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Abstract BabyIAXO is the intermediate stage of the International Axion Observatory (IAXO) to be hosted at DESY. Its primary goal is the detection of solar axions following the axion helioscope technique. Axions are converted into photons in a large magnet that is pointing to the sun. The resulting X-rays are focused by appropriate X-ray optics and detected by sensitive low-background detectors placed at the focal spot. The aim of this article is to provide an accurate quantitative description of the different components (such as the magnet, optics, and X-ray detectors) involved in the detection of axions. Our efforts have focused on developing robust and integrated software tools to model these helioscope components, enabling future assessments of modifications or upgrades to any part of the IAXO axion helioscope and evaluating the potential impact on the experiment’s sensitivity. In this manuscript, we demonstrate the application of these tools by presenting a precise signal calculation and response analysis of BabyIAXO’s sensitivity to the axion-photon coupling. Though focusing on the Primakoff solar flux component, our virtual helioscope model can be used to test different production mechanisms, allowing for direct comparisons within a unified framework.

Background: We describe the epidemiological and clinical characteristics of thrombosis with thrombocytopenia syndrome (TTS) cases reported in Spain. Methods: We included all cases of venous or arterial thrombosis with thrombocytopenia following administration of adenoviral vector vaccines (AstraZeneca or Janssen) against COVID-19 disease between 1 February and 26 September 2021. We describe the crude rate and the standardised morbidity ratio. We assessed the predictors of mortality. Results: Sixty-one cases were reported and 45 fulfilled eligibility criteria; 82% of patients were women. The crude TTS rate was 4 cases/1 000 000 doses, and 14-15 cases/1 000 000 doses among patients aged 30-49 years. The number of observed cases of cerebral venous thrombosis was 6-18 times higher than that expected in patients younger than 49 years. Symptoms started a median (quartiles 1 and 3 [Q1-Q3]) of 10 (7-14) days after vaccination. Eighty percent (95% confidence interval [CI]: 65%-90%) had thrombocytopenia at the time of the emergency department visit, and 65% (49%-78%) had D-dimer levels > 2000 ng/mL. Patients had thromboses affecting multiple locations in 36% of cases and fatal outcomea in 24%. Platelet nadir 2.000 ng/mL). La trombosis fue de múltiples localizaciones en 36% y fatal en 24% de los pacientes. Un valor nadir de trombocitopenia

Resumen: Introducción: Se describen las características epidemiológicas y clínicas de los casos de síndrome de trombosis con trombocitopenia (STT) notificados en España. Métodos: Se incluyeron los casos de trombosis venosa o arterial con trombocitopenia tras recibir vacuna con vectores de adenovirus no replicantes frente a la COVID-19 (AstraZeneca y Janssen) del 1 de febrero al 26 de septiembre de 2021. Se describe la tasa de notificación (número de casos notificados/número de dosis administradas), y el análisis de casos observados vs. esperados (O/E). Se evaluaron los predictores de mortalidad. Resultados: Se notificaron 61 casos, cumpliendo 45 los criterios de elegibilidad, 82% mujeres. La tasa de notificación global fue 4/1.000.000 dosis y 14-15/1.000.000 dosis entre los 30-49 años. El número de casos de trombosis de senos cerebrales observados fue 6-18 veces superior al esperado en menores de 49 años. Los síntomas comenzaron 10 (rango intercuartílico: 7-14) días tras la vacunación. El 80% (intervalo de confianza [IC] al 95%: 65-90%) tenía trombocitopenia en el momento de su visita a urgencias y el 65% (IC 95%: 49-78%) elevación del dímero D (> 2.000 ng/mL). La trombosis fue de múltiples localizaciones en 36% y fatal en 24% de los pacientes. Un valor nadir de trombocitopenia < 50.000 /μL (odds ratio [OR]: 7,4; IC 95%: 1,2-47,5) y la presencia de hemorragia cerebral (OR: 7,9; IC 95%: 1,3-47,0) se asociaron a un desenlace fatal. Conclusiones: Debe sospecharse el STT en pacientes que presenten síntomas unos 10 días tras la vacunación y presenten trombocitopenia y/o elevación de dímero D. Abstract: Background: We describe the epidemiological and clinical characteristics of thrombosis with thrombocytopenia syndrome (TTS) cases reported in Spain. Methods: We included all venous or arterial thrombosis with thrombocytopenia following adenovirus vector-based vaccines (AstraZeneca or Janssen) to prevent COVID-19 disease between February 1st and September 26th, 2021. We describe the crude rate and the standardized morbidity ratio. We assessed the predictors of mortality. Results: Sixty-one cases were reported and 45 fulfilled eligibility criteria, 82% women. The crude TTS rate was 4/1,000,000 doses and 14-15/1,000,000 doses between 30-49 years. The number of observed cases of cerebral venous thrombosis was 6-18 higher than the expected in patients younger than 49 years. Symptoms started 10 (interquartile range [IQR]: 7-14) days after vaccination. Eighty percent (95% confidence interval [CI]: 65-90%) had thrombocytopenia at the time of the emergency department visit, and 65% (95% CI: 49-78%) had D-dimer >2,000 ng/mL. Patients had multiple location thrombosis in 36% and fatal outcome in 24% cases. A platelet nadir < 50,000/μL (odds ratio [OR]: 7.4; CI 95%: 1.2-47.5) and intracranial hemorrhage (OR: 7.9; IC 95%: 1.3-47.0) were associated with fatal outcome. Conclusion: TTS must be suspected in patients with symptoms 10 days after vaccination and thrombocytopenia and/or D-dimer increase.

Abstract This article describes BabyIAXO, an intermediate experimental stage of the International Axion Observatory (IAXO), proposed to be sited at DESY. IAXO is a large-scale axion helioscope that will look for axions and axion-like particles (ALPs), produced in the Sun, with unprecedented sensitivity. BabyIAXO is conceived to test all IAXO subsystems (magnet, optics and detectors) at a relevant scale for the final system and thus serve as prototype for IAXO, but at the same time as a fully-fledged helioscope with relevant physics reach itself, and with potential for discovery. The BabyIAXO magnet will feature two 10 m long, 70 cm diameter bores, and will host two detection lines (optics and detector) of dimensions similar to the final ones foreseen for IAXO. BabyIAXO will detect or reject solar axions or ALPs with axion-photon couplings down to g aγ ∼ 1.5 × 10 −11 GeV −1, and masses up to m a ∼ 0.25 eV. BabyIAXO will offer additional opportunities for axion research in view of IAXO, like the development of precision x-ray detectors to identify particular spectral features in the solar axion spectrum, and the implementation of radiofrequency-cavity-based axion dark matter setups.

Resumen: Introducción: La pandemia ocasionada por la aparición del SARS-CoV-2, ha transformado la práctica médica, y ha alterado gravemente la formación de los médicos residentes a nivel mundial. Desde la Sociedad Española de Neurología (SEN) se ha querido conocer el grado de repercusión que la COVID-19 ha tenido en el ámbito formativo entre los residentes de neurología. Método: Se realizó un estudio descriptivo transversal mediante el envío de una encuesta por email a todos los residentes de neurología miembros de dicha sociedad. Se incluyeron preguntas relativas a aspectos demográficos, actividad asistencial y repercusión a nivel formativo y personal durante la pandemia, así como su previsión sobre el futuro laboral «post-COVID». Resultados: De 422 encuestas, respondió un total de 152 (36%) residentes, 79 mujeres (52%) y 73 varones (48%). La distribución por año de residencia fue R4: 51 (33,6%), R3: 45 (29,6%), R2: 28 (18,4%) y R1: 28 (18,4%). La actividad de hospitalización se vio alterada en 139 (90,8%) casos. Consideraron que la situación afectaría negativamente a su formación 126 (82,8%) residentes, de los que 99 (64,7%) perdieron rotaciones no recuperables. Manifestaron deseo de alargar el periodo de residencia 101 (66%). Conclusiones: La pandemia ha tenido un gravísimo impacto en todo el sistema sanitario, siendo los médicos en formación uno de los colectivos más afectados. En los residentes de neurología ha provocado notables deficiencias de su actividad formativa y asistencial como consecuencia de la suspensión de rotaciones específicas. Un alto porcentaje manifestó deseo de ampliar el periodo de residencia. Abstract: Introduction: The COVID-19 pandemic has transformed medical practice and severely disrupted the training of medical residents worldwide. The Spanish Society of Neurology conducted a study to assess its impact on the training of neurology residents in Spain. Methods: We performed a descriptive, cross-sectional study through a survey distributed by e-mail to all neurology residents belonging to the Society. The survey included questions on demographic variables, care activity, and personal and educational impact of the pandemic, as well as respondents’ expectations for the future of their work in the post-pandemic era. Results: Of 422 surveys sent, we received a total of 152 responses (36%); 79 respondents (52%) were women and 73 (48%) were men. By year of residency, 51 respondents (33.6%) were in the fourth year, 45 (29.6%) in the third year, 28 (18.4%) in the second year, and 28 (18.4%) in the first year. A total of 139 respondents (90.8%) reported changes in hospital activity, and 126 (82.8%) considered the situation to have had a negative impact on their training, with 99 (64.7%) having lost non-recoverable rotations. Sixty-six percent of respondents (n=101) expressed a desire to extend their residency period. Conclusions: The pandemic has had an extremely severe impact on all areas of the health system, with trainee physicians being one of the most affected groups. Among neurology residents, the crisis has caused significant shortcomings in their training and clinical activities, through the suspension of specific rotations. A high percentage of respondents wished to extend the residency period.

Objetivo: Presentar en una serie de casos los posibles errores técnicos durante el bloqueo epidural, ya que se pueden prevenir y corregir durante el procedimiento. Materiales y métodos: Se evaluaron retrospectivamente, entre enero de 2013 y abril de 2014, 118 pacientes con dolor lumbar y/o radicular tratados con antiinflamatorio/analgésico mínimamente invasivo mediante una inyección selectiva guiada por tomografía computada (TC) en el espacio epidural. En todos los casos se utilizó una aguja espinal 21 G, y se inyectó esteroide de depósito (betametasona 3 mg) y anestésicos (lidocaína 1 ml al 2% + bupivacaína 0,5 ml al 0,5%) o solo esteroide en los pacientes con sospecha de duramadre perforada. Se seleccionaron únicamente aquellos casos en los que hubo errores de técnica durante el procedimiento. Resultados: Cinco pacientes (4,23%) tuvieron complicaciones técnicas durante el bloqueo epidural. Estas se observaron luego de una inadecuada posición del extremo de la aguja (perforación de la duramadre y falta de acceso al espacio epidural) y se objetivaron por la aspiración directa del líquido cefalorraquídeo (LCR) o por la disposición del aire, utilizado como trazador antes de la inyección del medicamento. Los errores se detectaron y corrigieron con rapidez, sin mayores inconvenientes ni necesidad de tratamientos complementarios. Conclusión: El bloqueo epidural es una práctica frecuentemente usada en el manejo del dolor lumbar crónico. Los errores técnicos y las complicaciones del procedimiento son poco comunes, pero para su manejo y posterior corrección es importante conocerlos y contar con un médico experimentado.

INTRODUCCIÓN La producción lechera y sus sistemas de alimentación, a base de pastoreo, en el austro ecuatoriano (sierra sur) se encuentran ante una problemática de importancia debido a los efectos de las alteraciones del tipo nutricional, metabólico y reproductivo que se presentan durante el periodo de transición. La vaca lechera, en el periodo de transición, enfrenta un gran desafío metabólico asociado a desequilibrios homeostáticos, siendo las características más importantes la disminución del consumo de materia seca y el balance energético negativo (BEN), causados por el aumento progresivo de la producción de leche hacia el pico de lactancia (Chapinal, Carson, Le Blanc, Leslie, Godden et al 2012). En lo referente a prácticas de nutrición en rumiantes, Ipek (2012) propone una modificación mediante la suplementación de aditivos para piensos, con propiedades antioxidantes, que mitiguen los efectos nocivos de estrés oxidativo y tenga un impacto beneficioso sobre el comportamiento productivo y reproductivo de las vacas lecheras. Es probable que los factores dietéticos tales como los antioxidantes y el balance de energía positivo sean importantes para la función de neutrófilos y la respuesta inmune (Garzón et al 2017). En los rumiantes, las bacterias ruminales requieren cobalto para producir vitaminas B12 y ácidos grasos volátiles (Asimbaya & Fernando, 2014). La endometritis subclínica (ES) está asociada con una involución uterina tardía y afecta negativamente algunos índices reproductivos (Rutter, 2015), entre ellos una reducción de la tasa de concepción (TC) presentando un 53% en vacas con ES y del 47% de las vacas sin ES (Maurino, Bernardi, Rinaudo, & Marini, 2012). En consecuencia, esta investigación fue dirigida a investigar si el aditivo Roughage MateÒ, en dosis crecientes, influye sobre la involución uterina, salud uterina y retorno de la actividad ovárica en vacas lecheras criadas al pastoreo durante el período de transición en la provincia de Cañar en Ecuador.

Resumen: Introducción: Las psicosis epilépticas se dividen respecto de su relación con las crisis en periictales e interictales. Las psicosis periictales tienen una estrecha relación temporal con las crisis epilépticas y ocurren antes (preictales), durante (ictales) o después de las mismas (postictales). Generalmente, tienen un inicio y final agudo, corta duración y una remisión completa, con riesgo de recurrencia. Las psicosis interictales o crónicas no guardan relación temporal con las crisis epilépticas. Existe otro tipo de psicosis epilépticas que se relaciona con la respuesta al tratamiento de la epilepsia: psicosis epiléptica por fenómeno de normalización forzada (psicosis alternativa) y dentro de esta se encuentra la psicosis epiléptica secundaria a cirugía de la epilepsia. Aunque se ha generalizado la combinación de antiepilépticos y neurolépticos para su manejo, no existen unas pautas estandarizadas de tratamiento en las psicosis epilépticas. Casos clínicos: Presentamos 5 casos de psicosis epilépticas periictales y remarcamos la excelente respuesta al tratamiento con levetiracetam. Consiguiendo un buen control tanto de las crisis como de los episodios psicóticos. Este fármaco resultó inocuo al asociarlo con neurolépticos en nuestros pacientes y no se precisaron dosis elevadas de estos últimos. Conclusiones: La diferenciación de los estados psicóticos asociados con la epilepsia según la relación temporal con las crisis epilépticas tiene utilidad clínica y pronóstica, dado que aporta aspectos importantes respecto al tratamiento y a la evolución de la enfermedad. El tratamiento de los trastornos mentales periictales o agudos se basa en el control de las crisis epilépticas, mientras que el tratamiento de los interictales o crónicos guarda más similitud con el de los trastornos de origen puramente psiquiátrico. El control estricto de las crisis puede, además de mejorar la calidad de vida del paciente y su discapacidad, prevenir el desarrollo de una psicosis interictal, por lo que consideramos que sería necesario establecer un protocolo de tratamiento para estos casos. Abstract: Introduction: Epileptic psychoses are categorised as peri-ictal and interictal according to their relationship with the occurrence of seizures. There is a close temporal relationship between peri-ictal psychosis and seizures, and psychosis may present before (preictal), during (ictal) or after seizures (postictal). Epileptic psychoses usually have acute initial and final phases, with a short symptom duration and complete remission with a risk of recurrence. There is no temporal relationship between interictal or chronic psychosis and epileptic seizures. Another type of epileptic psychosis is related to the response to epilepsy treatment: epileptic psychosis caused by the phenomenon of forced normalisation (alternative psychosis), which includes epileptic psychosis secondary to epilepsy surgery. Although combination treatment with antiepileptic and neuroleptic drugs is now widely used to manage this condition, there are no standard treatment guidelines for epileptic psychosis. Clinical cases: We present 5 cases of peri-ictal epileptic psychosis in which we observed an excellent response to treatment with levetiracetam. Good control was achieved over both seizures and psychotic episodes. Levetiracetam was used in association with neuroleptic drugs with no adverse effects, and our patients did not require high doses of the latter. Conclusions: Categorising psychotic states associated with epilepsy according to their temporal relationship with seizures is clinically and prognostically useful because it provides important information regarding disease treatment and progression. The treatment of peri-ictal or acute mental disorders is based on epileptic seizure control, while the treatment of interictal or chronic disorders has more in common with managing disorders which are purely psychiatric in origin. In addition to improving the patient's quality of life and reducing disability, achieving strict control over seizures may also prevent the development of interictal psychosis. For this reason, we believe that establishing a treatment protocol for such cases is necessary. Palabras clave: Epilepsia, Crisis, Levetiracetam, Periictal, Psicosis, Psicosis epiléptica, Keywords: Epilepsy, Seizure, Levetiracetam, Peri-ictal, Psychosis, Epileptic psychosis

Introduction: Epileptic psychoses are categorised as peri-ictal and interictal according to their relationship with the occurrence of seizures. There is a close temporal relationship between peri-ictal psychosis and seizures, and psychosis may present before (preictal), during (ictal) or after seizures (postictal). Epileptic psychoses usually have acute initial and final phases, with a short symptom duration and complete remission with a risk of recurrence. There is no temporal relationship between interictal or chronic psychosis and epileptic seizures. Another type of epileptic psychosis is related to the response to epilepsy treatment: epileptic psychosis caused by the phenomenon of forced normalisation (alternative psychosis), which includes epileptic psychosis secondary to epilepsy surgery. Although combination treatment with antiepileptic and neuroleptic drugs is now widely used to manage this condition, there are no standard treatment guidelines for epileptic psychosis. Clinical cases: We present 5 cases of peri-ictal epileptic psychosis in which we observed an excellent response to treatment with levetiracetam. Good control was achieved over both seizures and psychotic episodes. Levetiracetam was used in association with neuroleptic drugs with no adverse effects, and our patients did not require high doses of the latter. Conclusions: Categorising psychotic states associated with epilepsy according to their temporal relationship with seizures is clinically and prognostically useful because it provides important information regarding disease treatment and progression. The treatment of peri-ictal or acute mental disorders is based on epileptic seizure control, while the treatment of interictal or chronic disorders has more in common with managing disorders which are purely psychiatric in origin. In addition to improving the patient's quality of life and reducing disability, achieving strict control over seizures may also prevent the development of interictal psychosis. For this reason, we believe that establishing a treatment protocol for such cases is necessary. Resumen: Introducción: Las psicosis epilépticas se dividen respecto de su relación con las crisis en periictales e interictales. Las psicosis periictales tienen una estrecha relación temporal con las crisis epilépticas y ocurren antes (preictales), durante (ictales) o después de las mismas (postictales). Generalmente, tienen un inicio y final agudo, corta duración y una remisión completa, con riesgo de recurrencia. Las psicosis interictales o crónicas no guardan relación temporal con las crisis epilépticas. Existe otro tipo de psicosis epilépticas que se relaciona con la respuesta al tratamiento de la epilepsia: psicosis epiléptica por fenómeno de normalización forzada (psicosis alternativa) y dentro de esta se encuentra la psicosis epiléptica secundaria a cirugía de la epilepsia. Aunque se ha generalizado la combinación de antiepilépticos y neurolépticos para su manejo, no existen unas pautas estandarizadas de tratamiento en las psicosis epilépticas. Casos clínicos: Presentamos 5 casos de psicosis epilépticas periictales y remarcamos la excelente respuesta al tratamiento con levetiracetam. Consiguiendo un buen control tanto de las crisis como de los episodios psicóticos. Este fármaco resultó inocuo al asociarlo con neurolépticos en nuestros pacientes y no se precisaron dosis elevadas de estos últimos. Conclusiones: La diferenciación de los estados psicóticos asociados con la epilepsia según la relación temporal con las crisis epilépticas tiene utilidad clínica y pronóstica, dado que aporta aspectos importantes respecto al tratamiento y a la evolución de la enfermedad. El tratamiento de los trastornos mentales periictales o agudos se basa en el control de las crisis epilépticas, mientras que el tratamiento de los interictales o crónicos guarda más similitud con el de los trastornos de origen puramente psiquiátrico. El control estricto de las crisis puede, además de mejorar la calidad de vida del paciente y su discapacidad, prevenir el desarrollo de una psicosis interictal, por lo que consideramos que sería necesario establecer un protocolo de tratamiento para estos casos. Keywords: Epilepsy, Seizure, Levetiracetam, Peri-ictal, Psychosis, Epileptic psychosis, Palabras clave: Epilepsia, Crisis, Levetiracetam, Periictal, Psicosis, Psicosis epiléptica

Objetivo: Se comparan dos metodologías para el análisis de la relación entre contaminación atmosférica y salud. Una de las metodologías (ME) está basada en el modelo lineal generalizado, mientras que la otra (MN) incorpora el modelo aditivo generalizado (GAM). Aparte del modelo estadístico utilizado, las dos metodologías presentan discrepancias adicionales en cuanto al tipo y número de variables empleadas en el control de la confusión. Método: Se realizó un análisis para cada retardo de humos negros (de 0 a 5) y diversos indicadores de salud con datos relativos a la ciudad de Valencia y siguiendo ambas metodologías. Los resultados obtenidos se compararon mediante el examen de la secuencia y retardo de mayor efecto, el cálculo de la razón de las amplitudes de los intervalos de confianza y el cálculo de la diferencia porcentual en las estimaciones. Resultados: El cambio en los resultados según la metodología fue pequeño. La forma de la secuencia y, en general, el retardo de mayor efecto permanecieron invariables. Los coeficientes se mantuvieron estables (la diferencia porcentual de MN metodológicas con respecto a ME no superó el 10%) y los intervalos de confianza resultaron más precisos con MN, aunque la disminución de la amplitud de los intervalos de confianza no fue drástica (la razón de amplitudes se situó en torno al 90%). Conclusiones: La escasa variación de los resultados ofrece garantías en cuanto a la aplicabilidad de ambas metodologías, MN y ME, si bien la reducción sistemática del error estándar con MN apoya el uso de este último método como el procedimiento más eficiente en el control de la confusión.Objective: We compare two methods to analyse the relationship between air pollution and health. One of them (ME) is based on a generalized linear model, while the other one (MN) incorporates a generalized additive model (GAM). Besides the statistical model used, both methods schow additional discrepancies for the type and number of variables used in the control of confounding. Method: An analysis was carried out for each lag of black smoke (0 to 5) and several health indicators from the city of Valencia (Spain) following both methods. Results were compared examining the sequence and the lag of the higher coefficient. The ratio between confidence intervals width and the percent difference in the estimates were also obtained. Results: The discrepancies in results according to the methodology were small. The sequence shaped and the lag of higher coefficient generally remained invariant. Coefficients were similar (percent difference of MN over ME was not greater than 10%). Confidence intervals were more precise for MN, although the reduction was not very strong (the width ratio was around 90%). Conclusions: The short variation of the results guarantees the applicability of both MN and ME methods, although the systematic reduction of the standard error of MN supports its use as a more efficient procedure to control for confounding.

Objetivo: Estimar la asociación a corto plazo entre los valores de contaminación atmosférica por partículas en suspensión y diferentes indicadores de morbilidad y mortalidad en la ciudad de Valencia. Métodos: Estudio ecológico de series temporales en el que se relacionan las variaciones diarias en los valores de contaminación atmosférica por humos negros e indicadores de mortalidad, ingresos hospitalarios y visitas a urgencias en la ciudad de Valencia, durante el período 1994-1996. La magnitud de la asociación se estimó mediante regresión autorregresiva de Poisson utilizando modelos aditivos generalizados. Se examinó la forma de la relación, el efecto retardado de la contaminación y la posible modificación de efecto por otros contaminantes o períodos del año. Resultados: Existe una asociación significativa entre los valores de partículas en suspensión y varios indicadores analizados en Valencia. La forma de dicha relación es lineal. Un incremento de 10 μg/m³ en los valores diarios de humos negros se asoció con un incremento del 1,8% (intervalo de confianza [IC] del 95%, 0,9-2,7%) en el número de defunciones del día siguiente. El mismo incremento en la contaminación se asoció con un aumento del 1,5% (0,1-2,8%) en las defunciones por causa circulatoria, en un 1,3% (0,0-2,6%) en los ingresos por causas circulatorias y en un 5,4 (0,6-10,4%) en el número de visitas a urgencias por asma. Esta asociación no está confundida por los valores de otros contaminantes. No se encontró asociación de los humos negros con la mortalidad por enfermedades respiratorias, los ingresos hospitalarios por enfermedades cerebrovasculares ni las visitas a urgencias por enfermedad pulmonar obstructiva crónica (EPOC). Conclusiones: Este estudio proporciona evidencia de que los valores de partículas en suspensión en Valencia se asocian con las urgencias por asma, los ingresos por enfermedades circulatorias y las defunciones diarias. La asociación encontrada es consistente con los resultados de otros estudios realizados y es coherente con conocimientos recientes sobre los mecanismos fisiopatológicos.Objective: To estimate the short-term association between levels of air pollution due to suspended particulates and several indicators of morbidity and mortality in the city of Valencia, Spain. Methods: We performed an ecological time-series study. Daily levels of air pollution from black smoke were related to indicators of mortality, hospital admissions, and visits to emergency departments in the city of Valencia between 1994 and 1996. The magnitude of the association was estimated through Poisson autoregression using generalized additive models. The form of the relationship, the delayed effect of pollution, and the possible modification of this effect by other pollutants or periods of the year were assessed. Results: A significant association was found between levels of suspended particulates and several of the indicators analyzed in Valencia. The form of this relationship was linear. An increment of 10 μg/m3 in the daily levels of black smoke was associated with an increase of 1.8% (95% confidence interval: 0.9-2.7%) in the number of deaths on the following day. The same increment in pollutant levels was associated with an increase of 1.5% (0.1-2.8%) in deaths from all cardiovascular causes, an increase of 1.3% (0.0-2.6%) in admissions for all cardiovascular diseases and in an increase of 5.4% (0.6-10.4%) in the number of emergency visits for asthma. This association was not confounded by levels of other pollutants. Black smoke was not associated with mortality from respiratory diseases, with hospital admissions for cerebrovascular diseases, or with emergency visits for chronic obstructive pulmonary disease. Conclusions: This study provides evidence that levels of suspended particles in Valencia are associated with emergency visits for asthma, hospital admissions for cardiovascular diseases, and daily deaths. The association found is consistent with the results of previous studies and fits with recent knowledge of psychopathological mechanisms.

Background: Heterogeneity in temperature-mortality relationships across locations may partly result from differences in the demographic structure of populations and their cause-specific vulnerabilities. Here we conduct the largest epidemiological study to date on the association between ambient temperature and mortality by age and cause using data from 532 cities in 33 countries., Methods: We collected daily temperature and mortality data from each country. Mortality data was provided as daily death counts within age groups from all, cardiovascular, respiratory, or noncardiorespiratory causes. We first fit quasi-Poisson regression models to estimate location-specific associations for each age-by-cause group. For each cause, we then pooled location-specific results in a dose-response multivariate meta-regression model that enabled us to estimate overall temperature-mortality curves at any age. The age analysis was limited to adults., Results: We observed high temperature effects on mortality from both cardiovascular and respiratory causes compared to noncardiorespiratory causes, with the highest cold-related risks from cardiovascular causes and the highest heat-related risks from respiratory causes. Risks generally increased with age, a pattern most consistent for cold and for nonrespiratory causes. For every cause group, risks at both temperature extremes were strongest at the oldest age (age 85 years). Excess mortality fractions were highest for cold at the oldest ages., Conclusions: There is a differential pattern of risk associated with heat and cold by cause and age; cardiorespiratory causes show stronger effects than noncardiorespiratory causes, and older adults have higher risks than younger adults., Competing Interests: The authors declare that they have no conflicts of interest with regard to the content of this report., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The Environmental Epidemiology. All rights reserved.)

The literature informing susceptible periods of exposure on children's neurodevelopment is limited. We evaluated the impacts of pre- and postnatal fine particulate matter (PM 2.5 ) exposure on children's cognitive and motor function among 1303 mother-child pairs in the Spanish INMA (Environment and Childhood) Study. Random forest models with temporal back extrapolation were used to estimate daily residential PM 2.5 exposures that we averaged across 1-week lags during the prenatal period and 4-week lags during the postnatal period. The McCarthy Scales of Children's Abilities (MSCA) were administered around 5 years to assess general cognitive index (GCI) and several subscales (verbal, perceptual-performance, memory, fine motor, gross motor). We applied distributed lag nonlinear models within the Bayesian hierarchical framework to explore periods of susceptibility to PM 2.5 on each MSCA outcome. Effect estimates were calculated per 5 μg/m 3 increase in PM 2.5 and aggregated across adjacent statistically significant lags using cumulative β (β cum) and 95% Credible Intervals (95%CrI). We evaluated interactions between PM 2.5 with fetal growth and child sex. We did not observe associations of PM 2.5 exposure with lower GCI scores. We found a period of susceptibility to PM 2.5 on fine motor scores in gestational weeks 1-9 (β cum  = -2.55, 95%CrI = -3.53,-1.56) and on gross motor scores in weeks 7-17 (β cum  = -2.27,95%CrI = -3.43,-1.11) though the individual lags for the latter were only borderline statistically significant. Exposure in gestational week 17 was weakly associated with verbal scores (β cum  = -0.17, 95%CrI = -0.26,-0.09). In the postnatal period (from age 0.5-1.2 years), we observed a window of susceptibility to PM 2.5 on lower perceptual-performance (β = -2.42, 95%CrI = -3.37,-1.46). Unexpected protective associations were observed for several outcomes with exposures in the later postnatal period. We observed no evidence of differences in susceptible periods by fetal growth or child sex. Preschool-aged children's motor function may be particularly susceptible to PM 2.5 exposures experienced in utero whereas the first year of life was identified as a period of susceptibility to PM 2.5 for children's perceptual-performance., Competing Interests: Declaration of competing interest All authors declare they have no actual or potential competing financial interest., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Background: Gestational vitamin D levels may influence offspring growth and modulate adipogenesis. Findings from prospective studies are inconsistent, and few have evaluated the persistence of these associations into late childhood., Objective: To examine the association between prenatal vitamin D levels and growth and adiposity in late childhood., Methods: We included 2027 mother-child pairs from the INMA birth cohort. 25-hydroxyvitamin D 3 (vitamin D 3 ) levels were measured in serum at 13 weeks of pregnancy. Sex- and age-specific body mass index z-scores were calculated at 7 and 11 years, overweight was defined as z-score ≥ 85th percentile, and body fat mass was measured at 11 years. Z-score body mass index (zBMI) trajectories from birth to 11 years were identified using latent class growth analysis., Results: The prevalence of vitamin D 3 deficiency (<20 ng/mL) was 17.5%, and around 40% of the children had overweight at both ages. Associations between vitamin D levels and outcomes differed by sex. In boys, maternal vitamin D 3 deficient status was associated with higher zBMI, higher fat mass percentage, higher odds of being overweight, and with an increased risk of belonging to lower birth size followed by accelerated BMI gain trajectory. In girls no associations were observed., Conclusion: Our results support a sex-specific programming effect of early pregnancy vitamin D 3 levels on offspring body composition into late childhood observed in boys.

While prior studies report associations between fine particulate matter (PM 2.5 ) exposure and fetal growth, few have explored temporally refined susceptible windows of exposure. We included 2328 women from the Spanish INMA Project from 2003 to 2008. Longitudinal growth curves were constructed for each fetus using ultrasounds from 12, 20, and 34 gestational weeks. Z-scores representing growth trajectories of biparietal diameter, femur length, abdominal circumference (AC), and estimated fetal weight (EFW) during early (0-12 weeks), mid- (12-20 weeks), and late (20-34 weeks) pregnancy were calculated. A spatio-temporal random forest model with back-extrapolation provided weekly PM 2.5 exposure estimates for each woman during her pregnancy. Distributed lag non-linear models were implemented within the Bayesian hierarchical framework to identify susceptible windows of exposure for each outcome and cumulative effects [β cum , 95% credible interval (CrI)] were aggregated across adjacent weeks. For comparison, general linear models evaluated associations between PM 2.5 averaged across multi-week periods (i.e., weeks 1-11, 12-19, and 20-33) and fetal growth, mutually adjusted for exposure during each period. Results are presented as %change in z-scores per 5 μg/m 3 in PM 2.5 , adjusted for covariates. Weeks 1-6 [β cum  = -0.77%, 95%CrI (-1.07%, -0.47%)] were identified as a susceptible window of exposure for reduced late pregnancy EFW while weeks 29-33 were positively associated with this outcome [β cum  = 0.42%, 95%CrI (0.20%, 0.64%)]. A similar pattern was observed for AC in late pregnancy. In linear regression models, PM 2.5 exposure averaged across weeks 1-11 was associated with reduced late pregnancy EFW and AC; but, positive associations between PM 2.5 and EFW or AC trajectories in late pregnancy were not observed. PM 2.5 exposures during specific weeks may affect fetal growth differentially across pregnancy and such associations may be missed by averaging exposure across multi-week periods, highlighting the importance of temporally refined exposure estimates when studying the associations of air pollution with fetal growth., 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 © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Structure-function analysis is a powerful strategy to characterize the contribution of specific residues to the biogenesis and function of a protein. This approach requires the characterization of strains that express mutant alleles in the absence of the wild-type protein. When studying nonessential bacterial genes, collections of mutants can be easily constructed by introducing plasmid-encoded alleles of interest into a strain that already lacks the wild-type gene. However, this high-throughput approach is not applicable to studying essential genes since their respective null strains are not viable. While there are several tools currently available to modify essential genes, they can be greatly limited by the amount of effort it takes to build and analyze each mutant strain. Here, we describe a high-throughput system for the rapid structure-function analysis of essential genes involved in lipopolysaccharide transport in Escherichia coli. This method, which can be applied to study any essential gene, relies on the initial construction of a single bacterial strain that can be used to generate and functionally characterize multiple plasmid-encoded alleles in under 24 h. We will discuss the advantages and possible shortcomings of our protocol in comparison to other commonly used methods., (© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Climate change affects human health; however, there have been no large-scale, systematic efforts to quantify the heat-related human health impacts that have already occurred due to climate change. Here, we use empirical data from 732 locations in 43 countries to estimate the mortality burdens associated with the additional heat exposure that has resulted from recent human-induced warming, during the period 1991-2018. Across all study countries, we find that 37.0% (range 20.5-76.3%) of warm-season heat-related deaths can be attributed to anthropogenic climate change and that increased mortality is evident on every continent. Burdens varied geographically but were of the order of dozens to hundreds of deaths per year in many locations. Our findings support the urgent need for more ambitious mitigation and adaptation strategies to minimize the public health impacts of climate change., Competing Interests: Competing interests The authors declare no competing interests.

Highly prevalent and typically beginning in childhood, asthma is a burdensome disease, yet the risk factors for this condition are not clarified. To enhance understanding, this study assessed the cohort-specific and pooled risk of maternal education on asthma in children aged 3-8 across 10 European countries. Data on 47,099 children were obtained from prospective birth cohort studies across 10 European countries. We calculated cohort-specific prevalence difference in asthma outcomes using the relative index of inequality (RII) and slope index of inequality (SII). Results from all countries were pooled using random-effects meta-analysis procedures to obtain mean RII and SII scores at the European level. Final models were adjusted for child sex, smoking during pregnancy, parity, mother's age and ethnicity. The higher the score the greater the magnitude of relative (RII, reference 1) and absolute (SII, reference 0) inequity. The pooled RII estimate for asthma risk across all cohorts was 1.46 (95% CI 1.26, 1.71) and the pooled SII estimate was 1.90 (95% CI 0.26, 3.54). Of the countries examined, France, the United Kingdom and the Netherlands had the highest prevalence's of childhood asthma and the largest inequity in asthma risk. Smaller inverse associations were noted for all other countries except Italy, which presented contradictory scores, but with small effect sizes. Tests for heterogeneity yielded significant results for SII scores. Overall, offspring of mothers with a low level of education had an increased relative and absolute risk of asthma compared to offspring of high-educated mothers.

Background: Maternal smoking during pregnancy is linked to reduced birth weight but the gestation at onset of this relationship is not certain. We present a systematic review of the literature describing associations between maternal smoking during pregnancy and ultrasound measurements of fetal size, together with an accompanying meta-analysis., Methods: Studies were selected from electronic databases (OVID, EMBASE and Google Scholar) that examined associations between maternal smoking or smoke exposure and antenatal fetal ultrasound measurements. Outcome measures were first, second or third trimester fetal measurements., Results: There were 284 abstracts identified, 16 papers were included in the review and the meta-analysis included data from eight populations. Maternal smoking was associated with reduced second trimester head size (mean reduction 0.09 standard deviation (SD) [95% CI 0.01, 0.16]) and femur length (0.06 [0.01, 0.10]) and reduced third trimester head size (0.18 SD [0.13, 0.23]), femur length (0.27 SD [0.21, 0.32]) and estimated fetal weight (0.18 SD [0.11, 0.24]). Higher maternal cigarette consumption was associated with a lower z score for head size in the second (mean difference 0.09 SD [0, 0.19]) and third (0.15 SD [0.03, 0.26]) trimesters compared to lower consumption. Fetal measurements were not reduced for those whose mothers quit before or after becoming pregnant compared to mothers who had never smoked., Conclusions: Maternal smoking during pregnancy is associated with reduced fetal measurements after the first trimester, particularly reduced head size and femur length. These effects may be attenuated if mothers quit or reduce cigarette consumption during pregnancy.

Introduction: Acute cerebrovascular disease is a major cause of disability and mortality, with important socio-economic and health impacts. Early stroke care can reduce mortality and improve prognosis. Right now, we can apply treatments in the acute phase, with capacity to reverse the symptoms, but few patients who benefit not reach the hospital soon. One reason for this delay is the lack of recognition of symptoms and poor perception of gravity., Aim: To find out the knowledge of the public about the stroke., Subjects and Methods: The sample analyzed was the population of Sector III of Zaragoza, with random selection. The tool used was a telephone survey structured. We analyzed 583 surveys., Results: 63.5% of respondents did not know any symptoms of stroke. 48% do not know any vascular risk factor. Only 9% recognized at least two symptoms and two risk factors. Regarding the attitude, 56% act properly against 44% who do not. Multivariate analysis showed that the factors more related to knowledge are the cultural level and young age. Living in town, and female, they are associated with the best attitude., Conclusions: Knowledge about stroke is poor, with a low sense of urgency. The factors most associated with the best knowledge are young age and cultural level.

Introduction: Headache as a symptom is a very common disease and one of the main reasons for consultation in primary care., Aim: To analyze the characteristics of patients referred from primary care to general neurology whose chief complaint was headache and/or neuralgia and diagnostic agreement., Patients and Methods: Cross-sectional study of all patients referred from primary care; demographic/clinical variables were collected and diagnostic hypothesis by primary care and general neurology were compared by determining their agreement., Results: 2,514 were referred from primary care patients (588 of them on a preferential basis); in 378 cases the reason for consultation was headache and/or neuralgia (average 42.46 years; 77.8% female). In 139 patients it was established only a semiological diagnostic and other episodic migraine predominated (49.79%), chronic tension headache (18.41%) and trigeminal neuralgia (12.13%). Since general neurology, the most common diagnoses were, respectively, 33.86%, 24.05% and 18.67%. A compatible kappa coefficient of 0.543 (p < 0.05) with a moderate agreement when considering only those patients referred from primary care to a specific diagnosis was obtained., Conclusions: Headaches are a very common reason for consultation in primary care (15%). The diagnostic agreement is moderate in our health sector so it is necessary to design training programs to help outline the criteria for referral to specialists and improve care for our patients.

Introduction: The sexual erectile dysfunction are common symptoms and many chronic diseases whose diagnosis will determine the therapeutic management of patients., Aim: To assess sexual function in men with migraine or cluster headache (CH) compared with a control group., Subjects and Methods: Cross-sectional study of 34 patients with migraine, 31 patients with CH and 60 control subjects less than 46 years old. Erectile dysfunction was assessed using the International Index of Erectile Dysfunction (IIEF). Emotional state was evaluated using the Beck Depression Inventory., Results: The average score on the IIEF was 68.41 ± 10.09, 64.26 ± 5.73 and 59.33 ± 15.89 in the control group, migraine and CH respectively (p = 0.041) being the significant difference between controls and CH (p = 0.036). In the group of migraine patients, three patients had mild and one moderate erectile dysfunction. In the group of patients with CH, twelve scored in rank of mild erectile dysfunction, and two met the criteria for severe erectile dysfunction (p < 0.05). By analyzing differences in the different domains of IIEF, they were significant in the domain of overall satisfaction (p = 0.015) between the control group and patients with CH (p = 0.012)., Conclusions: In our study we found a higher frequency of and involvement in sexual function in terms of overall satisfaction in patients with migraine and CH. We believe that the evaluation of sexual function in this type of headache should be integrated into our clinical practice.

Adverse pregnancy outcomes entail a large health burden for the mother and offspring; a part of it might be avoided by better understanding the role of environmental factors in their etiology. Our aims were to review the assessment tools to characterize fecundity troubles and pregnancy-related outcomes in human populations and their sensitivity to environmental factors. For each outcome, we reviewed the possible study designs, main sources of bias, and their suggested cures. In terms of study design, for most pregnancy outcomes, cohorts with recruitment early during or even before pregnancy allow efficient characterization of pregnancy-related events, time-varying confounders, and in utero exposures that may impact birth outcomes and child health. Studies on congenital anomalies require specific designs, assessment of anomalies in medical pregnancy terminations, and, for congenital anomalies diagnosed postnatally, follow-up during several months after birth. Statistical analyses should take into account environmental exposures during the relevant time windows; survival models are an appropriate approach for fecundity, fetal loss, and gestational duration/preterm delivery. Analysis of gestational duration could distinguish pregnancies according to delivery induction (and possibly pregnancy-related conditions). In conclusion, careful design and analysis are required to better characterize environmental effects on human reproduction.

In this paper the postnatal changes in the cytoskeleton of the rat optic nerve fibers are described and quantified. These changes are also compared with other parameters such as myelination and axonal caliber with the aim of describing a general pattern of optic nerve maturation from a morphological point of view. The results showed that during the first postnatal week microtubules outnumbered neurofilaments but between days 8 and 20 the neurofilaments rapidly increased and on day 20 were about twice as numerous as microtubules. This proportion remained almost unaltered from the end of the third week to the 44th postnatal day. The comparison with other parameters suggested that the cytoskeleton, and in particular the proportion between its components, may be a more reliable index for measuring optic nerve maturation than other variables commonly used.