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Alzheimer's disease (AD) constitutes a major public-health issue of our time. Regrettably, despite our considerable understanding of the pathophysiological aspects of this disease, current interventions lead to poor outcomes. Furthermore, experimentally promising compounds have continuously failed when translated to clinical trials. Along with increased population ageing, Type 2 Diabetes Mellitus (T2DM) has become an extremely common condition, mainly due to unbalanced dietary habits. Substantial epidemiological evidence correlates T2DM with cognitive impairment as well. Considering that brain insulin resistance, mitochondrial dysfunction, oxidative stress, and amyloidogenesis are common phenomena, further approaching the common features among these pathological conditions. Metformin constitutes the first-choice drug to preclude insulin resistance in T2DM clinical management. Experimental evidence suggests that its functions might include neuroprotective effects, in addition to its hypoglycemic activity. This review aims to summarize and discuss current knowledge of experimental data on metformin on this path towards translational medicine. Finally, we discuss the controversial data of responses to metformin in vitro, and in vivo, animal models and human studies.

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Lithium therapy received approval during the 1970s, and it has been used for its antidepressant, antimanic, and anti-suicidal effects for acute and long-term prophylaxis and treatment of bipolar disorder (BPD). These properties have been well established; however, the molecular and cellular mechanisms remain controversial. In the past few years, many studies demonstrated that at the cellular level, lithium acts as a regulator of neurogenesis, aging, and Ca2+ homeostasis. At the molecular level, lithium modulates aging by inhibiting glycogen synthase kinase-3ß (GSK-3ß), and the phosphatidylinositol (PI) cycle; latter, lithium specifically inhibits inositol production, acting as a non-competitive inhibitor of inositol monophosphatase (IMPase). Mitochondria and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) have been related to lithium activity, and its regulation is mediated by GSK-3ß degradation and inhibition. Lithium also impacts Ca2+ homeostasis in the mitochondria modulating the function of the lithium-permeable mitochondrial Na+-Ca2+exchanger (NCLX), affecting Ca2+ efflux from the mitochondrial matrix to the endoplasmic reticulum (ER). A close relationship between the protease Omi, GSK-3ß, and PGC-1α has also been established. The purpose of this review is to summarize some of the intracellular mechanisms related to lithium activity and how, through them, neuronal aging could be controlled.

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Introduction: The COVID-19 pandemic has exacerbated mental health challenges, particularly depression among college students. Detecting at-risk students early is crucial but remains challenging, particularly in developing countries. Utilizing data-driven predictive models presents a viable solution to address this pressing need. Aims: 1) To develop and compare machine learning (ML) models for predicting depression in Argentinean students during the pandemic. 2) To assess the performance of classification and regression models using appropriate metrics. 3) To identify key features driving depression prediction. Methods: A longitudinal dataset (N = 1492 college students) captured T1 and T2 measurements during the Argentinean COVID-19 quarantine. ML models, including linear logistic regression classifiers/ridge regression (LogReg/RR), random forest classifiers/regressors, and support vector machines/regressors (SVM/SVR), are employed. Assessed features encompass depression and anxiety scores (at T1), mental disorder/suicidal behavior history, quarantine sub-period information, sex, and age. For classification, models' performance on test data is evaluated using Area Under the Precision-Recall Curve (AUPRC), Area Under the Receiver Operating Characteristic curve, Balanced Accuracy, F1 score, and Brier loss. For regression, R-squared (R2), Mean Absolute Error, and Mean Squared Error are assessed. Univariate analyses are conducted to assess the predictive strength of each individual feature with respect to the target variable. The performance of multi- vs univariate models is compared using the mean AUPRC score for classifiers and the R2 score for regressors. Results: The highest performance is achieved by SVM and LogReg (e.g., AUPRC: 0.76, 95% CI: 0.69, 0.81) and SVR and RR models (e.g., R2 for SVR and RR: 0.56, 95% CI: 0.45, 0.64 and 0.45, 0.63, respectively). Univariate models, particularly LogReg and SVM using depression (AUPRC: 0.72, 95% CI: 0.64, 0.79) or anxiety scores (AUPRC: 0.71, 95% CI: 0.64, 0.78) and RR using depression scores (R2: 0.48, 95% CI: 0.39, 0.57) exhibit performance levels close to those of the multivariate models, which include all features. Discussion: These findings highlight the relevance of pre-existing depression and anxiety conditions in predicting depression during quarantine, underscoring their comorbidity. ML models, particularly SVM/SVR and LogReg/RR, demonstrate potential in the timely detection of at-risk students. However, further studies are needed before clinical implementation.

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Porphyromonas gingivalis (P. gingivalis) is a gram-negative oral pathogen associated with chronic periodontitis. Previous studies have linked poor oral health and periodontitis with oral cancer. Severe cases of periodontal disease can result in advanced periodontitis, leading to tissue degradation, tooth loss, and may also correlate with higher gastric cancer (GC) risk. In fact, tooth loss is associated with an elevated risk of cancer. However, the clinical evidence for this association remains inconclusive. Periodontitis is also characterized by chronic inflammation and upregulation of members of the Programmed Death 1/PD1 Ligand 1 (PD1/PDL1) axis that leads to an immunosuppressive state. Given that chronic inflammation and immunosuppression are conditions that facilitate cancer progression and carcinogenesis, we hypothesize that oral P. gingivalis and/or its virulence factors serve as a mechanistic link between oral health and gastric carcinogenesis/GC progression. We also discuss the potential impact of P. gingivalis' virulence factors (gingipains, lipopolysaccharide (LPS), and fimbriae) on inflammation and the response to immune checkpoint inhibitors in GC which are part of the current standard of care for advanced stage patients.

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Coronavirus Anxiety Scale (CAS) is a widely used measure that captures somatic symptoms of coronavirus-related anxiety. In a large-scale collaboration spanning 60 countries (Ntotal = 21,513), we examined the CAS's measurement invariance and assessed the convergent validity of CAS scores in relation to the fear of COVID-19 (FCV-19S) and the satisfaction with life (SWLS-3) scales. We utilized both conventional exact invariance tests and alignment procedures, with results revealing that the single-factor model fit the data well in almost all countries. Partial scalar invariance was supported in a subset of 56 countries. To ensure the robustness of results, given the unbalanced samples, we employed resampling techniques both with and without replacement and found the results were more stable in larger samples. The alignment procedure demonstrated a high degree of measurement invariance with 9% of the parameters exhibiting noninvariance. We also conducted simulations of alignment using the parameters estimated in the current model. Findings demonstrated reliability of the means but indicated challenges in estimating the latent variances. Strong positive correlations between CAS and FCV-19S estimated with all three different approaches were found in most countries. Correlations of CAS and SWLS-3 were weak and negative but significantly differed from zero in several countries. Overall, the study provided support for the measurement invariance of the CAS and offered evidence of its convergent validity while also highlighting issues with variance estimation. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

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El objetivo de la presente revisión sistemática fue examinar las características de las interven-ciones centradas en reducir el consumo de sustancias, sus potenciales consecuencias negativas o incrementar el uso de estrategias de protección en jóvenes impartidas a través de medios tecnológicos. Las intervenciones fueron categorizadas según el formato de implementación (i. e., mensajes, páginas webs o apps). Se identificaron 29 intervenciones. Las intervenciones por mensajes y páginas web impactaron positivamente en las tres variables dependientes analiza-das. Ninguna de las intervenciones por apps mostró cambios significativos. La mayoría de las in-tervenciones estuvieron dirigidas a estudiantes universitarios y centradas en el consumo de al-cohol. Esto destaca la necesidad de desarrollar y evaluar intervenciones dirigidas a población no-universitaria y centradas en sustancias diferentes al alcohol. La síntesis proporcionada po-dría ser útil para guiar el diseño de intervenciones mediadas por tecnologías para reducir el impacto del consumo de sustancias en jóvenes. (AU)

The aim of the present systematic review was to examine the characteristics of mHealth in-terventions focused on reducing substance use, negative consequences or increasing protective behavioural strategies use in young adult population. Interventions were categorized accord-ing to the format of implementation (i. e., messages, web page or apps). We identified 29 in-terventions. Interventions delivered by messages and web pages impacted on the three de-pendent variables analysed. None of the interventions delivered by app showed significant changes. Most of the interventions were intended for college students and focused on alcohol consumption. Our results stand out the need to develop and evaluate interventions for non-college population and focused on substances different to alcohol. The evidence provided could be a useful for designing mHealth interventions focused on reduce substance use among young people. (AU)

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El cáncer seguirá siendo uno de los mayores desafíos para la salud pública a nivel local y mundial. Actualmente, en nuestro país, el cáncer es la principal causa de muerte. Gracias al enorme conocimiento acumulado en las últimas décadas sobre las bases celulares y moleculares del cáncer, se ha desarrollado la oncología de precisión, un enfoque que permite dirigir de manera cada vez más precisa el tratamiento farmacológico en función de los exámenes de diagnóstico. Para ello se utilizan tecnologías avanzadas, como la secuenciación de próxima generación. Es imprescindible implementar estas tecnologías en los sistemas sanitarios actuales y futuros para optimizar el arsenal de estrategias para el control del cáncer. En esta revisión, se discuten algunos alcances de la oncología de precisión, especialmente aplicada a tumores sólidos. Se aborda el estado del arte de los biomarcadores mínimos necesarios para el diagnóstico de este importante grupo de neoplasias, la situación local en cuanto a las capacidades tecnológicas instaladas en el territorio nacional ya sea con fines de investigación o diagnóstico, y el potencial impacto sanitario que tendría la aplicación de todo este conocimiento práctico al servicio de las personas con cáncer, tanto en el sector público como privado.

Cancer will remain one of the most significant challenges for public health, locally and globally. Currently, cancer is the leading cause of death in our country. Thanks to the enormous knowledge accumulated in recent decades on the cellular and molecular bases of cancer, precision oncology has been developed, an approach that allows for increasingly precise pharmacological treatment based on diagnostic tests. Advanced technologies such as next-generation sequencing are used for this purpose. It is essential to implement these technologies in current and future health systems to optimize the arsenal of strategies for cancer control. This review discusses some of the achievements of precision oncology, particularly applied to solid tumors. It addresses the state-of-the-art minimum biomarkers required for the diagnosis of this important group of neoplasms, the local situation regarding technological capabilities installed in the national territory, either for research or diagnosis, and the potential health impact of applying all this practical knowledge to serve people with cancer, both in the public and private sectors.

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Background: The COVID-19 pandemic and lockdowns are known to affect alcohol consumption. This study examines drinking expectancies and contexts upon alcohol consumption of Argentinean students.Objectives: To assess within-person changes in alcohol consumption in Argentinean college students (aged 18-24), from August 2019 with a one-year follow-up during the COVID-19 lockdown, considering alcohol expectancies, drinking contexts, and main socio-demographic variables. To validate the stability of these predictors, we discuss the effects on the alcohol consumption across dependent and independent measures.Methods: We assessed one longitudinal (N = 300, 70% female) and one cross-sectional (N = 165, 78% female) sample via online surveys and applied multilevel analysis and regressions, respectively.Results: Alcohol consumption significantly increased during lockdown compared to one-year before (mean: 6.91 and 8.26 alcohol units, correspondingly). In the longitudinal sample, social facilitation (medium effect sizes [ES]: 0.21, 0.22) and parental presence (medium ES: 0.12, 0.21) significantly and stable (through time) predicted increasing effects on consumption. In the cross-sectional sample, stress control (high ES: 0.78) and parental presence (high ES: 0.42) were associated with higher consumption during lockdown.Conclusion: College students increased their alcohol consumption during lockdown, suggesting that restrictive sanitary measures may negatively affect consumption. Literature is not conclusive as both decreases and increases in alcohol consumption in students from developed countries were reported. Before and during COVID-19 lockdown, parental presence is a stable predictor of increased alcohol consumption, though unusual according to the literature. Health policies aimed at modifying the behavior of parents who promote/share alcohol consumption with their offspring may help reduce drinking in college students.

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BACKGROUND: The Argentinean quarantine is among the strictest and longest quarantines in the world. To determine if a worsening pattern on mental health would emerge with a prolonged quarantine duration, a longitudinal analysis pertaining to the lengthy mandatory Argentinean quarantine was conducted. AIM: To examine depression and anxiety changes in college students, as a function of quarantine duration, demographic and health-related factors, during successive time cuts of the lengthy mandatory quarantine in Argentina. METHODS: We used a longitudinal design, N = 1492 college students. For the first measurement, successive samplings were carried out across quarantine sub-periods of up to 106-days duration. The follow-up was one month later. RESULTS: Particularly women, young, and having a history of mental disorder and suicidal behavior, were more depressed and anxious under mandatory restrictive quarantine conditions. Repeated measures of both depression and anxiety scores remained constantly high during the more restrictive quarantine sub-periods of up to 13 and 53-days duration, and decreased during the less restrictive quarantine sub-period of up to 106-days duration, but with small effect sizes (0.10-0.08). CONCLUSIONS: Restrictive quarantine has negative effects on mental health outcomes. Partial spontaneous remissions of depression and anxiety symptoms may be expected with further quarantine relaxations.

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Colorectal Cancer (CRC) is the third most frequent neoplasia worldwide. Despite the significant advances in surgical techniques and the development of new targeted antineoplastic therapies for this type of tumor, primary prevention and early diagnosis of malignant precursor lesions will continue to be the best strategies to reduce their incidence, morbidity, and mortality. Technologies for CRC screening can be classified into two groups, those of an invasive nature, such as colonoscopy and all its different modalities of use, and those of a non-invasive nature, such as laboratory tests and imaging. This review, will focus exclusively on non-invasive screening tests, excluding imaging. Specifically, it will address those that use depositions as a sample. This review will approach the latest international recommendations, regarding the age at which they should be used, their technical-biological bases, the two main types currently used (biochemical and immunological), and we will put into perspective their advantages and their possible disadvantages. Towards the end of this article, the most recent biotechnological developments in relation to molecular tests based on the study of blood samples, will be discussed. Although these tests are not yet in routine clinical use given their high costs, they are promising for the early detection of CRC.

El cáncer colorrectal (CCR) es la tercera neoplasia más común en todo el mundo. A pesar de los avances significativos en las técnicas quirúrgicas y en el desarrollo de nuevas terapias antineoplásicas para este tipo de tumor, la prevención primaria y el diagnóstico precoz de lesiones precursoras malignas siguen siendo las mejores estrategias para reducir la incidencia, morbilidad y mortalidad asociadas al CCR. Existen dos tipos de tecnologías para el tamizaje del CCR: las invasivas, como la colonoscopia, y las no invasivas, como los ensayos de laboratorio y la imagenología. Esta revisión, se centrará exclusivamente en las pruebas de tamizaje no invasivas que utilizan muestras de deposiciones, excluyendo las imágenes. Se abordarán las últimas recomendaciones internacionales sobre el momento etario en que se deben utilizar, sus bases técnico-biológicas, los dos principales tipos utilizados en la actualidad (bioquímico e inmunológico) y pondremos en perspectiva sus ventajas y posibles desventajas. Al final de esta revisión, se discutirá brevemente los últimos avances biotecnológicos relacionados con pruebas moleculares basadas en el estudio de muestras sanguíneas. Aunque estas pruebas aún no son de uso clínico habitual debido a sus altos costos, representan una prometedora innovación para la detección temprana del CCR.

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Cancer will remain one of the most significant challenges for public health, locally and globally. Currently, cancer is the leading cause of death in our country. Thanks to the enormous knowledge accumulated in recent decades on the cellular and molecular bases of cancer, precision oncology has been developed, an approach that allows for increasingly precise pharmacological treatment based on diagnostic tests. Advanced technologies such as next-generation sequencing are used for this purpose. It is essential to implement these technologies in current and future health systems to optimize the arsenal of strategies for cancer control. This review discusses some of the achievements of precision oncology, particularly applied to solid tumors. It addresses the state-of-the-art minimum biomarkers required for the diagnosis of this important group of neoplasms, the local situation regarding technological capabilities installed in the national territory, either for research or diagnosis, and the potential health impact of applying all this practical knowledge to serve people with cancer, both in the public and private sectors.

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With the COVID-19 pandemic, behavioural scientists aimed to illuminate reasons why people comply with (or not) large-scale cooperative activities. Here we investigated the motives that underlie support for COVID-19 preventive behaviours in a sample of 12,758 individuals from 34 countries. We hypothesized that the associations of empathic prosocial concern and fear of disease with support towards preventive COVID-19 behaviours would be moderated by trust in the government. Results suggest that the association between fear of disease and support for COVID-19 preventive behaviours was strongest when trust in the government was weak (both at individual- and country-level). Conversely, the association with empathic prosocial concern was strongest when trust in the government was high, but this moderation was only found at individual-level scores of governmental trust. We discuss how motivations may be shaped by socio-cultural context, and outline how findings may contribute to a better understanding of collective action during global crises.

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Resumen La desregulación emocional es un constructo multidimensional determinado por formas poco adaptativas de responder frente a las emociones. Las personas adultas emergentes (i.e., entre 18 y 25/30 años de edad), particularmente universitarias, son vulnerables a involucrarse en comportamientos riesgosos en contextos emocionales. La Escala de Dificultades en la Regulación Emocional Estado (S-DERS) resulta adecuada para medir dimensiones de desregulación emocional momentánea en esta población; sin embargo, no se conocen estudios confirmatorios de su estructura factorial ni estudios de adaptación al idioma español. El objetivo del presente estudio fue examinar las propiedades psicométricas de la S-DERS. Se evaluaron 178 adultos emergentes universitarios argentinos (18-28 años; 53.9% mujeres; Medad= 22.03; DE ±2.06). Se analizó la estructura y la consistencia interna del modelo original (S-DERS; cuatro factores: aceptación, conciencia, claridad y modulación) y un modelo alternativo (S-DERS-R; 3 factores) sin el factor claridad. Ambos modelos presentaron un ajuste satisfactorio de su estructura factorial y valores aceptables de consistencia interna, a excepción de la subescala claridad. Mayormente, para las subescalas aceptación y modulación y puntajes totales de ambos modelos, se obtuvieron evidencias de validez convergente con dos escalas de desregulación emocional rasgo concurrente con una escala de afecto positivo y negativo y predictiva con una medida de activación emocional. Los resultados muestran propiedades psicométricas adecuadas. S-DERS-R, que prescinde del factor claridad, mejora el ajuste y mantiene valores de consistencia interna aceptables respecto a S-DERS. Se espera que este instrumento sea útil en estudios transversales y longitudinales de la desregulación emocional estado en universitarios.

Abstract: Emotion dysregulation is a multidimensional construct determined by maladaptive ways of responding to emotions. Emerging adults (i.e., aged from 18 to 25/30), particularly college students, are vulnerable to involvement in risky behaviors under emotions. The State Difficulties in Emotion Regulation Scale (S-DERS) became suitable to measure facets of momentary emotion dysregulation in this population; however, there are no confirmatory studies or studies of adaptation to the Spanish language. The aim of this study was to examine psychometric properties of S-DERS. A sample of 178 Argentine emerging college-age adults was evaluated (18-28 years old; 53.9% women; Mage= 22.03; DE ± 2.06). Internal structure and consistency of the original model (i.e., S-DERS; four factors: Nonacceptance, Awareness, Clarity, Modulation) and an alternative model without Clarity (i.e., S-DERS-R; three factors) was analyzed. Both models presented a factor structure with satisfactory fit and acceptable values of internal consistency, with the exception of the Clarity subscale. Mainly to Nonacceptance and Modulation subscales, we observed evidence of convergent validity with two-trait emotion dysregulation scales, concurrent validity with a positive and negative affect scale, and predictive validity with an emotion arousal measure. Results show suitable sychometric properties. The S-DERS-R model (i.e., without Clarity factor) improves the model fit and maintains acceptable internal consistency values with respect to the S-DERS model. This instrument is expected to be useful in cross-sectional and longitudinal studies of state emotion dysregulation in college students.

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This research is aimed to: analyze differences in mental health state (MHS) indicators (depression, state-anxiety, trait-anxiety, and suicidal risk), during three quarantine sub-periods (starting since the first quarantine extension); assess multiple relationships between each MHS indicator and potentially affecting factors. We used a cross-sectional design with a convenience sample including 1100 participants. Data were collected online. Depression revealed a worsening pattern as quarantine sub-periods went by. Anxiety (both state and trait), just like suicidal risk, partially follow such a pattern, with mean scores increasing from the first to the second/third quarantine extensions, but then maintaining to the fourth extension. Predictors having protective effects on almost all the MHS indicators were: availability of current economic income (except for state-anxiety, without significant effect) and absence of suicide attempt history. Conversely, sex (woman), younger age, and mental disorder history had an increasing risk effect on all the MHS indicators. Overall, our findings indicate that quarantine have negative mental health impacts and that quarantine duration is a relevant aspect to be taken into account when measuring such an impact. More attention needs to be paid to vulnerable groups such as the young, women, and people with history of mental disorder.

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Objective: This study examines Argentinean health care workers in order to 1) test self-perceived job performance levels and the presence of psychological symptoms compatible with common mental disorders, and 2) examine within-person changes in general discomfort and psychological distress, adjusting for demographic factors, region, and health-related factors during two time points of the COVID-19 pandemic.Method: This longitudinal study comprised 305 healthcare workers who completed a survey at two time points approximately 4 months apart. We used the General Health Questionnaire and the Kessler Psychological Distress Scale to measure mental health outcomes. To address the first aim we calculated differences (Student's t test for paired samples) and correlations (Pearson's r coefficient). To address the second aim we used fixed effects model by means of a multilevel approach, a linear model that considers dependency in the data.Results: Self-perceived job performance deteriorated across time. From the first measurement to the four-month follow-up, more health care workers presented common mental disorders (40% vs 45.57%), depression, and/or anxiety (52.46% vs 62.62%). A meaningful worsening of mental health was observed in healthcare workers who expressed concern about being infected with COVID-19, whether asymptomatic (greater general discomfort and psychological distress) or symptomatic (greater general discomfort). Likewise, there were significant interactions between a history of mental disorder and concern about COVID-19 infection.Conclusions: Among healthcare workers, the uncertainty about the COVID-19 infection may have larger negative mental health impacts than actually being infected.

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With or without a COVID19 pandemic, cancer is and will continue to be one of the greatest health challenges on the planet. In Chile, during 2016, this disease was the second cause of death in the country and during 2019, it was the first cause in seven Chilean regions, surpassing cardiovascular diseases. With the advent of precision medicine as a powerful tool for cancer control, it is necessary to have genomic, proteomic, and molecular data in general, ideally on a population scale. This is essential for decision-making, for example in public and private oncology, to be as cost-effective as possible. Chile has a mass of high-quality researchers in cancer. However, until today the investment in research and development is far below the peers in the OECD. In this work we put into perspective the role of precision medicine and omic sciences as essential tools for public health. We offer a brief national diagnosis of the knowledge collected to date by the local scientific community regarding onco-genomic data from our own population. We finally discuss the potential behind the strengthening of this scientific knowledge, aiming to optimize the comprehensive management of cancer.

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Evidence on the within-person changes of healthcare workers' mental health across waves of COVID-19 cases during this pandemic is absent. The aim of this study is to examine the within-person changes of anxiety in Argentinean healthcare workers, adjusting for main demographic factors, region of residence, mental disorder history, and COVID-19 contagion, during the COVID-19 pandemic. A longitudinal web survey (N = 305) was conducted during two time points of the pandemic, one of which was an infection peak. Anxiety significantly increased across time. However, there were significant interaction effects modulating anxiety levels. The largest anxiety increases occurred in healthcare workers who were not sure if they had contracted COVID-19 while symptomatic. Irrespective of the time point, anxiety was the highest in healthcare workers from a region inside the country who were not sure if they had contracted COVID-19, either asymptomatic or symptomatic. An interaction effect between the mental disorder history and the COVID-19 contagion suggested that the anxiety outcomes were mainly due to the concern about the COVID-19 contagion, rather than due to pre-existing mental health vulnerabilities. Regardless of the starting point in anxiety levels, an increasing anxiety outcome may be expected among healthcare workers as the pandemic progresses. The uncertainty regarding COVID-19 contagion is a preventable and modifiable interacting factor to produce the worst anxiety outcomes among healthcare workers.

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BACKGROUND: Wnt signaling plays key roles in cellular and physiological processes, including cell proliferation, differentiation and migration during development and tissue homeostasis in adults. This pathway can be defined as Wnt/ß-catenin-dependent or ß-catenin-independent or "non-canonical", both signaling are involved in neurite and synapse development/maintenance. Porcupine (PORCN), an acylase that o-acylates Wnt ligands, a major modification in secretion and interaction with its receptors. We use Wnt-C59, a specific PORCN inhibitor, to block the secretion of endogenous Wnts in embryonic hippocampal neurons (DIV 4). Under these conditions, the activity of exogenous Wnt ligands on the complexity of the dendritic tree and axonal polarity were evaluated METHODS: Cultured primary embryonic hippocampal neurons obtained from Sprague-Dawley rat fetuses (E18), were cultured until day in vitro (DIV) 4 (according to Banker´s protocol) and treated with Wnt-C59 for 24 h, Wnt ligands were added to the cultures on DIV 3 for 24 h. Dendritic arbors and neurites were analysis by fluorescence microscopy. Transfection with Lipofectamine 2000 on DIV 2 of plasmid expressing eGFP and KIF5-Cherry was carried out to evaluate neuronal polarity. Immunostaining was performed with MAP1B and Tau protein. Immunoblot analysis was carried out with Wnt3a, ß-catenin and GSK-3ß (p-Ser9). Quantitative analysis of dendrite morphology was carried out with ImageJ (NIH) software with Neuron J Plugin. RESULTS: We report, here, that Wnt-C59 treatment changed the morphology of the dendritic arbors and neurites of embryonic hippocampal neurons, with decreases ß-catenin and Wnt3a and an apparent increase in GSK-3ß (p-Ser9) levels. No effect was observed on axonal polarity. In sister cultures, addition of exogenous Wnt3a, 5a and 7a ligands rescued the changes in neuronal morphology. Wnt3a restored the length of neurites to near that of the control, but Wnt7a increased the neurite length beyond that of the control. Wnt5a also restored the length of neurites relative to Wnt concentrations. CONCLUSIONS: Results indicated that Wnt ligands, added exogenously, restored dendritic arbor complexity in embryonic hippocampal neurons, previously treated with a high affinity specific Porcupine inhibitor. We proposed that PORCN is an emerging molecular target of interest in the search for preclinical options to study and treat Wnt-related diseases. Video Abstract.

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Mitochondria play key roles in ATP supply, calcium homeostasis, redox balance control and apoptosis, which in neurons are fundamental for neurotransmission and to allow synaptic plasticity. Their functional integrity is maintained by mitostasis, a process that involves mitochondrial transport, anchoring, fusion and fission processes regulated by different signaling pathways but mainly by the peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α). PGC-1α also favors Ca2+ homeostasis, reduces oxidative stress, modulates inflammatory processes and mobilizes mitochondria to where they are needed. To achieve their functions, mitochondria are tightly connected to the endoplasmic reticulum (ER) through specialized structures of the ER termed mitochondria-associated membranes (MAMs), which facilitate the communication between these two organelles mainly to aim Ca2+ buffering. Alterations in mitochondrial activity enhance reactive oxygen species (ROS) production, disturbing the physiological metabolism and causing cell damage. Furthermore, cytosolic Ca2+ overload results in an increase in mitochondrial Ca2+, resulting in mitochondrial dysfunction and the induction of mitochondrial permeability transition pore (mPTP) opening, leading to mitochondrial swelling and cell death through apoptosis as demonstrated in several neuropathologies. In summary, mitochondrial homeostasis is critical to maintain neuronal function; in fact, their regulation aims to improve neuronal viability and to protect against aging and neurodegenerative diseases.

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AIM: This study aimed to examine longitudinal changes on suicidal risk levels, adjusting for impulsivity-related traits, quarantine duration, main demographic factors, mental disorder history, and loneliness, in young Argentinean college students with (ideation; attempt) and without suicidal behavior history, during a quarantine of up to 103-day duration of the COVID-19 pandemic. METHODS: A longitudinal design with two-repeated measures was used (N = 1202). Follow-up was a month later from the first measurement. Three groups were analyzed: with suicidal ideation history, with suicide attempt history, and without suicidal behavior history. RESULTS: Percentages of college students with high or moderate suicidal risk were alarming (accumulated: 62.23% first measurement, 57.65% second measurement). Multilevel analysis on the three groups showed that suicidal risk diminished from the first measurement to the follow-up, having mental disorder history predicted higher suicidal risk, and negative urgency had the largest increasing effects on suicidal risk which persisted over time. CONCLUSIONS: Suicidal risk widely affects college students during lengthy quarantines of the COVID-19 pandemic and it should be tracked in those having pre-existing vulnerabilities, but also in those without. Education on managing negative emotions may help decrease suicide risk in college students during the COVID-19 pandemic.

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