Age-related differences in the functional topography of the locus coeruleus and their implications for cognitive and affective functions.

The locus coeruleus (LC) is an important noradrenergic nucleus that has recently attracted a lot of attention because of its emerging role in cognitive and psychiatric disorders. Although previous histological studies have shown that the LC has heterogeneous connections and cellular features, no studies have yet assessed its functional topography in vivo, how this heterogeneity changes over aging, and whether it is associated with cognition and mood. Here, we employ a gradient-based approach to characterize the functional heterogeneity in the organization of the LC over aging using 3T resting-state fMRI in a population-based cohort aged from 18 to 88 years of age (Cambridge Centre for Ageing and Neuroscience cohort, n=618). We show that the LC exhibits a rostro-caudal functional gradient along its longitudinal axis, which was replicated in an independent dataset (Human Connectome Project [HCP] 7T dataset, n=184). Although the main rostro-caudal direction of this gradient was consistent across age groups, its spatial features varied with increasing age, emotional memory, and emotion regulation. More specifically, a loss of rostral-like connectivity, more clustered functional topography, and greater asymmetry between right and left LC gradients was associated with higher age and worse behavioral performance. Furthermore, participants with higher-than-normal Hospital Anxiety and Depression Scale (HADS) ratings exhibited alterations in the gradient as well, which manifested in greater asymmetry. These results provide an in vivo account of how the functional topography of the LC changes over aging, and imply that spatial features of this organization are relevant markers of LC-related behavioral measures and psychopathology.

Sex differences in multilayer functional network topology over the course of aging in 37543 UK Biobank participants.

Aging is a major risk factor for cardiovascular and neurodegenerative disorders, with considerable societal and economic implications. Healthy aging is accompanied by changes in functional connectivity between and within resting-state functional networks, which have been associated with cognitive decline. However, there is no consensus on the impact of sex on these age-related functional trajectories. Here, we show that multilayer measures provide crucial information on the interaction between sex and age on network topology, allowing for better assessment of cognitive, structural, and cardiovascular risk factors that have been shown to differ between men and women, as well as providing additional insights into the genetic influences on changes in functional connectivity that occur during aging. In a large cross-sectional sample of 37,543 individuals from the UK Biobank cohort, we demonstrate that such multilayer measures that capture the relationship between positive and negative connections are more sensitive to sex-related changes in the whole-brain connectivity patterns and their topological architecture throughout aging, when compared to standard connectivity and topological measures. Our findings indicate that multilayer measures contain previously unknown information on the relationship between sex and age, which opens up new avenues for research into functional brain connectivity in aging.

Rebound activity after fingolimod cessation: A case - control study.

BACKGROUND: There has been an increase in the number of reports of multiple sclerosis (MS) rebound activity (RA), which is usually defined as a severe disease reactivation after natalizumab or fingolimod withdrawal that exceeds pre-treatment baseline inflammatory activity. The frequency and risk factors that could predict RA remain unknown. Fingolimod is currently the most frequently prescribed disease modifying therapy for MS in Argentina, so that there is a need to determine possible predictors of RA. OBJECTIVES: To identify risk factors for developing RA after fingolimod cessation; to describe RA characteristics, management and evolution. METHODS: The study was a multicenter, retrospective, case-control study of patients with MS who had discontinued fingolimod and were followed up to nine months after discontinuation. Demographic, clinical and paraclinical data was extracted, including age, gender, MS phenotype, reason for discontinuation, number of relapses during the year prior to suspension, time treated with fingolimod, EDSS before, during and after rebound, MRI findings. RESULTS: 26 cases of RA were matched 1:1 with patients without RA. The median time elapsed to RA was 50 days. 68% showed worsening of the EDSS in the evaluation at 3 months of RA. When compared with the control group, no difference was found in terms of age, gender, phenotype, EDSS at the moment of suspension, reason for discontinuation, number of relapses in the previous year, and time on therapy. CONCLUSION: In this case-controlled study, no risk factors could be identified to predict RA after fingolimod cessation. Further controlled, prospective, better powered studies are needed to confirm these findings.

Multiplex Connectome Changes across the Alzheimer's Disease Spectrum Using Gray Matter and Amyloid Data.

The organization of the Alzheimer's disease (AD) connectome has been studied using graph theory using single neuroimaging modalities such as positron emission tomography (PET) or structural magnetic resonance imaging (MRI). Although these modalities measure distinct pathological processes that occur in different stages in AD, there is evidence that they are not independent from each other. Therefore, to capture their interaction, in this study we integrated amyloid PET and gray matter MRI data into a multiplex connectome and assessed the changes across different AD stages. We included 135 cognitively normal (CN) individuals without amyloid-ß pathology (Aß-) in addition to 67 CN, 179 patients with mild cognitive impairment (MCI) and 132 patients with AD dementia who all had Aß pathology (Aß+) from the Alzheimer's Disease Neuroimaging Initiative. We found widespread changes in the overlapping connectivity strength and the overlapping connections across Aß-positive groups. Moreover, there was a reorganization of the multiplex communities in MCI Aß + patients and changes in multiplex brain hubs in both MCI Aß + and AD Aß + groups. These findings offer a new insight into the interplay between amyloid-ß pathology and brain atrophy over the course of AD that moves beyond traditional graph theory analyses based on single brain networks.

[Evolution and spatial analysis of leishmaniasis cases in a rural area bordering a community outbreak in Madrid: 2001-2017]. / Evolución y análisis espacial de los casos de leishmaniasis en una zona rural colindante al brote comunitario de Madrid: 2001-2017.

OBJECTIVE: Leishmaniasis is a zoonotic disease, widely spread all over the world, and an endemic disease in some Spanish regions. Within the Autonomous Region of Madrid, some south populations were affected by an outbreak from 2009. This outbreak had special features and implications related to epidemiology, reservoir and environment intervention. An increased rate in rural areas bordering the outbreak area was detected by epidemiological surveillance. This area has the same environment characteristics. The objective of this study was to research and analyze the evolution of leishmaniasis cases declared in a rural area and their comparison with the cases of the outbreak area. METHODS: The cases declared to Epidemiology Surveillance Network have been used. Kulldorff´s tools were used for the cluster analysis. A hot spot analysis (Getis-Ord Gi*) was made. Leporidae and vector information of the area was related to the location of cases. RESULTS: The number of observed cases exceeded the number of expected cases in this area (epidemic index 7.8 in 2013), after the outbreak. This showed a relation between both incidence rates. It seemed to be spatial correlation when the number of cases was analyzed by census sections and grids (Moran´s I 0,208; z= 9,336). Using the hot-spot analysis, a higher incidence of the study area could be observed, and within Health Basic Area of Griñón after the outbreak years. A spatial relation between cases and a greater presence of vectors and leporidae was found. CONCLUSIONS: The distribution of leishmaniasis cases, in the period and study area suggests a link between the community outbreak and the increase of cases in the study area last years, overall in the rural area. It would be useful to strengthen surveillance and it should apply effective measures used in the bordering area if they were necessary. These measures can help to control the spread of the outbreak.

OBJETIVO: La leishmaniasis en una enfermedad zoonótica muy extendida a nivel mundial y es endémica en algunas regiones de España. Desde 2009 un brote de leishmaniasis ha afectado a algunos municipios del sur de Madrid con características e implicaciones especiales en cuanto a epidemiología, reservorio e intervención medioambiental. Se ha observado un aumento de casos en las zonas rurales adyacentes con características ambientales similares. El objetivo de este trabajo fue estudiar y analizar la evolución de los casos de leishmaniasis declarados en una zona rural colindante y compararlos con el brote comunitario. METODOS: Se utilizó la información de los casos declarados a la Red de Vigilancia Epidemiológica de la Comunidad de Madrid en la zona de estudio desde 2001-2017 y se compararon las tasas de incidencia con las del área del brote. Se realizó un análisis espacial de los casos y de los conglomerados para cuatro unidades espaciales. Se realizó análisis de conglomerados según la técnica de Kulldorff y análisis de puntos calientes según Gi* de Getis-Ord. Se relacionó la información disponible de lepóridos y vectores con la ubicación de los casos. RESULTADOS: Los casos observados en el área de estudio superaron a los esperados tras al inicio del brote (índice epidémico 7,8 en 2013) mostrándose una relación gráfica entre las tasas de incidencia. Existió una autocorrelación espacial cuando se analizaron el número de casos por secciones censales y por cuadrículas (índice de Moran de 0,208; z= 9,336). En el análisis de puntos calientes se pudo apreciar una mayor incidencia en el área de estudio en el periodo posterior al brote, en particular en la Zona Básica de Salud de Griñón. Se constató una relación espacial entre casos y zonas de mayor presencia de lepóridos y vectores. CONCLUSIONES: La distribución de casos de leishmaniasis en el periodo y área de estudio sugiere que puede existir una asociación entre el brote comunitario y el aumento de casos de los últimos años en el área de estudio, específicamente en la zona rural, por lo que sería necesario reforzar la vigilancia y aplicar medidas de control ambiental en caso necesario, lo cual puede contribuir a limitar la extensión del brote.

Evolución y análisis espacial de los casos de leishmaniasis en una zona rural colindante al brote comunitario de Madrid: 2001-2017 / Evolution and spatial analysis of leishmaniasis cases in a rural area bordering a community outbreak in Madrid: 2001-2017

Fundamentos: La leishmaniasis en una enfermedad zoonótica muy extendida a nivel mundial y es endémica en algunas regiones de España. Desde 2009 un brote de leishmaniasis ha afectado a algunos municipios del sur de Madrid con características e implicaciones especiales en cuanto a epidemiología, reservorio e intervención medioambiental. Se ha observado un aumento de casos en las zonas rurales adyacentes con características ambientales similares. El objetivo de este trabajo fue estudiar y analizar la evolución de los casos de leishmaniasis declarados en una zona rural colindante y compararlos con el brote comunitario. Métodos: Se utilizó la información de los casos declarados a la Red de Vigilancia Epidemiológica de la Comunidad de Madrid en la zona de estudio desde 2001-2017 y se compararon las tasas de incidencia con las del área del brote. Se realizó un análisis espacial de los casos y de los conglomerados para cuatro unidades espaciales. Se realizó análisis de conglomerados según la técnica de Kulldorff y análisis de puntos calientes según Gi* de Getis-Ord. Se relacionó la información disponible de lepóridos y vectores con la ubicación de los casos. Resultados: Los casos observados en el área de estudio superaron a los esperados tras al inicio del brote (índice epidémico 7,8 en 2013) mostrándose una relación gráfica entre las tasas de incidencia. Existió una auto-correlación espacial cuando se analizaron el número de casos por secciones censales y por cuadrículas (índice de Moran de 0,208; z= 9,336). En el análisis de puntos calientes se pudo apreciar una mayor incidencia en el área de estudio en el periodo posterior al brote, en particular en la Zona Básica de Salud de Griñón. Se constató una relación espacial entre casos y zonas de mayor presencia de lepóridos y vectores. Conclusión: La distribución de casos de leishmaniasis en el periodo y área de estudio sugiere que puede existir una asociación entre el brote comunitario y el aumento de casos de los últimos años en el área de estudio, específicamente en la zona rural, por lo que sería necesario reforzar la vigilancia y aplicar medidas de control ambiental en caso necesario, lo cual puede contribuir a limitar la extensión del brote

Background: Leishmaniasis is a zoonotic disease, widely spread all over the world, and an endemic disease in some Spanish regions. Within the Autonomous Region of Madrid, some south populations were affected by an outbreak from 2009. This outbreak had special features and implications related to epidemiology, reservoir and environment intervention. An increased rate in rural areas bordering the outbreak area was detected by epidemiological surveillance. This area has the same environment characteristics. The objective of this study was to research and analyze the evolution of leishmaniasis cases declared in a rural area and their comparison with the cases of the outbreak area. Methods: The cases declared to Epidemiology Surveillance Network have been used. Kulldorff's tools were used for the cluster analysis. A hot spot analysis (Getis-Ord Gi*) was made. Leporidae and vector information of the area was related to the location of cases. Results: The number of observed cases exceeded the number of expected cases in this area (epidemic index 7.8 in 2013), after the outbreak. This showed a relation between both incidence rates. It seemed to be spatial correlation when the number of cases was analyzed by census sections and grids (Moran's I 0,208; z= 9,336). Using the hot-spot analysis, a higher incidence of the study area could be observed, and within Health Basic Area of Griñón after the outbreak years. A spatial relation between cases and a greater presence of vectors and leporidae was found. Conclusion: The distribution of leishmaniasis cases, in the period and study area suggests a link between the community outbreak and the increase of cases in the study area last years, overall in the rural area. It would be useful to strengthen surveillance and it should apply effective measures used in the bordering area if they were necessary. These measures can help to control the spread of the outbreak

Implementación del mapa de la vulnerabilidad en salud en la Comunidad de Madrid / Health vulnerability mapping in the Community of Madrid (Spain)

Desde el modelo de los determinantes sociales de la salud y el enfoque de equidad, la Dirección General de Salud Pública de Madrid ha desarrollado la metodología de los mapas de la vulnerabilidad en salud para facilitar a los equipos sociosanitarios la planificación, la priorización y la intervención en salud en un territorio. A partir de la selección de las zonas básicas de salud con peores indicadores de vulnerabilidad en salud, se inicia un proceso de relación con los actores clave del territorio a fin de identificar conjuntamente áreas prioritarias de intervención y desarrollar un plan de acción consensuado. Se presentan el desarrollo de esta experiencia y su conexión con los modelos teóricos del mapeo en activos, los sistemas de georreferenciación integrados en salud y las intervenciones de salud comunitaria (AU)

The Public Health General Directorate of Madrid has developed a health vulnerability mapping methodology to assist regional social health teams in health planning, prioritisation and intervention based on a model of social determinants of health and an equity approach. This process began with the selection of areas with the worst social indicators in health vulnerability. Then, key stakeholders of the region jointly identified priority areas of intervention and developed a consensual plan of action. We present the outcomes of this experience and its connection with theoretical models of asset-based community development, health-integrated georeferencing systems and community health interventions (AU)

[Health vulnerability mapping in the Community of Madrid (Spain)]. / Implementación del mapa de la vulnerabilidad en salud en la Comunidad de Madrid.

The Public Health General Directorate of Madrid has developed a health vulnerability mapping methodology to assist regional social health teams in health planning, prioritisation and intervention based on a model of social determinants of health and an equity approach. This process began with the selection of areas with the worst social indicators in health vulnerability. Then, key stakeholders of the region jointly identified priority areas of intervention and developed a consensual plan of action. We present the outcomes of this experience and its connection with theoretical models of asset-based community development, health-integrated georeferencing systems and community health interventions.

[Age-dependent seroprevalence of Toscana virus in the Community of Madrid: 1993-1994 and 1999-2000]. / Seroprevalencia edad dependiente frente al virus Toscana en la Comunidad de Madrid: años 1993-1994 y 1999-2000.

OBJECTIVE: The aim of this study was to assess the seroprevalence of Toscana virus (TOSV) in the Community of Madrid. METHODS: Samples from two serosurveys obtained during 1993-1994 (2262 individuals) and 1999-2000 (1945 individuals) were studied. Samples were tested by ELISA for TOSV IgG detection. RESULTS: The seroprevalence of TOSV IgG was significantly higher in 1993-1994 (7.2%; 95% CI 6.2-8.4) than in 1999-2000 (5.7%; 95% CI 4.7-6.9) (chi-square, p < 0.05). In both periods, the prevalence increased significantly with age. CONCLUSION: These results confirm that TOSV has been circulating in the Community of Madrid over the last years.

Seroprevalencia edad dependiente frente al virus Toscana en la Comunidad de Madrid: años 1993-1994 y 1999-2000 / Age-dependent seroprevalence of Toscana virus in the Community of Madrid: 1993-1994 and 1999-2000

Este trabajo ha sido presentado en parte en el XII Congreso de la Sociedad Española de Microbiología Clínica y Enfermedades Infecciosas (Valencia del 10 al 13 de mayo de 2006). Objetivo. Valorar la seroprevalencia frente a virus Toscana (VTOS) en la Comunidad de Madrid. Métodos. Se estudiaron muestras de dos encuestas de serovigilancia obtenidas durante 1993-1994 (2.262 individuos) y 1999-2000 (1.945 individuos). Las muestras se procesaron mediante análisis inmunoenzimático (ELISA) para la detección de IgG frente a VTOS. Resultados. La seroprevalencia en 1993-1994 (7,2%; IC 95%: 6,2-8,4) resultó significativamente mayor (x2; p < 0,05) que en 1999-2000 (5,7%; IC 95%: 4,7-6,9). En ambos períodos la prevalencia aumentó significativamente según la edad. Conclusión. Estos resultados confirman la circulación de VTOS en la Comunidad de Madrid durante los últimos años (AU)

Objective. The aim of this study was to assess the seroprevalence of Toscana virus (TOSV) in the Community of Madrid. Methods. Samples from two serosurveys obtained during 1993-1994 (2262 individuals) and 1999-2000 (1945 individuals) were studied. Samples were tested by ELISA for TOSV IgG detection. Results. The seroprevalence of TOSV IgG was significantly higher in 1993-1994 (7.2%; 95% CI 6.2-8.4) than in 1999-2000 (5.7%; 95% CI 4.7-6.9) (chi-square, p < 0.05). In both periods, the prevalence increased significantly with age. Conclusion. These results confirm that TOSV has been circulating in the Community of Madrid over the last years (AU)

The temporal pattern of mortality responses to air pollution: a multicity assessment of mortality displacement.

Although the association between particulate matter and mortality or morbidity is generally accepted, controversy remains about the importance of the association. If it is due solely to the deaths of frail individuals, which are brought forward by only a brief period of time, the public health implications of the association are fewer than if there is an increase in the number of deaths. Recently, other research has addressed the mortality displacement issue in single-city analysis. We analyzed this issue with a distributed lag model in a multicity hierarchic modeling approach, within the Air Pollution and Health: A European Approach (APHEA-2) study. We fit a Poisson regression model and a polynomial distributed lag model with up to 40 days of delay in each city. In the second stage we combined the city-specific results. We found that the overall effect of particulate matter less than 10 microM in aerodynamic diameter (PM10) per 10 microg/m3 for the fourth-degree distributed lag model is a 1.61% increase in daily deaths (95% CI = 1.02-2.20), whereas the mean of PM10 on the same day and the previous day is associated with only a 0.70% increase in deaths (95% CI = 0.43-0.97). This result is unchanged using an unconstrained distributed lag model. Our study confirms that the effects observed in daily time-series studies are not due primarily to short-term mortality displacement. The effect size estimate for airborne particles more than doubles when we consider longer-term effects, which has important implications for risk assessment.