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.

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.

Real-time visualization of mRNA synthesis during memory formation in live mice.

Memories are thought to be encoded in populations of neurons called memory trace or engram cells. However, little is known about the dynamics of these cells because of the difficulty in real-time monitoring of them over long periods of time in vivo. To overcome this limitation, we present a genetically encoded RNA indicator (GERI) mouse for intravital chronic imaging of endogenous Arc messenger RNA (mRNA)-a popular marker for memory trace cells. We used our GERI to identify Arc-positive neurons in real time without the delay associated with reporter protein expression in conventional approaches. We found that the Arc-positive neuronal populations rapidly turned over within 2 d in the hippocampal CA1 region, whereas ∼4% of neurons in the retrosplenial cortex consistently expressed Arc following contextual fear conditioning and repeated memory retrievals. Dual imaging of GERI and a calcium indicator in CA1 of mice navigating a virtual reality environment revealed that only the population of neurons expressing Arc during both encoding and retrieval exhibited relatively high calcium activity in a context-specific manner. This in vivo RNA-imaging approach opens the possibility of unraveling the dynamics of the neuronal population underlying various learning and memory processes.

Dynamics of axonal ß-actin mRNA in live hippocampal neurons.

Localization of mRNA facilitates spatiotemporally controlled protein expression in neurons. In axons, mRNA transport followed by local protein synthesis plays a critical role in axonal growth and guidance. However, it is not yet clearly understood how mRNA is transported to axonal subcellular sites and what regulates axonal mRNA localization. Using a transgenic mouse model in which endogenous ß-actin mRNA is fluorescently labeled, we investigated ß-actin mRNA movement in axons of hippocampal neurons. We cultured neurons in microfluidic devices to separate axons from dendrites and performed single-particle tracking of axonal ß-actin mRNA. Compared with dendritic ß-actin mRNA, axonal ß-actin mRNA showed less directed motion and exhibited mostly subdiffusive motion, especially near filopodia and boutons in mature dissociated hippocampal neurons. We found that axonal ß-actin mRNA was likely to colocalize with actin patches (APs), regions that have a high density of filamentous actin (F-actin) and are known to have a role in branch initiation. Moreover, simultaneous imaging of F-actin and axonal ß-actin mRNA in live neurons revealed that moving ß-actin mRNA tended to be docked in the APs. Our findings reveal that axonal ß-actin mRNA localization is facilitated by actin networks and suggest that localized ß-actin mRNA plays a potential role in axon branch formation.

Single-Cell and Single-Molecule Analysis of Gene Expression Regulation.

Recent advancements in single-cell and single-molecule imaging technologies have resolved biological processes in time and space that are fundamental to understanding the regulation of gene expression. Observations of single-molecule events in their cellular context have revealed highly dynamic aspects of transcriptional and post-transcriptional control in eukaryotic cells. This approach can relate transcription with mRNA abundance and lifetimes. Another key aspect of single-cell analysis is the cell-to-cell variability among populations of cells. Definition of heterogeneity has revealed stochastic processes, determined characteristics of under-represented cell types or transitional states, and integrated cellular behaviors in the context of multicellular organisms. In this review, we discuss novel aspects of gene expression of eukaryotic cells and multicellular organisms revealed by the latest advances in single-cell and single-molecule imaging technology.

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.

STING facilitates nuclear import of herpesvirus genome during infection.

Once inside the host cell, DNA viruses must overcome the physical barrier posed by the nuclear envelope to establish a successful infection. The mechanism underlying this process remains unclear. Here, we show that the herpesvirus exploits the immune adaptor stimulator of interferon genes (STING) to facilitate nuclear import of the viral genome. Following the entry of the viral capsid into the cell, STING binds the viral capsid, mediates capsid docking to the nuclear pore complex via physical interaction, and subsequently enables accumulation of the viral genome in the nucleus. Silencing STING in human cytomegalovirus (HCMV)-susceptible cells inhibited nuclear import of the viral genome and reduced the ensuing viral gene expression. Overexpressing STING increased the host cell's susceptibility to HCMV and herpes simplex virus 1 by improving the nuclear delivery of viral DNA at the early stage of infection. These observations suggest that the proviral activity of STING is conserved and exploited by the herpesvirus family. Intriguingly, in monocytes, which act as latent reservoirs of HCMV, STING deficiency negatively regulated the establishment of HCMV latency and reactivation. Our findings identify STING as a proviral host factor regulating latency and reactivation of herpesviruses.

Aicardi-Goutières syndrome-associated gene SAMHD1 preserves genome integrity by preventing R-loop formation at transcription-replication conflict regions.

The comorbid association of autoimmune diseases with cancers has been a major obstacle to successful anti-cancer treatment. Cancer survival rate decreases significantly in patients with preexisting autoimmunity. However, to date, the molecular and cellular profiles of such comorbidities are poorly understood. We used Aicardi-Goutières syndrome (AGS) as a model autoimmune disease and explored the underlying mechanisms of genome instability in AGS-associated-gene-deficient patient cells. We found that R-loops are highly enriched at transcription-replication conflict regions of the genome in fibroblast of patients bearing SAMHD1 mutation, which is the AGS-associated-gene mutation most frequently reported with tumor and malignancies. In SAMHD1-depleted cells, R-loops accumulated with the concomitant activation of DNA damage responses. Removal of R-loops in SAMHD1 deficiency reduced cellular responses to genome instability. Furthermore, downregulation of SAMHD1 expression is associated with various types of cancer and poor survival rate. Our findings suggest that SAMHD1 functions as a tumor suppressor by resolving R-loops, and thus, SAMHD1 and R-loop may be novel diagnostic markers and targets for patient stratification in anti-cancer therapy.

Beyond Legal Boundaries: Public and Clinician Perspectives on Treatment Withdrawal in Infants With Poor Neurological Prognosis.

BACKGROUND: Despite medical advancements in neonatal survival rates, many children have poor neurological outcomes. Because the law in Korea restricts the withdrawal of life-sustaining treatment to only cases of imminent death, treatment discontinuation may not be an option, even in patients with poor neurological prognosis. This study investigated the opinions of the general population and clinicians regarding life-sustaining treatment withdrawal in such cases using hypothetical scenarios. METHODS: We conducted a cross-sectional study on the general population and clinicians using a web-based questionnaire. The sample of the general population from an online panel comprised 500 individuals aged 20-69 years selected by quota sampling. The clinician sample comprised 200 clinicians from a tertiary university hospital. We created hypothetical vignettes and questionnaire items to assess attitudes regarding mechanical ventilation withdrawal for an infant at risk of poor neurological prognosis due to birth asphyxia at 2 months and 3 years after the incidence. RESULTS: Overall, 73% of the general population and 74% of clinicians had positive attitudes toward mechanical ventilator withdrawal at 2 months after birth asphyxia. The proportion of positive attitudes toward mechanical ventilator withdrawal was increased in the general population (84%, P < 0.001) and clinicians (80.5%, P = 0.02) at 3 years after birth asphyxia. Religion, spirituality, the presence of a person with a disability in the household, and household income were associated with the attitudes of the general population. In the multivariable logistic regression analysis of the general population, respondents living with a person with a disability or having a disability were more likely to find the withdrawal of the ventilator at 2 months and 3 years after birth asphyxia not permissible. Regarding religion, respondents who identified as Christians were more likely to find the ventilator withdrawal at 2 months after birth asphyxia unacceptable. CONCLUSION: The general population and clinicians shared the perspective that the decision to withdraw life-sustaining treatment in infants with a poor neurological prognosis should be considered before the end of life. A societal discussion about making decisions centered around the best interest of pediatric patients is warranted.

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.

Association between insomnia disorder and mortality among patients who underwent craniotomy for brain tumor resection: a South Korean nationwide cohort study.

PURPOSE: To assess the prevalence and related factors of a newly developed insomnia disorder following craniotomy for brain tumor resection. Furthermore, we examined the association of pre- and postoperative insomnia with the 2-year mortality rate. METHODS: The South Korean national registration cohort database was used as the data source. This study includes all adult patients who underwent craniotomy for brain tumor resection from January 1, 2011, to December 31, 2017. G47.0 and F51.0 (International Statistical Classification of Diseases and Related Health Problems 10th Revision codes) were used to identify insomnia disorders. RESULTS: In total, 4,851 patients were included. Among them, 913 (18.8%) and 447 (9.2%) patients were assigned to the preoperative and postoperative insomnia groups, respectively. After modeling using multivariable logistic regression, older age (odds ratio (OR) 1.02, 95% confidence interval (CI) 1.01-1.03; P < 0.001), reoperation within 1 year (OR 2.12, 95% CI 1.47-3.06; P < 0.001), and newly acquired brain disability (OR 1.32, 95% CI 1.01-1.71; P = 0.043) were associated with an increased prevalence of newly developed postoperative insomnia disorder. After modeling using multivariable Cox regression, the preoperative and postoperative insomnia disorder groups showed a 1.17-fold (hazard ratio (HR) 1.17, 95% CI 1.02-1.34; P = 0.021) and a 1.85-fold (HR 1.85, 95% CI 1.59-2.15, P < 0.001) increased 2-year all-cause mortality risk compared to the control group, respectively. CONCLUSION: In South Korea, 9.2% of the patients with brain tumors were newly diagnosed with an insomnia disorder following craniotomy for brain tumor resection, which was associated with an increased risk of 2-year mortality.

Influence of Biogenetic Explanations of Mental Disorders on Stigma and Help-Seeking Behavior: A Systematic Review and Meta-Analysis.

BACKGROUND: Biogenetic causal explanations of mental disorders are commonly used for public education and campaigns. However, the influence of biogenetic explanations on the ideas about and attitudes toward mental illness is unclear. We examined the influence of biogenetic explanations on attitudes toward mental disorders using a meta-analytic method accompanied by subgroup analyses. METHODS: The protocol for this meta-analysis was registered in PROSPERO (CRD42020158656) in March 2020. Experimental and correlational studies were analyzed separately. Five outcome measures related to attitudes toward mental disorders were included: 'attitude toward help-seeking,' 'blame,' 'perceived dangerousness,' 'prognostic pessimism,' and 'social distance.' Subgroup analyses were performed for the type of mental disorder, population, and geographic region for which a biogenetic explanation was provided. RESULTS: A total of 44 studies were included, of which 24 were experimental and 20 were correlational. A positive attitude toward help-seeking was associated with having a biogenetic concept (d = 0.43; 95% confidence interval [CI], 0.18 to 0.67; P < 0.001) in general population and in Eastern countries in particular. Although a biogenetic explanation was associated with a decreased level of blame (d = -0.20; 95% CI, -0.38 to -0.02; P = 0.029) in the general population, it was also associated with significantly higher levels of perceived dangerousness (d = 0.13; 95% CI, 0.03 to 0.23; P = 0.008). A tendency toward a higher level of prognostic pessimism and social distance was associated with a biogenetic concept of mental disorders although there was no statistical significance. CONCLUSION: Having a biogenetic concept of the cause of mental disorders was related with a positive attitude toward help-seeking, particularly in the general population and individuals living in Eastern countries. Providing a biogenetic explanation decreased blame toward individuals with mental illness but was associated with increased perceived dangerousness and prognostic pessimism. Therefore, although a biogenetic explanation promotes public use of mental health services, it should be carefully applied to avoid an increase in negative thoughts, such as that mental illness is biologically irreversible and untreatable.

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.

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.

Pre-existing and new-onset depression among patients undergoing esophageal cancer surgery: a nationwide cohort study in South Korea.

BACKGROUND: Esophageal cancer is believed to be related to psychological stress. This study aimed to examine the prevalence and risk factors for new-onset depression after esophageal cancer surgery among patients who had no pre-existing depression. In addition, we examined whether pre-existing depression affected postoperative 1-year mortality. METHODS: The National Health Insurance Service database in South Korea was used for data extraction in this population-based cohort study. This study included all adult patients diagnosed with esophageal cancer who underwent esophageal surgery between January 1, 2011, and December 31, 2018. RESULTS: A total of 7039 adult patients who underwent esophageal cancer surgery at 95 South Korean hospitals were included in the analyses. Of the total, 608 patients (8.6%) were diagnosed with new-onset depression within 1 year after esophageal cancer surgery. Female sex, adjuvant chemotherapy, increased Charlson comorbidity index, pre-existing anxiety disorder, and pre-existing insomnia disorder were potential risk factors for new-onset depression. In multivariable Cox regression analysis, the pre-existing depression group showed a 1.27-fold (hazard ratio: 1.27; 95% confidence interval: 1.08-1.48; P = 0.004) higher risk of 1-year all-cause mortality than those who had no pre-existing depression. CONCLUSION: In South Korea, 8.6% of patients are newly diagnosed with depression after esophageal cancer surgery, and some potential risk factors have been identified. Moreover, pre-existing depression was associated with increased 1-year all-cause mortality. Patients with esophageal cancer and pre-existing depression may be at high risk, requiring interventions after esophageal cancer surgery.

Live-cell imaging of single mRNA dynamics using split superfolder green fluorescent proteins with minimal background.

The MS2 system, with an MS2 binding site (MBS) and an MS2 coat protein fused to a fluorescent protein (MCP-FP), has been widely used to fluorescently label mRNA in live cells. However, one of its limitations is the constant background fluorescence signal generated from free MCP-FPs. To overcome this obstacle, we used a superfolder GFP (sfGFP) split into two or three nonfluorescent fragments that reassemble and emit fluorescence only when bound to the target mRNA. Using the high-affinity interactions of bacteriophage coat proteins with their corresponding RNA binding motifs, we showed that the nonfluorescent sfGFP fragments were successfully brought close to each other to reconstitute a complete sfGFP. Furthermore, real-time mRNA dynamics inside the nucleus as well as the cytoplasm were observed by using the split sfGFPs with the MS2-PP7 hybrid system. Our results demonstrate that the split sfGFP systems are useful tools for background-free imaging of mRNA with high spatiotemporal resolution.

Insomnia disorder and long-term mortality in adult patients treated with extracorporeal membrane oxygenation in South Korea.

We investigated the prevalence of insomnia in extracorporeal membrane oxygenation (ECMO)-treated patients and examined the association between post-ECMO insomnia disorder and long-term mortality. In the present population-based cohort study, we used data from the National Health Insurance Claims database in South Korea. All adult patients who underwent ECMO between 2006 and 2014 were included, and ECMO-treated patients were defined as those who survived >365 days after ECMO. Insomnia disorder was identified using the International Classification of Diseases 10th Revision codes G47.0 and F51.0. Overall, 3,055 ECMO-treated patients were included in the final analysis: 431 (14.1%) had pre-ECMO insomnia disorder, while 148 (4.8%) were newly diagnosed with insomnia disorder up to 1 year after ECMO. In multivariable Cox regression model, patients with post-ECMO insomnia disorder had higher 5-year all-cause mortality (ACM) than controls (hazard ratio [HR] 1.71, 95% confidence interval [CI] 1.21-2.42; p = 0.003); however, those with pre-ECMO insomnia disorder did not (p = 0.655). In sensitivity analysis, post-ECMO insomnia disorder with underlying psychiatric illness was associated with a 2.39-fold higher 5-year ACM in ECMO-treated patients (HR 2.39, 95% CI 1.52-3.75; p < 0.001). In conclusion, at 1-year after ECMO, 4.8% of ECMO-treated patients were newly diagnosed with insomnia disorder, and post-ECMO insomnia disorder was associated with higher 5-year ACM, especially in those with underlying psychiatric illness. Our present results suggest that the development of insomnia disorder might be related to poorer long-term survival in ECMO-treated patients, especially in case of underlying psychiatric illness.

Delirium and Long-Term Outcomes among Survivors of Extracorporeal Membrane Oxygenation Therapy: A Nationwide Cohort Study in South Korea.

Background: The prevalence of delirium and its association with long-term outcomes of extracorporeal membrane oxygenation (ECMO) therapy have not yet been identified. We aimed to investigate the prevalence of delirium and its associated factors during hospitalization among ECMO survivors. We also examined whether the occurrence of delirium was associated with 1-year all-cause mortality among ECMO survivors. Methods: As a population-based cohort study, data were obtained from the National Health Insurance Service database in South Korea. Adults older than 18 years who received ECMO therapy between 2005 and 2018 were included in this study. ECMO survivors were defined as patients who were discharged from the hospital. Results: The analysis included a total of 8153 ECMO survivors, of whom 551 (6.8%) experienced delirium during hospitalization. Older age (odds ratio [OR]: 1.01, 95% confidence interval [CI]: 1.00-1.02; P = 0.004), male sex (OR: 1.38, 95% CI: 1.13-1.68; P = 0.002), underlying depression (OR: 1.90, 95% CI: 1.49-2.41; P < 0.001), and longer length of hospital stay (OR: 1.02, 95% CI: 1.02-1.03; P < 0.001) were associated with a higher incidence of delirium. In multivariable Cox regression modeling, the occurrence of delirium was not significantly associated with the risk of 1-year all-cause mortality (hazard ratio: 0.90, 95% CI: 0.76-1.07; P = 0.229). Conclusion: The prevalence of delirium among ECMO survivors during hospitalization was 6.8% in South Korea, and old age, male sex, longer duration of hospital stay, and underlying depression were associated with it. However, there was no significant association between delirium and 1-year all-cause mortality among ECMO survivors.

Perceived barriers to psychiatric help-seeking in South Korea by age groups: text mining analyses of social media big data.

BACKGROUND: The psychiatric treatment gap is substantial in Korea, implying barriers in seeking help. OBJECTIVES: This study aims to explore barriers of seeing psychiatrists, expressed on the internet by age groups. METHODS: A corpus of data was garnered extensively from internet communities, blogs and social network services from 1 January 2016 to 31 July 2019. Among the texts collected, texts containing words linked to psychiatry were selected. Then the corpus was dismantled into words by using natural language processing. Words linked to barriers to seeking help were identified and classified. Then the words from web communities that we were able to identify the age groups were additionally organized by age groups. RESULTS: 97,730,360 articles were identified and 6,097,369 were included in the analysis. Words implying the barriers were selected and classified into four groups of structural discrimination, public prejudice, low accessibility, and adverse drug effects. Structural discrimination was the greatest barrier occupying 34%, followed by public prejudice (27.8%), adverse drug effects (18.6%), and cost/low accessibility (16.1%). In the analysis by age groups, structural discrimination caused teenagers (51%), job seekers (64%) and mothers with children (43%) the most concern. In contrast, the public prejudice (49%) was the greatest barriers in the senior group. CONCLUSIONS: Although structural discrimination may most contribute to barriers to visiting psychiatrists in Korea, variation by generations may exist. Along with the general attempt to tackle the discrimination, customized approach might be needed.

Enhanced Extraction Efficiency of Flavonoids from Pyrus ussuriensis Leaves with Deep Eutectic Solvents.

In this study, deep eutectic solvents (DESs) were synthesized using different ratios of choline chloride (CC) and dicarboxylic acids, and their eutectic temperatures were determined. The DES synthesized using CC and glutaric acid (GA), which showed a higher extraction efficiency than conventional solvents, was used for the extraction of flavonoid components from Pyrus ussuriensis leaves (PUL), and the extraction efficiency was evaluated using the response surface methodology. The flavonoid components rutin, hyperoside, and isoquercitrin were identified through high-performance liquid chromatography (HPLC), equipped with a Waters 2996 PDA detector, and HPLC mass spectrometry (LC-MS/MS) analyses. The optimum extraction was achieved at a temperature of 30 °C using DES in a concentration of 30.85 wt.% at a stirring speed of 1113 rpm and an extraction time of 1 h. The corresponding flavonoid content was 217.56 µg/mL. The results were verified by performing three reproducibility experiments, and a high significance, with a confidence range of 95%, was achieved. In addition, the PUL extracts exhibited appreciable antioxidant activity. The results showed that the extraction process using the DES based on CC and GA in a 1:1 molar ratio could effectively improve the yield of flavonoids from PUL.