Relevance of chronic stress and the two faces of microglia in Parkinson’s disease

This review is aimed to highlight the importance of stress and glucocorticoids (GCs) in modulating the inflammatory response of brain microglia and hence its potential involvement in Parkinson’s disease (PD). The role of inflammation in PD has been reviewed extensively in the literature and it is supposed to play a key role in the course of the disease. Historically, GCs have been strongly associated as anti-inflammatory hormones. However, accumulating evidence from the peripheral and central nervous system have clearly revealed that, under specific conditions, GCs may promote brain inflammation including pro-inflammatory activation of microglia. We have summarized relevant data linking PD, neuroinflamamation and chronic stress. The timing and duration of stress response may be critical for delineating an immune response in the brain thus probably explain the dual role of GCs and/or chronic stress in different animal models of P

Intervención no farmacológica como estrategia para favorecer el control de la hipertensión arterial y mejorar el cumplimiento antihipertensivo

ResumenObjetivoComprobar la eficacia de una intervención mediante una revista educacional en el cumplimiento antihipertensivo de la hipertensión arterial (HTA) no controlada.DiseñoEstudio clínico controlado, aleatorizado y multicéntrico.EmplazamientoOchenta y siete Centros de Salud de España.ParticipantesSe incluyeron 450 pacientes hipertensos diagnosticados de HTA no controlada.IntervenciónSe formaron 2 grupos con 225 individuos: a) grupo de intervención (GI), los que recibieron una revista educacional domiciliaria bimensual y b) grupo de control (GC), que tuvieron práctica clínica habitual.Mediciones principalesEl cumplimiento se midió mediante monitores electrónicos (MEMS-Aardex). Se calculó el porcentaje de cumplimiento, el porcentaje de cumplidores del total de dosis y de días en los que tomaba una dosis y el NNT (number needed to treat 'número de pacientes que es necesario tratar'). Se definió cumplidor un consumo del 80 al 110%. Se calculó la presión arterial media y los porcentajes de los controlados.ResultadosConcluyeron 393 individuos (edad: 62,4 años [desviación estándar de 11,6 años]), 196 pacientes del GI y 197 pacientes del GC. Ciento ochenta y cuatro eran varones (46,8%).Fueron cumplidores del total de las dosis tomadas el 83,2% en el GI (del 78 al 88,4%) y el 49,2% del GC (IC del 95%: del 42,2 al 56,2%) (p=0,0001) y fueron cumplidores diarios el 74% del GI (IC del 95%: del 67,9 al 80,1%) y el 42,6% del GC (IC del 95%: del 35,7 al 49,5%) (p=0,0001).El control de la HTA fue del 81,6% en el GI (IC del 95%: del 76,2 al 86,5%) y del 56,3% en el GC (IC del 95%: del 49,4 al 63,2%). El NNT con la intervención fue de 3,3 pacientes.ConclusionesEl incumplimiento del tratamiento fue muy alto. La revista educacional es una estrategia eficaz para disminuir el incumplimiento y mejorar el grado de control de la HTA.AbstractObjetiveTo evaluate the efficacy of an intervention by means of an educational magazine on treatment compliance in uncontrolled arterial hypertension (AHT).DesignControlled, randomised clinical trial.Setting87 primary care centres. Spain.ParticipantsA total of 450 patients with uncontrolled hypertension were included.InterventionTwo groups of 225 patients were formed: 1) Control group (CG): standard health intervention; 2) Intervention Group (IG): received a twice monthly educational magazine at home.Main measurementsCompliance was measured using the Medication Event Monitoring System (MEMS-Aardex). Compliance rate (CR) was recorded. Compliers were defined as individuals with a treatment compliance of 80–110%. The percentage of compliers, the mean percentage of doses taken and the percentage of patients taking the medication at the correct times were estimated. The mean blood pressures (BPs) and the percentage of controlled patientswere calculated. The number needed to treat (NNT) was calculated.ResultsA total of 393 individuals were evaluable (Age: 62.4 years), 196 in the IG and 197 in the CG. There were 83.2% (95% CI 78–88.4) and 49.2% (95% CI 42.2–56.2) (P=0.0001) of overall compliers in the IG and CG, respectively and 74% (95% CI: 67.9–80.1) and 42.6% (95% CI=35.7–49.5) (P=0.0001) of correct times compliers. A total of 81.6% (95% CI=76.2–86.5%)) were controlled in the IG and 56.3% (95% CI=49.4–63.2) in the CG. The NNT was 3.3 patients.ConclusionsTherapeutic non-compliance was very high. The educational magazine is an effective strategy to improve the compliance and degree of control of the AHT

The Absence of Caspase-8 in the Dopaminergic System Leads to Mild Autism-like Behavior

In the last decade, new non-apoptotic roles have been ascribed to apoptotic caspases. This family of proteins plays an important role in the sculpting of the brain in the early stages of development by eliminating excessive and nonfunctional synapses and extra cells. Consequently, impairments in this process can underlie many neurological and mental illnesses. This view is particularly relevant to dopamine because it plays a pleiotropic role in motor control, motivation, and reward processing. In this study, we analyze the effects of the elimination of caspase-8 (CASP8) on the development of catecholaminergic neurons using neurochemical, ultrastructural, and behavioral tests. To do this, we selectively delete the CASP8 gene in cells that express tyrosine hydroxylase with the help of recombination through the Cre-loxP system. Our results show that the number of dopaminergic neurons increases in the substantia nigra. In the striatum, the basal extracellular level of dopamine and potassium-evoked dopamine release decreased significantly in mice lacking CASP8, clearly showing the low dopamine functioning in tissues innervated by this neurotransmitter. This view is supported by electron microscopy analysis of striatal synapses. Interestingly, behavioral analysis demonstrates that mice lacking CASP8 show changes reminiscent of autism spectrum disorders (ASD). Our research reactivates the possible role of dopamine transmission in the pathogenesis of ASD and provides a mild model of autism.Ministerio de Economía y Competitividad RTI2018-098645-B-I00, PID2019-109569GB-I00, RTI2018-099778-B-I00Junta de Andalucía P18-RT-1372, US-1264806, PI-0080-2017, PI-0009-2017, PI-0134-2018, PEMP-0008-2020, P20_00958, CTS-510Instituto de Salud Carlos III PI18/01691Instituto de Investigación e Innovación en Ciencias Biomédicas de Cádiz-INiBICA LI19/06IN-CO22, IN-C09European Union 95568

Stratification of radiosensitive brain metastases based on an actionable S100A9/RAGE resistance mechanism

© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Whole-brain radiotherapy (WBRT) is the treatment backbone for many patients with brain metastasis; however, its efficacy in preventing disease progression and the associated toxicity have questioned the clinical impact of this approach and emphasized the need for alternative treatments. Given the limited therapeutic options available for these patients and the poor understanding of the molecular mechanisms underlying the resistance of metastatic lesions to WBRT, we sought to uncover actionable targets and biomarkers that could help to refine patient selection. Through an unbiased analysis of experimental in vivo models of brain metastasis resistant to WBRT, we identified activation of the S100A9-RAGE-NF-κB-JunB pathway in brain metastases as a potential mediator of resistance in this organ. Targeting this pathway genetically or pharmacologically was sufficient to revert the WBRT resistance and increase therapeutic benefits in vivo at lower doses of radiation. In patients with primary melanoma, lung or breast adenocarcinoma developing brain metastasis, endogenous S100A9 levels in brain lesions correlated with clinical response to WBRT and underscored the potential of S100A9 levels in the blood as a noninvasive biomarker. Collectively, we provide a molecular framework to personalize WBRT and improve its efficacy through combination with a radiosensitizer that balances therapeutic benefit and toxicity.info:eu-repo/semantics/publishedVersio

Critical role of interleukin (IL)-17 in inflammatory and immune disorders: An updated review of the evidence focusing in controversies

Interleukin 17 (IL-17) is a proinflammatory cytokine that has been the focus of intensive research because of its crucial role in the pathogenesis of different diseases across many medical specialties. In this context, the present review in which a panel of 13 experts in immunology, dermatology, rheumatology, neurology, hematology, infectious diseases, hepatology, cardiology, ophthalmology and oncology have been involved, puts in common the mechanisms through which IL-17 is considered a molecular target for the development of novel biological therapies in these different fields. A comprehensive review of the literature and analysis of the most outstanding evidence have provided the basis for discussing the most relevant data related to IL-17A blocking agents for the treatment of different disorders, such as psoriasis, psoriatic arthritis, rheumatoid arthritis, ankylosing spondylitis, cardiovascular disorders, non alcoholic fatty liver disease, multiple sclerosis, inflammatory bowel disease, uveitis, hematological and solid cancer. Current controversies are presented giving an opening line for future research.This work was supported by Novartis Pharmaceuticals Spain

Base de datos de abejas ibéricas

Las abejas son un grupo extremadamente diverso con más de 1000 especies descritas en la península ibérica. Además, son excelentes polinizadores y aportan numerosos servicios ecosistémicos fundamentales para la mayoría de ecosistemas terrestres. Debido a los diversos cambios ambientales inducidos por el ser humano, existen evidencias del declive de algunas de sus poblaciones para ciertas especies. Sin embargo, conocemos muy poco del estado de conservación de la mayoría de especies y de muchas de ellas ignoramos cuál es su distribución en la península ibérica. En este trabajo presentamos un esfuerzo colaborativo para crear una base de datos de ocurrencias de abejas que abarca la península ibérica e islas Baleares que permitirá resolver cuestiones como la distribución de las diferentes especies, preferencia de hábitat, fenología o tendencias históricas. En su versión actual, esta base de datos contiene un total de 87 684 registros de 923 especies recolectados entre 1830 y 2022, de los cuales un 87% presentan información georreferenciada. Para cada registro se incluye información relativa a la localidad de muestreo (89%), identificador y colector de la especie (64%), fecha de captura (54%) y planta donde se recolectó (20%). Creemos que esta base de datos es el punto de partida para conocer y conservar mejor la biodiversidad de abejas en la península ibérica e Islas Baleares. Se puede acceder a estos datos a través del siguiente enlace permanente: https://doi.org/10.5281/zenodo.6354502ABSTRACT: Bees are a diverse group with more than 1000 species known from the Iberian Peninsula. They have increasingly received special attention due to their important role as pollinators and providers of ecosystem services. In addition, various rapid human-induced environmental changes are leading to the decline of some of its populations. However, we know very little about the conservation status of most species and for many species, we hardly know their true distributions across the Iberian Peninsula. Here, we present a collaborative effort to collate and curate a database of Iberian bee occurrences to answer questions about their distribution, habitat preference, phenology, or historical trends. In total we have accumulated 87 684 records from the Iberian Peninsula and the Balearic Islands of 923 different species with 87% of georeferenced records collected between 1830 and 2022. In addition, each record has associated information such as the sampling location (89%), collector and person who identified the species (64%), date of the capture (54%) and plant species where the bees were captured (20%). We believe that this database is the starting point to better understand and conserve bee biodiversity in the Iberian Peninsula. It can be accessed at: https://doi.org/10.5281/zenodo.6354502Esta base de datos se ha realizado con la ayuda de los proyectos EUCLIPO (Fundação para a Ciência e a Tecnologia, LISBOA-01-0145-FEDER-028360/EUCLIPO) y SAFEGUARD (ref. 101003476 H2020 -SFS-2019-2).info:eu-repo/semantics/publishedVersio

Eficacia de un programa de automedida domiciliaria de la presión arterial como estrategia para disminuir la inercia terapéutica

ResumenObjetivoEvaluar si un programa de automedida domiciliaria de presión arterial (AMPA) es eficaz para obtener una menor inercia terapéutica (IT) en el tratamiento de la HTA.DiseñoEstudio clínico controlado, aleatorizado y multicéntrico.Emplazamiento35 centros de salud de España.ParticipantesSe incluyeron 232 hipertensos.IntervenciónSe formaron 2 grupos con 116 individuos: 1, grupo de control (GC): recibieron la intervención habitual; 2, grupo de intervención: se inscribieron en un programa de AMPA.Mediciones principalesLa IT se midió mediante el cociente: (Número de pacientes sin modificación del tratamiento farmacológico en cada visita / Número de pacientes con cifras medias de PA ≥ 140 mmHg y/o ≥ 90 mmHg en población general o ≥ 130 y/o 80 mmHg en diabéticos) y multiplicado por 100. Se calculó la IT por visitas, las PA medias y grado de control de la HTA.ResultadosConcluyeron 209 individuos (edad media 69,28±11,6 años) (p=NS por grupos) (GI 107 individuos y GC 102).La IT fue 35,64% de las visitas de la muestra (IC=29,85-41,43%) y en el 71,63% (IC=63,9-79,36%) en hipertensos no controlados.La IT fue del 22,42% (IC=24,2-37%) en el GI y 50% (IC=37,75-62,25) en el GC (p < 0,05) en visita 2, y del 25,23% (IC=14,84-35,62) y 46,07% (IC=33,85-58,29) en visita final para GI y GC respectivamente (p<0,05).ConclusionesLa IT ha sido muy relevante. El programa de AMPA es eficaz para obtener una menor IT.AbstractObjectiveTo evaluate the efficacy of a program of home blood pressure monitoring (HBPM) on therapeutic Inertia (TI) in mild-to-moderate hypertension (AHT).DesignControlled, randomised clinical trial.SettingForty six clinics in 35 primary care centres. Spain.ParticipantsA total of 232 patients with uncontrolled hypertension were included.InterventionTwo groups with 116 patients were formed: 1) Control group (CG): standard health intervention; 2) Intervention group (IG): patients who were included in the HBPM program.Main measurementsTI was calculated by the ratio: Number of patients whose pharmacological treatment was not changed in each visit/Number of patients with an average BP 140mmHg and/or 90mmHg in the general population or 130 and/or 90 mmHg in diabetics. The mean BPs and the percentage of controlled patients were calculated. The mean number of people that required an intervention in order to avoid TI was calculated (NI).ResultsA total of 209 patients completed the study, with TI in 35.64% (95% CI=29.85%-41.43%) of the sample, and in 71.63% (95% CI=63.9-79.36%) of the uncontrolled hypertensive patients.The TI was 22.42% (95% CI=24.2-37%) in the IG and 50% (95% CI=37.75-62.25) in the CG (p<.05) in visit 2, and 25.23% (95% CI=14.84-35.62) and 46.07% (95% CI=33.85-58.29) in the final visit for IG and CG, respectively (P<.05). The NI was 4.3.ConclusionsTI was very significant among the uncontrolled hypertensive patients. The studied interventions are effective for improving TI

Smart Bus Stops as Interconnected Public Spaces for Increasing Social Inclusiveness and Quality of Life of Elder Users

As the Smart City concept evolves, it necessarily incorporates more sustainability and inclusiveness features. In this context, the mobility of people is still one of the major challenges for cities. Among the most vulnerable group of citizens are the elderly, as they demand special requirements in the design of smart mobility. At the same time, smart cities’ technologies could be used to maintain their quality of life. From an architectural and sociological point of view, smart cities change the meaning and the use of public spaces, from physical meeting places to relational public spaces, in which humans use interposed technological means and information flows. This leads to the concept of Interconnected Public Spaces: a mixture of physical and virtual environments, generating interconnections at a planetary scale, that can be used to attract elderly people for collectively sharing experiences outdoor in public spaces (parks, squares or bus stops, in any city on our planet), increasing their physical form and stimulating them mentally, socially and emotionally. This paper describes the development of an inclusive smart bus stop prototype and the use of its ICT infrastructure to build Interconnected Public Spaces.UEM19No data 2020UE