Mental Health and Homelessness in the Community of Madrid (Spain): The Impact of Discrimination and Violence.

The aim of this study was to analyze the impact of experiences of violence and discrimination on mental health among people in situations of homelessness (PSH). For this purpose, a quantitative, descriptive, and correlational investigation was conducted by conducting a survey with 603 PSH living in the Community of Madrid (Spain). The results show high levels of mental health impairment, as well as approximately half of the participants having experienced discrimination and violence in the course of their homelessness. Perceived experiences of discrimination are associated with higher levels of mental health impairment (OR = 0.458; p = < 0.001; 95% IC 0.31-0.68). This deterioration is also related to a negative self-assessment of the general state of health among participants (OR = 0.262; p = < 0.001; 95% IC 0.12-0.57). However, impaired mental health is not associated with experiences of violence. The findings also indicate that there are intersections in terms of being female, young, and foreign that result in greater psychological impairment and a higher risk of experiencing violence and discrimination. This study provides an insight into the PSH experiences in relation to mental health, violence, and discrimination and the need to implement actions aimed at improving their psychosocial wellbeing from the perspective of respect for citizens' rights.

Switching Roles: Beneficial Effects of Adipose Tissue-Derived Mesenchymal Stem Cells on Microglia and Their Implication in Neurodegenerative Diseases.

Neurological disorders, including neurodegenerative diseases, are often characterized by neuroinflammation, which is largely driven by microglia, the resident immune cells of the central nervous system (CNS). Under these conditions, microglia are able to secrete neurotoxic substances, provoking neuronal cell death. However, microglia in the healthy brain carry out CNS-supporting functions. This is due to the ability of microglia to acquire different phenotypes that can play a neuroprotective role under physiological conditions or a pro-inflammatory, damaging one during disease. Therefore, therapeutic strategies focus on the downregulation of these neuroinflammatory processes and try to re-activate the neuroprotective features of microglia. Mesenchymal stem cells (MSC) of different origins have been shown to exert such effects, due to their immunomodulatory properties. In recent years, MSC derived from adipose tissue have been made the center of attention because of their easy availability and extraction methods. These cells induce a neuroprotective phenotype in microglia and downregulate neuroinflammation, resulting in an improvement of clinical symptoms in a variety of animal models for neurological pathologies, e.g., Alzheimer's disease, traumatic brain injury and ischemic stroke. In this review, we will discuss the application of adipose tissue-derived MSC and their conditioned medium, including extracellular vesicles, in neurological disorders, their beneficial effect on microglia and the signaling pathways involved.

Tratamiento quirúrgico de pie diabético basado en clasificación Wagner / Surgical treatment of diabetic foot based on Wagner classification

Se realizó un estudio que caracterizó a los pacientes que reciben tratamiento quirúrgico en el Hospital Roosevelt por pie diabético según la Clasificación Wagner. El objetivo era determinar el tratamiento quirúrgico brindado al paciente con pie diabético, basado en la clasificación Wagner, en el Departamento de Cirugía del Hospital Roosevelt durante el período de enero a octubre 2015. Se realizó un estudio descriptivo estudiando a los pacientes con diagnóstico de pie diabético, con una muestra de 81 pacientes. Se encontró que 56% presentaron grado IV, edad de 56-65 años en 38%, de sexo masculino 65%. 134 procedimientos quirúrgicos realizados, más común lavado y desbridamiento en 38%. Principalmente diagnóstico de Diabetes mellitus tipo II, con tiempo diagnóstico mayor a 10 años en 51%. Uso de hipoglucemiantes orales 49%. De los estudiados, 41% no presentaba ninguna comorbilidad. Se concluyó que el tratamiento quirúrgico más frecuente para Pie diabético Wagner II y III fue el lavado y desbridamiento, grado IV amputación de dedos y grado V las amputaciones femorales supracondíleas. Caracterizados como pacientes en rango de edad entre los 56-65 años, de sexo masculino, que padece Diabetes mellitus tipo II, clasificado como pie diabético Wagner IV, ameritando tratamiento quirúrgico como amputación de dedos seguido de amputaciones radicales descritas como amputación supracondílea, con tiempo de diagnóstico mayor a 10 años, con tratamiento de hipoglucemiantes orales, y sin ninguna comorbilidad médica asociada. (AU)

A study was conducted that characterized patients receiving surgical treatment at Roosevelt Hospital for diabetic foot according to the Wagner Classification. The objective was to determine the surgical treatment provided to the patient with diabetic foot, based on the Wagner classification, in the Department of Surgery at Roosevelt Hospital during the period from January to October 2015. A descriptive study was carried out studying patients with a diagnosis of diabetic foot, with a sample of 81 patients. It was found that 56% had grade IV, age 56-65 years in 38%, male 65%. 134 surgical procedures performed, the most common was lavage and debridement in 38%. Mainly diagnosis of type II diabetes mellitus, with a diagnosis time greater than 10 years in 51%. Use of oral hypoglycemic agents 49%. Of those studied, 41% did not present any comorbidity. The conclusion was that the most frequent surgical treatment for Wagner II and III was lavage and debridement, grade IV finger amputation and grade V supracondylar femoral amputations. Characterized as patients in the age range between 56-65 years, male, suffering from type II diabetes mellitus, classified as Wagner IV diabetic foot, meriting surgical treatment such as amputation of fingers followed by radical amputations described as supracondylar amputation, with time of diagnosis greater than 10 years, with treatment of oral ypoglycemic agents, and without any associated medical comorbidity. (AU)

Evaluation of Cleaning Processes Using Colorimetric and Spectral Data for the Removal of Layers of Limewash from Medieval Plasterwork.

In the cultural heritage preservation of medieval buildings, it is common to find plaster walls covered in lime, which previously were painted in polychromy. The conservation interventions usually try to remove the whitewash, whilst maintaining the original color of the painted wall as much as possible. However, there is no agreement on which cleaning technique best preserves the original appearance of the colored plaster. Different pigments found below the lime layer may behave differently depending on the cleaning technique used. Usually, colorimetric or photometric area-based measurements are carried out to study the color of the cleaned areas to compare with their original color, obtained from pre-made plaster probes. However, this methodology fails when the mean color difference is not enough to fully characterize the changes in texture and color appearance. This study presents a set of experiments carried out using two different pigments (cinnabar and malachite) covered with lime, and treated with nine different cleaning techniques on plaster probes prepared according to medieval techniques. We have studied the effect of the cleaning process on the color and the homogeneity of the samples using a hyperspectral imaging workflow. Four different analysis methods are presented and discussed. Our results show that the proposed analysis is able to provide a much more comprehensive and diversified characterization of the quality of the cleaning method compared to the commonly used colorimetric or photometric area-based measurements.

COVID-19 y su asociación con síntomas depresivos en población española / COVID-19 and its association with depressive mood symptoms in the Spanish Population

RESUMEN. Introducción: la emergencia sanitaria por el COVID-19 ha generado una conmoción mundial que conlleva una serie de problemáticas relacionadas con la salud, los factores psicosociales y la situación económica. Objetivo: evaluar el efecto del confinamiento en el ánimo depresivo en población residente en España mayor de 18 años durante el estado de alarma provocada por la pandemia de la COVID-19, analizando, además, la posible incidencia de las variables sexo, edad, tamaño de la vivienda e ingresos económicos. Material y Métodos: diseño transversal, descriptivo y correlacional con metodología de carácter cuantitativo. El acceso a la muestra fue no probabilístico a través de la técnica bola de nieve. Para evaluar la condición de ánimo depresivo se utilizó la escala CES-D. Para recopilar los datos relacionados con el sexo, la edad, el tamaño de vivienda y la situación económica, se crearon preguntas ad hoc en la propia encuesta. Resultados: las mujeres presentan valores de ánimo depresivo superiores a los hombres. Además, los valores de ánimo depresivo son mayores cuanto menor es la edad. Las personas que residen en viviendas con un tamaño menor, presentan valores de ánimo depresivo superiores respecto a las personas que viven en residencias con superficies mayores. A su vez, las personas con peores condiciones económicas perciben mayores niveles de ánimo depresivo. Conclusiones: los resultados indican que los síntomas de ánimo depresivo y las consecuencias psicosociales en la población española durante el confinamiento, se encuentran condicionadas por el sexo, la edad, el tamaño de la vivienda y la situación económica(AU)

ABSTRACT Introduction: Health emergency due to the COVID-19 pandemic has generated a global commotion, leading to a series of problems related to health, psychosocial factors and economic situation. Objective: To evaluate the effect of confinement on depressive mood in Spanish residents who are over 18 years old during the state of emergency which was declared due to the COVID-19 pandemic. Additionally, this paper aims to analyze the possible impact of some variables such as sex, age, size of dwelling and income. Materials and Methods: Cross-sectional, descriptive and correlational design with quantitative methodology. Access to the sample was based on a non-probabilistic sampling through snowball technique. CES-D scale was used to evaluate the state of depressive mood. In order to collect data related to sex, age, size of dwelling and economic situation, ad hoc questions were included in the survey. Results: Women presented higher values of depressive mood than men. Furthermore, depressive mood values are higher in younger individuals. People who live in smaller dwellings showed higher values of depressive mood compared to those who live in larger dwellings. Similarly, individuals with less favorable economic conditions perceive higher levels of depressive mood. Conclusions: The results show that depressive mood symptoms and their psychosocial consequences in the Spanish population during confinement are conditioned by sex, age, dwelling size and economic situation(AU)

ß-Amyloid exacerbates inflammation in astrocytes lacking fatty acid amide hydrolase through a mechanism involving PPAR-α, PPAR-γ and TRPV1, but not CB1 or CB2 receptors.

BACKGROUND AND PURPOSE: The endocannabinoid system may regulate glial cell functions and their responses to pathological stimuli, specifically, Alzheimer's disease. One experimental approach is the enhancement of endocannabinoid tone by blocking the activity of degradative enzymes, such as fatty acid amide hydrolase (FAAH). EXPERIMENTAL APPROACH: We examined the role of FAAH in the response of astrocytes to the pathologic form of ß-amyloid (Aß). Astrocytes from wild-type mice (WT) and from mice lacking FAAH (FAAH-KO) were incubated with Aß for 8, 24 and 48 h, and their inflammatory responses were quantified by elisa, western-blotting and real-time quantitative-PCR. KEY RESULTS: FAAH-KO astrocytes were significantly more responsive to Aß than WT astrocytes, as shown by the higher production of pro-inflammatory cytokines. Expression of COX-2, inducible NOS and TNF-α was also increased in Aß-exposed KO astrocytes compared with that in WTs. These effects were accompanied by a differential pattern of activation of signalling cascades involved in mediating inflammatory responses, such as ERK1/2, p38MAPK and NFκB. PPAR-α and PPAR-γ as well as transient receptor potential vanilloid-1 (TRPV1), but not cannabinoid CB1 or CB2 receptors, mediate some of the differential changes observed in Aß-exposed FAAH-KO astrocytes. The pharmacological blockade of FAAH did not render astrocytes more sensitive to Aß. In contrast, exogenous addition of several acylethanolamides (anandamide, palmitoylethanolamide and oleoylethanolamide) induced an antiinflammatory response. CONCLUSIONS: The genetic deletion of FAAH in astrocytes exacerbated their inflammatory phenotype against Aß in a process involving PPAR-α, PPAR-γ and TRPV1 receptors.

The activation of cannabinoid CB2 receptors stimulates in situ and in vitro beta-amyloid removal by human macrophages.

The endocannabinoid system is a promising therapeutic target in a wide variety of diseases. However, the non-desirable psychotropic effects of natural and synthetic cannabinoids have largely counteracted their clinical usefulness. These effects are mostly mediated by cannabinoid receptors of the CB(1) type, that exhibit a wide distribution in neuronal elements of the CNS. Thus, the presence of other elements of this system in the CNS, such as CB(2) receptors, may open new possibilities for the development of cannabinoid-based therapies. These receptors are almost absent from the CNS in normal conditions but are up-regulated in glial cells under chronic neuroinflammatory stimuli, as has been described in Alzheimer's disease. To understand the functional role of these receptors, we tested their role in the process of beta-amyloid removal, that is currently considered as one of the most promising experimental approaches for the treatment of this disease. Our results show that a CB(2) agonist (JWH-015) is capable of inducing the removal of native beta-amyloid removal from human frozen tissue sections as well as of synthetic pathogenic peptide by a human macrophage cell line (THP-1). Remarkably, this effect was achieved at low doses (maximum effect at 10 nM) and was specific for this type of cells, as U373MG astrocytoma cells did not respond to the treatment. The effect was CB(2)-mediated, at least partially, as the selective CB(2) antagonist SR144528 prevented the JWH-015-induced plaque removal in situ. These data corroborate the possible therapeutic interest of CB(2) cannabinoid specific chemicals in the treatment of Alzheimer's disease.

Activation of the human immunodeficiency virus type I long terminal repeat by 1 alpha,25-dihydroxyvitamin D3.

The genetic predisposition of the host and the virus is the most important determinant for prediction of the course of human immunodeficiency virus type I (HIV-1) viral infection and acquired immune deficiency syndrome (AIDS) progression. Transcription from the HIV-1 long terminal repeat (LTR) is a crucial step for viral replication. Here, we describe a stimulatory role of the vitamin D receptor (VDR) on HIV-1 LTR transactivation. Transient transfections reveal that VDR activates the LTR in HeLa, U937, and Cos-1 cells in a ligand-dependent manner. 1alpha,25-Dihydroxyvitamin D3 (vitD3) promotes activation of a minimal LTR construct (from nucleotides -35 to +89), lacking a previously described hormone response element that binds several nuclear receptors. NF-kappaB (nuclear factor-kappa B) and Sp1-binding sites, which are responsible for most basal LTR activity in HeLa cells, are also dispensable for vitD3-dependent HIV-1 transcription. Although the tat response element element is not required for VDR-mediated HIV-1 gene expression, the viral protein Tat acts in a synergistic manner with the receptor to stimulate LTR activity. Furthermore, our data also show cooperation of the receptor with various cellular coactivators for HIV-1 transactivation by vitD3. Paradoxically, mutations in the VDR ligand-dependent transcriptional activation function-2 that abrogate vitD3-dependent stimulation through classical vitamin D response elements, do not reduce vitD3-mediated LTR transactivation. Furthermore, point mutations in the DNA-binding domain that abolish receptor binding to consensus DNA sequences do not affect ligand-dependent HIV-1 stimulation. These results show that VDR activates the HIV-1 LTR through different mechanisms, including non-classical nuclear receptor transcriptional actions that may ensure viral transcription under different physiological scenarios.

Characterization of vitamin D receptor ligands with cell-specific and dissociated activity.

Although the main role of 1alpha,25-dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)] is to regulate calcium homeostasis, the valuable therapeutic applications of this compound have led to the search of new 1,25-(OH)(2)D(3)-vitamin D receptor (VDR) ligands with less side effects. In this work we have characterized seven 1,25-(OH)(2)D(3) derivatives (ZK136607, ZK161422, ZK157202, ZK159222, ZK168492, ZK191732, and ZK168289). ZK157202 is an agonist that gives a pattern similar to that of 1,25-(OH)(2)D(3) or ZK161422 in limited trypsin digestion assays, is able to recruit p160 and VDR-interacting protein 205 coactivators, is as potent as 1,25-(OH)(2)D(3) to stimulate vitamin D response element-dependent transcription in HeLa cells, and acts as a superagonist in human embryonic kidney 293T cells. This compound is also more potent than the natural ligand to transrepress the activation of the retinoic acid receptor beta2 promoter by retinoic acid and the response of the collagenase promoter to 4alpha-12-O-tetradecanoylphorbol 13-acetate. ZK136607, ZK168492, ZK191732, and ZK168289 have a profile similar to that of the partial antagonist ZK159222. They induce an antagonistic-type proteolytic pattern, do not recruit classical coactivators, and have little transactivation potency. However, they act in a cell context-dependent manner because they lack activity in HeLa cells while presenting some agonistic activity in human embryonic kidney 293T cells, or vice versa. Furthermore, some of these compounds have a dissociated activity: they cannot transactivate but they are as potent as 1,25-(OH)(2)D(3) in transrepression assays. Together our results demonstrate the existence of novel VDR ligands with variable biological functions and dissociated activity. They should represent useful tools for studying VDR function and could have therapeutic utility.