Terapia Cognitivo-Conductual y Niveles de Ansiedad y Depresión en el Trastorno Obsesivo-Compulsivo Pediátrico: una Revisión Sistemática y Meta-Análisis

©. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ This document is the Published, version of a Published Work that appeared in final form in Psicothema. To access the final edited and published work see https://doi.org/10.7334/psicothema2021.478Background: Although some meta-analyses have identified potential moderators associated with treatment outcomes for pediatric obsessive-compulsive disorder (OCD), there is as yet no consensus regarding the influence of anxiety and depression symptoms on the recovery from pediatric OCD. A meta-analysis was conducted to investigate the effects of depression and anxiety symptoms and their comorbidities on the efficacy of CBT in pediatric OCD, as well as other potential moderators that may be associated with outcomes. Method: An exhaustive literature search from 1983 to March 2021 located 22 published articles that applied cognitive-behavioral therapy (CBT) to pediatric OCD, producing a total of 26 treatment groups. Some of the moderator variables analyzed included age, gender, comorbidity baseline in anxiety, depression and obsession, and methodological quality. Results: Results showed that the psychological treatment of OCD achieves clinically significant effectiveness, both for measures of obsessions and compulsions (d+ = 2.030), and for anxiety (d = 0.613) and depression (d = 0.451). An explanatory model for the CY-BOCS effect sizes + + showed that three moderator variables were statistically related: the mean of the CY-BOCS (Children’s Yale Brown Obsessive Compulsive Scale) in pretest, the effect size for anxiety, and the mean age of the sample. Conclusions: CBT reduced obsessive-compulsive symptoms and, to a lesser extent, anxiety and depression symptoms. Since anxiety symptoms are reduced with the same therapy, resources would be saved compared to other treatments.Antecedentes: Aunque algunos metanálisis han identificado posibles moderadores asociados con los resultados del tratamiento en el trastorno obsesivo compulsivo (TOC) pediátrico, todavía no existe consenso sobre la influencia de los síntomas de ansiedad y depresión en la recuperación de éste. Se realizó un metanálisis para investigar los efectos de los síntomas ansioso-depresivos y sus comorbilidades sobre la eficacia de la TCC en el TOC pediátrico, así como otras posibles variables moderadoras que pudieran estar asociados con el resultado. Método: Realizamos una búsqueda exhaustiva de la literatura desde 1983 hasta marzo de 2021 que nos permitió localizar 22 artículos publicados que aplicaban la terapia cognitivo-conductual (TCC) en el TOC pediátrico, produciendo un total de 26 grupos de tratamiento. Algunas variables moderadoras analizadas fueron: edad, sexo, comorbilidad, linea base en ansiedad, depresión y obsesion-compulsión, calidad metodológica. Resultados: Los resultados mostraron que el tratamiento psicológico del TOC consigue una eficacia clínicamente relevante, tanto para las medidas de obsesiones y compulsiones (d+= 2.030), como para la ansiedad (d+= 0,613) y la depresión (d+= 0,451). Un modelo explicativo para los tamaños del efecto CYBOCS (Escala obsesiva compulsiva de Yale-Brown para niños) reveló que tres variables moderadoras estaban relacionadas estadísticamente: la media del CYBOCS en el pretest, el tamaño del efecto para la ansiedad y la media de edad de la muestra. Conclusiones: La TCC redujo los síntomas obsesivo-compulsivos y, en menor medida, los síntomas de ansiedad y depresión. Dado que los síntomas de ansiedad se reducen con la misma terapia, se ahorrarían recursos con respecto a la implementación y adición de otros tratamientos

¿Existe relación entre uso problemático de Internet y las respuestas de ansiedad social, obsesivo-compulsivas y el bienestar psicológico en adolescentes?

ElusoexcesivodeInternetenadolescentesy jóvenesseconsidera relacionadocon problemasintrapersonaleseinterpersonales.Elobjetivode esta investigaciónfueestudiar larelaciónentreelusoproblemático deInternet,bienestar psicológicoy respuestasdeansiedadsocialy obsesivo-compulsivas.Lamuestraestuvo formadapor132varonesy 178mujeresdeedadescomprendidasentre16y 23añosque cursabanBachilleratoy estudiosuniversitarios.Losresultadosindicaronquelaedad influyóenlamayorpartedefactoresdelUsocompulsivodeInternet.Elsexoafectóa losnivelesdelusoproblemáticodeInternetsiendoloschicoslos quemayores puntuacionesalcanzaronenusocompulsivoyconsecuenciasnegativas.Seconfirmó una correlación significativaydirectaentreuso problemático deInternety respuestasde ansiedadsocialy obsesivo-compulsivas.Lospredictoresmásimportantedeluso problemático de Internet fueron el dominio del entorno,la ansiedad social y los síntomasobsesivo-compulsivos.Sepodría concluir,aunqueconcautela,quemientras que losjóvenesconansiedadsocialpodríanbuscar elusode internetcomounmediode interacciónplacentero, losjóvenesconsíntomasobsesivo-compulsivospodríanllegar a un uso excesivo como medio de eliminar la ansiedad compulsiva.El uso excesivo de Internet en adolescentes y jóvenes se considera relacionado con problemas intrapersonales e interpersonales. El objetivo de esta investigación fue estudiar la relación entre el uso problemático de Internet, bienestar psicológico y respuestas de ansiedad social y obsesivo-compulsivas. La muestra estuvo formada por 132 varones y 178 mujeres de edades comprendidas entre 16 y 23 años que cursaban Bachillerato y estudios universitarios. Los resultados indicaron que la edad influyó en la mayor parte de factores del Uso compulsivo de Internet. El sexo afectó a los niveles del uso problemático de Internet siendo los chicos los que mayores puntuaciones alcanzaron en uso compulsivo y consecuencias negativas. Se confirmó una correlación significativa y directa entre uso problemático de Internet y respuestas de ansiedad social y obsesivo-compulsivas. Los predictores más importante del uso problemático de Internet fueron el dominio del entorno, la ansiedad social y los síntomas obsesivo-compulsivos. Se podría concluir, aunque con cautela, que mientras que los jóvenes con ansiedad social podrían buscar el uso de internet como un medio de interacción placentero, los jóvenes con síntomas obsesivo-compulsivos podrían llegar a un uso excesivo como medio de eliminar la ansiedad compulsiva.

Highly Anisotropic Organometal Halide Perovskite Nanowalls Grown by Glancing-Angle Deposition

Polarizers are ubiquitous components in current optoelectronic devices as displays or photographic cameras. Yet, control over light polarization is an unsolved challenge, since the main drawback of the existing display technologies is the significant optical losses. In such a context, organometal halide perovskites (OMHP) can play a decisive role given their flexible synthesis with tunable optical properties such as bandgap and photoluminescence, and excellent light emission with a low non-radiative recombination rate. Therefore, along with their outstanding electrical properties have elevated hybrid perovskites as the material of choice in photovoltaics and optoelectronics. Among the different OMHP nanostructures, nanowires and nanorods have lately arisen as key players in the control of light polarization for lighting or detector applications. Herein, the fabrication of highly aligned and anisotropic methylammonium lead iodide perovskite nanowalls by glancing-angle deposition, which is compatible with most substrates, is presented. Their high alignment degree provides the samples with anisotropic optical properties such as light absorption and photoluminescence. Furthermore, their implementation in photovoltaic devices provides them with a polarization-sensitive response. This facile vacuum-based approach embodies a milestone in the development of last-generation polarization-sensitive perovskite-based optoelectronic devices such as lighting appliances or self-powered photodetectors

Impact of hospitalization on nutritional status in persons aged 65 years and over (NUTRIFRAG Study): Protocol for a prospective observational study

[ES] Background Malnutrition is a recurring problem that has become more relevant in recent years. The aim of this study is to assess the risk of malnutrition and nutritional status on admission and its evolution until discharge in patients aged 65 and over admitted to medical and surgical hospitalization units in hospitals of the Spanish National Health System. Methods Prospective observational study to be carried out in the medical-surgical hospitalization units of 9 public hospitals between 01/09/2022 and 31/12/2024. Using consecutive sampling, a total of 4077 patients will be included (453 in each hospital). Variables included are related to the care process, functionality, cognition and comorbidity, risk profile, nutritional status and dysphagia; as well as frailty, dietary quality and contextual variables. The incidence of risk of malnutrition, undernutrition and dysphagia during the care process and at discharge will be calculated. The association with risk factors will be studied with logistic regression models and multivariate Cox regression models. In addition, an analysis of participants’ satisfaction with food services will be carried out. The study was approved by the Ethics and Research Committee on 30/09/2020, approved for funding on 02/12/2021 and with registration number RBR-5jnbyhk in the Brazilian clinical trials database (ReBEC) for observational studies. Discussion Some studies address nutritional status or dysphagia in older people in various care settings. However, there is a lack of large sample studies including both processes of the impact of hospitalization. The results of the project will provide information on the incidence and prevalence of both pathologies in the study subjects, their associated factors and their relationship with the average length of stay, mortality and early readmission. In addition, early detection of a problem such as malnutrition related to the disease and/or dysphagia during a hospital stay will favor the action of professionals to resolve both pathologies and improve the health status of patients.This study has been funded by Instituto de Salud Carlos III (ISCIII) through the Project "PI21/00738" and co-funded by the European Union. The funders did not and will not have a role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Extracellular cysteine disulfide bond break at Cys122 disrupts PIP2-dependent Kir2.1 channel function and leads to arrhythmias in Andersen-Tawil Syndrome

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Extracellular Kir2.1C122Y Mutant Upsets Kir2.1-PIP2 Bonds and Is Arrhythmogenic in Andersen-Tawil Syndrome.

BACKGROUND Andersen-Tawil syndrome type 1 is a rare heritable disease caused by mutations in the gene coding the strong inwardly rectifying K+ channel Kir2.1. The extracellular Cys (cysteine)122-to-Cys154 disulfide bond in the channel structure is crucial for proper folding but has not been associated with correct channel function at the membrane. We evaluated whether a human mutation at the Cys122-to-Cys154 disulfide bridge leads to Kir2.1 channel dysfunction and arrhythmias by reorganizing the overall Kir2.1 channel structure and destabilizing its open state. METHODS We identified a Kir2.1 loss-of-function mutation (c.366 A>T; p.Cys122Tyr) in an ATS1 family. To investigate its pathophysiological implications, we generated an AAV9-mediated cardiac-specific mouse model expressing the Kir2.1C122Y variant. We employed a multidisciplinary approach, integrating patch clamping and intracardiac stimulation, molecular biology techniques, molecular dynamics, and bioluminescence resonance energy transfer experiments. RESULTS Kir2.1C122Y mice recapitulated the ECG features of ATS1 independently of sex, including corrected QT prolongation, conduction defects, and increased arrhythmia susceptibility. Isolated Kir2.1C122Y cardiomyocytes showed significantly reduced inwardly rectifier K+ (IK1) and inward Na+ (INa) current densities independently of normal trafficking. Molecular dynamics predicted that the C122Y mutation provoked a conformational change over the 2000-ns simulation, characterized by a greater loss of hydrogen bonds between Kir2.1 and phosphatidylinositol 4,5-bisphosphate than wild type (WT). Therefore, the phosphatidylinositol 4,5-bisphosphate-binding pocket was destabilized, resulting in a lower conductance state compared with WT. Accordingly, on inside-out patch clamping, the C122Y mutation significantly blunted Kir2.1 sensitivity to increasing phosphatidylinositol 4,5-bisphosphate concentrations. In addition, the Kir2.1C122Y mutation resulted in channelosome degradation, demonstrating temporal instability of both Kir2.1 and NaV1.5 proteins. CONCLUSIONS The extracellular Cys122-to-Cys154 disulfide bond in the tridimensional Kir2.1 channel structure is essential for the channel function. We demonstrate that breaking disulfide bonds in the extracellular domain disrupts phosphatidylinositol 4,5-bisphosphate-dependent regulation, leading to channel dysfunction and defects in Kir2.1 energetic stability. The mutation also alters functional expression of the NaV1.5 channel and ultimately leads to conduction disturbances and life-threatening arrhythmia characteristic of Andersen-Tawil syndrome type 1.The authors thank the Centro Nacional de Investigaciones Cardiovasculares (CNIC) Viral Vectors Unit for producing the adeno-associated virus serotype 9. Confocal experiments were conducted at the CNIC Microscopy and Dynamic Imaging Unit. The authors thank the CNIC Bioinformatics Unit for generating the in silico homology modeling simulations, F-function analysis, and helpful discussions. The authors also thank the Centro de Supercomputación de Galicia for the use of the Finis Terrae III supercomputer to perform molecular dynamics studies. The CNIC was supported by the Instituto de Salud Carlos III, the Ministerio de Ciencia, Innovación y Universidades, and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (grant CEX2020-001041-S funded by MICIU/AEI/10.13039/501100011033). This work was supported by the National heart, Lung and Blood Institute under National Institutes of Health (NIH) grant R01HL163943; the La Caixa Banking Foundation project code HR18-00304 (grant LCF/PR/HR19/52160013); grants PI-FIS-2020, PI20/01220, PI-FIS-2023, and PI23/01039 from the Instituto de Salud Carlos III and cofunded by the Fondo Europeo de Desarrollo Regional (FEDER) and the European Union, respectively; grants PID2020-116935RB-I00 and BFU2016-75144-R funded by MICIU/AEI/10.13039/501100011033; the Fundación La Marató de TV3 (736/C/2020) amb el suport de la Fundació La Marató de TV3; the CIBER (Centro de Investigación Biomédica en Red) de Enfermedades Cardiovasculares (grant CB16/11/00458); the European Union’s Horizon 2020 grant agreement GA-965286; and the Program S2022/BMD7229-CM ARCADIACM funded by the Comunidad de Madrid to J. Jalife; grant PID2021-126423OB-C22 (to M. Martín-Martínez) funded by MICIU/AEI/10.13039/501100011033; and European Regional Development Fund (ERDF) grant PID2022-137214OB-C22 (to M. Gutierrez-Rodríguez) funded by MICIU/AEI/10.13039/501100011033. The imaging studies were performed in the TRIMA@CNIC (Infraestructura de Imagen Traslacional Avanzada del CNIC) node of the ICTS ReDIB (Infraestructuras Científicas y Técnicas Singulares: Red Distribuida de Imagen Biomédica) grant ICTS-2018- 04-CNIC-16 funded by MICIU/AEI/10.13039/501100011033 and ERDF, and project EQC2018-005070-P funded by MICIU/AEI/10.13039/501100011033 and FEDER. A.I. Moreno-Manuel holds an formación profesional universitaria (FPU) contract (FPU20/01569) from the Ministerio de Universidades. J.M. Ruiz Robles holds an FPU contract (FPU22/03253) from the Ministerio de Universidades. L.K. Gutiérrez holds an FPI contract (PRE2018-083530) from the Ministerio de Economía y Competitividad de España cofunded by the Fondo Social Europeo, attached to project SEV-2015-0505-18-2. I. Martínez-Carrascoso holds a PFIS (Contratos predoctorales de formación en investigación en salud) contract (FI21/00243) funded by Instituto de Salud Carlos III and the Fondo Social Europeo Plus cofunded by the European Union. M.L. Vera-Pedrosa held contract PEJD-2019-PRE/BMD15982 funded by the Consejería de Educación e Investigación de la Comunidad de Madrid y Fondo Social Europeo.S

Impact of hospitalization on nutritional status in persons aged 65 years and over (NUTRIFRAG Study): Protocol for a prospective observational study

Background: Malnutrition is a recurring problem that has become more relevant in recent years. The aim of this study is to assess the risk of malnutrition and nutritional status on admission and its evolution until discharge in patients aged 65 and over admitted to medical and surgical hospitalization units in hospitals of the Spanish National Health System. Methods: Prospective observational study to be carried out in the medical-surgical hospitalization units of 9 public hospitals between 01/09/2022 and 31/12/2024. Using consecutive sampling, a total of 4077 patients will be included (453 in each hospital). Variables included are related to the care process, functionality, cognition and comorbidity, risk profile, nutritional status and dysphagia; as well as frailty, dietary quality and contextual variables. The incidence of risk of malnutrition, undernutrition and dysphagia during the care process and at discharge will be calculated. The association with risk factors will be studied with logistic regression models and multivariate Cox regression models. In addition, an analysis of participants' satisfaction with food services will be carried out. The study was approved by the Ethics and Research Committee on 30/09/2020, approved for funding on 02/12/2021 and with registration number RBR-5jnbyhk in the Brazilian clinical trials database (ReBEC) for observational studies. Discussion: Some studies address nutritional status or dysphagia in older people in various care settings. However, there is a lack of large sample studies including both processes of the impact of hospitalization. The results of the project will provide information on the incidence and prevalence of both pathologies in the study subjects, their associated factors and their relationship with the average length of stay, mortality and early readmission. In addition, early detection of a problem such as malnutrition related to the disease and/or dysphagia during a hospital stay will favor the action of professionals to resolve both pathologies and improve the health status of patients.This study has been funded by Instituto de Salud Carlos III (ISCIII) through the project "PI21/00738" and co-funded by the European Union. The funders did not and will not have a role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.S

A Lower Baseline CD4/CD8 T-Cell Ratio Is Independently Associated with Immunodiscordant Response to Antiretroviral Therapy in HIV-Infected Subjects

We explored if baseline CD4/CD8 T-cell ratio is associated with immunodiscordant response to antiretroviral therapy in HIV-infected subjects. Comparing immunodiscordant and immunoconcordant subjects matched by pretreatment CD4 counts, we observed a lower pretreatment CD4/CD8 T-cell ratio in immunodiscordant subjects. Furthermore, pretreatment CD4/CD8 T-cell ratio, but not CD4 counts, correlated with the main immunological alterations observed in immunodiscordants, including increased regulatory T-cell (Treg) frequency and T-cell turnover-related markers. Then, in a larger cohort, only baseline CD4/CD8 T-cell ratio was independently associated with immunodiscordance, after adjusting by the viral CXCR4-tropic HIV variants. Our results suggest that the CD4/CD8 T-cell ratio could be an accurate biomarker of the subjacent immunological damage triggering immunodiscordance.The HIV BioBank, integrated in the Spanish AIDS Research Network, is supported by Instituto de Salud Carlos III, Spanish Health Ministry (grants RD06/0006/0035 and RD12/0017/0037), as part of the Plan Nacional R + D + I and cofinanced by ISCIII-Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER) and Fundación para la investigación y prevención del SIDA en España (FIPSE). The RIS Cohort (CoRIS) is funded by the Instituto de Salud Carlos III through the Red Temática de Investigación Cooperativa en SIDA by the RD12/0017/0018 project, as part of the Plan Nacional R + D + I, and cofinanced by ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER). The project number is RIS_EPICLIN 20/2015. This work was supported by grants from the Fondo de Investigación Sanitaria, ISCIII (FIS; PI14/01693), and the Consejería de Economía, Innovación, Ciencia y Empleo, Junta de Andalucía (Proyecto de Investigación de Excelencia; CTS2593), and cofunded by Fondos Europeos para el Desarrollo Regional (FEDER). I. Rosado-Sánchez was supported by the Spanish AIDS Research Network of Excellence (RIS; RD12/0017/0029). Y. M. Pacheco was supported by the Fondo de Investigación Sanitaria through the Miguel Servet program (CPII13/00037) and by the Servicio Andaluz de Salud through the Nicolás Monardes program (C-0010/13).Peer reviewe

Factors associated with the humoral response after three doses of COVID-19 vaccination in kidney transplant recipients

[Introduction] Kidney transplant recipients showed a weak humoral response to the mRNA COVID-19 vaccine despite receiving three cumulative doses of the vaccine. New approaches are still needed to raise protective immunity conferred by the vaccine administration within this group of high-risk patients.[Methods] To analyze the humoral response and identify any predictive factors within these patients, we designed a prospective monocentric longitudinal study of Kidney transplant recipients (KTR) who received three doses of mRNA-1273 COVID-19 vaccine. Specific antibody levels were measured by chemiluminescence. Parameters related to clinical status such as kidney function, immunosuppressive therapy, inflammatory status and thymic function were analyzed as potential predictors of the humoral response.[Results] Seventy-four KTR and sixteen healthy controls were included. One month after the administration of the third dose of the COVID-19 vaccine, 64.8% of KTR showed a positive humoral response. As predictive factors of seroconversion and specific antibody titer, we found that immunosuppressive therapy, worse kidney function, higher inflammatory status and age were related to a lower response in KTR while immune cell counts, thymosin-a1 plasma concentration and thymic output were related to a higher humoral response. Furthermore, baseline thymosin-a1 concentration was independently associated with the seroconversion after three vaccine doses.[Discussion] In addition to the immunosuppression therapy, condition of kidney function and age before vaccination, specific immune factors could also be relevant in light of optimization of the COVID-19 vaccination protocol in KTR. Therefore, thymosin-a1, an immunomodulatory hormone, deserves further research as a potential adjuvant for the next vaccine boosters.This study was supported by a grant from the Fondo de Investigación Sanitaria (FIS/PI21/00357), which is co-founded by Fondos Europeos para el Desarrollo Regional (FEDER) “Una manera de hacer Europa”. VG-R, IO-M and AB-R were supported by Instituto de Salud Carlos III (CD19/00143, FI19/00298 and CM19/00051, respectively). MP-B was supported by the Consejería de Transformación Económica, Industria, Conocimiento y Universidades [DOC_01646 to MP-B] and YP was supported by the Consejería de Salud y Familias of Junta de Andalucía through the “Nicolás Monardes” [RC-0006-2021].Peer reviewe

Genomic Characterization of Host Factors Related to SARS-CoV-2 Infection in People with Dementia and Control Populations: The GR@ACE/DEGESCO Study

Emerging studies have suggested several chromosomal regions as potential host genetic factors involved in the susceptibility to SARS-CoV-2 infection and disease outcome. We nested a COVID-19 genome-wide association study using the GR@ACE/DEGESCO study, searching for susceptibility factors associated with COVID-19 disease. To this end, we compared 221 COVID-19 confirmed cases with 17,035 individuals in whom the COVID-19 disease status was unknown. Then, we performed a meta-analysis with the publicly available data from the COVID-19 Host Genetics Initiative. Because the APOE locus has been suggested as a potential modifier of COVID-19 disease, we added sensitivity analyses stratifying by dementia status or by disease severity. We confirmed the existence of the 3p21.31 region (LZTFL1, SLC6A20) implicated in the susceptibility to SARS-CoV-2 infection and TYK2 gene might be involved in COVID-19 severity. Nevertheless, no statistically significant association was observed in the COVID-19 fatal outcome or in the stratified analyses (dementia-only and non-dementia strata) for the APOE locus not supporting its involvement in SARS-CoV-2 pathobiology or COVID-19 prognosis