The impact of meteorological factors on tuberculosis incidence in Spain: a spatiotemporal analysis.

Tuberculosis (TB) remains a global leading cause of death, necessitating an investigation into its unequal distribution. Sun exposure, linked to vitamin D (VD) synthesis, has been proposed as a protective factor. This study aimed to analyse TB rates in Spain over time and space and explore their relationship with sunlight exposure. An ecological study examined the associations between rainfall, sunshine hours, and TB incidence in Spain. Data from the National Epidemiological Surveillance Network (RENAVE in Spanish) and the Spanish Meteorological Agency (AEMET in Spanish) from 2012 to 2020 were utilized. Correlation and spatial regression analyses were conducted. Between 2012 and 2020, 43,419 non-imported TB cases were reported. A geographic pattern (north-south) and distinct seasonality (spring peaks and autumn troughs) were observed. Sunshine hours and rainfall displayed a strong negative correlation. Spatial regression and seasonal models identified a negative correlation between TB incidence and sunshine hours, with a four-month lag. A clear spatiotemporal association between TB incidence and sunshine hours emerged in Spain from 2012 to 2020. VD levels likely mediate this relationship, being influenced by sunlight exposure and TB development. Further research is warranted to elucidate the causal pathway and inform public health strategies for improved TB control.

Sexual differences in locus coeruleus neurons and related behavior in C57BL/6J mice.

BACKGROUND: In addition to social and cultural factors, sex differences in the central nervous system have a critical influence on behavior, although the neurobiology underlying these differences remains unclear. Interestingly, the Locus Coeruleus (LC), a noradrenergic nucleus that exhibits sexual dimorphism, integrates signals that are related to diverse activities, including emotions, cognition and pain. Therefore, we set-out to evaluate sex differences in behaviors related to LC nucleus, and subsequently, to assess the sex differences in LC morphology and function. METHODS: Female and male C57BL/6J mice were studied to explore the role of the LC in anxiety, depressive-like behavior, well-being, pain, and learning and memory. We also explored the number of noradrenergic LC cells, their somatodendritic volume, as well as the electrophysiological properties of LC neurons in each sex. RESULTS: While both male and female mice displayed similar depressive-like behavior, female mice exhibited more anxiety-related behaviors. Interestingly, females outperformed males in memory tasks that involved distinguishing objects with small differences and they also showed greater thermal pain sensitivity. Immunohistological analysis revealed that females had fewer noradrenergic cells yet they showed a larger dendritic volume than males. Patch clamp electrophysiology studies demonstrated that LC neurons in female mice had a lower capacitance and that they were more excitable than male LC neurons, albeit with similar action potential properties. CONCLUSIONS: Overall, this study provides new insights into the sex differences related to LC nucleus and associated behaviors, which may explain the heightened emotional arousal response observed in females.

Exploring sex differences in the brain is important to understand the impact of such differences in pathological conditions characterized by gender bias, as well as their therapeutic implications. In this manuscript, we examined sex differences in the mouse locus coeruleus (LC) and how this might affect related behaviours. The LC is a sexually dimorphic nucleus that integrates signals associated with attention, anxiety, stress, arousal, pain, memory and learning. Our findings reveal that female mice exhibit more intense anxiety-related behaviors but that they perform better than males in recognizing small differences between objects. Additionally, we found pronounced sex differences in the LC, which contained fewer noradrenergic cells in females, with a larger dendritic volume and displaying enhanced cell excitability. These differences in the LC, a nucleus that fulfils a pivotal role in stress and pain, could be important for understanding the higher prevalence of stress-related disorders in women, such as anxiety and depression, but also of chronic pain. Hence, it is clearly important to consider sex differences in both preclinical and clinical research studies that attempt to understand pathologies related to these phenomena.

Chemogenetic activation of locus coeruleus neurons ameliorates the severity of multiple sclerosis.

BACKGROUND: Most current disease-modifying therapies approved for multiple sclerosis (MS) are immunomodulatory drugs that counteract the aberrant activity of the immune system. Hence, new pharmacological interventions that drive anti-inflammatory activity and neuroprotection would represent interesting alternative therapeutic approaches or complementary strategies to treat progressive forms of MS. There is evidence of reduced noradrenaline levels and alterations to locus coeruleus (LC) noradrenergic neurons in MS patients, as well as in animal models of this disease, potentially factors contributing to the pathophysiology. Drugs that enhance noradrenaline appear to have some beneficial effects in MS, suggesting their potential to dampen the underlying pathology and disease progression. METHODS: Therefore, we explored the consequences of chronic LC noradrenergic neurons activation by chemogenetics in experimental autoimmune encephalomyelitis (EAE) mice, the most widely used experimental model of MS. LC activation from the onset or the peak of motor symptoms was explored as two different therapeutic approaches, assessing the motor and non-motor behavioral changes as EAE progresses, and studying demyelination, inflammation and glial activation in the spinal cord and cerebral cortex during the chronic phase of EAE. RESULTS: LC activation from the onset of motor symptoms markedly alleviated the motor deficits in EAE mice, as well as their anxiety-like behavior and sickness, in conjunction with reduced demyelination and perivascular infiltration in the spinal cord and glial activation in the spinal cord and prefrontal cortex (PFC). When animals exhibited severe paralysis, LC activation produced a modest alleviation of EAE motor symptoms and it enhanced animal well-being, in association with an improvement of the EAE pathology at the spinal cord and PFC level. Interestingly, the reduced dopamine beta-hydroxylase expression associated with EAE in the spinal cord and PFC was reversed through chemogenetic LC activation. CONCLUSION: Therefore, clear anti-inflammatory and neuroprotective effects were produced by the selective activation of LC noradrenergic neurons in EAE mice, having greater benefits when LC activation commenced earlier. Overall, these data suggest noradrenergic LC neurons may be targets to potentially alleviate some of the motor and non-motor symptoms in MS.

Lifting COVID-19 mitigation measures in Spain (May-June 2020).

Introduction: The state of alarm was declared in Spain due to the COVID-19 epidemic on March 14, 2020, and established population confinement measures. The objective is to describe the process of lifting these mitigation measures. Methods: The Plan for the Transition to a New Normality, approved on April 28, contained four sequential phases with progressive increase in socio-economic activities and population mobility. In parallel, a new strategy for early diagnosis, surveillance and control was implemented. A bilateral decision mechanism was established between the Spanish Government and the autonomous communities (AC), guided by a set of qualitative and quantitative indicators capturing the epidemiological situation and core capacities. The territorial units were established ad-hoc and could be from Basic Health Zones to entire AC. Results: The process run from May 4 to June 21, 2020. AC implemented plans for reinforcement of core capacities. Incidence decreased from a median (50% of territories) of 7.4 per 100,000 in 7 days at the beginning to 2.5 at the end. Median PCR testing increased from 53% to 89% of suspected cases and PCR total capacity from 4.5 to 9.8 per 1000 inhabitants weekly; positivity rate decreased from 3.5% to 1.8%. Median proportion of cases with traced contacts increased from 82% to 100%. Conclusion: Systematic data collection, analysis, and interterritorial dialogue allowed adequate process control. The epidemiological situation improved but, mostly, the process entailed a great reinforcement of core response capacities nation-wide, under common criteria. Maintaining and further reinforcing capacities remained crucial for responding to future waves.

Introducción: El 14 de marzo de 2020 España declaró el estado de alarma por la pandemia por COVID-19 incluyendo medidas de confinamiento. El objetivo es describir el proceso de desescalada de estas medidas. Métodos: Un plan de transición hacia una nueva normalidad, del 28 de abril, incluía 4 fases secuenciales incrementando progresivamente las actividades socioeconómicas y la movilidad. Concomitantemente, se implementó una nueva estrategia de diagnóstico precoz, vigilancia y control. Se estableció un mecanismo de decisión bilateral entre Gobierno central y comunidades autónomas (CCAA), guiado por un panel de indicadores cualitativos y cuantitativos de la situación epidemiológica y las capacidades básicas. Las unidades territoriales evaluadas comprendían desde zonas básicas de salud hasta CCAA. Resultados: El proceso se extendió del 4 de mayo al 21 de junio y se asoció a planes de refuerzo de las capacidades en las CCAA. La incidencia disminuyó de una mediana inicial de 7,4 por 100.000 en 7 días a 2,5 al final del proceso. La mediana de pruebas PCR aumentó del 53% al 89% de los casos sospechosos, y la capacidad total de 4,5 a 9,8 pruebas semanales por 1.000 habitantes; la positividad disminuyó del 3,5% al 1,8%. La mediana de casos con contactos trazados aumentó del 82% al 100%. Conclusión: La recogida y análisis sistemático de información y el diálogo interterritorial logaron un adecuado control del proceso. La situación epidemiológica mejoró, pero sobre todo, se aumentaron las capacidades, en todo el país y con criterios comunes, cuyo mantenimiento y refuerzo fue clave en olas sucesivas.

Lifting COVID-19 mitigation measures in Spain (May-June 2020).

INTRODUCTION: The state of alarm was declared in Spain due to the COVID-19 epidemic on March 14, 2020, and established population confinement measures. The objective is to describe the process of lifting these mitigation measures. METHODS: The Plan for the Transition to a New Normality, approved on April 28, contained four sequential phases with progressive increase in socio-economic activities and population mobility. In parallel, a new strategy for early diagnosis, surveillance and control was implemented. A bilateral decision mechanism was established between the Spanish Government and the autonomous communities (AC), guided by a set of qualitative and quantitative indicators capturing the epidemiological situation and core capacities. The territorial units were established ad-hoc and could be from Basic Health Zones to entire AC. RESULTS: The process run from May 4 to June 21, 2020. AC implemented plans for reinforcement of core capacities. Incidence decreased from a median (50% of territories) of 7.4 per 100,000 in 7 days at the beginning to 2.5 at the end. Median PCR testing increased from 53% to 89% of suspected cases and PCR total capacity from 4.5 to 9.8 per 1000 inhabitants weekly; positivity rate decreased from 3.5% to 1.8%. Median proportion of cases with traced contacts increased from 82% to 100%. CONCLUSION: Systematic data collection, analysis, and interterritorial dialogue allowed adequate process control. The epidemiological situation improved but, mostly, the process entailed a great reinforcement of core response capacities nation-wide, under common criteria. Maintaining and further reinforcing capacities remained crucial for responding to future waves.

Altered expression of vesicular glutamate transporter-2 and cleaved caspase-3 in the locus coeruleus of nerve-injured rats.

Neuropathic pain is a debilitating chronic condition provoked by a lesion in the nervous system and it induces functional alterations to the noradrenergic locus coeruleus (LC), affecting distinct dimensions of pain, like sensorial hypersensitivity, pain-induced depression, and anxiety. However, the neurobiological changes induced by nerve damage in the LC remain unclear. Here, we analyzed excitatory and inhibitory inputs to the LC, as well as the possible damage that noradrenergic neurons suffer after the induction of neuropathic pain through chronic constriction injury (CCI). Neuropathic pain was induced in male Sprague-Dawley rats, and the expression of the vesicular glutamate transporter 1 or 2 (VGLUT1 or VGLUT2), vesicular GABA transporter (VGAT), and cleaved caspase-3 (CC3) was analyzed by immunofluorescence 7 (CCI7d) or 28 days after the original lesion (CCI28d). While no significant differences in the density of VGLUT1 puncta were evident, CCI7d induced a significant increase in the perisomatic VGLUT2/VGAT ratio relative to Sham-operated and CCI28d animals. By contrast, when the entire region of LC is evaluated, there was a significant reduction in the density of VGLUT2 puncta in CCI28d animals, without changes in VGLUT2/VGAT ratio relative to the CCI7d animals. Additionally, changes in the noradrenergic soma size, and a lower density of mitochondria and lysosomes were evident in CCI28d animals. Interestingly, enhanced expression of the apoptotic marker CC3 was also evident in the CCI28d rats, mainly co-localizing with glial fibrillary acidic protein but not with any neuronal or noradrenergic marker. Overall, short-term pain appears to lead to an increase of markers of excitatory synapses in the perisomatic region of noradrenergic cells in the LC, an effect that is lost after long-term pain, which appears to activate apoptosis.

The Role of the Locus Coeruleus in Pain and Associated Stress-Related Disorders.

The locus coeruleus (LC)-noradrenergic system is the main source of noradrenaline in the central nervous system and is involved intensively in modulating pain and stress-related disorders (e.g., major depressive disorder and anxiety) and in their comorbidity. However, the mechanisms involving the LC that underlie these effects have not been fully elucidated, in part owing to the technical difficulties inherent in exploring such a tiny nucleus. However, novel research tools are now available that have helped redefine the LC system, moving away from the traditional view of LC as a homogeneous structure that exerts a uniform influence on neural activity. Indeed, innovative techniques such as DREADDs (designer receptors exclusively activated by designer drugs) and optogenetics have demonstrated the functional heterogeneity of LC, and novel magnetic resonance imaging applications combined with pupillometry have opened the way to evaluate LC activity in vivo. This review aims to bring together the data available on the efferent activity of the LC-noradrenergic system in relation to pain and its comorbidity with anxiodepressive disorders. Acute pain triggers a robust LC stress response, producing spinal cord-mediated endogenous analgesia while promoting aversion, vigilance, and threat detection through its ascending efferents. However, this protective biological system fails in chronic pain, and LC activity produces pain facilitation, anxiety, increased aversive memory, and behavioral despair, acting at the medulla, prefrontal cortex, and amygdala levels. Thus, the activation/deactivation of specific LC projections contributes to different behavioral outcomes in the shift from acute to chronic pain.

Nerve injury induces transient locus coeruleus activation over time: role of the locus coeruleus-dorsal reticular nucleus pathway.

ABSTRACT: The transition from acute to chronic pain results in maladaptive brain remodeling, as characterized by sensorial hypersensitivity and the ensuing appearance of emotional disorders. Using the chronic constriction injury of the sciatic nerve as a model of neuropathic pain in male Sprague-Dawley rats, we identified time-dependent plasticity of locus coeruleus (LC) neurons related to the site of injury, ipsilateral (LCipsi) or contralateral (LCcontra) to the lesion, hypothesizing that the LC→dorsal reticular nucleus (DRt) pathway is involved in the pathological nociception associated with chronic pain. LCipsi inactivation with lidocaine increased cold allodynia 2 days after nerve injury but not later. However, similar blockade of LCcontra reduced cold allodynia 7 and 30 days after inducing neuropathy but not earlier. Furthermore, lidocaine blockade of the LCipsi or LCcontra reversed pain-induced depression 30 days after neuropathy. Long-term pain enhances phosphorylated cAMP-response element binding protein expression in the DRtcontra but not in the DRtipsi. Moreover, inactivation of the LCcontra→DRtcontra pathway using dual viral-mediated gene transfer of designer receptor exclusively activated by designer drugs produced consistent analgesia in evoked and spontaneous pain 30 days postinjury. This analgesia was similar to that produced by spinal activation of α2-adrenoreceptors. Furthermore, chemogenetic inactivation of the LCcontra→DRtcontra pathway induced depressive-like behaviour in naïve animals, but it did not modify long-term pain-induced depression. Overall, nerve damage activates the LCipsi, which temporally dampens the neuropathic phenotype. However, the ensuing activation of a LCcontra→DRtcontra facilitatory pain projection contributes to chronic pain, whereas global bilateral LC activation contributes to associated depressive-like phenotype.

Pain and depression comorbidity causes asymmetric plasticity in the locus coeruleus neurons.

There is strong comorbidity between chronic pain and depression, although the neural circuits and mechanisms underlying this association remain unclear. By combining immunohistochemistry, tracing studies and western blotting, with the use of different DREADDS (designer receptor exclusively activated by designer drugs) and behavioural approaches in a rat model of neuropathic pain (chronic constriction injury), we explore how this comorbidity arises. To this end, we evaluated the time-dependent plasticity of noradrenergic locus coeruleus neurons relative to the site of injury: ipsilateral (LCipsi) or contralateral (LCcontra) locus coeruleus at three different time points: short (2 days), mid (7 days) and long term (30-35 days from nerve injury). Nerve injury led to sensorial hypersensitivity from the onset of injury, whereas depressive-like behaviour was only evident following long-term pain. Global chemogenetic blockade of the LCipsi system alone increased short-term pain sensitivity while the blockade of the LCipsi or LCcontra relieved pain-induced depression. The asymmetric contribution of locus coeruleus modules was also evident as neuropathy develops. Hence, chemogenetic blockade of the LCipsi→spinal cord projection, increased pain-related behaviours in the short term. However, this lateralized circuit is not universal as the bilateral chemogenetic inactivation of the locus coeruleus-rostral anterior cingulate cortex pathway or the intra-rostral anterior cingulate cortex antagonism of alpha1- and alpha2-adrenoreceptors reversed long-term pain-induced depression. Furthermore, chemogenetic locus coeruleus to spinal cord activation, mainly through LCipsi, reduced sensorial hypersensitivity irrespective of the time post-injury. Our results indicate that asymmetric activation of specific locus coeruleus modules promotes early restorative analgesia, as well as late depressive-like behaviour in chronic pain and depression comorbidity.

Perfil Lipídico como factor de riesgo de Preeclampsia en mujeres embarazadas / Lipid profile as a risk factor for preeclampsia in pregnant women / rfil lipídico como fator de risco para pré-eclâmpsia em gestantes

La preeclampsia es una complicación del embarazo, cuya prevalencia se calcula entre 4 y 7% de los embarazos en el mundo. En Ecuador los trastornos hipertensivos fueron causantes del 20,6% de mortalidad materna (años 2017-2018). De allí la importancia de estudios de su diagnóstico oportuno. OBJETIVO: asociar el perfil lipídico como factor de riesgo en el padecimiento de preeclampsia de mujeres embarazadas que acudieron al Hospital Sagrado Corazón de Jesús, durante los años 2020-2021. MATERIALES Y MÉTODOS: el tipo de diseño utilizado para la investigación, en una población de 300 embarazadas, fue no experimental, documental, de cohorte, observacional, correlacional y cuantitativo. En el análisis de diferencias significativas entre variables categóricas se usó la prueba Chi cuadrado. Para calcular la relación el padecimiento de Preeclampsia o no en el embarazo con las variables que conforman el perfil lipídico se usó la técnica U de Mann-Whitney. RESULTADOS: el 35,33% de la población de estudio padece preeclampsia. En las variables analizadas como parte del perfil lipídico, mediante la técnica U de Mann-Whitney, se obtuvo un p-valor inferior a 0,5, como se describe a continuación: para triglicéridos <,001; para colesterol HDL 0,421; para colesterol LDL 0,003; y para Colesterol Total <,001. En análisis comparativos con otros estudios se describen resultados similares, pero no en todos coinciden los promedios de comparación. CONCLUSIONES: Existe diferencia estadísticamente significativa en el perfil lipídico de mujeres con preeclampsia, en comparación con el perfil lipídico de mujeres que no padecen preeclampsia.

Preeclampsia is a complication of pregnancy, whose prevalence is estimated between 4 and 7% of pregnancies worldwide. In Ecuador, hypertensive disorders were responsible for 20.6% of maternal mortality (years 2017-2018). Hence the importance of studies of their timely diagnosis.OBJECTIVE: to associate the lipid profile as a risk factor in the suffering of preeclampsia in pregnant women who attended the Hospital Sagrado Corazón de Jesús, during the years 2020-2021. MATERIALS AND METHODS: the type of design used for the research, in a population of 300 pregnant women, was non-experimental, documentary, cohort, observational, correlational and quantitative. The Chi-square test was used in the analysis of significant differences between categorical variables. The Mann-Whitney U test was used to calculate the relationship between preeclampsia or not during pregnancy and the variables that make up the lipid profile. RESULTS: preeclampsia was found in 35.33% of the study population. In the variables analyzed as part of the lipid profile, using the Mann-Whitney U technique, a p-value of less than 0.5 was obtained, as described below: for triglycerides <.001; for HDL cholesterol 0.421; for LDL cholesterol 0.003; and for total cholesterol <.001. In comparative analyses with other studies, similar results are described, but not in all the comparison averages coincide. CONCLUSIONS: there is a statistically significant difference in the lipid profile of women with preeclampsia compared to the lipid profile of women without preeclampsia

A pré-eclâmpsia é uma complicação da gravidez, cuja prevalência é estimada entre 4 e 7% das gestações em todo o mundo. No Equador, as doenças hipertensivas foram responsáveis por 20,6% da mortalidade materna (2017-2018). Daí a importância dos estudos de seu diagnóstico oportuno. OBJETIVO: associar o perfil lipídico como fator de risco para pré-eclâmpsia em gestantes que freqüentaram o Hospital Sagrado Corazón de Jesús, durante os anos de 2020-2021. MATERIAIS E MÉTODOS: o tipo de projeto de pesquisa utilizado em uma população de 300 mulheres grávidas foi não-experimental, documentário, coorte, observacional, correlacional e quantitativo. O teste Qui-quadrado foi utilizado para analisar diferenças significativas entre as variáveis categóricas. O teste Mann-Whitney U foi usado para calcular a relação entre a pré-eclâmpsia ou não durante a gravidez e as variáveis que compõem o perfil lipídico. RESULTADOS: a pré-eclâmpsia foi encontrada em 35,33% da população do estudo. Nas variáveis analisadas como parte do perfil lipídico, usando a técnica Mann-Whitney U, foi obtido um valor p inferior a 0,5, como segue: para triglicerídeos <,001; para colesterol HDL 0,421; para colesterol LDL 0,003; e para colesterol total <,001. Resultados semelhantes são descritos em análises comparativas com outros estudos, mas nem todas as médias comparativas estão de acordo. CONCLUSÕES: ha uma diferença estatisticamente significativa no perfil lipídico das mulheres com pré-eclâmpsia em comparação com o perfil lipídico das mulheres sem pré-eclâmpsia

Scabies in Spain? A comprehensive epidemiological picture.

INTRODUCTION: Scabies is a neglected disease stablished worldwide with a fairy well determined incidence. In high-income countries, it often causes outbreaks affecting the residents and staff of institutions and long-term facilities, usually hard to detect and control due to the difficult diagnosis and notification delay. This study aim at characterizing the affected population, geographical distribution, and evolution of scabies in Spain from 1997-2019 as well as to describe the main environments of transmission using different data sources. METHODS: We carried out a nationwide retrospective study using four databases, which record data from different perspectives: hospital admissions, patients attended at primary healthcare services, outbreaks, and occupational diseases. We described the main characteristics from each database and calculated annual incidences in order to evaluate temporal and geographical patterns. We also analyzed outbreaks and occupational settings to characterize the main transmission foci and applied Joinpoint regression models to detect trend changes. RESULTS: The elderly was the most frequent collective among the hospital admitted patients and notified cases in outbreaks, while children and young adults were the most affected according to primary care databases. The majority of the outbreaks occurred in homes and nursing homes; however, the facilities with more cases per outbreak were military barracks, healthcare settings and nursing homes. Most occupational cases occurred also in healthcare and social services settings, being healthcare workers the most common affected professional group. We detected a decreasing trend in scabies admissions from 1997 to 2014 (annual percentage change -APC- = -11.2%) and an increasing trend from 2014 to 2017 (APC = 23.6%). Wide geographical differences were observed depending on the database explored. DISCUSSION: An increasing trend in scabies admissions was observed in Spain since 2014, probably due to cutbacks in social services and healthcare in addition to worsen of living conditions as a result of the 2008 economic crisis, among other reasons. The main transmission foci were healthcare and social settings. Measures including enhancing epidemic studies and national registries, reinforcing clinical diagnosis and early detection of cases, hygiene improvements and training of the staff and wide implementation of scabies treatment (considering mass drug administration in institutions outbreaks) should be considered to reduce the impact of scabies among most vulnerable groups in Spain.

Lifting COVID-19 mitigation measures in Spain (May-June 2020).

INTRODUCTION: The state of alarm was declared in Spain due to the COVID-19 epidemic on March 14, 2020, and established population confinement measures. The objective is to describe the process of lifting these mitigation measures. METHODS: The Plan for the Transition to a New Normality, approved on April 28, contained four sequential phases with progressive increase in socio-economic activities and population mobility. In parallel, a new strategy for early diagnosis, surveillance and control was implemented. A bilateral decision mechanism was established between the Spanish Government and the autonomous communities (AC), guided by a set of qualitative and quantitative indicators capturing the epidemiological situation and core capacities. The territorial units were established ad-hoc and could be from Basic Health Zones to entire AC. RESULTS: The process run from May 4 to June 21, 2020. AC implemented plans for reinforcement of core capacities. Incidence decreased from a median (50% of territories) of 7.4 per 100,000 in 7 days at the beginning to 2.5 at the end. Median PCR testing increased from 53% to 89% of suspected cases and PCR total capacity from 4.5 to 9.8 per 1000 inhabitants weekly; positivity rate decreased from 3.5% to 1.8%. Median proportion of cases with traced contacts increased from 82% to 100%. CONCLUSION: Systematic data collection, analysis, and interterritorial dialogue allowed adequate process control. The epidemiological situation improved but, mostly, the process entailed a great reinforcement of core response capacities nation-wide, under common criteria. Maintaining and further reinforcing capacities remained crucial for responding to future waves.

Selective deletion of Caspase-3 gene in the dopaminergic system exhibits autistic-like behaviour.

Apoptotic caspases are thought to play critical roles in elimination of excessive and non-functional synapses and removal of extra cells during early developmental stages. Hence, an impairment of this process may thus constitute a basis for numerous neurological and psychiatric diseases. This view is especially relevant for dopamine due to its pleiotropic roles in motor control, motivation and reward processing. Here, we have analysed the effect of caspase-3 depletion on the development of catecholaminergic neurons and performed a wide array of neurochemical, ultrastructural and behavioural assays. To achieve this, we performed selective deletion of the Casp3 gene in tyrosine hydroxylase (TH)-expressing cells using Cre-loxP-mediated recombination. Histological evaluation of most relevant catecholaminergic nuclei revealed the ventral mesencephalon as the most affected region. Stereological analysis demonstrated an increase in the number of TH-positive neurons in both the substantia nigra and ventral tegmental area along with enlarged volume of the ventral midbrain. Analysis of main innervating tissues revealed a rather contrasting profile. In striatum, basal extracellular levels and potassium-evoked DA release were significantly reduced in mice lacking Casp3, a clear indication of dopaminergic hypofunction in dopaminergic innervating tissues. This view was sustained by analysis of TH-labelled dopaminergic terminals by confocal and electron microscopy. Remarkably, at a behavioural level, Casp3-deficient mice exhibited impaired social interaction, restrictive interests and repetitive stereotypies, which are considered the core symptoms of autism spectrum disorder (ASD). Our study revitalizes the potential involvement of dopaminergic transmission in ASD and provides an excellent model to get further insights in ASD pathogenesis.

The impact of climate change on mosquito-borne diseases in Africa.

Despite being one of the continents with the least greenhouse gas emissions, no continent is being struck as severely by climate change (CC) as Africa. Mosquito-borne diseases (MBD) cause major human diseases in this continent. Current knowledge suggests that MBD range could expand dramatically in response to CC. This study aimed at assessing the relationship between CC and MBD in Africa. Methods For this purpose, a systematic peer review was carried out, considering all articles indexed in PubMed, Scopus, Embase and CENTRAL. Search terms referring to MBD, CC and environmental factors were screened in title, abstract and keywords.Results A total of twenty-nine studies were included, most of them on malaria (61%), being Anopheles spp. (61%) the most commonly analyzed vector, mainly in Eastern Africa (48%). Seventy-nine percent of these studies were based on predictive models. Seventy-two percent of the reviewed studies considered that CC impacts on MBD epidemiology. MBD prevalence will increase according to 69% of the studies while 17% predicted a decrease. MBD expansion throughout the continent was also predicted. Most studies showed a positive relationship between observed or predicted results and CC. However, there was a great heterogeneity in methodologies and a tendency to reductionism, not integrating other variables that interact with both the environment and MBD. In addition, most results have not yet been tested. A global health approach is desirable in this kind of research. Nevertheless, we cannot wait for science to approve something that needs to be addressed now to avoid greater effects in the future.

Transmissibility of influenza during the 21st-century epidemics, Spain, influenza seasons 2001/02 to 2017/18.

BackgroundUnderstanding influenza seasonality is necessary for determining policies for influenza control.AimWe characterised transmissibility during seasonal influenza epidemics, including one influenza pandemic, in Spain during the 21th century by using the moving epidemic method (MEM) to calculate intensity levels and estimate differences across seasons and age groups.MethodsWe applied the MEM to Spanish Influenza Sentinel Surveillance System data from influenza seasons 2001/02 to 2017/18. A modified version of Goldstein's proxy was used as an epidemiological-virological parameter. We calculated the average starting week and peak, the length of the epidemic period and the length from the starting week to the peak of the epidemic, by age group and according to seasonal virus circulation.ResultsIndividuals under 15 years of age presented higher transmissibility, especially in the 2009 influenza A(H1N1) pandemic. Seasons with dominance/co-dominance of influenza A(H3N2) virus presented high intensities in older adults. The 2004/05 influenza season showed the highest influenza-intensity level for all age groups. In 12 seasons, the epidemic started between week 50 and week 3. Epidemics started earlier in individuals under 15 years of age (-1.8 weeks; 95% confidence interval (CI):-2.8 to -0.7) than in those over 64 years when influenza B virus circulated as dominant/co-dominant. The average time from start to peak was 4.3 weeks (95% CI: 3.6-5.0) and the average epidemic length was 8.7 weeks (95% CI: 7.9-9.6).ConclusionsThese findings provide evidence for intensity differences across seasons and age groups, and can be used guide public health actions to diminish influenza-related morbidity and mortality.

Pain in neuropsychiatry: Insights from animal models.

Pain is the most common symptom reported in clinical practice, meaning that it is associated with many pathologies as either the origin or a consequence of other illnesses. Furthermore, pain is a complex emotional and sensorial experience, as the correspondence between pain and body damage varies considerably. While these issues are widely acknowledged in clinical pain research, until recently they have not been extensively considered when exploring animal models, important tools for understanding pain pathophysiology. Interestingly, chronic pain is currently considered a risk factor to suffer psychiatric disorders, mainly stress-related disorders like anxiety and depression. Conversely, pain appears to be altered in many psychiatric disorders, such as depression, anxiety and schizophrenia. Thus, pain and psychiatric disorders have been linked in epidemiological and clinical terms, although the neurobiological mechanisms involved in this pathological bidirectional relationship remain unclear. Here we review the evidence obtained from animal models about the co-morbidity of pain and psychiatric disorders, placing special emphasis on the different dimensions of pain.

Carbapenem-Resistant Enterobacteriaceae Outbreak in a Medical Ward in Spain: Epidemiology, Control Strategy, and Importance of Environmental Disinfection.

Introduction: Carbapenem-resistant Enterobacteriaceae (CRE) are a growing public health problem. We describe an outbreak by CRE and the measures to control it in a hospitalization unit in Spain. Methods: In June 2015, the system of prevention and control of CRE implemented in the hospital detected an increase in the incidence of patients with CRE in a mixed hospitalization facility (geriatrics, internal medicine, and pneumology), with the appearance of four related patients in 2 weeks, three of them being nosocomial cases. A multidisciplinary group was created and carried out: weekly screenings, general cleaning, four training sessions for personnel, two hand hygiene observation studies and environmental sampling. A higher incidence of new cases was detected in three adjoining rooms, in which environmental decontamination was performed with vaporized hydrogen peroxide. Results: In 5 months, a total of 18 cases were detected, 14 of them were nosocomial. Four different clones of Klebsiella pneumoniae OXA-48 were responsible for 83.3% of the cases. Adherence to hand hygiene increased from 36% to 85% after the training sessions. Seven percent of the environmental samples were positive for CRE in rooms with high incidence, moving to 0% after decontamination with hydrogen peroxide. Three patients died, one of them possibly associated with clinical infection due to CRE. Conclusions: Multidisciplinary information strategies, personnel training, and control of environmental reservoirs are effective to address outbreaks of CRE.

El reto de la medición de la gravedad y la letalidad en el curso de la pandemia de COVID-19 / No disponible

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Imported dengue in Spain: a nationwide analysis with predictive time series analyses.

BACKGROUND: Of febrile illnesses in Europe, dengue is second only to malaria as a cause of travellers being hospitalized. Local transmission has been reported in several European countries, including Spain. This study assesses the evolution of dengue-related admissions in Spain in terms of time, geographical distribution and individuals' common characteristics; it also creates a predictive model to evaluate the risk of local transmission. METHODS: This is a retrospective study using the Hospital Discharge Records Database from 1997 to 2016. We calculated hospitalization rates and described clinical characteristics. Spatial distribution and temporal behaviour were also assessed, and a predictive time series model was created to estimate expected cases in the near future. Figures for resident foreign population, Spanish residents' trips to endemic regions and the expansion of Aedes albopictus were also evaluated. RESULTS: A total of 588 dengue-related admissions were recorded: 49.6% were women, and the mean age was 34.3 years. One person died (0.2%), 82% presented with mild-to-moderate dengue and 7-8% with severe dengue. We observed a trend of steady and consistent increase in incidence (P < 0.05), in parallel with the increase in trips to dengue-endemic regions. Most admissions occurred during the summer, showing significant seasonality with 3-year peaks. We also found important regional differences. According to the predictive time series analysis, a continuing increase in imported dengue incidence can be expected in the near future, which, in the worst case scenario (upper 95% confidence interval), would mean an increase of 65% by 2025. CONCLUSION: We present a nationwide study based on hospital, immigration, travel and entomological data. The constant increase in dengue-related hospitalizations, in combination with wider vector distribution, could imply a higher risk of autochthonous dengue transmission in the years to come. Strengthening the human and vector surveillance systems is a necessity, as are improvements in control measures, in the education of the general public and in fostering their collaboration in order to reduce the impact of imported dengue and to prevent the occurrence of autochthonous cases.

Does Socioeconomic Status Influence the Risk of Subclinical Atherosclerosis?: A Mediation Model.

BACKGROUND: Socioeconomic status (SES)-education, income level, and occupation-is associated with cardiovascular risk. OBJECTIVES: This study aimed to investigate the association between SES and subclinical atherosclerosis and the potential mechanisms involved. METHODS: SES, lifestyle habits (smoking, dietary patterns, physical activity, and hours of sleep), traditional risk factors, and subclinical atherosclerosis extent were prospectively assessed in 4,025 individuals aged 40 to 54 years without known cardiovascular disease enrolled in the PESA (Progression of Early Subclinical Atherosclerosis) study. After factors associated with atherosclerosis were identified, a multiple mediation model was created to quantify the effect of SES on subclinical atherosclerosis as explained by lifestyle behaviors. RESULTS: Although education level was significantly associated with the presence of atherosclerosis, no differences were found according to income level in this population. Participants with lower education presented with a higher risk of generalized atherosclerosis than those with higher education (odds ratio: 1.46; 95% confidence interval: 1.15 to 1.85; p = 0.002). Lifestyle behaviors associated with both education level and atherosclerosis extent were: smoking status, number of cigarettes/day, and dietary pattern, which explained 70.5% of the effect of SES on atherosclerosis. Of these, tobacco habit (smoking status 35% and number of cigarettes/day 32%) accounted for most of the explained differences between groups, whereas dietary pattern did not remain a significant mediator in the multiple mediation model. CONCLUSIONS: Despite the relative economic homogeneity of the cohort, lower education level is associated with increased subclinical atherosclerosis, mainly mediated by the higher and more frequent tobacco consumption. Smoking cessation programs are still needed, particularly in populations with lower education level.