Association of hair cortisol concentration with brain-derived neurotrophic factor gene methylation: The role of sex as a moderator.

Hair cortisol concentration (HCC) reflects the long-term activity of the hypothalamus-pituitary-adrenal (HPA) axis in response to stress. Brain-derived neurotrophic factor DNA methylation (BDNF DNAM) may affect HCC, and sex and Val66Met may contribute to this association. Thus, the aim of this study was to investigate the associations between HCC and Brain-derived neurotrophic factor (BDNF) DNAM, and the moderating effects of Val66Met and sex. We recruited 191 healthy young participants (96 women, mean age 23.0 ± 2.6 years) and collected body samples to evaluate HCC, and to determine BDNF DNAM and Val66Met genotypes. We analyzed the effects of BDNF DNAM, sex, and Val66Met on HCC. We also evaluated the associations between BDNF DNAM and HCC in groups separated by sex and genotypes. We found a marked association of BDNF DNAM with HCC across men and women. After dividing the data by sex, a positive correlation of HCC with BDNF DNAM was found only in women. There was no substantial moderation effect of Val66Met genotypes on the association between BDNF DNAM and HCC. Therefore, BDNF DNAM was found to have positive association with HCC only in healthy young women, indicating that sex moderates the association of BDNF DNAM with long-term HPA axis activity.

Prevalence and Associated Factors of Depression and Anxiety Among Healthcare Workers During the Coronavirus Disease 2019 Pandemic: A Nationwide Study in Korea.

BACKGROUND: A healthcare system's collapse due to a pandemic, such as the coronavirus disease 2019 (COVID-19), can expose healthcare workers (HCWs) to various mental health problems. This study aimed to investigate the impact of the COVID-19 pandemic on the depression and anxiety of HCWs. METHODS: A nationwide questionnaire-based survey was conducted on HCWs who worked in healthcare facilities and public health centers in Korea in December 2020. Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) were used to measure depression and anxiety. To investigate factors associated with depression and anxiety, stepwise multiple logistic regression analysis was performed. RESULTS: A total of 1,425 participating HCWs were included. The mean depression score (PHQ-9) of HCWs before and after COVID-19 increased from 2.37 to 5.39, and the mean anxiety score (GAD-7) increased from 1.41 to 3.41. The proportion of HCWs with moderate to severe depression (PHQ-9 ≥ 10) increased from 3.8% before COVID-19 to 19.5% after COVID-19, whereas that of HCWs with moderate to severe anxiety (GAD-7 ≥ 10) increased from 2.0% to 10.1%. In our study, insomnia, chronic fatigue symptoms and physical symptoms after COVID-19, anxiety score (GAD-7) after COVID-19, living alone, and exhaustion were positively correlated with depression. Furthermore, post-traumatic stress symptoms, stress score (Global Assessment of Recent Stress), depression score (PHQ-9) after COVID-19, and exhaustion were positively correlated with anxiety. CONCLUSION: In Korea, during the COVID-19 pandemic, HCWs commonly suffered from mental health problems, including depression and anxiety. Regularly checking the physical and mental health problems of HCWs during the COVID-19 pandemic is crucial, and social support and strategy are needed to reduce the heavy workload and psychological distress of HCWs.

Optogenetic control of mRNA condensation reveals an intimate link between condensate material properties and functions.

Biomolecular condensates, often assembled through phase transition mechanisms, play key roles in organizing diverse cellular activities. The material properties of condensates, ranging from liquid droplets to solid-like glasses or gels, are key features impacting the way resident components associate with one another. However, it remains unclear whether and how different material properties would influence specific cellular functions of condensates. Here, we combine optogenetic control of phase separation with single-molecule mRNA imaging to study relations between phase behaviors and functional performance of condensates. Using light-activated condensation, we show that sequestering target mRNAs into condensates causes translation inhibition. Orthogonal mRNA imaging reveals highly transient nature of interactions between individual mRNAs and condensates. Tuning condensate composition and material property towards more solid-like states leads to stronger translational repression, concomitant with a decrease in molecular mobility. We further demonstrate that ß-actin mRNA sequestration in neurons suppresses spine enlargement during chemically induced long-term potentiation. Our work highlights how the material properties of condensates can modulate functions, a mechanism that may play a role in fine-tuning the output of condensate-driven cellular activities.

Thermodynamic modulation of gephyrin condensation by inhibitory synapse components.

Phase separation drives compartmentalization of intracellular contents into various biomolecular condensates. Individual condensate components are thought to differentially contribute to the organization and function of condensates. However, how intermolecular interactions among constituent biomolecules modulate the phase behaviors of multicomponent condensates remains unclear. Here, we used core components of the inhibitory postsynaptic density (iPSD) as a model system to quantitatively probe how the network of intra- and intermolecular interactions defines the composition and cellular distribution of biomolecular condensates. We found that oligomerization-driven phase separation of gephyrin, an iPSD-specific scaffold, is critically modulated by an intrinsically disordered linker region exhibiting minimal homotypic attractions. Other iPSD components, such as neurotransmitter receptors, differentially promote gephyrin condensation through distinct binding modes and affinities. We further demonstrated that the local accumulation of scaffold-binding proteins at the cell membrane promotes the nucleation of gephyrin condensates in neurons. These results suggest that in multicomponent systems, the extent of scaffold condensation can be fine-tuned by scaffold-binding factors, a potential regulatory mechanism for self-organized compartmentalization in cells.

New-onset mental illness and long-term survival in survivors of critical illness: population-based cohort study in South Korea.

BACKGROUND: Critical care unit (CCU) survivors have a high risk of developing mental illness. AIMS: We aimed to examine the incidence and associated factors of newly developed mental illness among CCU survivors of critical illness. Moreover, we examined the association between newly developed mental illness and 2-year all-cause mortality. METHOD: All adult patients (≥20 years) who were admitted to the CCU during hospitalisation between 2010 and 2018 and survived for 1 year were defined as CCU survivors and were included in this nationwide population-based cohort study. CCU survivors with a history of mental illness before CCU admission were excluded from the study. RESULTS: A total of 1 353 722 CCU survivors were included in the analysis; of these, 33 743 survivors (2.5%) had newly developed mental illness within 1 year of CCU admission. Old age, longer CCU stay, hospital admission through the emergency room, increased total cost of hospitalisation, mechanical ventilatory support, extracorporeal membrane oxygenation support and continuous renal replacement therapy were associated with an increased incidence of newly developed mental illness. Moreover, the newly developed mental illness group showed a 2.36-fold higher 2-year all-cause mortality rate than the no mental illness group (hazard ratio: 2.36; 95% CI: 2.30-2.42; P < 0.001). CONCLUSIONS: In South Korea, 2.5% of CCU survivors had newly developed mental illness within 1 year of CCU admission. Moreover, newly developed mental illness was associated with an increased 2-year all-cause mortality.

Insomnia disorder and cancer mortality in South Korea: a secondary analysis of musculoskeletal disease cohort.

PURPOSE: The association between insomnia disorder and cancer-related mortality risk remains controversial. Therefore, this study aimed to investigate the correlation between insomnia disorder and cancer-related mortality. METHODS: Patients who were diagnosed with musculoskeletal disease (MSD) between 2010 and 2015 were included in this study as a secondary analysis of a patient cohort with MSD in South Korea. Cancer mortality was evaluated between January 1, 2016, and December 31, 2020, using multivariable Cox regression modeling. Patients with and without insomnia disorder constituted the ID and non-ID groups, respectively. RESULTS: The final analysis incorporated a total of 1,298,314 patients diagnosed with MSDs, of whom 11,714 (0.9%) died due to cancer. In the multivariable Cox regression model, the risk of total cancer-related mortality was 14% (hazard ratio [HR], 1.14; 95% confidence interval [CI], 1.10-1.19; P < 0.001) higher in the ID group than in the non-ID group. Moreover, the ID group had a higher risk of mortality due to esophageal (HR, 1.46; 95% CI, 1.08-1.96; P = 0.015), colorectal (HR, 1.20; 95% CI, 1.05-1.36; P = 0.007), head and neck (HR, 1.39; 95% CI, 1.01-1.94; P = 0.049), lung (HR, 1.17; 95% CI, 1.08-1.27; P < 0.001), and female genital organ (HR: 1.39, 95% CI: 1.09, 1.77; P = 0.008) cancers; leukemia; and lymphoma (HR, 1.30; 95% CI, 1.12-1.49; P < 0.001). CONCLUSION: Insomnia disorder was associated with elevated overall cancer mortality in patients with MSDs, which was more evident for cancer mortality due to esophageal, colorectal, head and neck, lung, and female genital organ cancers; leukemia; and lymphoma.

Predicting delirium and the effects of medications in hospitalized COVID-19 patients using machine learning: A retrospective study within the Korean Multidisciplinary Cohort for Delirium Prevention (KoMCoDe).

Objective: Delirium is commonly reported from the inpatients with Coronavirus disease 2019 (COVID-19) infection. As delirium is closely associated with adverse clinical outcomes, prediction and prevention of delirium is critical. We developed a machine learning (ML) model to predict delirium in hospitalized patients with COVID-19 and to identify modifiable factors to prevent delirium. Methods: The data set (n = 878) from four medical centers was constructed. Total of 78 predictors were included such as demographic characteristics, vital signs, laboratory results and medication, and the primary outcome was delirium occurrence during hospitalization. For analysis, the extreme gradient boosting (XGBoost) algorithm was applied, and the most influential factors were selected by recursive feature elimination. Among the indicators of performance for ML model, the area under the curve of the receiver operating characteristic (AUROC) curve was selected as the evaluation metric. Results: Regarding the performance of developed delirium prediction model, the accuracy, precision, recall, F1 score, and the AUROC were calculated (0.944, 0.581, 0.421, 0.485, 0.873, respectively). The influential factors of delirium in this model included were mechanical ventilation, medication (antipsychotics, sedatives, ambroxol, piperacillin/tazobactam, acetaminophen, ceftriaxone, and propacetamol), and sodium ion concentration (all p < 0.05). Conclusions: We developed and internally validated an ML model to predict delirium in COVID-19 inpatients. The model identified modifiable factors associated with the development of delirium and could be clinically useful for the prediction and prevention of delirium in COVID-19 inpatients.

Spiritual Care Guide in Hospice∙Palliative Care.

The Spiritual Care Guide in Hospice∙Palliative Care is evidence-based and focuses on the universal and integral aspects of human spirituality-such as meaning and purpose, interconnectedness, and transcendence-which go beyond any specific religion. This guide was crafted to improve the spiritual well-being of adult patients aged 19 and older, as well as their families, who are receiving end-of-life care. The provision of spiritual care in hospice and palliative settings aims to assist patients and their families in finding life's meaning and purpose, restoring love and relationships, and helping them come to terms with death while maintaining hope. It is recommended that spiritual needs and the interventions provided are periodically reassessed and evaluated, with the findings recorded. Additionally, hospice and palliative care teams are encouraged to pursue ongoing education and training in spiritual care. Although challenges exist in universally applying this guide across all hospice and palliative care organizations in Korea-due to varying resources and the specific environments of medical institutions-it is significant that the Korean Society for Hospice and Palliative Care has introduced a spiritual care guide poised to enhance the spiritual well-being and quality of care for hospice and palliative care patients.

Suicidal Thinking Among Patients With Spinal Conditions in South Korea: A Population-Based Cross-Sectional Study.

OBJECTIVE: Chronic pain increases the risk of suicide because it is often accompanied by depressive symptoms. However, the existing information regarding suicidal thinking in patients with chronic pain such as spinal conditions is insufficient. We aimed to examine the prevalence of suicidal thinking and the factors associated with it among patients with spinal conditions. METHODS: Data from the National Health Insurance Service database in South Korea were used in this population-based, cross-sectional study, and 2.5% of adult patients diagnosed with spinal conditions (low back pain and/or neck pain) between 2018 and 2019 were selected using a stratified random sampling technique. Patient Health Questionnaire-9 was used to determine the presence of suicidal thoughts and depressive symptoms. RESULTS: 33,171 patients with spinal conditions were included in this study. Among them, 5.9% had suicidal thinking and 20.7% had depressive symptoms. In the multivariable logistic regression model, old age, male sex, and employment were associated with a decreased prevalence of suicidal thinking. Current smokers, previous smokers, medical aid program recipients, and patients with mild-to-moderate or severe disability showed increased suicidal thinking. Underlying depression, bipolar disorder, insomnia disorder, and substance abuse were also associated with increased suicidal thinking. CONCLUSION: In South Korea, 5.9% and 20.7% of patients with spinal conditions had suicidal thoughts and depressive symptoms, respectively. Some factors were associated with an increased prevalence of suicidal thoughts among patients with spinal conditions. Our results suggest that screening for these factors can help prevent suicide in patients with spinal conditions.

Statistical modeling of mRNP transport in dendrites: A comparative analysis of ß-actin and Arc mRNP dynamics.

Localization of messenger RNA (mRNA) in dendrites is crucial for regulating gene expression during long-term memory formation. mRNA binds to RNA-binding proteins (RBPs) to form messenger ribonucleoprotein (mRNP) complexes that are transported by motor proteins along microtubules to their target synapses. However, the dynamics by which mRNPs find their target locations in the dendrite have not been well understood. Here, we investigated the motion of endogenous ß-actin and Arc mRNPs in dissociated mouse hippocampal neurons using the MS2 and PP7 stem-loop systems, respectively. By evaluating the statistical properties of mRNP movement, we found that the aging Lévy walk model effectively describes both ß-actin and Arc mRNP transport in proximal dendrites. A critical difference between ß-actin and Arc mRNPs was the aging time, the time lag between transport initiation and measurement initiation. The longer mean aging time of ß-actin mRNP (~100 s) compared with that of Arc mRNP (~30 s) reflects the longer half-life of constitutively expressed ß-actin mRNP. Furthermore, our model also permitted us to estimate the ratio of newly generated and pre-existing ß-actin mRNPs in the dendrites. This study offers a robust theoretical framework for mRNP transport, which provides insight into how mRNPs locate their targets in neurons.

Cortical astrocytes modulate dominance behavior in male mice by regulating synaptic excitatory and inhibitory balance.

Social hierarchy is established as an outcome of individual social behaviors, such as dominance behavior during long-term interactions with others. Astrocytes are implicated in optimizing the balance between excitatory and inhibitory (E/I) neuronal activity, which may influence social behavior. However, the contribution of astrocytes in the prefrontal cortex to dominance behavior is unclear. Here we show that dorsomedial prefrontal cortical (dmPFC) astrocytes modulate E/I balance and dominance behavior in adult male mice using in vivo fiber photometry and two-photon microscopy. Optogenetic and chemogenetic activation or inhibition of dmPFC astrocytes show that astrocytes bidirectionally control male mouse dominance behavior, affecting social rank. Dominant and subordinate male mice present distinct prefrontal synaptic E/I balance, regulated by astrocyte activity. Mechanistically, we show that dmPFC astrocytes control cortical E/I balance by simultaneously enhancing presynaptic-excitatory and reducing postsynaptic-inhibitory transmission via astrocyte-derived glutamate and ATP release, respectively. Our findings show how dmPFC astrocyte-neuron communication can be involved in the establishment of social hierarchy in adult male mice.

Association between Depression and Mortality in Patients with Pain Conditions: A South Korean Nationwide Cohort Study.

PURPOSE: Patients with pain conditions may experience depression that greatly complicates treatment. In this study, we examined risk factors for depression in patients with pain conditions and associations between depression and long-term mortality in such patients. MATERIALS AND METHODS: Data from the National Health Insurance Service database in South Korea were used in this cohort study. A total of 2.5% of adult patients diagnosed with pain conditions in 2010 were selected using a stratified random sampling technique and included for analysis. We performed multivariate logistic regression modelling to identify risk factors associated with depression and multivariate Cox regression modelling to determine whether depression is associated with 10-year survival outcomes in patients with pain conditions. RESULTS: In total, data from 1808043 patients with pain conditions in 2010 were analyzed. Among them, 70148 (3.9%) patients had depression. Multivariate logistic regression modelling identified older age, comorbidities, analgesics, female sex, living in an urban area, and other underlying psychiatric morbidities as potential risk factors for depression in patients with pain conditions. Multivariate Cox regression revealed that 10-year all-cause mortality in patients with depression was 1.13-fold (hazard ratio, 1.13; 95% confidence interval, 1.11-1.16; p<0.001) higher than that in patients without depression and pain conditions. CONCLUSION: We identified a few potential risk factors for depression among South Korean patients with pain conditions. Depression was associated with elevated 10-year all-cause mortality in patients with pain conditions.

How Can We Deal with Psychosocial Issues in an Emerging Infectious Disease Outbreak? Lessons from a Qualitative Study for the MERS Outbreak in Korea.

BACKGROUND: The 2015 Middle East respiratory syndrome (MERS) coronavirus outbreak in Korea led to profound emotional and social burdens, especially in patients and health care professionals. MATERIALS AND METHODS: Focus group interviews were conducted with 2 patients, 1 family member and 6 health care professionals about psychological distress related to MERS in 2017 and analyzed the interview data using the consensual qualitative research method. RESULTS: Four domains and 17 core ideas were identified within three interview groups, including psychological distress during the outbreak, problems regarding the response to the outbreak, positive experiences, and future directions for enhancing intervention to improve mental health and prevent psychosocial problems during the outbreak. Psychological consequences were affected by the characteristics of the emerging infectious disease and the structure and process of institutional or governmental response to the MERS outbreak. Mental health services and psychosocial support reduced the negative impact on psychological distress. CONCLUSION: The MERS outbreak in 2015 gave rise to emotional and social injuries to patients and health care professionals, some of which can be long-lasting constraints in their lives. Preparedness in a society's response to a pandemic considering mental health in related parties can minimize negative psychological consequences and enhance resilience at the individual and society levels.

Association between Preoperative Psychiatric Morbidities and Mortality after Oncologic Surgery: A Nationwide Cohort Study from 2002 to 2019 in South Korea.

We aimed to examine whether preoperative psychiatric morbidities affect 30-day postoperative mortality. Using a nationwide registration database in South Korea, the study included all patients who underwent curative cancer surgery from 1 January 2002 to 31 December 2019. Patients underwent surgery for breast, laryngeal, lung, thyroid, gastric, colorectal, esophageal, liver, pancreatic, kidney, bladder, testicular, prostate, vulvar, uterine, or brain cancer. Depression, anxiety disorder, substance abuse, and post-traumatic stress disorder were considered preoperative psychiatric morbidities. Among the 944,794 patients in the final analysis, 5490 (0.6%) died within 30 days of the surgery, and 24,370 (2.6%) had preoperative psychiatric morbidities. Multivariable logistic regression analysis showed that preoperative psychiatric morbidities were associated with a higher (adjusted odds ratio [aOR]: 1.23; 95% confidence interval [CI]: 1.09, 1.39; p = 0.001) 30-day mortality rate than the rate noted for patients without preoperative psychiatric morbidities. This association was significant in the breast (aOR: 3.31, 95% CI: 1.36, 8.07; p = 0.009), lung (aOR: 1.54, 95% CI: 1.19, 2.01; p = 0.001), and kidney (aOR: 1.87, 95% CI: 1.06, 3.31; p = 0.03) cancer groups in the subgroup analyses. In South Korea, preoperative psychiatric morbidities are considered to be associated with increased 30-day postoperative mortality.

Moral Distress Regarding End-of-Life Care Among Healthcare Personnel in Korean University Hospitals: Features and Differences Between Physicians and Nurses.

BACKGROUND: Healthcare professionals often experience moral distress while providing end-of-life care. This study explored how physicians and nurses experienced moral distress when they cared for critically and terminally ill patients in tertiary hospitals in South Korea. METHODS: This study used semi-structured in-depth interviews. A total of 22 people in two tertiary hospitals were interviewed, nine (40.9%) of which were physicians and 13 (59.1%) were nurses. The recorded interview files and memos were analyzed using grounded theory. RESULTS: Most physicians and nurses encountered similar feelings of anger, helplessness, and burden owing to a lack of appropriate resources for end-of-life care. However, the factors and contexts of their moral distress differed. Nurses mainly addressed poorly organized end-of-life care, intensive labor conditions without support for nurses, and providing care without participation in decision-making. Meanwhile, physicians addressed the prevailing misperceptions on end-of-life care, communication failure between physicians owing to hierarchy and fragmented disciplines, the burden of responsibility in making difficult decisions, and the burden of resource allocation. CONCLUSION: Differences in moral distress between physicians and nurses leave them isolated and can affect communication regarding healthcare. Mutual understanding between job disciplines will enhance their communication and help resolve conflicts in end-of-life care.

Ethical Issues Referred to Clinical Ethics Support at a University Hospital in Korea: Three-Year Experience After Enforcement of Life-Sustaining Treatment Decisions Act.

BACKGROUND: Clinical ethics support is a form of preventive ethics aimed at mediating ethics-related conflicts and managing ethical issues arising in the healthcare setting. However, limited evidence exists regarding the specific ethical issues in clinical practice. This study aimed to explore the diverse ethical issues of cases referred to clinical ethics support after the new legislation on hospice palliative care and end-of-life decision-making was implemented in Korea in 2018. METHODS: A retrospective study of cases referred to clinical ethics support at a university hospital in Korea from February 2018 to February 2021 was conducted. The ethical issues at the time of referral were analyzed via qualitative content analysis of the ethics consultation-related documents. RESULTS: A total of 60 cases of 57 patients were included in the study, of whom 52.6% were men and 56.1% were older than 60 years of age. The majority of cases (80%) comprised patients from the intensive care unit. One-third of the patients were judged as being at the end-of-life stage. The most frequent ethical categories were identified as goals of care/treatment (78.3%), decision-making (75%), relationship (41.7%), and end-of-life issues (31.7%). More specifically, best interests (71.7%), benefits and burdens/harms (61.7%), refusal (53.3%), and surrogate decision-making (33.3%), followed by withholding or withdrawal (28.3%) were the most frequent ethical issues reported, which became diversified by year. In addition, the ethical issues appeared to differ by age group and judgment of the end-of-life stage. CONCLUSION: The findings of this study expand the current understanding of the diverse ethical issues including decision-making and goals of care/treatment that have been referred to clinical ethics support since the enforcement of the new legislation in Korea. This study suggests a need for further research on the longitudinal exploration of ethical issues and implementation of clinical ethics support in multiple healthcare centers.

Resting-state heart rate variability, level of stress and resilience in internet gaming disorder and alcohol use disorder.

Stress and resilience are involved in the pathophysiology of addictive disorders, and heart rate variability (HRV) is an index of an individual's global capability to regulate psychological responses. In this study, we aimed to identify transdiagnostic and disorder-specific markers in people with addictive disorders by analyzing resting-state HRV and associations with the levels of stress and resilience. We compared relevant data between patients with internet gaming disorder (IGD) and/or alcohol use disorder (AUD) and healthy controls (HCs). In all, 163 adults aged 18-35 years (53 with IGD, 49 with AUD, 61 HCs) participated. The levels of stress and resilience were measured using the Psychosocial Wellbeing Index and the Connor-Davidson Resilience Scale, respectively. The HRV was obtained from each participant during a 5 min resting-state. The IGD and AUD patients exhibited increased levels of stress and decreased resilience compared to the HCs. Patients with either addictive disorder exhibited a lower standard deviation of the normal-to-normal beat interval (SDNN) index [SDNNi] compared to HCs even after adjusting for clinical variables such as depression, anxiety, and impulsivity. In multiple comparison tests among the three groups, the AUD group had lower HRV than HCs, but no differences were observed among the groups after adjusting for the clinical variables. The HRV indices were correlated with the levels of stress, resilience, and disease severity. In conclusion, IGD and AUD patients exhibit lower HRV as indicated by the SDNNi compared to HCs, revealing their vulnerability to stress as well as a common transdiagnostic marker of addiction.

Causing trouble and being transmissible: COVID-19 survivors' experiences of stigma and discrimination in South Korea.

Background: The stigma associated with coronavirus disease (COVID-19) is relatively neglected in policies for handling the disease. Stigmatization occurs only within specific social contexts in local societies. Objective: This study aims to examine COVID-19 survivors' experiences of social stigma and discrimination in South Korea in the first 2 years of the pandemic. Methods: Semi-structured interviews were conducted. Results: Of 52 participants, 45 reported that they had to cope with stigma and discrimination in their intimate social relationships, workplaces, and children's schools, ranging from subtle actions to job loss. Sexual minorities who were involved in mass disease transmission in the early part of the pandemic experienced a higher level of stigmatization. The stigmatization dealt with in this study was related to two themes: survivors' sense of causing trouble and possibility of transmission. Conclusion: By intertwining this stigma with the experiences of public health measures through the voices of survivors, this study reveals the local context of East Asia in terms of culture-specific aspects of COVID-19-related stigma.