Membrane Atg8ylation, stress granule formation, and MTOR regulation during lysosomal damage.

The functions of mammalian Atg8 proteins (mATG8s) expand beyond canonical autophagy and include processes collectively referred to as Atg8ylation. Global modulation of protein synthesis under stress conditions is governed by MTOR and liquid-liquid phase separated condensates containing ribonucleoprotein particles known as stress granules (SGs). We report that lysosomal damage induces SGs acting as a hitherto unappreciated inhibitor of protein translation via EIF2A/eIF2α phosphorylation while favoring an ATF4-dependent integrated stress response. SGs are induced by lysosome-damaging agents, SARS-CoV-2 open reading frame 3a protein (ORF3a) expression, Mycobacterium tuberculosis infection, and exposure to proteopathic MAPT/tau. Proteomic studies revealed recruitment to damaged lysosomes of the core SG proteins NUFIP2 and G3BP1 along with the GABARAPs of the mATG8 family. The recruitment of these proteins is independent of SG condensates or canonical autophagy. GABARAPs interact directly with NUFIP2 and G3BP1 whereas Atg8ylation is needed for their recruitment to damaged lysosomes. At the lysosome, NUFIP2 contributes to MTOR inactivation together with LGALS8 (galectin 8) via the Ragulator-RRAGA-RRAGB complex. The separable functions of NUFIP2 and G3BP1 in SG formation vis-a-vis their role in MTOR inactivation are governed by GABARAP and Atg8ylation. Thus, cells employ membrane Atg8ylation to control and coordinate SG and MTOR responses to lysosomal damage.Abbreviations: Atg8: autophagy related 8; ATG: autophagy related; ATF4: activating transcription factor 4; EIF2A/eIF2α: eukaryotic translation initiation factor 2A; GABARAP: GABA type A receptor-associated protein; G3BP1: G3BP stress granule assembly factor 1; LLOMe: L-leucyl-L-leucine methyl ester; LysoIP: lysosome immunopurification; mRNA: messenger ribonucleic acid; MTOR: mechanistic target of rapamycin kinase; NUFIP2: nuclear FMR1 interacting protein 2; ORF3a: open reading frame 3a protein; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; SG: stress granule; TIA1: TIA1 cytotoxic granule associated RNA binding protein.

Human activities at night negatively impact Little Penguin (Eudyptula minor) numbers and behaviours

The presence of humans within the natural environment is increasing worldwide. Assessing the impact of such activities on wildlife is crucial for declining populations where human disturbance adds to existing pressures. Here, we investigated how human activities at night influenced Little Penguin Eudyptula minor numbers and behaviours (specifically return time, number of vocalizations and time spent in vigilance) on Granite Island, a declining population in South Australia, Australia. We combined data from regular night surveys with continuous video and audio monitoring to assess the impact of human activities on the Little Penguins. The use of white light (i.e. from torches or camera flashes) by people was the most frequent activity recorded at night (recorded on 65% of the monitored nights). Fewer penguins were found on land at night when Dogs Canis lupus familiaris were present, but not when the number of people increased, when concerts occurred, or when white lights were used. Little Penguins were observed more often returning late from sea at night when Dogs were present and when white lights were used, but not when concerts occurred. An increase in penguin vocalizations at night correlated with the presence of Dogs and the occurrence of concerts, whereas penguins vocalized less when white lights were used. The time Little Penguins spent in vigilance did not correlate with any of the disturbances analysed. Our study also highlights the impact of coronavirus disease 2019 (COVID-19) on wildlife, as the occurrence of human activities increased significantly following the implementation of the COVID-19 health protection measures. These results add to a growing body of literature suggesting that human activities on land, and their consequent disturbance(s), may affect the numbers and behaviours of wildlife and that appropriate measures need to be developed to limit such impacts.

Parental perception of the relationship between stress responses and the changes in lifestyle habits of elementary school students during a temporary leave of absence for COVID-19

This study was conducted to investigate the relationship between stress responses and the lifestyle habit changes of elementary school students during a temporary leave of absence from school during measures to prevent the spread of COVID-19 infections. We surveyed 637 parents of elementary school students about their lifestyle habit changes and stress responses during their temporary leave and finally analyzed 510 subjects. Variance analysis, showed that there were significant differences in "irregular sleep," "disordered eating habits," and "increased use of games and smartphones," but the effect size was small. When the correlation was calculated, "disordered eating habits" was associated with all stress responses, and six lifestyle-related changes were associated with lethargy. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

The psychological stress response of COVID-19 to medical staff and prevention: A large sample study from China.

Objectives: In the face of the COVID-19 pandemic, medical staff in China were more likely to suffer from psychological problems. By investigating the actual state of psychological stress response of medical staff during the COVID-19 outbreak, the study discussed and analyzed the influencing factors of different psychological states in order to prevent the occurrence of serious adverse emotional events in medical staff. Methods: In the Xiangyang Central Hospital, 1,466 medical staff members have adopted the Psychological Questionnaire for Emergencies Events of Public Health (PQEEPH), which includes questions about depression, neurasthenia, fear, obsessive anxiety, and hypochondriac disorders. The questionnaire also asks about gender, age, education level, health, department, position, and whether personnel exposure history correlation analysis has been confirmed. Results: The survey revealed that 55% had depression, 26.7% had neurasthenia, 95% had fear, 47.9% had obsessive anxiety, and 69.3% had hypochondria. The effects of depression and hypochondriac emotional stress were significantly greater in female workers than in male workers (p < 0.05). Those with higher educational levels had a stronger emotional stress response. Medical professionals with or without contact histories, those who were suspected or confirmed, as well as those in various positions and departments, all demonstrated significant differences in their stress emotions (p < 0.05). Conclusion: Emotional stress affected medical professionals, especially doctors and nurses, who were on the front lines of clinical work in the face of significant public health emergencies. Therefore, to reduce the stress burden and enhance mental health on medical staff, hospitals were suggested to improve their emergency management practices. In addition, the sensitization knowledge training and psychological counseling for front-line clinical staff should be strengthened.

Comparison of oxidative stress response of in vitro retinal cells exposed to blue light from emissive versus reflective displays

During COVID-19, there was increased use of handheld displays in educational settings. There is growing concern that eye health may be affected by prolonged exposure to the light-emitting diodes used as frontlights or backlights in handheld displays. The potential impact of light exposure from tablet-sized devices with different display technologies and various spectral outputs was assessed in an in vitro model using human retinal epithelial (ARPE-19) cells. Cellular response was quantified by measuring reactive oxidative species (ROS) and by analyzing mitochondrial morphology. Control experiments established a baseline ROS response to hazardous blue light exposure and also that red light resulted in no detectable ROS response. Under identical conditions, ROS response increased with time for all devices. However, different device spectra caused ROS to accumulate at different rates. When operating the devices in the same mode (day or night), cells accumulated ROS two to three times more slowly on exposure to frontlit electronic paper displays compared to backlit liquid crystal displays. With increasing ROS accumulation, mitochondrial morphology shifted from elongate interconnected features typically observed under normal conditions to rounded disconnected features associated with oxidative stress response. © 2023 E Ink Corporation. Journal of the Society for Information Display published by Wiley Periodicals LLC on behalf of Society for Information Display.

Bibliometric analysis of post-traumatic stress disorder in forensic medicine: Research trends, hot spots, and prospects.

Background: Post-traumatic stress disorder (PTSD) has various risk factors, complex pathogenesis, and diverse symptoms, and is often comorbid with other injuries and diseases, making forensic diagnosis difficult. Methods: To explore the current research status and trends of PTSD, we used the Web of Science Core Collection databases to screen PTSD-related literature published between 2010 and 2021 and CiteSpace to perform bibliometric analysis. Results: In recent years, PTSD-related research has grown steadily. The countries and institutions with the most research results were the United States and England, and King's College London and Boston University, respectively. Publications were identified from 2,821 different journals, including 13 forensic-related journals, but the journal distribution was relatively scattered and there was a lack of professional core journals. Keyword co-occurrence and clustering identified many hot topics; "rat model," "mental health," and "satisfaction" were the topics most likely to have a clear effect on future research. Analysis extracted nine turning points from the literature that suggested that neural network centers, the hypothalamic-pituitary-adrenal axis, and biomarkers were new research directions. It was found that COVID-19 can cause severe psychological stress and induce PTSD, but the relationship needs further study. The literature on stress response areas and biomarkers has gradually increased over time, but specific systemic neural brain circuits and biomarkers remain to be determined. Conclusion: There is a need to expand the collection of different types of biological tissue samples from patients with different backgrounds, screen PTSD biomarkers and molecular targets using multi-omics and molecular biology techniques, and establish PTSD-related molecular networks. This may promote a systematic understanding of the abnormal activation of neural circuits in patients with PTSD and help to establish a personalized, accurate, and objective forensic diagnostic standard.

When asking 'are you stressed?' is not enough: Hair cortisol, subjective stress, and alcohol use during the first year of the pandemic.

The onset of the COVID-19 pandemic was accompanied by an increase in alcohol use in a third of the population worldwide. To date, the literature shows that subjective reports of stress predicted increased alcohol use during the early stages of the pandemic. However, no studies have investigated the effect of physiological stress (via the stress hormone cortisol) on alcohol use during the pandemic. This study aimed to identify the predictive value of cortisol and/or subjective stress on alcohol use during the first year of the pandemic. Every three months, between June 2020 and March 2021, 79 healthy adults (19-54 years old) answered online questionnaires assessing alcohol use. In May 2020, participants reported pre-pandemic alcohol use, while in June 2020, participants reported current alcohol use, subjective stress measures, and provided a 6 cm hair sample. The latter allowed us to quantify the cumulative levels of cortisol produced in the three months prior to and following the start of the mandatory lockdown measures in March 2020 in Quebec, Canada. A relative change in hair cortisol was computed to quantify the physiological stress response. While controlling for sex, age, and psychiatric diagnoses, multilevel linear regressions revealed that alcohol use increased only among people with concomitant high subjective stress and elevated hair cortisol concentrations. Moreover, this increased alcohol use remained elevated one year later. This study documents the importance of simultaneously considering stress biomarkers and subjective stress to identify people at risk of increasing their alcohol use during major stressful life events.

Stress response and influencing factors among fever outpatients and children's families during normalisation of the COVID-19 epidemic: A cross-sectional study.

AIM: To examine the demographic characteristics associated with stress response of fever outpatients and children's families during normalisation of the COVID-19 epidemic and to examine the relationship between stress response, coping style and resilience. DESIGN: Online cross-sectional study. METHODS: A total of 541 fever clinic participants from Yiwu, China, were recruited via WeChat from February to November 2021. Online self-administered questionnaires were used to collect data. Data were analysed using t-tests, one-way analyses of variance, Pearson's correlation analyses and multiple linear regression analyses. RESULTS: There were apparent physical and emotional responses among the fever outpatients, especially the adult patients. The main coping style was negative coping, and the degree of psychological resilience was low. Income, comorbidities, religious beliefs, tenacity, negative coping and positive coping were independent predictors of stress response.

Adult attachment insecurity and responses to prolonged severe occupational stress in hospital workers during the COVID-19 pandemic.

Background: The stress response includes appraisal of the threat and one's resources, coping (including interpersonal interactions), distress, and recovery. Relationships between patterns of adult attachment and stress response have received little study in the context of prolonged, severe occupational stress, limiting knowledge about how attachment patterns contribute to occupational burnout and recovery. Aim: This study aimed to assess the relationship of adult attachment to aspects of the stress response over time in hospital workers during a pandemic. Methods: This study included 538 hospital workers within a general and a rehabilitation hospital in Toronto, Canada between September 2020 and November 2021. Half, selected at random, completed validated measures of adult attachment, resilience, self-efficacy, coping, interpersonal problems, and various stress outcomes. Attachment insecurity severity was calculated as the vector addition of attachment anxiety and attachment avoidance. Correlations between these measures were determined at individual time-points and temporal patterns of adverse outcomes using repeated-measures ANOVA. Results: All correlations between measures of attachment and resilience or self-efficacy were significant and moderately strong (r = .30-.48), while most correlations with coping strategies were weak (<.20). Attachment avoidance was more strongly correlated with interpersonal problems related to being cold, whereas attachment anxiety was more strongly correlated with problems related to being intrusive, overly-nurturant, exploitable and non-assertive. Attachment insecurity severity was moderately correlated with every dimension of interpersonal problems. A significant main effect of each attachment measure on each stress outcome was found (effects sizes: .18-.26). Attachment insecurity severity was significantly associated with outcome X time interactions for burnout, consistent with greater resilience for those with lower attachment insecurity. Conclusions: Severity of insecure attachment was correlated with each measure of self-appraisal, interpersonal problems, and all measured stress outcomes. Severity of attachment insecurity performed well as a summary attachment measure. Greater security is associated with patterns of recovery that indicate resilience.

Stressors related to the Covid-19 pandemic, climate change, and the Ukraine crisis, and their impact on stress symptoms in Germany: analysis of cross-sectional survey data.

BACKGROUND: Climate change, the Covid-19 pandemic, and the Ukraine crisis are considered unprecedented global stressors, potentially associated with serious health consequences. However, simultaneous effects of these stressors are not yet understood, making it difficult to evaluate their relative contribution to the population burden and potential future manifestations in clinically significant psychiatric disorders. This study aimed at disentangling the relative contribution of the three stressor groups on current sub-clinical stress symptoms. METHODS: A cross-sectional, representative survey study was conducted two months after the outbreak of the Ukraine war in Germany. Proportional quota sampling was applied for age, gender, income, and regional characteristics. Data were recruited by means of an online survey. 3094 data sets (1560 females) were included. Age ranged from 18-89 (M: 50.4 years; SD: 17.2). The Subclinical Stress Questionnaire (SSQ-25) served as main outcome measure. In collaboration with a professional media agency, 20 items were generated to capture salient population stressors. A three-factor exploratory structural equation model confirmed the appropriateness of this scale. RESULTS: (1) Differences in subjective rankings revealed that stressors related to the Ukraine crisis were rated as most worrying, followed by climate change, and the Covid-19 pandemic (Generalized-Linear-Model: Epsilon = .97; F(1.94, 6001.14) = 1026.12, p < .001; ηp2 = .25). (2) In a linear regression model (R2 = .39), Covid-19 pandemic stressors were the only meaningful predictors for current ill-health (standardized ß = .48). Ukraine crisis did not predict stress symptom profiles in the present sample. (3) Older and male individuals report less and/or less severe stress symptoms, although effect sizes were small (range: η2 .11-.21). An older age also reduced the impact of Covid-19 stressors. CONCLUSIONS: Researchers from the health sciences must consider overlapping effects from population stressors. Although the Ukraine crisis and climate change mark salient stressors, including economic threats, the Covid-19 pandemic still has a profound effect on ill-health and must be considered as a relevant factor in future manifestations of psychiatric and associated health consequences.

Introduction: The Science of Stress

[...]in addition to the direct biological consequences of SARS-CoV2 infection on the brain, chronic stress associated with the COVID-19 pandemic impacts similar neuronal signaling pathways in the CNS and PNS that hamper normal physiological function. Davis et al. examine how increased reactive oxygen species in the embryonic brain generated due to prenatal stress affect the morphology and activity of neuronal cells during development and in mature brains. Available from:https://www.apa.org/news/press/releases/stress/2020/report-october World Health Organization. .2013..Who releases guidance on mental health care after trauma..

Development and validation of a stress response measure: the Daily Stress Response Scale (DSRS)

BACKGROUND To date, there is a lack of measures for capturing a broad spectrum of psychophysiological stress reactions that can be administered on a daily basis and in different contexts. A need for such a measure is especially salient in settings where stress processes can unfold momentarily and substantially fluctuate daily. Therefore, the main aim of the current study was to develop and validate the Daily Stress Response Scale (DSRS), an instrument capturing a broad spectrum of psychophysiological stress reactions that can be administered in real time and in different contexts. PARTICIPANTS AND PROCEDURE The study was conducted in the early stages of the COVID-19 pandemic in Europe. Participants were 7228 (81% female) Polish university students. The data were collected anonymously through self-completion questionnaires. The DSRS was subject to confirmatory factor analyses (CFA). RESULTS The DSRS is a 30-item, easy-to-use stress response measure with excellent psychometric properties. Based on CFA results, the scale consists of two subscales, psychological and physiological stress response, which form associations with related external criteria. CONCLUSIONS The DSRS is a reliable and valid measure of psychological and physiological stress reactions that can be used to assess the stress response to daily stressors, including those of an acute nature, such as a crisis, trauma, or surgery. © 2022 Revista Latinoamericana de Ciencias Sociales, Ninez y Juventud. All rights reserved.

Social environment as a modulator of immunosenescence.

Immune system aging, a process known as immunosenescence, involves a striking rearrangement affecting all immune cells, resulting in an increased rate of infections and a major incidence of autoimmune diseases and cancer. Nonetheless, differences in how individuals of the same chronological age carry out this immunosenescence establishment and thus the aging rate have been reported. In the context of neuroimmunoendocrine communication and its role in the response to stress situations, growing evidence suggests that social environments profoundly influence all physiological responses, especially those linked to immunity. Accordingly, negative contexts (loneliness in humans/social isolation in rodents) were associated with immune impairments and decreased lifespan. However, positive social environments have been correlated with adequate immunity and increased lifespan. Therefore, the social context in which an individual lives is proposed as a decisive modulator of the immunosenescence process and, consequently, of the rate of aging. In this review, the most important findings regarding how different social environments (negative and positive) modulate immunosenescence and therefore the aging rate, as well as the role of stress responses, hormesis, and resilience in these environments will be explained. Finally, several possible molecular mechanisms underlying the effects of negative and positive environments on immunosenescence will be suggested.

The effects of momentary loneliness and COVID-19 stressors on hypothalamic-pituitary adrenal (HPA) axis functioning: A lockdown stage changes the association between loneliness and salivary cortisol.

The COVID-19 pandemic can be characterized as a chronic stressor affecting the hypothalamic-pituitary-adrenal (HPA) axis, indexed by glucocorticoids (e.g., cortisol). We investigated whether salivary cortisol level is increased during a lockdown and whether a lockdown condition affects the association between loneliness, specific COVID-19 related stressors and salivary cortisol level. We conducted a smartphone-based ecological momentary assessment (EMA) study with 280 participants in Germany who experienced at least mild loneliness and distress amid COVID-19 from August 2020 to March 2021. We measured their momentary loneliness and COVID-related stressors including worries, information seeking behaviors and feelings of restriction during "no-lockdown" or "lockdown" stages amid COVID-19. Their salivary cortisol was measured 4 times on the last day of a 7-day EMA study. We found a significant increase in salivary cortisol levels during lockdown compared to no-lockdown. Lockdown stage was found to moderate the relationship between momentary loneliness and salivary cortisol level, i.e., loneliness was positively related to cortisol level specifically during lockdown. Mechanisms explaining the effect of forced social isolation on the association between loneliness and salivary cortisol need to be investigated in future studies.

Soluble RAGE as a Prognostic Marker of Worsening in Patients Admitted to the ICU for COVID-19 Pneumonia: A Prospective Cohort Study.

BACKGROUND: The different waves of SARS-CoV-2 infection have strained hospital resources and, notably, intensive care units (ICUs). Identifying patients at risk of developing a critical condition is essential to correctly refer patients to the appropriate structure and to spare limited resources. The soluble form of RAGE (sRAGE), the endoplasmic stress response and its surrogates, GRP78 and VEGF-A, may be interesting markers. METHODS: This was a prospective monocenter cohort study of adult patients admitted to the ICU for severe COVID-19 pneumonia. The plasma levels of sRAGE, GRP78 and VEGF-A were measured within the first 24 h. Patients were classified as critical if they further needed vasopressor therapy, renal replacement therapy, or invasive mechanical ventilation, or died during their ICU stay, and were otherwise classified as not critical. RESULTS: A total of 98 patients were included and 39 developed a critical condition. Critical patients presented higher sRAGE (626 [450-1043] vs. 227 [137-404] pg/mL, p < 0.0001), interleukin-6 (43 [15-112] vs. 11 [5-20] pg/mL, p < 0.0001), troponin T (17 [9-39] vs. 10 [6-18] pg/mL, p = 0.003) and NT-pro-BNP (321 [118-446] vs. 169 [63-366] pg/mL, p = 0.009) plasma levels. No difference was observed for VEGF-A and GRP78. The variables independently associated with worsening in the ICU were sRAGE (1.03 [1.01-1.05] per 10 pg/mL) and age (1.7 [1.2-2.4] per 5 years). An sRAGE value of 449.5 pg/mL predicted worsening with a sensitivity of 77% and a specificity of 80%. CONCLUSION: sRAGE may allow the identification of patients at risk of developing a critical form of COVID-19 pneumonia, and thus may be useful to correctly refer patients to the appropriate structure of care.

MINI REVIEW: ASSOCIATION BETWEEN SERUM CORTISOL LEVELS AND COVID-19 DISEASE

Serum cortisol concentration indicates the severity of the underlying condition. More severe disease results in increased cortisol concentrations in the blood, increasing the probability of a catastrophic outcome. A high level of serum cortisol is found in patients with community-acquired pneumonia, and these patients are more likely to develop major complications and death. Corticosteroids are endogenous hormones that are produced by the hypothalamus pituitary adrenal pathway, which is involved for stress response. Considering, known risk factors of endocrine disturbance, there has been minimal discussion on measuring the serum cortisol concentration in COVID-19 patients. SARS-CoV-2 mediated pathogenetic pathways, may also affect endogenous steroid synthesis, particularly cortisol. For the purpose of improving survival rate in severe COVID-19 individuals, we discuss briefly about the current and new findings in the support of measuring the serum cortisol levels in severe COVID-19 individuals and facilitate better treatment management in this article.

Moderating Role of Resilience Between Depression and Stress Response of Vocational Middle School Students During the COVID-19 Pandemic.

Object: In this study, we aimed to explore the influences of stress responses and psychological resilience on depression of vocational middle school students during the initial COVID-19 outbreak in China. Methods: An online questionnaire survey on the students of a medical school in Jiangxi Province, China, and obtained 3,532 valid questionnaires. A self-compiled general situation questionnaire, Stress Response of COVID-19 Questionnaire, the Resilience Scale for Chinese Adolescents and Center for Epidemiological Studies Depression Scale (CES-D) were used. Hierarchical regression analysis was used to explore the regulatory role of psychological resilience between stress response and depression. Results: (1) There were significant differences in gender between vocational middle school students' evaluation (t = 3.07, P = 0.002) and defense (t = 3.28, P = 0.001) of the pandemic. Males had higher cognitive evaluation of the pandemic than females, and females had more defense against the pandemic than males. (2) There is a significant difference between vocational middle school students from different grades in depression level (F = 3.62, P = 0.03), pneumonia defense (F = 13.65, P < 0.001) and pneumonia panic (F = 3.10, P = 0.045). (3) Depression level (F = 7.17, P < 0.001), pneumonia evaluation (F = 2.78, P = 0.04) and pneumonia panic (F = 3.32, P = 0.02) of the students concerning the spatial distance of the pandemic. (4) The severity of urban pandemic affects the evaluation of pneumonia among vocational middle school students. (5) Depression was negatively correlated with psychological resilience and pneumonia evaluation, and positively correlated with pneumonia panic. Psychological resilience was positively correlated with pneumonia evaluation and pneumonia defense, and negatively correlated with pneumonia panic. (6) Psychological resilience could reduce the level of depression caused by pneumonia evaluation and pneumonia panic. Conclusion: There were significant differences in depression level and stress responses in grades, gender and spatial distance of pandemic. Resilience has a significant negative moderator effect on the relationship between pandemic panic and depression. Resilience has a significant positive moderator effect on the relationship between pandemic evaluation and depression.

PRE-EXPOSURE TO ALCOHOL IMPAIRS ANTI-COVID DRUGS TREATMENTASSOCIATED CELLULAR STRESS RESPONSES IN LIVER CELLS

As the delta and omicron SARS-CoV-2 variants spread across the world, more tools to fight off serious infection have been developed. COVID antiviral drugs that can be taken orally at home could cut serious illness and reduce the risk of hospitalization and death. However, significant population of people consume alcohol before the infection and use of the antiviral drugs, which could potentiate side effects of the drugs on the liver. We investigated the role of alcohol in anti-Covid drug-induced stress responses in live cells. METHODS: HepG2 cells or primary mouse hepatocytes (PMH) were pre-treated with alcohol (50 mMlow dose or 100 mMhigh dose) for 6-24 hours and then treated with the newly developed oral anti-Covid drugs: nirmatrelvir, ritonavir, molnupiravir, and remdesivir at 10- 30 lg/ml for 6-24 hours. Unfolded protein response (UPR)/ER stress molecular markers (e.g. IRE1 GRP78, PERK, Xbp1 and CHOP), Golgi stress response (GSR) markers of GCP60, HSP47 and TFE3, and STAT3 were measured after the treatments. Cell death was assessed through double staining the liver cells with Syntox Green and Hoesche's Blue. RESULTS: ER stress response as indicated by IRE1, Xbp1 and CHOP was insignificant or mild in either HepG2 or PMH treated individually with alcohol at the low dose, nirmatrelvir, ritonavir, molnupiravir, or remdesivir. Alcohol or remdesivir induced moderate GSR based on mRNA increase of GCP60, HSP47 and TFE3, which was accompanied with apparent Golgi fragmentation in either HepG2 or PMH. Cell death rates in HepG2 treated with alcohol, nirmatrelvir, ritonavir, molnupiravir, or remdesivir individually were less than 5%. Pre-exposure to alcohol combined with subsequent treatment with nirmatrelvir, ritonavir molnupiravir, or remdesivir significantly increased both ER stress and GSR markers and expression of phosphorylated STAT3 (p-STAT3). Most significantly, cell death rates in HepG2 or PMH were increased by 2- to 5-fold by pre-alcohol exposure plus ritonavir, nirmatrelvir, molnupiravir, or remdesivir. The organelle stress markers, p-STAT3 and cell death were all further increased in alcoholand anti-Covid drug-treated HepG2 or primary mouse hepatocytes that were pre-infected with the lentiviruses that were pseudotyped with the SARS-CoV-2 spike protein. CONCLUSION: Our results indicate that pre-exposure to alcohol potentiates the liver cells to anti-Covid-19 drugs induced stress responses and cell death.

Differences in college students' occupational dysfunction and mental health considering trait and state anxiety during the COVID-19 pandemic.

Background: Due to the COVID-19 pandemic, university education has shifted from face-to-face classes to online and distance learning. Effects of exposure may manifest in terms of psychological, cognitive, or musculoskeletal impairments that affect an individual's daily functioning and quality of life. There is a dearth of studies exploring anxiety states, occupational dysfunction, and mental health associated with the new standard of increased telecommunication. Accordingly, the present study aimed to identify the differences in occupational dysfunction, health literacy, positive and negative emotions, and stress response considering the anxiety states of college students during the COVID-19 pandemic. Another purpose is to identify relationships among the parameters such as occupational dysfunction and mental health. Methods: This cross-sectional study included 358 students (average age: 18.5 years, age range: 18-29 years). Five tools were used: the State-Trait Anxiety Inventory (STAI), Classification and Assessment of Occupational Dysfunction (CAOD), European Health Literacy Survey Questionnaire (HLS-EU-Q47), Profile of Mood States 2nd Edition (POMS-2), and Stress Response Scale-18 (SRS-18). Based on the cutoff value of state and trait anxiety of the STAI, the participants were classified into four groups and compared using one-way analysis of variance and multiple comparison tests. The relationship between all parameters was analyzed using Pearson's correlation coefficient. Results: The group with high trait anxiety and high state anxiety had the highest CAOD total score, Total Mood Disturbance score on the POMS-2, SRS-18 score, and scores on many sub-items of the three parameters. The prevalence of occupational dysfunction was 47% for university students, and there was a variation of from 19 to 61% in each group. The correlation coefficients of the state and trait anxiety scores of the STAI, Total Mood Disturbance score, and SRS-18 ranged from .64 to .75. Additionally, the correlation coefficient between the CAOD total score and these parameters ranged from .44 to .48. Conclusion: The prevalence of occupational dysfunction was highest in the group with high trait anxiety and high state anxiety, and occupational dysfunction, negative emotions, and stress responses were strongest in this group. Our findings point to potential areas for targeted support and interventions.

Association of Self-Leadership With Acute Stress Responses and Acute Stress Disorders in Chinese Medics During the COVID-19 Pandemic: A Cross-Sectional Study.

Background: The outbreak of the highly infectious coronavirus disease 2019 (COVID-19) renders a huge physical and psychological risk to the public, especially to the medics. Additionally, self-leadership has proven to improve self-efficacy and mediate tension, such as nervousness and depression. Therefore, a cross-sectional survey was conducted to explore the association of self-leadership with acute stress responses (ASRs) and acute stress disorders (ASDs) in medics during the COVID-19 epidemic. Methods: Self-reported online questionnaires were administered, and 627 participants were finally included. The data were analyzed using the univariate analysis and the logistical regression model to identify whether self-leadership and sociodemographic and epidemic characteristics were associated with mental health, including ASRs and ASDs. Results: Initially, 790 medics responded. Of these, 627 remained after excluding for invalid questionnaires and those with a substantial amount of missing data. Therefore, the participation validity rate was 79.37%. Frontline medical staff (ß = 0.338; p < 0.001), possibility of infection among people around the medic being mild (ß = 0.141; p < 0.001), subjective estimation of epidemic duration being 3-6 months (ß = 0.074; p < 0.05), self-sets (ß = -0.022; p < 0.001), self-punishment (ß = 0.229; p < 0.001), belief hypothesis and evaluation (ß = -0.147; p < 0.05), and successful foresight (ß = 0.105; p < 0.05) were statistically significant with ASRs. Marital status [adjusted odds ratio (AOR) =1.813; 95% CI (1.141, 2.881); p = 0.012], being a frontline worker [AOR = 25.760; 95% CI (14.220, 46.667); p < 0.001], visiting Hubei in the previous 14 days [AOR = 3.656; 95% CI (1.500, 8.911); p = 0.004], self-punishment [AOR = 1.352; 95% CI (1.180, 1.548); p < 0.001], and self-dialogue [AOR = 1.256; 95% CI (11.063, 1.483); p = 0.007] were the risk factors for ASD. Conversely, having frontline medical staff in one's family [AOR = 0.523; 95% CI (0.297, 0.923); p = 0.025], self-sets [AOR = 0.814; 95% CI (0.715, 0.826); p = 0.002], and belief hypothesis and evaluation [AOR = 0.796; 95% CI (0.672, 0.943); p = 0.038] were the protective factors. Conclusion: The special working environment of the COVID-19 epidemic resulted in ASR and ASD. Notably, findings revealed a positive association between ASR symptoms and frontline medical staff, the subjective estimation of epidemic duration, self-punishment, and successful foresight. Nevertheless, marital status, having visited Hubei in the previous 14 days, and self-dialogue were the risk factors accounting for ASD symptoms. Surprisingly, having frontline medical staff in one's family, self-sets, and belief hypothesis and evaluation had potential benefits for ASD symptoms.