Search

Background: Switching between calcitonin gene-related peptide (CGRP) and monoclonal antibodies (mAbs) may be a beneficial strategy after discontinuation. The aim of this study was to evaluate switching outcomes of effectiveness/tolerability. Methods: Retrospective multicentric study of migraine patients who switched to another CGRP–mAb due to lack of tolerability or effectiveness (defined as

Introduction: Older patients are more likely to have cognitive dysfunction, and a great proportion of patients undergone surgical procedures are older adults. Postoperative cognitive dysfunction (POCD) has been shown as a consistent complication after major surgical procedures such as heart surgery. Aim: To determine the presence of long-term POCD in ≥65-year-old patients undergoing coronary artery bypass grafting and aortic valve replacement, and to establish related risk factors. Methods: We prospectively and sequentially included 44 patients with coronary disease and aortic stenosis scheduled for heart surgery. Follow-up of all patients was standardized and a neurocognitive evaluation were performed preoperatively and at 1, 6 and 12 months after surgery. Results: Patients experienced a significantly postoperative cognitive dysfunction (33.5%, 63.4% and 38.9% at 1, 6 and 12 months, respectively) from baseline (20.5%). Patient-associated aspects such as age (p

Resumen: Introducción y objetivo: La cefalea representa un motivo de consulta frecuente entre los médicos de atención primaria, urgencias y especialistas en Neurología, que no siempre es bien manejada. El Grupo de Cefaleas de la Sociedad Andaluza de Neurología (SANCE) se plantea conocer su manejo entre los distintos niveles asistenciales. Material y métodos: Estudio descriptivo transversal realizado mediante una encuesta retrospectiva en julio de 2019. Los participantes completaron una serie de cuestionarios estructurados recogiéndose distintas variables socio-laborales en cuatro grupos sanitarios distintos (Atención Primaria, Servicios de Urgencias, Neurología General, Unidades de Cefalea). Resultados: Se llevaron a cabo un total de 204 entrevistas repartidas entre los distintos grupos profesionales: 35 médicos de urgencias, 113 de atención primaria, 37 neurólogos generales y 19 neurólogos especialistas en cefaleas. El 85% de los médicos de AP prescribe fármacos preventivos, que mantiene durante al menos seis meses (59%), siendo flunarizina y amitriptilina los más utilizados. La atención primaria representa la vía principal de llegada a las consultas de Neurología General (65%), siendo los cambios en el patrón de la cefalea el principal motivo de derivación (74%). Todos los niveles asistenciales incluidos en el trabajo muestran gran interés en la cefalea y en la posibilidad de asistir a cursos de formación (97% AP, 100% médicos de urgencias, 100% neurólogos generales). Conclusiones: El presente trabajo ha observado escasez de recursos reflejado por prolongadas listas de esperas, así como gran interés en las cefaleas por parte de los participantes. Es necesario buscar otras formas de comunicación bilateral entre los distintos ámbitos asistenciales, como por ejemplo el correo electrónico. Abstract: Introduction and objective: Headache is a frequent reason for consultation between primary care physicians, emergency services physicians, and neurology specialists; however, it is not always well managed. The Andalusian Society of Neurology's Headache Study Group (SANCE) aimed to analyse headache management at different levels of care. Material and methods: We conducted a descriptive cross-sectional study with data gathered through a retrospective survey in July 2019. Participants completed a series of structured questionnaires on different social and work-related variables from 4 different groups of healthcare professionals (primary care [PC], emergency departments, neurology departments, headache units). Results: A total of 204 healthcare professionals completed the survey: 35 emergency department physicians, 113 PC physicians, 37 general neurologists, and 19 neurologists specialising in headache. Eighty-five percent of PC physicians reported prescribing preventive drugs, which were maintained for at least 6 months (59%), with flunarizine and amitriptyline being the most commonly used. Most patients attended at neurology consultations (65%) are referred by PC physicians, with changes in the headache pattern being the main reason for referral (74%). Healthcare professionals across all levels of care showed great interest in headache and in receiving training in headache management (97% of PC physicians, 100% of emergency services physicians, 100% of general neurologists). Conclusions: Migraine sparks great interest among healthcare professionals from different levels of care. Our results also reveal a lack of resources for headache management, which is reflected in the long waiting times. Other means of bilateral communication between different levels of care should be explored (e.g., e-mail).

Introduction: Ischaemic stroke is the most common neurological complication of cardiac catheterisation. This study aims to analyse the clinical and prognostic differences between post-catheterisation stroke code (SC) and all other in-hospital and prehospital SC. Methods: We prospectively recorded SC activation at our centre between March 2011 and April 2016. Patients were grouped according to whether SC was activated post-catheterisation, in-hospital but not post-catheterisation, or before arrival at hospital; groups were compared in terms of clinical and radiological characteristics, therapeutic approach, functional status, and three-month mortality. Results: The sample included 2224 patients, of whom 31 presented stroke post-catheterisation. Baseline National Institutes of Health Stroke Scale score was lower for post-catheterisation SC than for other in-hospital SC and pre-hospital SC (5, 10, and 7, respectively; P = .02), and SC was activated sooner (50, 100, and 125 minutes, respectively; P

Various studies have reported that the photochemical nucleation of new ultrafine particles (UFPs) in urban environments within high insolation regions occurs simultaneously with high ground ozone (O3) levels. In this work, we evaluate the atmospheric dynamics leading to summer O3 episodes in the Madrid air basin (central Iberia) by means of measuring a 3-D distribution of concentrations for both pollutants. To this end, we obtained vertical profiles (up to 1200 m above ground level) using tethered balloons and miniaturised instrumentation at a suburban site located to the SW of the Madrid Metropolitan Area (MMA), the Majadahonda site (MJDH), in July 2016. Simultaneously, measurements of an extensive number of air quality and meteorological parameters were carried out at three supersites across the MMA. Furthermore, data from O3 soundings and daily radio soundings were also used to interpret atmospheric dynamics.The results demonstrate the concatenation of venting and accumulation episodes, with relative lows (venting) and peaks (accumulation) in O3 surface levels. Regardless of the episode type, the fumigation of high-altitude O3 (arising from a variety of origins) contributes the major proportion of surface O3 concentrations. Accumulation episodes are characterised by a relatively thinner planetary boundary layer ( 2400 m a.s.l.). This orographic–meteorological setting causes the vertical recirculation of air masses and enrichment of O3 in the lower tropospheric layers. When the highly polluted urban plume from Madrid is affected by these dynamics, the highest Ox (O3+ NO2) concentrations are recorded in the MMA.Vertical O3 profiles during venting episodes, with strong synoptic winds and a deepening of the planetary boundary layer reaching > 2000 m a.s.l., were characterised by an upward gradient in O3 levels, whereas a reverse situation with O3 concentration maxima at lower levels was found during the accumulation episodes due to local and/or regional production. The two contributions to O3 surface levels (fumigation from high-altitude strata, a high O3 background, and/or regional production) require very different approaches for policy actions. In contrast to O3 vertical top-down transfer, UFPs are formed in the planetary boundary layer (PBL) and are transferred upwards progressively with the increase in PBL growth.

Ground-level and vertical measurements (performed using tethered and non-tethered balloons), coupled with modelling, of ozone (O3), other gaseous pollutants (NO, NO2, CO, SO2) and aerosols were carried out in the plains (Vic Plain) and valleys of the northern region of the Barcelona metropolitan area (BMA) in July 2015, an area typically recording the highest O3 episodes in Spain. Our results suggest that these very high O3 episodes were originated by three main contributions: (i) the surface fumigation from high O3 reservoir layers located at 1500–3000 m a.g.l. (according to modelling and non-tethered balloon measurements), and originated during the previous day(s) injections of polluted air masses at high altitude; (ii) local/regional photochemical production and transport (at lower heights) from the BMA and the surrounding coastal settlements, into the inland valleys; and (iii) external (to the study area) contributions of both O3 and precursors. These processes gave rise to maximal O3 levels in the inland plains and valleys northwards from the BMA when compared to the higher mountain sites. Thus, a maximum O3 concentration was observed within the lower tropospheric layer, characterised by an upward increase of O3 and black carbon (BC) up to around 100–200 m a.g.l. (reaching up to 300 µg m−3 of O3 as a 10 s average), followed by a decrease of both pollutants at higher altitudes, where BC and O3 concentrations alternate in layers with parallel variations, probably as a consequence of the atmospheric transport from the BMA and the return flows (to the sea) of strata injected at certain heights the previous day(s). At the highest altitudes reached in this study with the tethered balloons (900–1000 m a.g.l.) during the campaign, BC and O3 were often anti-correlated or unrelated, possibly due to a prevailing regional or even hemispheric contribution of O3 at those altitudes. In the central hours of the days a homogeneous O3 distribution was evidenced for the lowest 1 km of the atmosphere, although probably important variations could be expected at higher levels, where the high O3 return strata are injected according to the modelling results and non-tethered balloon data. Relatively low concentrations of ultrafine particles (UFPs) were found during the study, and nucleation episodes were only detected in the boundary layer. Two types of O3 episodes were identified: type A with major exceedances of the O3 information threshold (180 µg m−3 on an hourly basis) caused by a clear daily concatenation of local/regional production with accumulation (at upper levels), fumigation and direct transport from the BMA (closed circulation); and type B with regional O3 production without major recirculation (or fumigation) of the polluted BMA/regional air masses (open circulation), and relatively lower O3 levels, but still exceeding the 8 h averaged health target. To implement potential O3 control and abatement strategies two major key tasks are proposed: (i) meteorological forecasting, from June to August, to predict recirculation episodes so that NOx and VOC abatement measures can be applied before these episodes start; (ii) sensitivity analysis with high-resolution modelling to evaluate the effectiveness of these potential abatement measures of precursors for O3 reduction.

Introduction: The Umbilical Cord Blood Units (UCBU) for transplant are a therapeutic possibility for patients with a wide range of onco-hematologic disorders, especially in children. In Mexico, 48.5% of oncological diseases in children from 1 to 4 years old are leukemias; while in patients from 5 to 14 and 15 to 24 years of age lymphomas and leukemias are predominant and represent the second and third causes of death in these age groups, respectively. Therefore, is it necessary to have registries of UCBU to ensure the representation of the genetic diversity in Mexico in order to attend this requirement. Objective: To estimate the genetic diversity of HLA Class I (A, B) and Class II (DRB1) loci in cryopreserved UCBU of the Cord Blood Bank (CBB) at the National Center of Blood Transfusion (NCBT). Methods: HLA typing of 533 UCBU for transplant was performed at the Research Department (evaluated by “Los Angeles Ca. Inmunogenetics Center”). Class I HLA-A, HLA-B and Class II HLA-DRB1 typing was performed using medium resolution Sequence-Specific Primer (SSP). In cases of an ambiguity by SSP; Sequence-Specific Oligonucleotide (SSO) method was carried out. Results: 46.5% of the UCBU were obtained from Mexico City donors, 30.95% from the State of Mexico, 8.06% Puebla, 6.37% Morelos and 3.37% from Veracruz. The remaining UCBU 4.75% were represented by other states of the country. The most frequent loci for the HLA-A founded were *02/24, *02/68, *02/02, *02/30, *01/02, *02/31; for HLA-B, *35/39, *15/35, *35/40, *39/44, *07/35, *35/48, *39/40 and for HLA-DRB1, *04/08, *04/07, *04/15, *04/15, *04/03, *04/14. The genetic distances analysis showed that the top five populations analyzed in this study are significatively different from each other. Conclusions: The majority of the genotypes found suggest Amerindian and European origins and in a lesser proportion Oriental and African. The NCBT is therefore establishing agreements with different states of Mexico to promote the donation of UCBU in order to enrich the genetic diversity in the archives of the NCBT.

Introduction: Cervical artery dissection (CAD) is the cause of 2% to 3% of ischaemic strokes and 10% to 25% of the ischaemic strokes in young people. Our objective is to evaluate whether the implementation of a comprehensive stroke centre (CSC) improves the diagnosis and modifies the prognosis of patients with acute stroke due to CAD. Patients and methods: Retrospective study of a registry of consecutive patients with acute stroke due to CAD. They were classified according to the period of care at our centre: pre-CSC (October 2004 to March 2008, 42 months) or post-CSC (April 2008 to June 2012, 51 months). We compared baseline characteristics, methods of diagnosis, treatment and outcome of these patients in both periods. Results: Nine patients were diagnosed with CAD in the pre-CSC and 26 in the post-CSC, representing 0.8% and 2.1% of all ischaemic strokes treated in each period, respectively. The diagnosis of CAD was made within the first 24 hours in 42.3% of the patients in the post-CSC versus 0% in the pre-CSC, through the use of urgent cerebral angiography as a diagnostic test in 46.2% of cases in the second period compared to 0% in the first. The severity of stroke (median NIHSS score 11 vs. 3, P = .014) and time to neurological care (265 min vs. 148, P = .056) were higher in the post-CSC period. Endovascular treatment was performed in 34.3%, all in the post-CSC. The functional outcome was comparable in both periods. Conclusions: The implementation of a CSC increases the frequency of the diagnosis of CAD, as well as the treatment options for these patients in the acute phase of stroke. Resumen: Introducción: La disección de arterias cervicales (DAC) es la causa del 2-3% de ictus isquémicos y del 10-25% en pacientes jóvenes. Nuestro objetivo es evaluar si la implementación de un centro terciario de ictus (CTI) facilita el diagnóstico y modifica el pronóstico de los pacientes con ictus agudo por DAC. Pacientes y métodos: Estudio retrospectivo de un registro de pacientes consecutivos con ictus agudo por DAC. Se clasificaron según el periodo de atención: pre-CTI (octubre 2004-marzo 2008, 42 meses) o post-CTI (abril 2008-junio 2012, 51 meses). Se compararon las características basales, el método diagnóstico, el tratamiento y la evolución de estos pacientes entre ambos periodos. Resultados: Se diagnosticó a 9 pacientes con DAC en el periodo pre-CTI y 26 en el post-CTI, representando el 0,8 y el 2,1% de los ictus isquémicos atendidos en cada periodo. El diagnóstico de DAC se realizó en las primeras 24 h en el 42,3% de pacientes en el periodo post-CTI frente al 0% en el pre-CTI, gracias al uso de la arteriografía cerebral urgente como prueba diagnóstica en el 46,2% de los casos en el segundo periodo frente al 0% en el primero. La gravedad del ictus (mediana puntuación escala NIHSS 11 vs. 3, p = 0,014) y el tiempo hasta la atención neurológica (265 minutos vs. 148, p = 0,056) fueron mayores en la fase post-CTI. Se realizó tratamiento endovascular en el 34,3%, todos en el periodo post-CTI. El pronóstico funcional fue comparable en ambos periodos. Conclusiones: La implementación de un CTI incrementa la frecuencia en el diagnóstico de DAC y aumenta las opciones terapéuticas en la fase aguda del ictus en estos pacientes. Keywords: Cervical artery dissection, Stroke, Comprehensive stroke centre, Angiography, Systemic thrombolysis, Endovascular treatment, Palabras clave: Disección de arterias cervicales, Ictus, Centro terciario de ictus, Arteriografía, Trombólisis sistémica, Tratamiento endovascular

Resumen: Introducción: La disección de arterias cervicales (DAC) es la causa del 2-3% de ictus isquémicos y del 10-25% en pacientes jóvenes. Nuestro objetivo es evaluar si la implementación de un centro terciario de ictus (CTI) facilita el diagnóstico y modifica el pronóstico de los pacientes con ictus agudo por DAC. Pacientes y métodos: Estudio retrospectivo de un registro de pacientes consecutivos con ictus agudo por DAC. Se clasificaron según el periodo de atención: pre-CTI (octubre 2004-marzo 2008, 42 meses) o post-CTI (abril 2008-junio 2012, 51 meses). Se compararon las características basales, el método diagnóstico, el tratamiento y la evolución de estos pacientes entre ambos periodos. Resultados: Se diagnosticó a 9 pacientes con DAC en el periodo pre-CTI y 26 en el post-CTI, representando el 0,8 y el 2,1% de los ictus isquémicos atendidos en cada periodo. El diagnóstico de DAC se realizó en las primeras 24 h en el 42,3% de pacientes en el periodo post-CTI frente al 0% en el pre-CTI, gracias al uso de la arteriografía cerebral urgente como prueba diagnóstica en el 46,2% de los casos en el segundo periodo frente al 0% en el primero. La gravedad del ictus (mediana puntuación escala NIHSS 11 vs. 3, p = 0,014) y el tiempo hasta la atención neurológica (265 minutos vs. 148, p = 0,056) fueron mayores en la fase post-CTI. Se realizó tratamiento endovascular en el 34,3%, todos en el periodo post-CTI. El pronóstico funcional fue comparable en ambos periodos. Conclusiones: La implementación de un CTI incrementa la frecuencia en el diagnóstico de DAC y aumenta las opciones terapéuticas en la fase aguda del ictus en estos pacientes. Abstract: Introduction: Cervical artery dissection (CAD) is the cause of 2% to 3% of ischaemic strokes and 10% to 25% of the ischaemic strokes in young people. Our objective is to evaluate whether implementation of a comprehensive stroke centre (CSC) improves the diagnosis and modifies the prognosis of patients with acute stroke due to CAD. Patients and methods: Retrospective study of a registry of consecutive patients with acute stroke due to CAD. They were classified according to the period of care at our centre: pre-CSC (October 2004-March 2008, 42 months) or post-CSC (April 2008-June 2012, 51 months). We compared baseline characteristics, methods of diagnosis, treatment and outcome of these patients in both periods. Results: Nine patients were diagnosed with CAD in pre-CSC and 26 in post-CSC, representing 0.8% and 2.1% of all ischaemic strokes treated in each period, respectively. The diagnosis of CAD was made within the first 24 hours in 42.3% of the patients in post-CSC versus 0% in pre-CSC, by using urgent cerebral angiography as a diagnostic test in 46.2% of cases in the second period compared to 0% in the first. Both severity of stroke (median NIHSS score 11 vs. 3, P=.014) and time to neurological care (265 min vs 148, P=.056) were higher in the post-CSC period. Endovascular treatment was performed in 34.3%, and all treatments were post-CSC. The functional outcome was comparable for both periods. Conclusions: Implementation of a CSC increases the frequency of the diagnosis of CAD, as well as the treatment options for these patients in the acute phase of stroke. Palabras clave: Disección de arterias cervicales, Ictus, Centro terciario de ictus, Arteriografía, Trombólisis sistémica, Tratamiento endovascular, Keywords: Cervical artery dissection, Stroke, Comprehensive stroke center, Angiography, Systemic thrombolysis, Endovascular treatment

A three-dimensional air quality model based on a set of chemical species mass conservation equations describes the time evolution of chemical species in the atmosphere. In order to solve this set of equations, proper choices of initial and boundary conditions are needed. Ideally, initial and boundary conditions should be determined on the basis of observations. However, since such high-resolution observations are generally not available, it becomes necessary to use other information sources to specify the initial and boundary values. The fact that both the initial and the boundary conditions are specified with some degree of presumption makes it important to evaluate their influence in the model results. In this paper we present a study of the impact of initial and boundary concentrations on the modelled surface ozone concentration over two environments: Huelva and Badajoz, an industrial and a rural zone, respectively. The impacts are analysed for the same meteorological period (10–15 August 2003).

Throughout Europe the summer of 2003 was exceptionally warm, especially July and August. The European Environment Agency (EEA) reported several ozone episodes, mainly in the first half of August. These episodes were exceptionally long-lasting, spatially extensive, and associated to high temperatures. In this paper, the 10$ndash;15 August 2003 ozone pollution event has been analyzed using meteorological and regional air quality modelling. During this period the threshold values of the European Directive 2002/3/EC were exceeded in various areas of the Iberian Peninsula. The aim of this paper is to computationally understand and quantify the influence of biogenic volatile organic compound (BVOC) emissions in the formation of tropospheric ozone during this high ozone episode. Being able to differentiate how much ozone comes from biogenic emissions alone and how much comes from the interaction between anthropogenic and biogenic emissions would be helpful to develop a feasible and effective ozone control strategy. The impact on ozone formation was also studied in combination with various anthropogenic emission reduction strategies, i.e., when anthropogenic VOC emissions and/or NOx emissions are reduced. The results show a great dependency of the BVOC contribution to ozone formation on the antropoghenic reduction scenario. In rural areas, the impact due to a NOx and/or VOC reduction does not change the BVOC impact. Nevertheless, within big cities or industrial zones, a NOx reduction results in a decrease of the biogenic impact in ozone levels that can reach 85 μg/m3, whereas an Anthropogenic Volatile Organic Compound (AVOC) reduction results in a decrease of the BVOC contribution on ozone formation that varies from 0 to 30 μg/m3 with respect to the contribution at the same points in the 2003 base scenario. On the other hand, downwind of the big cities, a decrease in NOx produces a minor contribution of biogenic emissions and a decrease in AVOCs results in greater contributions of BVOCs to the formation of ozone.

Introduction: tonsillectomy, with or without adenoidectomy, is one of the most frequent surgical procedures generally performed, especially in young patients. Several studies suggest that there is a relationship between tonsillectomy and altered MALT immune system. Objective: to examine the possible association between tonsillectomy or adenoidectomy and the risk of subsequent appendicitis. Material and method: a cross-sectional study was performed in 650 patients admitted to the emergency department of a general hospital in Valencia, Spain. Previous history of tonsillectomy and/or adenoidectomy was related to a history of appendectomy. A descriptive study and an analysis of the relationship between previous operations and appendicitis was performed. A multivariable analysis controlled for age and sex was also performed, including the possible interaction of the gender variable. The independent effect of each of the procedures (tonsillectomy, adenoidectomy) was tested. Results: the 25.5% of patients had undergone tonsillectomy and 11.5% adenoidectomy; 17.5% had had an appendectomy. On average, women were operated on more frequently than men. In the bivariate analysis, both tonsillectomy and adenoidectomy were significantly associated with subsequent appendectomy. In the multivariate analysis, this association was only maintained for tonsillectomy (OR: 3.23; 95% CI: 2.11-4.94). A stratified analysis controlling for sex showed a modification of this effect, with a higher association in women (OR: 5.20; 95% CI: 2.91-9.28) than in men (OR: 1.74; 95% CI: 0.90-3.39). Conclusions: a clear association has been found, especially in women, between previous tonsillectomy and subsequent acute appendicitis. Due to a lack of data on acute appendicitis there should be further studies to explain the findings of this study, as this could be the first described risk factor of acute appendicitis.Introducción: la amigdalectomía, sola o acompañada de adenoidectomía, es una de las intervenciones quirúrgicas más frecuentes, especialmente en las personas más jóvenes. Diversos estudios sugieren la existencia de algún tipo de relación entre el hecho de sufrir una amigdalectomía y la inmunidad a nivel del sistema MALT digestivo. Objetivo: examinar la posible asociación entre el hecho de haber sido sometido a la extirpación de las amígdalas o las adenoides y padecer posteriormente una apendicitis aguda. Material y método: encuesta transversal en 650 pacientes que acuden al Servicio de Urgencias de un Hospital de Valencia, España. Se relacionaron los antecedentes de apendicectomía con amigdalectomía y/o adenoidectomía previa. Se llevó a cabo la descripción de las variables así como el análisis de la relación entre las intervenciones previas y la apendicitis. Se efectuó un análisis multivariante controlando por las variables edad y sexo así como la posible interacción con la variable sexo. Se comprobó el efecto independiente de cada una de las dos intervenciones (amigdalectomía, adenoidectomía). Resultados: el 25,5% de pacientes habían sido intervenidos de amigdalectomía, el 11,5% de adenoidectomía y el 17,5% de apendicectomía. En promedio, las mujeres han sido sometidas a intervenciones con mayor frecuencia que los hombres. En el análisis simple, los antecedentes, tanto de amigdalectomía, como de adenoidectomía, se asociaron significativamente con haber sido sometidos posteriormente a apendicectomía. En el análisis multivariante, dicha asociación sólo se mantuvo para la amigdalectomía (OR: 3,23; IC 95%: 2,11-4,94). Por otro lado, se encontró una modificación de dicho efecto según la variable sexo, siendo la asociación más alta en mujeres (OR: 5,20; IC 95% 2,91-9,28) que en hombres (OR: 1,74; IC 95%: 0,90-3,39). Conclusiones: se ha encontrado una asociación clara, especialmente en mujeres, entre el hecho de ser amigdalectomizado y sufrir apendicitis con posterioridad. Dada la escasez de conocimientos de apendicitis aguda se debería investigar con mayor profundidad los factores que explicaran los hallazgos de este estudio, ya que podría ser el primer factor de riesgo descrito de apendicitis aguda.

En este trabajo se describe una nueva caldera de colapso de 8 km de diámetro (la Caldera Mazahua) descubierta-en la parte central del Cinturón Volcánico Mexicano, en las proximidades de Villa de San Felipe del Progreso (Estado de México). Los datos volcanológicos obtenidos en el campo (procedencia de los mantos ignimbríticos, episodios y estructuras de alta energía en la periferia de la caldera) han confirmado una hipótesis predictiva basada en la interpretación de estructuras circulares en fotos aéreas y de satélite. doi: https://doi.org/10.22201/igeof.00167169p.1991.30.3.596

In the early 1990s, the Valencia region suffered a severe drought episode that led the scientific community to suspect that the Iberian Peninsula was heading towards generalized desertification. However, an analysis of the last 40 years shows that the Valencia region has experienced several drought episodes of different intensities, but always with important economic and social consequences. This paper studies the episodes occurring since 1950, with regard to their intensity, duration and spatial distribution. By using recurrence analysis, four such episodes have been identified: 1952–1955, 1963–1964, 1978–1985, 1993–1995. Despite Valencia being a relatively small region, intra-regional variations in the intensity and spatial and temporal distribution of drought episodes can be observed. Copyright © 2000 Royal Meteorological Society [ABSTRACT FROM AUTHOR]

Abstract preview not available - see full-text PDF article.

Historic Building Information Modelling (HBIM) has become the ideal tool for professionals studying building conservation and restoration. The BIM model allows one to identify structural deformations following three-dimensionally resolved models. In addition, this methodology is specifically designed to register parametric construction models, as an information manager by adding semantic components to the model, including information on the different transformations of the historical artefact, and allowing continuous progress in the building's life cycle. In this work, graphic information and data related to conservation projects are compiled that allow a management of all the documentation integrated in the same Project, from all the disciplinary fields related to the heritage conservation and rehabilitation process. Specifically, from the geometric identification and the restoration documents, it is intended to develop an experimental application where both terrestrial laser scanning records and the use of image processing routines can allow automatic operations to monitor alterations in façades, in order to subsequent control by conservation experts. For this, a building with certain characteristics has been chosen, such as the Miguel de Mañara palace in the city of Seville. A building that has a main façade of 43.30 metres in length by 6.75 metres in height and, in which its façade rotates in an angled guideline to adapt to the urban planning of the time. The analysis is based on the applicability of two segmentation algorithms and the construction of the multilayer enclosure model where the different stratigraphies of the results obtained are exposed.

Introduction:TULP1 exemplifies the remarkable clinical and genetic heterogeneity observed in inherited retinal dystrophies. Our research describes the clinical and molecular characteristics of a patient manifesting an atypical retinal dystrophy pattern, marked by the identification of both a previously unreported and a rarely encountered TULP1 variant.Methods: Whole-exome sequencing was performed to identify potential causative variants. The pathogenicity of the identified TULP1 variants was evaluated through in silico predictors and a minigene splice assay, specifically designed to assess the effect of the unreported TULP1 variant.Results: We identified two TULP1 gene variants in a patient exhibiting unusual and symmetrical alterations in both retinas, characterized by an increase in autofluorescence along the distribution of retinal vessels. These variants included a known rare missense variant, c.1376T>C, and a novel splice site variant, c.822G>T. For the latter variant (c.822G>T), we conducted a minigene splice assay that demonstrated the incorporation of a premature stop codon. This finding suggests a likely activation of the nonsense-mediated mRNA decay mechanism, ultimately resulting in the absence of protein production from this allele. Segregation analysis confirmed that these variants were in trans.Discussion: Our data support that individuals with biallelic TULP1 variants may present with a unique pattern of macular degeneration and periarteriolar vascular pigmentation. This study highlights the importance of further clinical and molecular characterization of TULP1 variants to elucidate genotype–phenotype correlations in the context of inherited retinal dystrophies.

Presents a letter to the editor about the possible association between tonsillectomy or adenoidectomy and the risk of subsequent acute appendicitis.

This work focuses on the study of the physicochemical changes that take place during the first stage of ripening of plantain, with particular attention to the changes in the orthorhombic and hexagonal nanocrystals present in this starch, and its relation shift with resistance starch. Significant changes were observed in the proximal analysis of plantain flour. A gradual increase in moisture content was attributed to the high content of crystalline structures and molecules that can be removed by drying. Water activity increased with ripening, which was attributed to the hygroscopic nature of the flours. The protein content increased, and the carbohydrate content decreased, indicating the progress of biochemical reactions. The changes in the fat content are consistent with the hydrolysis and resynthesis of lipids during the ripening process. The obtained results indicate a significant influence of the ripening stage on the physicochemical properties of flour and starch of plantain, which is associated with the occurrence of a climacteric peak on the 4th day of ripening.The hydration properties of plantain flour decreased significantly during the ripening days, consistent with the occurrence of a climacteric peak. Water holding capacity (WHC) and water binding capacity (WBC) were affected by the degree of digestion of native starch granules and protein denaturation during fruit ripening. Scanning electron microscopes (SEM) showed that during ripening the surface of the isolated starches do not suffer any significative damage. X-ray diffraction patterns were used to identify crystalline structures and to study the changes in the crystalline structures. These results showed that the starch contains orthorhombic and hexagonal nanocrystals, which play and important role and which show small structural damage during ripening reflected in a decrease in their relative crystallinity. This is the first time that these nanocrystals have been studied and considered in the ripening process. Differential scanning calorimetry was used to study the thermal transition in isolated starch. The results indicated that the gelatinization of starch corresponds to the solvation of orthorhombic and hexagonal nanocrystals, and that during ripening there is a decrease in the enthalpy reflecting some crystal structural damage. Pasting properties were studied using a Starch cell for flours and isolated starches, indicating that the pasting profile is governed by intrinsic and extrinsic factors. The resistant starch does not show significant changes at this stage of maturation. This starch is the one with the highest resistant starch content reported in the literature (38%). It was hypothesized that the resistant starch is directly related to the amount of whole starch granules, and more importantly, directly related to the number concentration of orthorhombic and hexagonal nanocrystals. Therefore, knowledge of the physicochemical and nutritional properties of plantain and flour at each stage of ripening allows better selection according to industrial applications.

La caracterización de un paisaje cultural permite la identificación de valores singulares y específicos que sirvan como base para su reactivación y recuperación, lo que es especialmente beneficioso al hablar de territorios en riesgo de despoblación. Se toma como caso de estudio a caracterizar el valle del río Beas (Beas de Segura, Jaén), que reúne recursos patrimoniales históricamente influenciados por la presencia del agua, tales como regadíos, producción molinera, industria textil, sistemas anti-inundaciones o infraestructuras de abastecimiento que, no obstante, ven comprometida su permanencia en la actualidad. El objeto de la investigación es establecer la relación directa entre la caracterización del paisaje y su recuperación sostenible: frente a una tendencia habitual en el mundo rural de sustitución de características locales por aquellas extraídas de modelos urbanos estandarizados, se propone la divulgación y re-significación de estos valores mediante una metodología de registro multiescalar y con soporte cartográfico. De esta manera, se pretende favorecer no solo la lucha contra la despoblación de Beas de Segura, sino también la definición de herramientas transferibles a otros municipios con problemáticas semejantes.

Abstract Inherited retinal dystrophies are a group of disorders characterized by the progressive degeneration of photoreceptors leading to loss of the visual function and eventually to legal blindness. Although next generation sequencing (NGS) has revolutionized the molecular diagnosis of these diseases, the pathogenicity of some mutations casts doubts. After the screening of 208 patients with a panel of 117 genes, we obtained 383 variants that were analysed in silico with bioinformatic prediction programs. Based on the results of these tools, we selected 15 variants for their functional assessment. Therefore, we carried out minigene assays to unveil whether they could affect the splicing of the corresponding gene. As a whole, seven variants were found to induce aberrant splicing in the following genes: BEST1, CACNA2D4, PRCD, RIMS1, FSCN2, MERTK and MAK. This study shows the efficacy of a workflow, based on the association of the Minimum Allele Frequency, family co-segregation, in silico predictions and in vitro assays to determine the effect of potential splice site variants identified by DNA-based NGS. These findings improve the molecular diagnosis of inherited retinal dystrophies and will allow some patients to benefit from the upcoming gene-based therapeutic strategies.

Background: As more risk factors are identified for Parkinson’s disease (PD), attention has increased toward hematological disorders, as studies have found increased eryptosis, a process characterized by increased erythrocyte apoptosis, in PD patients. We aimed to synthesize scientific evidence assessing the effect of anemia on future PD incidence. Material and methods: A systematic review was conducted on multiple electronic databases. Any study that assessed the effect or association between presence of anemia and future PD in a longitudinal manner was considered for inclusion. Results: Five of the 5525 articles met inclusion criteria; three retrospective cohort studies and two case–control studies. Anemia exposure definition varied among studies. Four of the five studies observed an increased risk for PD; pooled analysis showed a non-significantly increased risk for PD in the cohorts (RR = 1.10; 95% CI = 0.08-15.84) and case–control studies (RR = 1.44; 95% CI = 0.04-52.47). However, heterogeneity among studies was high (I2 = 97, p < 0.01 and I2 = 85, p < 0.01, respectively). Conclusion: There are few clinical studies on the association of anemia and PD, despite growing preclinical evidence on their connection. In this review, a tendency toward an increased risk for PD in anemic population was observed, with further research needed to reach a definite conclusion.

Inherited retinal dystrophies (IRD) are a group of diseases characterized by the loss or dysfunction of photoreceptors and a high genetic and clinical heterogeneity. Currently, over 270 genes have been associated with IRD which makes genetic diagnosis very difficult. The recent advent of next generation sequencing has greatly facilitated the diagnostic process, enabling to provide the patients with accurate genetic counseling in some cases. We studied 92 patients who were clinically diagnosed with IRD with two different custom panels. In total, we resolved 53 patients (57.6%); in 12 patients (13%), we found only one mutation in a gene with a known autosomal recessive pattern of inheritance; and 27 patients (29.3%) remained unsolved. We identified 120 pathogenic or likely pathogenic variants; 30 of them were novel. Among the cone-rod dystrophy patients, ABCA4 was the most common mutated gene, meanwhile, USH2A was the most prevalent among the retinitis pigmentosa patients. Interestingly, 10 families carried pathogenic variants in more than one IRD gene, and we identified two deep-intronic variants previously described as pathogenic in ABCA4 and CEP290. In conclusion, the IRD study through custom panel sequencing demonstrates its efficacy for genetic diagnosis, as well as the importance of including deep-intronic regions in their design. This genetic diagnosis will allow patients to make accurate reproductive decisions, enroll in gene-based clinical trials, and benefit from future gene-based treatments.

Spinal muscular atrophy (SMA) is a severe neuromuscular disorder caused by biallelic loss or pathogenic variants in the SMN1 gene. Copy number and modifier intragenic variants in SMN2, an almost identical paralog gene of SMN1, are known to influence the amount of complete SMN proteins. Therefore, SMN2 is considered the main phenotypic modifier of SMA, although genotype–phenotype correlation is not absolute. We present eleven unrelated SMA patients with milder phenotypes carrying the c.859G>C-positive modifier variant in SMN2. All were studied by a specific NGS method to allow a deep characterization of the entire SMN region. Analysis of two homozygous cases for the variant allowed us to identify a specific haplotype, Smn2-859C.1, in association with c.859G>C. Two other cases with the c.859G>C variant in their two SMN2 copies showed a second haplotype, Smn2-859C.2, in cis with Smn2-859C.1, assembling a more complex allele. We also identified a previously unreported variant in intron 2a exclusively linked to the Smn2-859C.1 haplotype (c.154-1141G>A), further suggesting that this region has been ancestrally conserved. The deep molecular characterization of SMN2 in our cohort highlights the importance of testing c.859G>C, as well as accurately assessing the SMN2 region in SMA patients to gain insight into the complex genotype–phenotype correlations and improve prognostic outcomes.

The term rare disease was coined in the 1970s to refer to diseases that have a low prevalence [...]

Usher syndrome (USH) is an autosomal recessive syndromic ciliopathy characterized by sensorineural hearing loss, retinitis pigmentosa and, sometimes, vestibular dysfunction. There are three clinical types depending on the severity and age of onset of the symptoms; in addition, ten genes are reported to be causative of USH, and six more related to the disease. These genes encode proteins of a diverse nature, which interact and form a dynamic protein network called the “Usher interactome”. In the organ of Corti, the USH proteins are essential for the correct development and maintenance of the structure and cohesion of the stereocilia. In the retina, the USH protein network is principally located in the periciliary region of the photoreceptors, and plays an important role in the maintenance of the periciliary structure and the trafficking of molecules between the inner and the outer segments of photoreceptors. Even though some genes are clearly involved in the syndrome, others are controversial. Moreover, expression of some USH genes has been detected in other tissues, which could explain their involvement in additional mild comorbidities. In this paper, we review the genetics of Usher syndrome and the spectrum of mutations in USH genes. The aim is to identify possible mutation associations with the disease and provide an updated genotype–phenotype correlation.

Usher syndrome (USH) is a rare autosomal recessive disease and the most common inherited form of combined visual and hearing impairment. Up to 13 genes are associated with this disorder, with USH2A being the most prevalent, due partially to the recurrence rate of the c.2299delG mutation. Excluding hearing aids or cochlear implants for hearing impairment, there are no medical solutions available to treat USH patients. The repair of specific mutations by gene editing is, therefore, an interesting strategy that can be explored using the CRISPR/Cas9 system. In this study, this method of gene editing is used to target the c.2299delG mutation on fibroblasts from an USH patient carrying the mutation in homozygosis. Successful in vitro mutation repair was demonstrated using locus-specific RNA-Cas9 ribonucleoproteins with subsequent homologous recombination repair induced by an engineered template supply. Effects on predicted off-target sites in the CRISPR-treated cells were discarded after a targeted deep-sequencing screen. The proven effectiveness and specificity of these correction tools, applied to the c.2299delG pathogenic variant of USH2A, indicates that the CRISPR system should be considered to further explore a potential treatment of USH. Keywords: Usher syndrome, USH2A, c.2299delG, CRISPR, gene editing, RNPs

BackgroundUsher syndrome (USH) is a recessive inherited disease characterized by sensorineural hearing loss, retinitis pigmentosa, and sometimes, vestibular dysfunction. Although the molecular epidemiology of Usher syndrome has been well studied in Europe and United States, there is a lack of studies in other regions like Africa or Central and South America.MethodsWe designed a NGS panel that included the 10 USH causative genes (MYO7A, USH1C, CDH23, PCDH15, USH1G, CIB2, USH2A, ADGRV1, WHRN, and CLRN1), four USH associated genes (HARS, PDZD7, CEP250, and C2orf71), and the region comprising the deep-intronic c.7595-2144A>G mutation in USH2A.ResultsNGS sequencing was performed in 11 USH patients from Cuba. All the cases were solved. We found the responsible mutations in the USH2A, ADGRV1, CDH23, PCDH15, and CLRN1 genes. Four mutations have not been previously reported. Two mutations are recurrent in this study: c.619C>T (p.Arg207∗) in CLRN1, previously reported in two unrelated Spanish families of Basque origin, and c.4488G>C (p.Gln1496His) in CDH23, first described in a large Cuban family. Additionally, c.4488G>C has been reported two more times in the literature in two unrelated families of Spanish origin.ConclusionAlthough the sample size is very small, it is tempting to speculate that the gene frequencies in Cuba are distinct from other populations mainly due to an “island effect” and genetic drift. The two recurrent mutations appear to be of Spanish origin. Further studies with a larger cohort are needed to elucidate the real genetic landscape of Usher syndrome in the Cuban population.

Valparaíso es el resultado de la unión de dos ciudades en una: la ciudad vertical de los cerros y la ciudad horizontal del Plan –parte plana–. Esta doble naturaleza ha ido configurando una dualidad obligada a convivir y a establecer un continuo diálogo, acabando en la mayoría de los casos en conflicto. Si por un lado está la ciudad global y ortogonal como resultado de la ocupación europea, por otro lado estará la ciudad onírica agarrada a los acantilados ajena a cualquier orden preestablecido. Cada una de estas dos ciudades irá materializando su propia arquitectura: una real y estandarizada, propia de cualquier periferia de ciudad, y otra imposible. Será esta segunda la que vaya evolucionando en un intento continuo de adaptación y será el propio lugar el encargado de rechazar cualquier construcción que no le sea propia. Esta dicotomía quedará plasmada en numerosos proyectos que nunca verán la luz. El objetivo del artículo será mostrar, a partir de numerosos proyectos inéditos descubiertos en Valparaíso, cómo la arquitectura pensada para los cerros nunca llegó a construirse y fue dando paso a unas construcciones a medio camino entre lo real y lo imaginario, entre la lógica y el sueño.

INTRODUCTION:Mutations in USH2A cause both isolated Retinitis Pigmentosa (RP) and Usher syndrome (that implies RP and hearing impairment). One of the most frequent variants identified in this gene and among these patients is the p.(Cys759Phe) change. However, the pathogenic role of this allele has been questioned since it was found in homozygosity in two healthy siblings of a Spanish family. To assess the causative role of USH2A p.(Cys759Phe) in autosomal recessive RP (ARRP) and Usher syndrome type II (USH2) and to establish possible genotype-phenotype correlations associated with p.(Cys759Phe), we performed a comprehensive genetic and clinical study in patients suffering from any of the two above-mentioned diseases and carrying at least one p.(Cys759Phe) allele. MATERIALS AND METHODS:Diagnosis was set according to previously reported protocols. Genetic analyses were performed by using classical molecular and Next-Generation Sequencing approaches. Probands of 57 unrelated families were molecularly studied and 63 patients belonging to these families were phenotypically evaluated. RESULTS:Molecular analysis characterized 100% of the cases, identifying: 11 homozygous patients for USH2A p.(Cys759Phe), 42 compound heterozygous patients (12 of them with another missense USH2A pathogenic variant and 30 with a truncating USH2A variant), and 4 patients carrying the p.(Cys759Phe) allele and a pathogenic variant in another RP gene (PROM1, CNGB1 or RP1). No additional causative variants were identified in symptomatic homozygous patients. Statistical analysis of clinical differences between zygosity states yielded differences (p≤0.05) in age at diagnosis of RP and hypoacusis, and progression of visual field loss. Homozygosity of p.(Cys759Phe) and compound heterozygosity with another USH2A missense variant is associated with ARRP or ARRP plus late onset hypoacusis (OR = 20.62, CI = 95%, p = 0.041). CONCLUSIONS:The present study supports the role of USH2A p.(Cys759Phe) in ARRP and USH2 pathogenesis, and demonstrates the clinical differences between different zygosity states. Phenotype-genotype correlations may guide the genetic characterization based upon specific clinical signs and may advise on the clinical management and prognosis based upon a specific genotype.

Alberto Campo Baeza is an architect and Project profesor in the Architecture School of Madrid. He has just been awarded the Teachinbg Excellency Award issued by the Technical University of Madrid and the 2013 Tessenow Gold Medal

By experimentation and modelling, this paper analyses the atmospheric dispersion of the SO2 emissions from a power plant on complex terrain under strong convective conditions, describing the main dispersion features as an ensemble of "stationary dispersive scenarios" and reformulating some "classical" dispersive concepts to deal with the systematically monitored summer dispersive scenarios in inland Spain. The results and discussions presented arise from a statistically representative study of the physical processes associated with the multimodal distribution of pollutants aloft and around a 343-m-tall chimney under strong dry convective conditions in the Iberian Peninsula. This paper analyses the importance of the identification and physical implications of transitional periods for air quality applications. The indetermination of a transversal plume to the preferred transport direction during these transitional periods implies a small (or null) physical significance of the classical definition of horizontal standard deviation of the concentration distribution.

Vertical profiles of CO2 concentration were collected during an intensive summer campaign in a coastal complex-terrain region within the frame of the European Project RECAB (Regional Assessment and Modelling of the Carbon Balance in Europe). The region presents marked diurnal mesoscale circulation patterns. These circulations result in a specific coupling between atmospherically transported CO2 and its surface fluxes. To understand the effects of this interaction on the spatial variability of the observed CO2 concentrations, we applied a high-resolution transport simulation to an idealized model of land biotic fluxes. The regional Net Ecosystem Exchange fluxes were extrapolated for different land-use classes by using a set of eddy-covariance measurements. The atmospheric transport model is a Lagrangian particle dispersion model, driven by a simulation of the RAMS mesoscale model. Our simulations were able to successfully reproduce some of the processes controlling the mesoscale transport of CO2. A semi-quantitative comparison between simulations and data allowed us to characterize how the coupling between mesoscale transport and surface fluxes produced CO2 spatial gradients in the domain. Temporal averages in the simulated CO2 field show a covariance between flux and transport consisting of: 1) horizontally, a CO2 deficit over land, mirrored by a CO2 excess over the sea and 2) vertically, the prevalence of a mean CO2 depletion between 500 and 2000 m, and a permanent build-up of CO2 in the lower levels.

We collected ground-based and aircraft vertical profile measurements of meteorological parameters during a 2-week intensive campaign over the Valencia basin, in order to understand how mesoscale circulations develop over complex terrain and affect the atmospheric transport of tracers. A high-resolution version of the RAMS model was run to simulate the campaign and characterize the diurnal patterns of the flow regime: night-time katabatic drainage, morning sea-breeze development and its subsequent coupling with mountain up-slopes, and evening flow-veering under larger-scale interactions. An application of this mesoscale model to the transport of CO2 is given in a companion paper. A careful evaluation of the model performances against diverse meteorological observations is carried out. Despite the complexity of the processes interacting with each other, and the uncertainties on modeled soil moisture boundary conditions and turbulence parameterizations, we show that it is possible to simulate faithfully the contrasted flow regimes during the course of one day, especially the inland progression and organization of the sea breeze. This gives confidence with respect to future applicability of mesoscale models to establish a reliable link between surface sources of tracers and their atmospheric concentration signals over complex terrain.

Two ozone episodes (occurring in June 2001 and June 2003) in the air quality monitoring network of the Basque Country (BC) are analyzed. The population information threshold was exceeded in many stations (urban, urban-background and rural). During this type of episodes, forced by a blocking anticyclone over the British Isles, ozone background concentrations over the area increase after the import of pollution from both, the continental Europe and the western Mediterranean areas (Gangoiti et al., 2002). For the present analysis, emphasis is made in the search for transport mechanisms, pathways and area sources contributing to the build-up of the episodes. Contributions from a selection of 17 urban and industrial conglomerates in the western European Atlantic (WEA) and the western Mediterranean (WM) are shown after the results of a coupled RAMS-HYPACT modelling system. Meteorological simulations are tested against both the high-resolution wind data recorded at the BC coastal area by a boundary layer wind-profiler radar (Alonso et al., 1998) and the wind soundings reported by the National Centres of Meteorology at a selection of European and north-African sites. Results show that during the accumulation phase of the episodes, background ozone concentrations increase in the whole territory as a consequence of transport from the Atlantic coast of France and the British Channel. For the peak phase, intrusions from new sources, located at the Western Mediterranean, Southern France, Ebro Valley, and, occasionally, the area of Madrid are added, resulting in a further increase in the ozone concentrations. Direct day and night transport within the north-easterly winds over the sea from the WEA source region, and night-time transport within the residual layer over continental areas (southern France, the Ebro Valley, and central Iberia) modulate the import sequence of pollutants and the local increase of ozone concentrations. The alternative direct use of low resolution meteorological data for the estimation of back-trajectories shows a more simple transport scheme with no contributions neither from the Western Mediterranean nor from the Madrid area.

A mesoscale model (MM5), a dispersive Langrangian particle model (FLEXPART), and intensive meteorological and COrrelation SPECtrometer (COSPEC) measurements from a field campaign are used to examine the advection and turbulent diffusion patterns associated with interactions and forcings between topography, synoptic atmospheric flows and thermally-driven circulations. This study describes the atmospheric dispersion of emissions from a power plant with a 343-m tall chimney, situated on very complex terrain in the North-East of Spain, under winter conditions. During the field campaign, the plume was transported with low transversal dispersion and deformed essentially due to the effect of mechanical turbulence. The main surface impacts appeared at long distances from the emission source (more than 30 km). The results show that the coupled models (MM5 and FLEXPART) are able to predict the plume integral advection from the power plant on very complex terrain. Integral advection and turbulent dispersion are derived from the dispersive Lagrangian model output for three consecutive days so that a direct quantitative comparison has been made between the temporal evolution of the predicted three-dimensional dispersive conditions and the COSPEC measurements. Comparison between experimental and simulated transversal dispersion shows an index of agreement between 80% and 90%, within distance ranges from 6 to 33 km from the stack. Linked to the orographic features, the simulated plume impacts on the ground more than 30 km away from the stack, because of the lee waves simulated by MM5.

Some of the meteorological approaches commonly considered in urban air pollution models do not take into account the importance of the smaller scales in the meteorology of complex-terrain coastal sites. The aim of this work is to estimate the impact of using the proper meteorological scales when simulating the behaviour of the pollutant concentrations emitted in the lower layers over coastal complex terrain areas. The availability of experimental measurements of a power plant plume near the Castellón conurbation (on the Spanish Mediterranean coast) has allowed us to use this plume as a tracer of opportunity of the lower atmosphere to check the results of a simulation exercise using the RAMS mesoscale model coupled to the HYPACT particle model. The results obtained show that in a complex-terrain coastal site, because of the strong effect of the meteorological interactions between the different scales on the integral advection and the turbulent dispersion of pollutants, using an inadequate scale to solve the meteorology can result in a very big gap in the simulation of lower-layer pollutant behaviour at urban scales.

La utilización de aleaciones policristalinas de Cu-Al-Ni con memoria de forma para aplicaciones tecnológicas había resultado tradicionalmente problemática debido a su elevada fragilidad. Este problema ha sido superado recientemente gracias a la introducción de un nuevo método de elaboración basado en la aplicación de las técnicas pulvimetalúrgicas, que permite aumentar la ductilidad de la aleación resultante sin afectar a sus propiedades de memoria de forma. Se ha estudiado mediante Microscopía Electrónica de Barrido y ensayos mecánicos el comportamiento a fractura de una aleación obtenida mediante este método de elaboración, observándose una fractura dúctil para una deformación próxima al 13%, lo que supone un mejor comportamiento que el observado en todos los trabajos realizados en policristales de Cu-Al-Ni. La microestructura de dicha aleación ha sido estudiada mediante Microscopía Electrónica de Transmisión, observándose que se encuentra poligonizada y que las plaquetas de martensita atraviesan fácilmente las sub juntas.

Patients suffering from Usher syndrome (USH) exhibit sensorineural hearing loss, retinitis pigmentosa (RP) and, in some cases, vestibular dysfunction. USH is the most common genetic disorder affecting hearing and vision and is included in a group of hereditary pathologies associated with defects in ciliary function known as ciliopathies. This syndrome is clinically classified into three types: USH1, USH2 and USH3. USH2 accounts for well over one-half of all Usher cases and mutations in the USH2A gene are responsible for the majority of USH2 cases, but also for atypical Usher syndrome and recessive non-syndromic RP. Because medaka fish (Oryzias latypes) is an attractive model organism for genetic-based studies in biomedical research, we investigated the expression and function of the USH2A ortholog in this teleost species. Ol-Ush2a encodes a protein of 5.445 aa codons, containing the same motif arrangement as the human USH2A. Ol-Ush2a is expressed during early stages of medaka fish development and persists into adulthood. Temporal Ol-Ush2a expression analysis using whole mount in situ hybridization (WMISH) on embryos at different embryonic stages showed restricted expression to otoliths and retina, suggesting that Ol-Ush2a might play a conserved role in the development and/or maintenance of retinal photoreceptors and cochlear hair cells. Knockdown of Ol-Ush2a in medaka fish caused embryonic developmental defects (small eyes and heads, otolith malformations and shortened bodies with curved tails) resulting in late embryo lethality. These embryonic defects, observed in our study and in other ciliary disorders, are associated with defective cell movement specifically implicated in left-right (LR) axis determination and planar cell polarity (PCP).

In all vertebrates hearing and touch represent two distinct sensory systems that both rely on the transformation of mechanical force into electrical signals. There is an extensive literature describing single gene mutations in humans that cause hearing impairment, but there are essentially none for touch. Here we first asked if touch sensitivity is a heritable trait and second whether there are common genes that influence different mechanosensory senses like hearing and touch in humans. Using a classical twin study design we demonstrate that touch sensitivity and touch acuity are highly heritable traits. Quantitative phenotypic measures of different mechanosensory systems revealed significant correlations between touch and hearing acuity in a healthy human population. Thus mutations in genes causing deafness genes could conceivably negatively influence touch sensitivity. In agreement with this hypothesis we found that a proportion of a cohort of congenitally deaf young adults display significantly impaired measures of touch sensitivity compared to controls. In contrast, blind individuals showed enhanced, not diminished touch acuity. Finally, by examining a cohort of patients with Usher syndrome, a genetically well-characterized deaf-blindness syndrome, we could show that recessive pathogenic mutations in the USH2A gene influence touch acuity. Control Usher syndrome cohorts lacking demonstrable pathogenic USH2A mutations showed no impairment in touch acuity. Our study thus provides comprehensive evidence that there are common genetic elements that contribute to touch and hearing and has identified one of these genes as USH2A.

Usher syndrome (USH) is an autosomal recessive disease characterized by hearing loss, retinitis pigmentosa (RP), and, in some cases, vestibular dysfunction. It is clinically and genetically heterogeneous and is the most common cause underlying deafness and blindness of genetic origin. Clinically, USH is divided into three types. Usher type I (USH1) is the most severe form and is characterized by severe to profound congenital deafness, vestibular areflexia, and prepubertal onset of progressive RP. Type II (USH2) displays moderate to severe hearing loss, absence of vestibular dysfunction, and later onset of retinal degeneration. Type III (USH3) shows progressive postlingual hearing loss, variable onset of RP, and variable vestibular response. To date, five USH1 genes have been identified: MYO7A (USH1B), CDH23 (USH1D), PCDH15 (USH1F), USH1C(USH1C), and USH1G(USH1G). Three genes are involved in USH2, namely, USH2A (USH2A), GPR98 (USH2C), and DFNB31 (USH2D). USH3 is rare except in certain populations, and the gene responsible for this type is USH3A.

Purpose: The main aim of this study was to determine the short- and long-term outcomes of the non-operative management of acute left-sided complicated diverticulitis (ALCD) in severely immunocompromised patients (IMS group) and compare them with immunocompetent patients (IC group). The secondary aim was to assess the necessity of an elective surgery following a successful prior non-operative management in the IMS group after a non-operative management of the first episode of ALCD., Methods: Patients presented with their first episode of ALCD between 2012 and 2018 were retrospectively reviewed. Only severely immunosuppressed patients were considered for the analysis, including the following: long-term oral or intravenous steroid intake, current malignancy undergoing chemotherapy, chronic kidney disease on hemodialysis, or solid organ transplant with immunosuppressive medication. For each group, demographic data, severity of the episode, management decisions (conservative or operative), and short- and long-term outcomes were recorded and compared. A sub-analysis of patients with ALCD associating and abscess (modified Hinchey classification Ib/II) was performed., Results: A total of 290 patients were included in the study: 50 among the IMS and 240 among the IC group. The rate of emergent surgery was higher in the IMS group (50.0% vs. 22.5%, p < 0.001) and was associated with increased morbidity (72.4% vs. 50.0%, p = 0.041) and mortality (24.1% vs. 4.3%, p = 0.003). The duration of the hospital stay was significantly longer in the IMS group (15 vs. 8 days, p < 0.001). The final stoma rate was significantly higher in the IMS group (82.1% vs. 22.9, p < 0.001), with a median follow-up of 51.4 months. A total of 141 patients presented ALCD with an abscess; 25 in the IMS and 116 in the IC group. There was a higher rate of surgical intervention among the IMS group as the initial treatment approach (24.0% vs. 5.2%, p = 0.002), even though the conservative treatment had a similar rate of success (81.3% vs. 92.0%, p = 0.178). The recurrence rate following a non-operative approach was similar (IMS: 31.2% vs. 35.4% in the IC group, p = 0.169). Furthermore, 81.2% of non-operatively managed IMS patients (13 out of 16) did not require a surgical intervention at the end of the follow-up, with similar findings in the IC group (78/96, 81.2%, p = 0.148)., Conclusion: Medical treatment of immunosuppressed patients during their first ALCD episode associated with an abscess is feasible, with a high success rate and results comparable with the IC group. Moreover, taking into account the readmission rates, the need for emergent surgery of the recurrence, and the perioperative mortality and morbidity in the IMS group, conservative management with no differed scheduled surgery seems to be a safe option in this subgroup of patients., (© 2024. The Author(s).)

Background: Ischemic stroke (IS) represents a significant health burden globally, necessitating a better understanding of its genetic underpinnings to improve prevention and treatment strategies. Despite advances in IS genetics, studies focusing on the Spanish population and sex-stratified analyses are lacking., Methods: A case-control genome-wide association study was conducted with 9081 individuals (3493 IS cases and 5588 healthy controls). IS subtypes using Trial of ORG 10172 in Acute Stroke Treatment criteria were explored in a sex-stratified approach. Replication efforts involved the MEGASTROKE, GIGASTROKE, and the UK Biobank international cohorts. Post-genome-wide association study analysis included: in silico proteomic analysis, gene-based analysis, quantitative trait loci annotation, transcriptome-wide association analysis, and bioinformatic analysis using chromatin accessibility data., Results: Identified as associated with IS and its subtypes were 4 significant and independent loci. Replication confirmed 5p15.2 as a new locus associated with small-vessel occlusion stroke, with rs59970332-T as the lead variant (beta [SE], 0.13 [0.02]; P =4.34×10 -8 ). Functional analyses revealed CTNND2 given proximity and its implication in pathways involved in vascular integrity and angiogenesis. Integration of Hi-C data identified additional potentially modulated genes, and in silico proteomic analysis suggested a distinctive blood proteome profile associated with the lead variant. Gene-set enrichment analyses highlighted pathways consistent with small-vessel disease pathogenesis. Gene-based associations with known stroke-related genes such as F2 and FGG were also observed, reinforcing the relevance of our findings., Conclusions: We found CTNND2 as a potential key molecule in small-vessel occlusion stroke risk, and predominantly in males. This study sheds light on the genetic architecture of IS in the Spanish population, providing novel insights into sex-specific associations and potential molecular mechanisms. Further research, including replication in larger cohorts, is essential for a comprehensive understanding of these findings and for their translation to clinical practice., Competing Interests: Dr Arenillas reports compensation from Medtronic, Daiichi Sankyo, Boehringer Ingelheim, and Pfizer for consultant services; grants from AstraZeneca, Instituto de Salud Carlos III, European Commission and Gerencia de Salud Castilla y León; compensation from Philips for data and safety monitoring services; travel support from Daiichi Sankyo Company. Dr Ribo reports stock holdings in Methinks, Nora, and Ancaonda Biomed; compensation from Cerenovus, Vesalio, Stryker Corporation, Philips, Rapid Pulse, AptaTargets, and Medtronic MiniMed Inc for consultant services; compensation from Sensome for data and safety monitoring services. Dr Heitsch reports employment by Washington University School of Medicine in St. Louis; reports funding from National Institutes of Health and American Heart Association. Dr Dhar reports grants from National Institute of Neurological Disorders and Stroke. The other authors report no conflicts.

Gastrointestinal (GI) environment is influenced by several factors (gender, genetics, sex, disease state, food) leading to oral drug absorption variability or to low bioavailability. In this scenario, gastroretentive drug delivery systems (GRDDS) have been developed in order to solve absorption problems, to lead to a more effective local therapy or to allow sustained drug release during a longer time period than the typical oral sustained release dosage forms. Among all GRDDS, floating systems seem to provide a promising and practical approach for achieving a long intra-gastric residence time and sustained release profile. In the last years, a novel technique is being used to manufacture this kind of systems: three-dimensional (3D) printing technology. This technique provides a versatile and easy process to manufacture personalized drug delivery systems. This work presents a systematic review of the main 3D printing based designs proposed up to date to manufacture floating systems. We have also summarized the most important parameters involved in buoyancy and sustained release of the systems, in order to facilitate the scale up of this technology to industrial level. Finally, a section discussing about the influence of materials in drug release, their biocompatibility and safety considerations have been included., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Migraine is the second most common type of primary headache disorder in Europe, accounting for 2.8% of visits to emergency departments. Some studies have shown that emergency departments may approach the disorder in ways that may be insufficient or inadequate., Materials and Methods: A retrospective observational study was conducted of patients with migraine who were discharged from the adult emergency department of the Hospital Universitario Virgen del Rocio in 2020. Variables related to their healthcare were analysed., Results: 73.9% were women, with a mean age of 38 years. They were not asked about the frequency of their migraines. The mean length of time patients spent in the emergency department before receiving initial medical care was 45 minutes (standard deviation: 41). Computed tomography scans were requested for 27.4% of the patients, and these were not pathological. Nonsteroidal anti-inflammatory drugs were the most commonly used treatment for the symptoms. Opioids were also used. Preventive treatments were prescribed in 6% of cases., Conclusions: Management of migraines by emergency departments is limited, and as such continuous and updated training is important. The use of triptans and occipital nerve blocks should be encouraged, and the use of opioids, among other drugs, should cease.