Ursodeoxycholic Acid Binds PERK and Ameliorates Neurite Atrophy in a Cellular Model of GM2 Gangliosidosis.

The Unfolded protein response (UPR), triggered by stress in the endoplasmic reticulum (ER), is a key driver of neurodegenerative diseases. GM2 gangliosidosis, which includes Tay-Sachs and Sandhoff disease, is caused by an accumulation of GM2, mainly in the brain, that leads to progressive neurodegeneration. Previously, we demonstrated in a cellular model of GM2 gangliosidosis that PERK, a UPR sensor, contributes to neuronal death. There is currently no approved treatment for these disorders. Chemical chaperones, such as ursodeoxycholic acid (UDCA), have been found to alleviate ER stress in cell and animal models. UDCA's ability to move across the blood-brain barrier makes it interesting as a therapeutic tool. Here, we found that UDCA significantly diminished the neurite atrophy induced by GM2 accumulation in primary neuron cultures. It also decreased the up-regulation of pro-apoptotic CHOP, a downstream PERK-signaling component. To explore its potential mechanisms of action, in vitro kinase assays and crosslinking experiments were performed with different variants of recombinant protein PERK, either in solution or in reconstituted liposomes. The results suggest a direct interaction between UDCA and the cytosolic domain of PERK, which promotes kinase phosphorylation and dimerization.

Psychosocial Effects of the COVID-19 Pandemic on Patients With Schizophrenia and Their Caregivers.

The aim of this study was to analyze the psychosocial effects of the COVID-19 pandemic on 120 patients with schizophrenia, and their caregivers (control group), in the city of Arica, northern Chile. The hypotheses of this study hold that (1) self-reports of the impact of the COVID-19 pandemic among patients and caregivers would be positively correlated, (2) caregivers would self-report a greater impact of the pandemic on their daily lives, and (3) patients infected with COVID-19 would experience lower levels of mental health improvement and higher levels of psychological distress. Hypotheses were tested using correlations, mean differences, and effect sizes (Cohen's d). The results showed that patients with schizophrenia who had been in quarantine for almost a year showed similar levels of concern as their caregivers in the domains of health and social life. However, caregivers showed significant differences from patients in the areas of income, concern, and employment status. In addition, patients who were infected with COVID-19 showed lower levels of well-being and worse psychological recovery. The implications of the findings highlight the need to incorporate mental health interventions in the pandemic health context for caregivers of people with schizophrenia. Finally, the results suggest that Covid-19 infection has a significant effect on the recovery and psychological well-being of patients with schizophrenia.

El efecto de la discriminación racial y étnica sobre la autoestima individual y colectiva según el fenotipo autoreportado en migrantes colombianos en Chile / The effect of racial and ethnic discrimination on individual and collective self-esteem according to the self-reported phenotype in Colombian migrants in Chile

Resumen Mediante un diseño no experimental, analítico y transversal, se analizó el efecto que tiene la discriminación racial y étnica sobre la autoestima individual (AI) y colectiva (AC), según el fenotipo declarado. Para esto fueron encuestados 481 migrantes de nacionalidad colombiana (54 % mujeres y 46 % hombres), con edades entre los 18 y los 65 años, con una media de 35 años. Se aplicaron las escalas de AI de Rosenberg, de discriminación percibida de Krieger et al y la adaptación de Basabe de la escala de AC de Luthanen et al. Se observan efectos diferenciales de la discriminación étnica y/o racial sobre la AI y sobre la AC. En personas que se autoidentifican como "blancos", la percepción de discriminación racial se relaciona leve y positivamente con la AI; en quienes se perciben como "mestizos o nativos americanos", la discriminación racial tiene un efecto positivo moderado sobre la AC; en quienes se identifican como "afrodescendientes", ambas discriminaciones tienen un efecto positivo leve sobre la AI, mientras que la discriminación racial perjudicaría moderadamente la AC; y, finalmente, en quienes se identifican como "mulatos", ambas discriminaciones tendrían efectos leves o moderados positivos en los dos tipos de autoestima. Estos resultados aportan evidencia al efecto del fenotipo en la relación establecida entre la discriminación y la autoestima.

Abstract Through a non-experimental, analytical and cross-sectional design, we analyze the effect that racial and ethnic discrimination has on individual (ISE) and collective (CSE) self-esteem, according to the declared phenotype. 481 Colombian migrants (54 % women and 46 % men), aged between 18 and 65 (average of 35 years), were surveyed. Were applied the Rosenberg ISE scales, perceived discrimination of Krieger et al. and Basabe's adaptation of the CSE scale of Luthanen et al. Differential effects of ethnic and / or racial discrimination on ISE and on CSE are observed. In people who identify themselves as "white", the perception of racial discrimination is slightly and positively related to ISE. In those who are perceived as "mixed or Native American", racial discrimination has a moderate positive effect on CSE. In those who identify themselves as "Afro-descendants," both discriminations have a slight positive effect on ISE, while racial discrimination would moderately harm CSE. Finally, in those who identify themselves as "mulattos," both discriminations would have mild or moderate positive effects on both types of self-esteem. These results provide evidence to the effect of the phenotype on the relationship established between discrimination and self-esteem.

The mediating effect of self-esteem on the relationship between perceived discrimination and psychological well-being in immigrants.

The aim of the study is to analyze the mediating effect of self-esteem on the relationship between perceived discrimination and psychological well-being in South American immigrants in Chile. An analytical, cross sectional, non-experimental design was used. We evaluated 853 Peruvians and Colombians living in the northern cities of Arica, Antofagasta, and Santiago de Chile, the capital located in the center of the country. The instruments used were the Ryff Psychological Well-being Scale, the Rosenberg Self-Esteem Scale and the Perceived Discrimination Scale by Basabe, Paez, Aierdi and Jiménez-Aristizabal. We used the estimation method (RWLS) and polychoric correlation matrices, to estimate the effect size and overall fit of the direct effect models of discrimination and self-esteem on psychological well-being, and indirect and total effects of discrimination mediated by self-esteem. While both populations reported similar levels of perceived discrimination, it was found that the means in psychological well-being and self-esteem of the Colombian population were significantly higher than that of the Peruvian population. Regarding self-esteem, the results provided evidence for the possible mediating effect on the relationship between perceived discrimination and psychological well-being. This research aims to contribute to the development of interventions seeking to strengthen self-esteem in order to circumvent possible negative consequences of perceived discrimination, as a consequent, improving immigrants´ personal resources to successfully cope with the diverse demands of their new context.

Afrontamiento del estrés por aculturación: inmigrantes latinos en Chile / Coping with Acculturation Stress: Latino Immigrants in Chile

Resumen Las minorías migrantes afrontan el estrés aculturativo con respuestas conductuales y cognitivas. Las fuentes de estrés por aculturación incluyen la discriminación, las diferencias socioculturales, la añoranza del origen y la ruptura familiar. Se entrevistaron 853 inmigrantes peruanos y colombianos en Chile (51 % mujeres y edad M = 33.19; DE = 9.54). Se aplicaron escalas de estrés por aculturación y formas de afrontamiento. La distancia y añoranza familiar fue la principal fuente de estrés siendo mayor entre los colombianos, quienes usan más la movilidad individual, la distracción y las comparaciones sociales, mientras los peruanos internalizan más el estigma del inmigrante. Las comparaciones intergrupales y temporales se relacionaron con menor estrés de aculturación. Se discute la importancia de las formas de afrontar el estrés en minorías migrantes.

Abstract Acculturative stress includes discrimination, socio-cultural differences, nostalgia for the place of origin and family separation, and immigrant minorities face it with behavioral and cognitive responses. 853 Peruvians and Colombians living in Chile were interviewed (51% woman, age M = 33.19, SD = 9.54) using acculturative stress and coping scales. Distance from home and family separation were the main source of stress among Colombians, who used more individual mobility, distraction and social comparisons as coping strategies, while Peruvians internalized more the immigrant stigma. Inter-group and temporary comparisons were more related to less acculturative stress. Stress coping strategies among immigrant minorities are discussed. Keyword: immigration; ethnicity; acculturative stress; coping Introducción

The influence of acculturation strategies in quality of life by immigrants in Northern Chile.

PURPOSE: To establish the influence of acculturation strategies on quality of life, henceforth QoL. METHODS: Using a cross-sectional design, two questionnaires were applied, the WHOQoL-BREF from the World Health Organization and Basabe's acculturation strategies. The questionnaires were applied to 853 Colombian and Peruvian immigrants living in Northern Chilean cities of Arica, Antofagasta and Santiago de Chile. RESULTS: In the psychological and social domains, as well as in the overall assessment of QoL, the most beneficial strategies are those where customs are maintained from the homeland, where "integration" then "separation" are the most beneficial. On the contrary, when the strategy for maintaining homeland customs is low, the QoL tends to be lower. The strategy of "marginalized" is associated with a lower QoL. CONCLUSIONS: Acculturation strategies mildly or moderately affect the psychological and social domains of quality of life as well as the overall assessment of QoL.

Desarrollo de una escala breve para medir actitudes hacia una alimentación saludable en población escolar preadolescente / Development of a brief scale to measure attitudes towards a healthy food in a school population of pre-adolescents

Unhealthy eating habits are one of the main causes that contribute to non-communicable diseases (NCD). Few instruments are available to evaluate the impact of interventions as well as associated factors. Our aim was to design and evaluate a brief scale to measure attitudes towards healthy eating habits in a school population. A psychometric study was carried out. The sample (non-probability sampling) was composed of 1,238 students from public and semi-private schools in Antofagasta, Chile with ages ranging between 10 and 13, and an average age of 11.98 (SD=1.3). A higher percentage of informants were female (52.9 %, n= 655). Results: Factor analysis showed good indicators of adjustment in the attitude scale for healthy eating. The scale was composed of a global dimension and two specific dimensions, "attitude towards food" and "healthy behavior." We conclude that the brief survey has adequate values based on the internal structure of the test that confirm its validity.

Uno de los principales factores que contribuye al aumento de las enfermedades no transmisibles es la alimentación no saludable. Dificultades en esta área son los escasos instrumentos dedicados a evaluar tanto el impacto de las intervenciones como de los factores asociados a esta. Nuestro objetivo fue desarrollar y evaluar una escala breve para medir actitudes hacia una alimentación saludable en población escolar. Para ello, se realizó un estudio psicométrico en datos recogidos de 1.238 estudiantes con edades entre los 10 y 13 años, con un promedio de 11,98 años (DT= 1,3 años). El 52,9% (n= 655) fueron mujeres. El muestreo fue no probabilístico con participantes de establecimientos municipales y particulares subvencionados de Antofagasta. Los análisis factoriales confirmatorios presentan buenos indicadores de ajuste para una escala de actitud hacia la alimentación saludable compuesta por una dimensión global y dos dimensiones específicas denominadas "actitud frente a los alimentos" y "conductas saludables". Concluimos que la escala breve desarrollada presenta adecuados valores que dan cuenta de su validez basada fundamentalmente en la estructura interna del test.

Afrontamiento y etnia: estrategias en niños y niñas aymara / Coping and ethnicity: strategies in aymara boys and girls

Menores aymara han experimentado un proceso migratorio importante durante las últimas décadas, sin embargo, se han desarrollado escasos estudios en población infantil perteneciente a esta etnia. El objetivo de esta investigación es evaluar y comparar las estrategias de afrontamiento utilizado por niños y niñas Aymara y no Aymara. La muestra estuvo compuesta por 685 niños/as entre 9 y 15 años de escuelas municipales y colegios particular subvencionados de la ciudad de Arica. Los resultados muestran la inexistencia de diferencias poblacionales entre niños/as aymara y no aymara en relación a los problemas experimentados (pχ2> .05), el uso de estrategias de afrontamiento utilizadas (pt> .05) y la eficacia de estas últimas (pt> .05). Se concluye que los niños/as pertenecientes a la etnia estarían logrando adecuados mecanismos de afrontamiento en contextos urbanos.

Aymara Childrens have experienced significant migration process over the past decades, however, few studies have been developed in children belonging to this ethnic group. In this reserch, the objective is to evaluate and compare the coping strategies used by Aymara and not Aymara Children. The sample consisted of 685 boys / girls aged 9 and 15 years of Municipal Schools and Private Schools Funded by the city of Arica. The results show the absence of differences population between Aymara and not Aymara boys and girls, in relation to problems experienced (pχ2> .05), the use of coping strategies used (pt> .05) and the effectiveness of the latter (pt > .05). We can conclude that children, as belonging to the ethnic group, are achieving adequate coping mechanisms in urban contexts.

Clinically meaningful change: false positives in the estimation of individual change.

In applied research as well as in clinical practice, it is common to evaluate the change that patients experience as a consequence of the treatment they receive. Various methods designed to evaluate this change are reviewed in this study. This review has focused on a specific aspect that has not been given proper attention: the false positive rate. For this reason, a nonchange situation was simulated (pre-post design with no differences between pre and post) and the behavior of 8 different methods was evaluated in this scenario. Different distributions as well as different sample sizes were simulated. A thousand samples were created for each simulated condition. The percentage of times each method detected a change was obtained in order to evaluate the behavior of the selected methods. Because the simulated situation is a nonchange one, any change alert was considered as a false positive. Out of the 8 evaluated methods, the standardized individual difference and the confidence intervals of linear regression are the ones with the best performance. The remaining methods fail to correctly identify and reject sampling random fluctuations. In most cases there is a tendency to consider changes that respond only to random variations as statistically reliable. However, a simple modification related in reliability estimation allows a considerable improvement in the behavior of some methods.

Significación clínica: falsos positivos en la estimación del cambio individual / Clinical significance: false positives in the estimation of individual change

Tanto en la investigación aplicada como en la práctica clínica es habitual tener que evaluar el cambio que experimentan los pacientes como consecuencia del tratamiento que reciben. En este trabajo se valora el comportamiento de varios métodos estadísticos diseñados para estimar ese cambio. La valoración se ha centrado en un aspecto al que todavía no se le ha prestado atención: la tasa de falsos positivos. Para ello, se ha simulado una situación de no-cambio (diseño pre-post sin cambio entre el pre y el post) y se ha valorado el comportamiento de nueve estadísticos distintos en ese escenario. Se han utilizado tres tamaños muestrales distintos (25, 50 y 100) y se han simulado 1000 muestras de cada tamaño. Para evaluar el comportamiento de los estadísticos elegidos se ha calculado el porcentaje de veces que cada estadístico ha detectado un cambio. Puesto que la situación simulada es de no-cambio, cualquier alerta de cambio debe ser considerada un falso positivo. Los resultados obtenidos son bastante llamativos: ninguno de los nueve estadísticos evaluados ofrece un comportamiento aceptable. Únicamente se consiguen resultados aceptables cuando se trabaja con la desviación típica de las diferencias pre-post y se aplican criterios clásicos en lugar de los propuestos por la literatura relacionada con la significación clínica (AU)

In applied research and in clinical practice we often need to assess the change experienced by patients as a result of the treatment they have received. This paper assesses the performance of several statistical methods designed to estimate such change. This study focuses on one aspect that still has not received attention: the rate of false positives. We have simulated a situation of no-change (pre-post design with no change between pre and post) in which the behavior of nine different statistics have been evaluated. Three different sample sizes (25, 50 and 100) were used and 1000 samples of each size were simulated. To evaluate the behavior of the chosen statistics we have calculated the percentage of times that each statistic has detected change. Since no-change is the simulated situation, any occurrence of change should be considered a false positive. Results are quite striking: none of the nine statistics evaluated offers an acceptable behavior. Good performance is achieved only when the standard deviation of pre-post differences and the traditional criteria are used and not when those proposed by the literature related to the clinical significance are used (AU)