La variabilidad espacio-temporal del régimen térmico en España como fundamento para evaluar los efectos potenciales del estado del tiempo sobre la salud humana

Ponencia presentada en: VIII Congreso de la Asociación Española de Climatología celebrado en Salamanca entre el 25 y el 28 de septiembre de 2012.[ES]La temperatura del aire resulta un elemento meteorológico determinante en los estudios para evaluar los efectos del estado del tiempo sobre la salud de los seres vivos, incluyendo al hombre. Las variaciones espacio-temporales de este elemento condicionan respuestas específicas del sistema termorregulador y, en consecuencia, por encima o por debajo de ciertos límites fisiológicos individuales, los cambios bruscos de la temperatura del aire pueden producir efectos meteoro-trópicos significativos entre la población más susceptible. Se utiliza un método de trabajo fundamentado en las variaciones espacio-temporales del complejo temperatura máxima-mínima diaria del aire. Este procedimiento ha sido adaptado a las condiciones españolas y se han procesado más de 100 puntos de observación con datos públicos de la AEMET estandarizados y representativos para el período 1981-2010. Se demuestra que las variaciones bruscas y anómalas del régimen térmico constituyen un significativo factor de riesgo para la salud humana.[EN]The air temperature is a decisive meteorological element in the studies to evaluate the effects of weather changes on the health of the living organisms, including man. The time and space variations of this element produce specific physiological responses of the thermal regulation system and, in consequence, above or below certain individual physiological threshold, the abrupt changes of the air temperature may produce significant meteor-tropic effects among the most sensitive population. A work method based upon the objective classification of the time and space variations of the daily extreme air temperatures was used. This procedure has been implemented to the Spanish conditions with the aim the AEMET public climate data from more than 100 climate stations. The whole information was completed and standardized for the period 1981-2010. It was demonstrated that the abrupt and anomalous variations of the thermal regime constitute a significant risk factor for the human health

Activity dependent internalization of the glutamate transporter GLT-1 requires calcium entry through the NCX sodium/calcium exchanger

GLT-1 is the main glutamate transporter in the brain and its trafficking controls its availability at the cell surface, thereby shaping glutamatergic neurotransmission under physiological and pathological conditions. Extracellular glutamate is known to trigger ubiquitin-dependent GLT-1 internalization from the surface of the cell to the intracellular compartment, yet here we show that internalization also requires the participation of calcium ions. Consistent with previous studies, the addition of glutamate (1 mM) to mixed primary cultures (containing neurons and astrocytes) promotes GLT-1 internalization, an effect that was suppressed in the absence of extracellular Ca. The pathways of Ca mobilization by astrocytes were analyzed in these mixed cultures using the genetically encoded calcium sensor GCaMP6f. A complex pattern of calcium entry was activated by glutamate, with a dramatic and rapid rise in the intracellular Ca concentration partially driven by glutamate transporters, especially in the initial stages after exposure to glutamate. The Na/Ca exchanger (NCX) plays a dominant role in this Ca mobilization and its blockade suppresses the glutamate induced internalization of GLT-1, both in astrocytes and in a more straightforward experimental system like HEK293 cells transiently transfected with GLT-1. This regulatory mechanism might be relevant to control the amount of GLT-1 transporter at the cell surface in conditions like ischemia or traumatic brain injury, where extracellular concentrations of glutamate are persistently elevated and they promote rapid Ca mobilization.This work was supported by grants from the Spanish MINECO (SAF2014- 55686-R) and the “Fundación Ramón Areces

Identification by proximity labeling of novel lipidic and proteinaceous potential partners of the dopamine transporter

Dopamine (DA) transporters (DATs) are regulated by trafficking and modulatory processes that probably rely on stable and transient interactions with neighboring proteins and lipids. Using proximity-dependent biotin identification (BioID), we found novel potential partners for DAT, including several membrane proteins, such as the transmembrane chaperone 4F2hc, the proteolipid M6a and a potential membrane receptor for progesterone (PGRMC2). We also detected two cytoplasmic proteins: a component of the Cullin1-dependent ubiquitination machinery termed F-box/LRR-repeat protein 2 (FBXL2), and the enzyme inositol 5-phosphatase 2 (SHIP2). Immunoprecipitation (IP) and immunofluorescence studies confirmed either a physical association or a close spatial proximity between these proteins and DAT. M6a, SHIP2 and the Cullin1 system were shown to increase DAT activity in coexpression experiments, suggesting a functional role for their association. Deeper analysis revealed that M6a, which is enriched in neuronal protrusions (filopodia or dendritic spines), colocalized with DAT in these structures. In addition, the product of SHIP2 enzymatic activity (phosphatidylinositol 3,4-bisphosphate [PI(3,4)P2]) was tightly associated with DAT, as shown by co-IP and by colocalization of mCherry-DAT with a specific biosensor for this phospholipid. PI(3,4)P2 strongly stimulated transport activity in electrophysiological recordings, and conversely, inhibition of SHIP2 reduced DA uptake in several experimental systems including striatal synaptosomes and the dopaminergic cell line SH-SY5Y. In summary, here we report several potential new partners for DAT and a novel regulatory lipid, which may represent new pharmacological targets for DAT, a pivotal protein in dopaminergic function of the brainOpen Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This work was supported by grants from the Spanish MINECO (RTI2018-098712-B-100) and the “Fundación Ramón Areces”, the latter also providing an institutional grant to CBMS

Clasificación compleja y objetiva de los estados del tiempo diarios según la estructura del régimen térmico del aire y otros indicadores biometeorológicos

Ponencia presentada en: VIII Congreso de la Asociación Española de Climatología celebrado en Salamanca entre el 25 y el 28 de septiembre de 2012.[ES]Recientes estudios han permitido demostrar que la estructura del régimen térmico del aire, definida según el comportamiento predominante de las temperaturas máximas y mínimas diarias, constituye un primer paso para evaluar los efectos potenciales de los cambios bruscos del tiempo atmosférico como factor de riesgo para la salud humana. En el presente trabajo se propone un criterio de clasificación compleja de los estados del tiempo diarios (ETD) para su aplicación biometeorológica en el territorio español. Se pone de manifiesto la estrecha relación existente entre los cambios inter-diarios de elevado contraste en el estado del tiempo y el aumento notable en la ocurrencia diaria de algunas enfermedades crónicas no transmisibles. Los resultados obtenidos permiten diseñar un sistema de alerta sanitaria a partir de pronósticos biometeorológicos con la capacidad de prevenir la ocurrencia de condiciones biometeorológicas peligrosas para la salud humana.[EN]Recent studies have demonstrated that the time and space variations of the air thermal regime, based upon the behavior of daily extreme air temperatures, constitutes a good approach to evaluate the potential effects of abrupt weather changes on human health, and therefore, they may be considered such a significant risk factor for human health. The present work gives the fundaments for the development of a complex classification criterium of daily weather types (DWT) for its biometeorological use into the Spanish territory. A strong relationship among the occurrence of interdaily contrasting weather changes and the remarkable daily increase of some chronic non communicable diseases was found. The obtained results allowed the design of an early health alert system, based upon objective models of biometeorological forecasts. This operational system may inform to the medical institutions up to 7 days in advance on the occurrence of dangerous meteortropic effects. It will permit to mitigate their impacts on the health of the most sensitive groups of the local population

Decreased salivary lactoferrin levels are specific to Alzheimer's disease

Background: Evidences of infectious pathogens in Alzheimer's disease (AD) brains may suggest a deteriorated innate immune system in AD pathophysiology. We previously demonstrated reduced salivary lactoferrin (Lf) levels, one of the major antimicrobial proteins, in AD patients. Methods: To assess the clinical utility of salivary Lf for AD diagnosis, we examine the relationship between salivary Lf and cerebral amyloid-beta (A beta) load using amyloid-Positron-Emission Tomography (PET) neuroimaging, in two different cross-sectional cohorts including patients with different neurodegenerative disorders. Findings: The diagnostic performance of salivary Lf in the cohort 1 had an area under the curve [AUC] of 0.95 (0.911-0.992) for the differentiation of the prodromal AD/AD group positive for amyloid-PET (PET+) versus healthy group, and 0.97 (0.924-1) versus the frontotemporal dementia (FTD) group. In the cohort 2, salivary Lf had also an excellent diagnostic performance in the health control group versus prodromal AD comparison: AUC 0.93 (0.876-0.989). Salivary Lf detected prodromal AD and AD dementia distinguishing them from FTD with over 87% sensitivity and 91% specificity. Interpretation: Salivary Lf seems to have a very good diagnostic performance to detect AD. Our findings support the possible utility of salivary Lf as a new non-invasive and cost-effective AD biomarker.This study was supported by Dr. Carro grants from Instituto de Salud Carlos III (FIS15/00780, FIS18/00118), FEDER, Comunidad de Madrid (S2017/BMD-3700; NEUROMETAB-CM), and CIBERNED (PI2016/01). This study was also supported by research grants from the Spanish Ministry of Economy and Competitiveness (SAF201785310-R to Dr. Cantero, PSI2017-85311-P to Dr. Atienza); International Centre on ageing CENIE-POCTEP (0348_CIE_6_E to Dr. Atienza); and CIBERNED (CB06/05/1111 to Dr. Cantero). Dr. Bueno receives research funding from the Instituto de Salud Carlos III, Spain (PIE16/00021, PI17/01799). The H2H-Spain Study was supported in Spain by grant PIE16/00021 from Instituto Carlos III, Ministry of Science, Innovation and Universities, and additional funds from the Centro Nacional de Investigaciones Cardiovasculares (CNIC). The CNIC is supported by the Ministry of Economy, Industry and Competitiveness and the Pro CNIC Foundation, and is a Severo Ochoa Centre of Excellence (SEV-2015-0505). The funders had no role in the conceptualisation, study design, data collection analysis and preparation of this manuscript

Matching microscopic and macroscopic responses in glasses

Primero reproducimos en las computadoras Janus y Janus II un experimento importante que mide la longitud de la coherencia de los hilados de vidrio a través de la reducción de las barreras de energía libre inducidas por el efecto Zeeman. En segundo lugar, determinamos el comportamiento de escala que permite un análisis cuantitativo de un nuevo experimento informado en la Carta complementaria [S. Guchhait y R. Orbach, Phys. Rev. Lett. 118, 157203 (2017)]. El valor de la longitud de coherencia estimada a través del análisis de las funciones de correlación microscópicas resulta ser cuantitativamente consistente con su medición a través de las funciones de respuesta macroscópica. Además, las susceptibilidades no lineales, recientemente medidas en líquidos formadores de vidrio, se escalan como potencias de la misma longitud microscópica.We first reproduce on the Janus and Janus II computers a milestone experiment that measures the spin glass coherence length through the lowering of free-energy barriers induced by the Zeeman effect. Secondly, we determine the scaling behavior that allows a quantitative analysis of a new experiment reported in the companion Letter [S. Guchhait and R. Orbach, Phys. Rev. Lett. 118, 157203 (2017)]. The value of the coherence length estimated through the analysis of microscopic correlation functions turns out to be quantitatively consistent with its measurement through macroscopic response functions. Further, nonlinear susceptibilities, recently measured in glass-forming liquids, scale as powers of the same microscopic length.• European Research Council. Beca No. NPRGGLASS. Ayuda para Marco Baity Jesi • Unión Europea. Marie Skłodowska- Curie. Beca No. 654971 • Consejo Europeo de Investigación (ERC). Subvención 694925 • University of Syracuse. Beca No. NSF-DMR-305184, para David Yllanes Mosquera • Ministerio de Economía y Competitividad. No. FIS2012-35719-C02, No. FIS2013-42840-P (I+D+i), No. FIS2015-65078-C2, No. FIS2016-76359-P (I+D+i), y No. TEC2016-78358-R • Junta de Extremadura y Fondos FEDER. Contrato parcial GRU10158 • Dipùtación General de Aragón y Fondos Social Europeo. AyudapeerReviewe

Plasma Gelsolin Reinforces the Diagnostic Value of FGF-21 and GDF-15 for Mitochondrial Disorders

Mitochondrial disorders (MD) comprise a group of heterogeneous clinical disorders for which non-invasive diagnosis remains a challenge. Two protein biomarkers have so far emerged for MD detection, FGF-21 and GDF-15, but the identification of additional biomarkers capable of improving their diagnostic accuracy is highly relevant. Previous studies identified Gelsolin as a regulator of cell survival adaptations triggered by mitochondrial defects. Gelsolin presents a circulating plasma isoform (pGSN), whose altered levels could be a hallmark of mitochondrial dysfunction. Therefore, we investigated the diagnostic performance of pGSN for MD relative to FGF-21 and GDF-15. Using ELISA assays, we quantified plasma levels of pGSN, FGF-21, and GDF-15 in three age- and gender-matched adult cohorts: 60 genetically diagnosed MD patients, 56 healthy donors, and 41 patients with unrelated neuromuscular pathologies (non-MD). Clinical variables and biomarkers’ plasma levels were compared between groups. Discrimination ability was calculated using the area under the ROC curve (AUC). Optimal cut-offs and the following diagnostic parameters were determined: sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios, and efficiency. Comprehensive statistical analyses revealed significant discrimination ability for the three biomarkers to classify between MD and healthy individuals, with the best diagnostic performance for the GDF-15/pGSN combination. pGSN and GDF-15 preferentially discriminated between MD and non-MD patients under 50 years, whereas FGF-21 best classified older subjects. Conclusion: pGSN improves the diagnosis accuracy for MD provided by FGF-21 and GDF-15

Evaluation of the potential association of SOHLH2 polymorphisms with non-obstructive azoospermia susceptibility in a large European population

Non-obstructive azoospermia (NOA) or spermatogenic failure is a complex disease with an important genetic component that causes infertility in men. Known genetic factors associated with NOA include AZF microdeletions of the Y chromosome or karyotype abnormalities; however, most causes of NOA are idiopathic. During the last decade, a large list of associations between single-nucleotide polymorphisms (SNP) and NOA have been reported. However, most of the genetic studies have been performed only in Asian populations. We aimed to evaluate whether the previously described association in Han Chinese between NOA and two SNPs of the SOHLH2 gene (involved in the spermatogenesis process) may also confer risk for NOA in a population of European ancestry. We genotyped a total of 551 NOA patients (218 from Portugal and 333 from Spain) and 1,050 fertile controls (226 from Portugal and 824 from Spain) for the genetic variants rs1328626 and rs6563386 using TaqMan assays. To test for association, we compared the allele and genotype frequencies between cases and controls using an additive model. A haplotype analysis and a meta-analysis using the inverse variance method with our data and those of the original Asian study were also performed. No statistically significant differences were observed in any of the analyses described above. Therefore, considering the high statistical power of our study, it is not likely that the two analysed SOHLH2 genetic variants are related with an increase susceptibility to NOA in the European population.info:eu-repo/semantics/publishedVersio

Heterozygous and Homozygous Variants in SORL1 Gene in Alzheimer's Disease Patients: Clinical, Neuroimaging and Neuropathological Findings

In the last few years, the SORL1 gene has been strongly implicated in the development of Alzheimer’s disease (AD). We performed whole-exome sequencing on 37 patients with early-onset dementia or family history suggestive of autosomal dominant dementia. Data analysis was based on a custom panel that included 46 genes related to AD and dementia. SORL1 variants were present in a high proportion of patients with candidate variants (15%, 3/20). We expand the clinical manifestations associated with the SORL1 gene by reporting detailed clinical and neuroimaging findings of six unrelated patients with AD and SORL1 mutations. We also present for the first time a patient with the homozygous truncating variant c.364C>T (p.R122*) in SORL1, who also had severe cerebral amyloid angiopathy. Furthermore, we report neuropathological findings and immunochemistry assays from one patient with the splicing variant c.4519+5G>A in the SORL1 gene, in which AD was confirmed by neuropathological examination. Our results highlight the heterogeneity of clinical presentation and familial dementia background of SORL1-associated AD and suggest that SORL1 might be contributing to AD development as a risk factor gene rather than as a major autosomal dominant gene.This work was supported by the Instituto de Salud Carlos III (PI17/01067) and AGAUR from the Autonomous Catalan Government (2017SGR1134). Dr. Víctor Antonio Blanco-Palmero is supported by the Instituto de Salud Carlos III (ISCIII, Spanish Biomedical Research Institute) through a “Río Hortega” contract (CM18/0095). Dr. Sara Llamas-Velasco is supported by the Instituto de Salud Carlos III (ISCIII; Spanish Biomedical Research Institute) through a “Juan Rodés” contract (JR 18/00046).S

Herramientas audiovisuales online y protocolos en la formación, adaptación y gestión de lentes de contacto. Un modelo innovador en la Clínica Universitaria de Optometría de la UCM

Con fines docentes y asistenciales, incluye Videos sobre manejo y limpieza de distintos tipos de lentes de contacto. Para la correcta formación de los estudiantes incluye varios manuales sobre el estudio ocular previo a la adaptación. Con fines asistenciales incorpora Material para acompañar la adaptación y entrega de las lentes de contacto. Para mejorar la gestión, incluye un Video-tutorial y los protocolos creados para los pedidos y gestión de las lentes de contacto