegeneration, a strategy was designed to knock-out the expression of STIM1 gene in the SH-SY5Y neuroblastoma cell line by CRISPR/Cas9-mediated genome editing, as an in vitro model to examine the phenotype of STIM1-deficient neuronal cells. It was proved that, while STIM1 is not required for the differentiation of SH-SY5Y cells, it is absolutely essential for cell survival in differentiating cells. Differentiated STIM1-KO cells showed a significant decrease of mitochondrial respiratory chain complex I activity, mitochondrial inner membrane depolarization, reduced mitochondrial free Ca2+ concentration, and higher levels of senescence as compared with wild-type cells. In parallel, STIM1-KO cells showed a potentiated Ca2+ entry in response to depolarization, which was sensitive to nifedipine, pointing to L-type voltage-operated Ca2+ channels as mediators of the upregulated Ca2+ entry. The stable knocking-down of CACNA1C transcripts restored mitocondrial function, increased mitochondrial Ca2+ levels, and dropped senescence to basal levels, emonstrating the essential role of the upregulation of voltage-operated Ca2+ entry through Cav1.2 channels in STIM1-deficient SHSY5Y cell death.• Ministerio de Educación, Cultura y Deporte. Beca FPU13/03430 • The Company of Biologists. Ayuda JCSTF-170507 • Ministerio de Economía, y Competitividad. Proyectos BFU2014-52401-P y BFU2017-82716, para Francisco Javier Martín Romero • Ministerio de Economía, y Competitividad. Proyectos BFU2014-53641-P y BFU2017-85723-P, para Ana María Mata Durán y Carlos Gutiérrez Merino • Junta de Extremadura. Ayudas GRU15077 e IB16088, para Francisco Javier Martín Romero • Junta de Extremadura. Ayuda GRU15139, para Ana María Mata DuránpeerReviewe

SARS-CoV-2 viral load in nasopharyngeal swabs is not an independent predictor of unfavorable outcome

The aim was to assess the ability of nasopharyngeal SARS-CoV-2 viral load at first patient’s hospital evaluation to predict unfavorable outcomes. We conducted a prospective cohort study including 321 adult patients with confirmed COVID-19 through RT-PCR in nasopharyngeal swabs. Quantitative Synthetic SARS-CoV-2 RNA cycle threshold values were used to calculate the viral load in log10 copies/mL. Disease severity at the end of follow up was categorized into mild, moderate, and severe. Primary endpoint was a composite of intensive care unit (ICU) admission and/or death (n = 85, 26.4%). Univariable and multivariable logistic regression analyses were performed. Nasopharyngeal SARS-CoV-2 viral load over the second quartile (≥ 7.35 log10 copies/mL, p = 0.003) and second tertile (≥ 8.27 log10 copies/mL, p = 0.01) were associated to unfavorable outcome in the unadjusted logistic regression analysis. However, in the final multivariable analysis, viral load was not independently associated with an unfavorable outcome. Five predictors were independently associated with increased odds of ICU admission and/or death: age ≥ 70 years, SpO2, neutrophils > 7.5 × 103/µL, lactate dehydrogenase ≥ 300 U/L, and C-reactive protein ≥ 100 mg/L. In summary, nasopharyngeal SARS-CoV-2 viral load on admission is generally high in patients with COVID-19, regardless of illness severity, but it cannot be used as an independent predictor of unfavorable clinical outcome

Reseñas

[ES] Seguí de la Riva , Javier. Sobre dibujar y proyectar (por Javier Seguí de la Riva) pp. 4.-- Dibujar, proyectar LVI y LVII Arte y muerte I y II ( por Javier Seguí de la Riva) pp. 6.-- dibujar, proyectar LVIII El imaginario del dibujar (por Javier Seguí de la Riva) pp. 6 y 7.-- Dibujar, proyectar LVI y LVII Diagrama, diagramar I y II ( por Javier Seguí de la Riva) pp. 7.-- DIBUJAR, proyectar LVIII El imaginario del dibujar ( por Javier Seguí de la Riva) pp. 6 y 7.-- DIBUJAR, PROYECTAR LVI y LVII Diagrama, diagramar I y II (por Javier Seguí de la Riva) pp.7.-- DIBUJAR, PROYECTAR LIX, LX y LXI Escritos críticos I, II y III ( por Javier Seguí de la Riva) pp. 7 .-- Rehabilitacion del Antiguo Hospital San Juan de Dios para Biblioteca y Archivo Historico de Orihuela (por Ana Torres Barchino) pp. 8.-- Arnau Amo, Joaquín. Arquitectura. Ritos y ritmos (por María Elia Gutiérrez Mozo) pp. 8 y 9.—Cardone, Vito. Viaggiatori d’architettura in Italia. Da Brunelleschi a Charles Garnier (por Cesare Cundari) pp. 9 y 10.-- Casado de Amezúa Vázquez, Joaquín. Las casas reales de la Alhambra. Geometría y espacio. Una aproximación al proceso de formación del espacio ( por Pilar Chías Navarro)pp. 10.-- Jaén i Urban, Gaspar; Baldomá Soto, Montserrat y Carrasco Martí, Maria Antonia. One century of photography and preservation in catalonia: the service for local architectural heritage ( por Pilar Chías Navarro) pp. 10 y 11.-- Jaén i Urban, Gaspar. El paisaje urbano de Nueva York en la obra escrita de Federico García Lorca (por Concepción López González y Jorge García valldecabres) pp. 11.—Trachana, Angelique. Urbe Ludens ( por Gonzalo García-Rosales) pp. 12.-- Fernández-Palacios, Victoria; Yanguas, Ana; Jiménez Fdez-Palacios, Luz. Manuel Aires Mateus. Cuaderno de La Alhambra ( por José Mª Gentil Baldrich) pp. 12 y 13.-- Agustín, Luis; Miret, Elena; Vallespín, Aurelio. Representación del espacio arquitectónico. 2011.12 (por Jesús Aparicio Guisado) pp. 14.—Herschdorfer, Nathalie y Lada Umstätter, Thames. Le Corbusier and the Power of Photography (por víctor A. Lafuente Sánchez) pp. 14 y 15.-- Roma en el bolsillo. Cuadernos de dibujo y aprendizaje artístico en el siglo XVIII ( por Fernando Linares García) pp. 15 y 16.-- Vicens y Hualde, Ignacio. Dicho y hecho ( por Fernando Linares García) pp 16.-- Le Corbusier. El arte decorativo de hoy ( por Carlos Montes Serrano )pp. 16 y 17.—Jenkins Birkhäuser, Eric J. Drawn to Design: Analyzing Architecture Through Freehand Drawing ( por víctor A. Lafuente Sánchez) pp. 17 y 18.—Sobrino, Miguel. Monasterios. Las biografías desconocidas de los cenobios de España ( por Javier García-Gutiérrez Mosteiro) pp. 18 y 19.-- Jiménez Martín, Alfonso. Anatomía de la Catedral de Sevilla ( por Francisco Pinto Puerto) pp. 19.-- Raposo Grau, Javier Fco; Butragueño Díaz-Guerra, Belen y Paredes Maldonado, Miguel. Dibujar, analizar, proyectar (2010) Título I. Colección dibujo, proyecto y arquitectura ( por Mariasun Salgado de la Rosa) pp. 19 y 20.-- Raposo Grau, Fco Javier; Butragueño Díaz-Guerra, Belen y Paredes Maldonado, Miguel. Dibujar, analizar, proyectar (2011) Título III. Colección dibujo, proyecto y arquitectura ( por Carlos L. Marcos Alba) pp. 20-22.-- García Doménech, Sergio. Reflexiones urbanas sobre el espacio público de Alicante. Una interpretación de la ciudad y sus escenarios ( por Juan Calduch Cervera) pp. 22 y 23.—Cundari, Casere. Il rilievo architettonico. Ragioni. Fondamenti. Applicazioni ( por Antonio Álvaro Tordesillas) pp. 23 y 24.—Autores varios. Perspectiva-Prospettiva. La práctica de la perspectiva ( por José Mª Gentil Baldrich) pp. 24 y 25.-- Soler Sanz, Felipe. Trazados Reguladores en la Arquitectura ( por Jorge García Valldecabres) pp. 25.-- Jiménez Alcañiz, Cesar. Análisis de las metodologías para la recuperación patrimonial de entornos urbanos protegidos. Propuesta metodológica: desde los valores históricos a los nuevos modelos energéticos. Russafa desde el siglo XIX( Por Pablo Navarro Esteve) pp. 26.-- de Coca Leicher, José. El recinto ferial de la Casa de Campo de Madrid (1950-75)( por Esteban Herrero Cantalapiedra) pp. 27.-- La arquitectura religiosa renacentista en tierras del Maestre: la iglesia de Nuestra Señora de la Asunción de Vistabella del Maestrazgo ( por José Teodoro Garfella Rubio) pp. 27 y 28.-- Arquitectura de los balnearios en Galicia. Cuenca del Miño. 1816-1936 ( por José Antonio Franco Taboada)pp. 28 y 29.-- Barros da Rocha e Costa. Historia de la representación gráfica del Castillo de Peñíscola. Del grafito al láser ( por Pablo Navarro Esteve) pp. 29.-- Rivas López, Esteban José. El Carmen de la fundación Rodríguez-Acosta. Una indagación gráfica ( por Joaquín Casado de Amezúa) pp.30.-- Verdejo Gimeno, Pedro. Estaciones intermedias de ferrocarril. La sección “Non nata” Teruel-Alcañiz (por Jorge Girbés Pérez) pp. 30 y 31.-- Sender Contell, Marina. El Monasterio de Santa María de la Murta. Análisis arquitectónico de un Monasterio Jerónimo ( por Pablo Navarro Esteve) pp. 32.-- Iñarra Abad, Susana. El Render de Arquitectura. Análisis de la Respuesta Emocional del Observador ( por Pablo Navarro Esteve) pp. 32 y 33.-- Fernández Morales, Angélica. De concreto a conceptual. Relaciones entre arte y arquitectura en el contexto helvético contemporáneo ( por Luis Agustín) pp. 33.—EXPOSICIÓN: Intervenciones cromáticas en los comercios del centro histórico ( por Jorge Llopis verdú) pp. 34 y 35.Seguí De La Riva, J.; Torres Barchino, A.; Gutiérrez Mozo, ME.; Cundari, C.; Chías Navarro, P.; López González, C.; García Valldecabres, J.... (2014). Reseñas. EGA. Revista de Expresión Gráfica Arquitectónica. 19(24):4-35. https://doi.org/10.4995/ega.2014.3268SWORD435192

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy:Study protocol of a cluster randomized clinical trial (Multi-PAP project)

This study was funded by the Fondo de Investigaciones Sanitarias ISCIII (Grant Numbers PI15/00276, PI15/00572, PI15/00996), REDISSEC (Project Numbers RD12/0001/0012, RD16/0001/0005), and the European Regional Development Fund ("A way to build Europe").Background: Multimorbidity is associated with negative effects both on people's health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12months, as compared with usual care. Methods/Design: Design:pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65-74years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3months). Sample size: n=400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle. Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes. Trial registration: Clinicaltrials.gov, NCT02866799Publisher PDFPeer reviewe

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Profilaxis tromboembólica en cirugía ortopédica y traumatología.

La profilaxis tromboembólica en cirugía ortopédica está muy bien establecida en la cirugía ortopédica mayor (artroplastia de cadera y rodilla y cirugía de fractura de cadera) y habitualmente el agente elegido son las Heparinas de Bajo Peso Molecular (HBPM), si bien en los últimos años los Anticoagulantes de Acción Directa (ACODs), están ganando terreno y pueden utilizarse en este escenario (salvo en la cirugía de fractura de cadera) ; incluso en EEUU la aspirina podría tener su indicación en pacientes de bajo riesgo que se intervengan de artroplastia de cadera o rodilla. En el resto de cirugía ortopédica (cirugía de extremidad inferior por debajo de la rodilla, tobillo y pie; artroscopia de rodilla, cirugía de extremidad superior y cirugía de columna), dado que el riesgo de Enfermedad Tromboembólica es menor, exige una individualización de la profilaxis tromboembólica, según los factores de riesgo del paciente y las características de la cirugía. En este grupo de pacientes el agente elegido son las HBPM, dado que los ACODs no están aprobados en estos tipos de cirugía.pre-print652 K

Obesidad infantil: causas y consecuencias

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid. Facultad de Medicina, Departamento de Medicina. Fecha de lectura: 21 de Diciembre de 200