Protocols and their effects for medical device-related pressure injury prevention among critically ill patients: a systematic review.

BACKGROUND: A pressure injury refers to localized damage to the skin and/or tissue due to prolonged pressure, and it has recently been defined to include pressure injuries related to medical devices. Medical device-related pressure injuries occur in various sites and are difficult to detect. Even if it is detected, medical devices are essential to life for critically ill patients. Thus, it is difficult to remove or change the position of the medical device; therefore, prevention is essential. This study aims to integrate the literature on medical device-related pressure injury prevention protocols among critically ill patients. METHODS: The literature inclusion criteria were (1) critically ill patients, (2) device-related pressure injury interventions, (3) randomized controlled trials and quasi-experimental designs, and (4) written in Korean or English. The literature search and selection were performed following the Cochrane Handbook for Systematic Reviews of Interventions with the support of the PRISMA Guidelines. RESULTS: Twelve articles were finally selected. The incidence of medical device-related pressure injury decreased from 8.1-96.7% before intervention to 0.3-53.3% after intervention, respectively. Medical device-related pressure injury prevention was effective in reducing medical device-related pressure injury incidence when applied to patients of all ages, from neonates to adults, in a variety of intensive care units. Medical device-related pressure injury prevention strategies include nurse education, assessment, documentation, and interventions (hygiene, repositioning, emergent therapy such as protective dressing or designed equipment reducing pressure) of pressure injury. Pressure injury dressings primarily included hydrocolloid foam dressings, but transparent hydrocolloid formulations also effectively reduced medical device-related pressure injury incidence rates. CONCLUSIONS: In the future, it is necessary to increase the level of evidence by applying specialized medical device-related pressure injury prevention methods for different medical devices and areas of pressure injuries, and verifying their effectiveness. TRIAL REGISTRATION: The review protocol was registered (PROSPERO registration number: CRD42022346450).

Monocarboxylate transporter functions and neuroprotective effects of valproic acid in experimental models of amyotrophic lateral sclerosis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a devasting neurodegenerative disorder for which no successful therapeutics are available. Valproic acid (VPA), a monocarboxylate derivative, is a known antiepileptic drug and a histone deacetylase inhibitor. METHODS: To investigate whether monocarboxylate transporter 1 (MCT1) and sodium-coupled MCT1 (SMCT1) are altered in ALS cell and mouse models, a cellular uptake study, quantitative real time polymerase chain reaction and western blot parameters were used. Similarly, whether VPA provides a neuroprotective effect in the wild-type (WT; hSOD1WT) and ALS mutant-type (MT; hSOD1G93A) NSC-34 motor neuron-like cell lines was determined through the cell viability assay. RESULTS: [3H]VPA uptake was dependent on time, pH, sodium and concentration, and the uptake rate was significantly lower in the MT cell line than the WT cell line. Interestingly, two VPA transport systems were expressed, and the VPA uptake was modulated by SMCT substrates/inhibitors in both cell lines. Furthermore, MCT1 and SMCT1 expression was significantly lower in motor neurons of ALS (G93A) model mice than in those of WT mice. Notably, VPA ameliorated glutamate- and hydrogen peroxide-induced neurotoxicity in both the WT and MT ALS cell lines. CONCLUSIONS: Together, the current findings demonstrate that VPA exhibits a neuroprotective effect regardless of the dysfunction of an MCT in ALS, which could help develop useful therapeutic strategies for ALS.

Modulation of histone H3K4 dimethylation by spermidine ameliorates motor neuron survival and neuropathology in a mouse model of ALS.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive paralysis due to motor neuron degeneration. It has been proposed that epigenetic modification and transcriptional dysregulation may contribute to motor neuron death. In this study, we investigate the basis for therapeutic approaches to target lysine-specific histone demethylase 1 (LSD1) and elucidate the mechanistic role of LSD1-histone H3K4 signaling pathway in ALS pathogenesis. METHODS: In order to examine the role of spermidine (SD), we administered SD to an animal model of ALS (G93A) and performed neuropathological analysis, body weight, and survival evaluation. RESULTS: Herein, we found that LSD1 activity is increased while levels of H3K4me2, a substrate of LSD1, is decreased in cellular and animal models of ALS. SD administration modulated the LSD1 activity and restored H3K4me2 levels in ChAT-positive motor neurons in the lumbar spinal cord of ALS mice. SD prevented cellular damage by improving the number and size of motor neurons in ALS mice. SD administration also reduced GFAP-positive astrogliogenesis in the white and gray matter of the lumbar spinal cord, improving the neuropathology of ALS mice. Moreover, SD administration improved the rotarod performance and gait analysis of ALS mice. Finally, SD administration delayed disease onset and prolonged the lifespan of ALS (G93A) transgenic mice. CONCLUSION: Together, modulating epigenetic targets such as LSD1 by small compounds may be a useful therapeutic strategy for treating ALS.

Efficacy of Post-Operative Medication to Prevent Recurrence of Endometrioma: Cyclic Oral Contraceptive (OC) After Gonadotropin-Releasing Hormone (GnRH) Agonist Versus Dienogest.

BACKGROUND: There are several medical treatment options for endometrioma. Progestin, especially dienogest, is an effective drug for preventing recurrence of endometrioma after surgery. Additionally, oral contraceptive (OC) use after conservative surgery has been reported to reduce significantly the risk of endometrioma recurrence. The aim of this study was to compare the long-term effects of gonadotropin-releasing hormone (GnRH) agonist followed by OC to those of dienogest alone to prevent recurrence of endometrioma after laparoscopic surgery. METHODS: A retrospective cohort study was performed on patients who underwent conservative laparoscopic surgery for endometrioma between January 2000 and December 2020, in the Endometriosis Clinic, Department of Gynecology, Samsung Medical Center. A total of 624 patients who received medical treatment at least six months after laparoscopic conservative surgery for endometrioma was included. Among them, 372 patients used OC after GnRH agonist therapy, and 252 patients used dienogest. Within the OC group, 148 used a 21/7 regiment and 224 used a 24/4 regimen. A cumulative endometrioma recurrence curve was presented using the Kaplan-Meier method to compare the recurrence of those groups. RESULTS: The cumulative recurrence rate of endometrioma for 60 months was 2.08% (n = 4) in the OC after GnRH agonist group and 0.40% (n = 1) in the dienogest group. There was no statistical difference in cumulative recurrence of endometrioma between the two groups. In subgroup analysis, the cumulative recurrence rate of endometrioma over 60 months was 4.21% (n = 2) in the 21/7 OC group and 1.09% (n = 2) in the 24/4 OC group and showed no significant difference. CONCLUSION: Long-term use of OC after GnRH agonist as well as that of dienogest treatment are effective postoperative medical therapies for preventing endometrioma recurrence. Thus, the choice of regimen can be individualized or used interchangeably depending on patient condition, need for contraception, and compliance with drug therapy.

Factors Associated with Pressure Injury Among Critically Ill Patients in a Coronary Care Unit.

OBJECTIVE: To ascertain the incidence of pressure injuries (PIs) in patients in the coronary care unit (CCU), identify PI characteristics, and determine associated risk factors. METHODS: Researchers conducted a retrospective investigational study of patients' medical records. A total of 820 patients who were admitted to the CCU between January 2018 and December 2020 met the study criteria. Of these, 200 patients who developed PIs after admission to the CCU were included in this study. This study examined the clinical features of PIs, as well as five PI risk factors: patient characteristics; length of stay; intrinsic factors; care factors, including medical devices; and vasopressor agents. RESULTS: The incidence of PIs among patients in the CCU was 24.4%. At initial detection, 79.5% of these injuries were already at stage 2 or higher. The results indicated a significant correlation between PI stage and hemoglobin level. Moreover, the authors also found relationships between the use of medical devices (eg, arterial catheters, oxygen tubes, and Levin tubes) and PI onset. CONCLUSIONS: Critically ill patients in the CCU use various medical devices for an extended period with severe consequences. The risk factors affecting PI are multifactorial. Therefore, the implementation of PI prevention and early detection strategies for patients in the CCU are crucial.

Non-Cell Autonomous and Epigenetic Mechanisms of Huntington's Disease.

Huntington's disease (HD) is a rare neurodegenerative disorder caused by an expansion of CAG trinucleotide repeat located in the exon 1 of Huntingtin (HTT) gene in human chromosome 4. The HTT protein is ubiquitously expressed in the brain. Specifically, mutant HTT (mHTT) protein-mediated toxicity leads to a dramatic degeneration of the striatum among many regions of the brain. HD symptoms exhibit a major involuntary movement followed by cognitive and psychiatric dysfunctions. In this review, we address the conventional role of wild type HTT (wtHTT) and how mHTT protein disrupts the function of medium spiny neurons (MSNs). We also discuss how mHTT modulates epigenetic modifications and transcriptional pathways in MSNs. In addition, we define how non-cell autonomous pathways lead to damage and death of MSNs under HD pathological conditions. Lastly, we overview therapeutic approaches for HD. Together, understanding of precise neuropathological mechanisms of HD may improve therapeutic approaches to treat the onset and progression of HD.

Suppression of TRPM7 enhances TRAIL-induced apoptosis in triple-negative breast cancer cells.

Transient receptor potential cation channel subfamily M member 7 (TRPM7) composed of an ion channel and a kinase domain regulates triple-negative breast cancer (TNBC) cell migration, invasion, and metastasis, but it does not modulate TNBC proliferation. However, previous studies have shown that the combination treatment of nonselective TRPM7 channel inhibitors (2-aminoethoxydiphenyl borate and Gd3+ ) with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) increases antiproliferative effects and apoptosis in prostate cancer cells and hepatic stellate cells. We, therefore, investigated the potential role of TRPM7 in proliferation and apoptosis of TNBC cells (MDA-MB-231 and MDA-MB-468 cells) with TRAIL. We demonstrated that suppression of TRPM7 via TRPM7 knockdown or pharmacological inhibition synergistically increases TRAIL-induced antiproliferative effects and apoptosis in TNBC cells. Furthermore, we showed that the synergistic interaction might be associated with TRPM7 channel activities using combination treatments of TRAIL and TRPM7 inhibitors (NS8593 as a TRPM7 channel inhibitor and TG100-115 as a TRPM7 kinase inhibitor). We reveal that downregulation of cellular FLICE-inhibitory protein via inhibition of Ca2+ influx might be involved in the synergistic interaction. Our study would provide both a new role of TRPM7 in TNBC cell apoptosis and a potential combinatorial therapeutic strategy using TRPM7 inhibitors with TRAIL in the treatment of TNBC.

The first small molecules capable of strongly suppressing proliferation of cancer cells harboring BRAF class I/II/III mutations.

BRAF mutants are categorized into three classes according to dependency on RAS signaling and RAF dimerization-dependency. Class I BRAF V600 mutants (RAS-independent monomer) are sensitive to vemurafenib. In contrast, both class II mutants (RAS-independent dimer) and class III mutants (RAS-dependent heterodimer) are insensitive to vemurafenib. It is not likely that BRAF inhibitors capable of inhibiting all classes of BRAF mutants are currently available. Herein, we report GNF-7 and its novel derivative, SIJ1227 as the first BRAF inhibitors capable of inhibiting all classes of BRAF mutants. Compared with vemurafenib and PLX8394, both GNF-7 and SIJ1227 possess much more strong anti-proliferative activities on melanoma (A375 and C8161) and lung cancer cells (H1755 and H1666) harboring BRAF V600E (class I mutant), BRAF G464E/G469A (class II mutant) and BRAF G466V (class III mutant), respectively. Also, both GNF-7 and SIJ1227 are capable of inhibiting more strongly colony formation than vemurafenib and PLX8394 in 3D soft agar assay using C8161 melanoma cells. In addition, GNF-7 and SIJ1227 suppress more strongly migration/invasion of these cancer cells than vemurafenib and PLX8394. Taken together, both GNF-7 and SIJ1227 are much superior to vemurafenib and PLX8394 in terms of capability to inhibit all classes of BRAF mutants.

Flexible Behavior of the Black-Tailed Godwit Limosa limosa is Key to Successful Refueling during Staging at Rice Paddy Fields in Midwestern Korea.

Successful refueling at staging sites is essential for the survival and reproduction of migratory birds. Understanding their staging ecology is therefore crucial for the conservation of migrant species. Rice fields in the mid-western region of the Korean Peninsula serve as staging habitats for the black-tailed godwit (Limosa limosa). We examined the behavior of staging black-tailed godwits in rice fields located in the East Asian-Australasian Flyway during their northward migration. Specifically, we tested the effect of flock size and water level on the foraging, vigilance, and resting behaviors of black-tailed godwits. Our observations revealed that as flock size increased, stepping rate, pecking rate, and vigilance duration decreased, while probing rate, preening duration, and foraging efficiency increased. Stepping and pecking rates increased at low water levels, compared with high water levels. We determined that the behavior of black-tailed godwits at the staging site is influenced by flock size and water level. These observations suggest that black-tailed godwits form larger flocks to increase foraging efficiency by lowering individual-level vigilance, and to spend more time on preening, which is critical for flight and survival. It can be also inferred, based on the shift in primary foraging mode between probing and pecking depending on the water level, that they obtain higher foraging efficiency by flexibly adapting their foraging mode to the conditions in rice fields that are subject to agricultural activities. Our results are expected to serve as basic data for establishing efficient management strategies for anthropogenic habitats for the conservation of migratory shorebirds such as black-tailed godwit.

Evaluation of the Korean version of the self-assessment of nursing informatics competencies scale.

BACKGROUND: In order to assess nursing students' informatics competency, we need a comprehensive Korean version scale that reflects the important advances in nursing informatics and can make up for the lack of an existing measure. This study aimed to cross-culturally adapt the Self-Assessment of Nursing Informatics Competencies Scale (SANICS) into Korean (K-SANICS) and verify its validity and reliability with nursing students. METHODS: The design of this study was a methodological approach to translate and evaluate the Korean version tool (K-SANICS). A total of 254 nursing students at four universities in Korea completed a structured questionnaire including background characteristics and the K-SANICS. Reliability and validity of the 30-item K-SANICS were evaluated using Cronbach's α, content validity, factor analysis, and contrasted groups approach. RESULTS: Cronbach's α was .95. Exploratory factor analysis was performed to verify the scale's construct validity, identifying 30 items across six categories: advanced skills for clinical informatics, basic application skills, basic computer skills, roles in nursing informatics, skills for clinical applications, and attitude toward computers in nursing. CONCLUSION: The K-SANICS may be used as a reliable assessment tool of nursing students' nursing informatics competencies. It is expected that the K-SANICS will contribute to establishing, operating, and evaluating nursing informatics curricula and also can be used in a clinical setting.

Workplace violence against nurses in Korea and its impact on professional quality of life and turnover intention.

AIM: To inform countermeasures against nurses' workplace violence by reviewing the experience of violence. BACKGROUND: Violence is an important issue in medical settings that influences turnover intention of nurses. However, few studies have dealt with the effects of violence experienced by nurses on professional quality of life and turnover intention. METHOD: A descriptive study using a structured questionnaire and data were analysed using t-test, one-way anova and hierarchical multiple regression analysis. RESULTS: Of 358 nurses 95.5% reported that they had experienced workplace violence during the previous 1 year. Findings indicated that turnover intention was positively associated with years worked as a nurse, functional nursing delivery system, exposure types of violence with physical threats, and mild or severe burnout. CONCLUSIONS: Nurses experienced diverse workplace violence, which could decrease their professional quality of life and be a factor affecting their turnover intention. IMPLICATIONS FOR NURSING MANAGEMENT: Role of leadership in creating a positive work environment is needed. Prevention of workplace violence should focus on at-risk groups to reduce workplace violence. Workplace violence should be communicated regularly and feedback should be given if there is unintentional non-physical violence. In particular it is important to investigate post-violence management in nurses who have experienced violence to reduce secondary trauma.

Identification of cornifelin and early growth response-1 gene as novel biomarkers for in vitro eye irritation using a 3D reconstructed human cornea model MCTT HCE™.

Evaluation of the eye irritation is essential in the development of new cosmetic products. Draize rabbit eye irritation test has been widely used in which chemicals are directly applied to rabbit eye, and the symptoms and signs of eyes are scored. However, due to the invasive procedure, it causes substantial pain and discomfort to animals. Recently, we reported in vitro eye irritation test method using a 3D human corneal epithelial model (MCTT HCE™) which is reconstructed from remaining human tissues after a corneal transplantation. This model exhibited an excellent predictive capacity for 25 reference chemicals (sensitivity 100%, specificity 77% and accuracy 88% vs. GHS). To improve the test performance, we explored new biomarkers for the eye irritation through transcriptomic approach. Three surfactants were selected as model eye irritants that include sodium lauryl sulfate, benzalkonium chloride and triton X-100. After test chemicals were treated, we investigated differentially expressed genes through a whole-gene microarray (Affymetrix GeneChip(®) Human Gene 2.0 ST Array, 48,000 probes). As a result, we identified that mRNAs of cornifelin (CNFN), a constituent of the insoluble cornified cell envelope of stratified squamous epithelia, and early growth response-1 (EGR1), a nuclear transcriptional regulator, were significantly up-regulated by all three irritants. Up-regulation of CNFN and EGR1 was further confirmed by Q-RT-PCR, and immunohistochemistry revealed increased level of CNFN in irritant-treated tissues, supporting the relevance of CNFN and EGR1 as new biomarkers for eye irritation.

Factors affecting advance directives completion among older adults in Korea.

Objective: Advance directives (ADs) provide an opportunity for patients to enhance the quality of their end-of-life care and prepare for a dignified death by deciding treatment plans. The purpose of this study was to explore the multiple factors that influence the advance directives completion among older adults in South Korea. Methods: This was a secondary analysis of a cross-sectional study of 9,920 older adults. The differences in ADs based on subjects' sociodemographic characteristics, health-related characteristics, and attitude toward death were tested using the chi-squared and t-test. A multinomial logistic regression model was used to identify the influencing factor of ADs. Results: The number of chronic diseases, number of prescribed medications, depression, insomnia, suicide intention, and hearing, vision, or chewing discomfort were higher in the ADs group compared to the non-ADs group. The influencing factors of the signing of ADs included men sex, higher education level, exercise, death preparation education, lower awareness of dying-well, and experience of fracture. Conclusion: Information dissemination regarding ADs should be promoted and relevant authorities should consider multiple options to improve the physical and psychological health of older adults, as well as their attitude toward death to increase the ADs completion rate.

Effects of Post-COVID-19 Syndrome on Quality of Life Among Airline Crew.

Background: Interest in post-coronavirus disease 2019 (COVID-19) syndrome following COVID-19 infection has been increasing. Maintaining quality of life (QoL) is vital for airline crews because they work in a special environment, where they are responsible for the passengers' safety. This study aims to closely investigate factors affecting the QoL of airline crews, including post-COVID-19 syndrome. Methods: This study was designed as a cross-sectional survey, comprising 167 crews. Findings: Age-specific significant differences were observed in social, overall, and total QoL scores. The physical domain QoL was significantly higher in the cockpit crews than that in the cabin crews. Significant differences were found in psychological and overall QoL depending on years of continuous service. Social domain and environmental QoL were lower in those who had no symptoms after being diagnosed with COVID-19 than in those who were symptomatic. Among the participants, 4.2% had post-COVID-19 syndrome, indicating significant differences in the physical domain, depending on whether they exhibit post-COVID-19 syndrome. Conclusion: It is urgent to develop measures to increase the QoL of airline crews, investigate post-COVID-19 syndrome before returning to work, and develop strategies to manage it. Application to practice: The QoL among airline crews differed not only by the demographic characteristics of the participants but also by the presence of symptoms during COVID-19 diagnosis and post-COVID-19 syndrome. Higher QoL among airline crews is associated with the safety of both airline crews and passengers. Therefore, it is necessary to establish a systematic management protocol for airline crews returning to work after following COVID-19 infection.

Loss of MEF2C function by enhancer mutation leads to neuronal mitochondria dysfunction and motor deficits in mice.

Genetic changes and epigenetic modifications are associated with neuronal dysfunction in the pathogenesis of neurodegenerative disorders. However, the mechanism behind genetic mutations in the non-coding region of genes that affect epigenetic modifications remains unclear. Here, we identified an ALS-associated SNP located in the intronic region of MEF2C (rs304152), residing in a putative enhancer element, using convolutional neural network. The enhancer mutation of MEF2C reduces own gene expression and consequently impairs mitochondrial function in motor neurons. MEF2C localizes and binds to the mitochondria DNA, and directly modulates mitochondria-encoded gene expression. CRISPR/Cas-9-induced mutation of the MEF2C enhancer decreases expression of mitochondria-encoded genes. Moreover, MEF2C mutant cells show reduction of mitochondrial membrane potential, ATP level but elevation of oxidative stress. MEF2C deficiency in the upper and lower motor neurons of mice impairs mitochondria-encoded genes, and leads to mitochondrial metabolic disruption and progressive motor behavioral deficits. Together, MEF2C dysregulation by the enhancer mutation leads to mitochondrial dysfunction and oxidative stress, which are prevalent features in motor neuronal damage and ALS pathogenesis. This genetic and epigenetic crosstalk mechanism provides insights for advancing our understanding of motor neuron disease and developing effective treatments.

Astrocytic autophagy plasticity modulates Aß clearance and cognitive function in Alzheimer's disease.

BACKGROUND: Astrocytes, one of the most resilient cells in the brain, transform into reactive astrocytes in response to toxic proteins such as amyloid beta (Aß) in Alzheimer's disease (AD). However, reactive astrocyte-mediated non-cell autonomous neuropathological mechanism is not fully understood yet. We aimed our study to find out whether Aß-induced proteotoxic stress affects the expression of autophagy genes and the modulation of autophagic flux in astrocytes, and if yes, how Aß-induced autophagy-associated genes are involved Aß clearance in astrocytes of animal model of AD. METHODS: Whole RNA sequencing (RNA-seq) was performed to detect gene expression patterns in Aß-treated human astrocytes in a time-dependent manner. To verify the role of astrocytic autophagy in an AD mouse model, we developed AAVs expressing shRNAs for MAP1LC3B/LC3B (LC3B) and Sequestosome1 (SQSTM1) based on AAV-R-CREon vector, which is a Cre recombinase-dependent gene-silencing system. Also, the effect of astrocyte-specific overexpression of LC3B on the neuropathology in AD (APP/PS1) mice was determined. Neuropathological alterations of AD mice with astrocytic autophagy dysfunction were observed by confocal microscopy and transmission electron microscope (TEM). Behavioral changes of mice were examined through novel object recognition test (NOR) and novel object place recognition test (NOPR). RESULTS: Here, we show that astrocytes, unlike neurons, undergo plastic changes in autophagic processes to remove Aß. Aß transiently induces expression of LC3B gene and turns on a prolonged transcription of SQSTM1 gene. The Aß-induced astrocytic autophagy accelerates urea cycle and putrescine degradation pathway. Pharmacological inhibition of autophagy exacerbates mitochondrial dysfunction and oxidative stress in astrocytes. Astrocyte-specific knockdown of LC3B and SQSTM1 significantly increases Aß plaque formation and GFAP-positive astrocytes in APP/PS1 mice, along with a significant reduction of neuronal marker and cognitive function. In contrast, astrocyte-specific overexpression of LC3B reduced Aß aggregates in the brain of APP/PS1 mice. An increase of LC3B and SQSTM1 protein is found in astrocytes of the hippocampus in AD patients. CONCLUSIONS: Taken together, our data indicates that Aß-induced astrocytic autophagic plasticity is an important cellular event to modulate Aß clearance and maintain cognitive function in AD mice.

The Effects of a Tailored Dietary Education Program for Older Adult Patients on Hemodialysis: A Preliminary Study.

This study aimed to investigate the overall effects of a tailored dietary education program for older adult patients on hemodialysis (HD) based on self-efficacy theory, dietary knowledge and habits, nutritional intake, and biochemical parameters. A nonequivalent control group pre-test-post-test design was conducted for 8 weeks. The experimental and control groups received a weekly nutritional program and standard nursing care with an additional educational session, respectively. A clinical survey was conducted before and after the intervention. After the intervention, self-efficacy, dietary knowledge, and dietary habits were higher in the experimental group than in the control group. Moreover, carbohydrate, phosphorus, and sodium intake significantly decreased post-intervention in the experimental group but not in the control group. The dietary education program for older HD patients showed positive effects on boosting their self-efficacy, increasing dietary knowledge, improving dietary habits, and decreasing carbohydrate, calcium, phosphorus, and sodium intake.

Functional characterization of allelic variants of polymorphic human cytochrome P450 2A6 (CYP2A6*5, *7, *8, *18, *19, and *35).

Cytochrome P450 2A6 (CYP2A6) catalyzes important metabolic reactions of many xenobiotic compounds, including coumarin, nicotine, cotinine, and clinical drugs. Genetic polymorphisms of CYP2A6 can influence its metabolic activities. This study analyzed the functional activities of six CYP2A6 allelic variants (CYP2A6*5, *7, *8, *18, *19, and *35) containing nonsynonymous single-nucleotide polymorphisms. Recombinant variant enzymes of CYP2A6*7, *8, *18, *19, and *35 were successfully expressed in Escherichia coli and purified. However, a P450 holoenzyme spectrum was not detected for the CYP2A6*5 allelic variant (G479V). Structural analysis shows that the G479V mutation may alter the interaction between the A helix and the F-G helices. Enzyme kinetic analyses indicated that the effects of mutations in CYP2A6 allelic variants on drug metabolism are dependent on the substrates. In the case of coumarin 7-hydroxylation, CYP2A6*8 and *35 displayed increased K(m) values whereas CYP2A6*18 and *19 showed decreased k(cat) values, which resulted in lower catalytic efficiencies (k(cat)/K(m)). In the case of nicotine 5-oxidation, the CYP2A6*19 variant exhibited an increased K(m) value, whereas CYP2A6*18 and *35 showed much greater decreases in k(cat) values. These results suggest that individuals carrying these allelic variants are likely to have different metabolisms for different CYP2A6 substrates. Functional characterization of these allelic variants of CYP2A6 can help determine the importance of CYP2A6 polymorphisms in the metabolism of many clinical drugs.

Factors Affecting Fatigue among Nurses during the COVID-19 Pandemic.

This study identified clinical nurses' fatigue and related factors during the COVID-19 pandemic. This was a cross-sectional study. Data were collected from South Korean hospitals on 234 nurses' general characteristics, fatigue, depression, occupational stress, insomnia, and perceived daytime sleepiness using a structured questionnaire. The prevalence of fatigue was 62.0%, depression 52.1%, insomnia 20.7%, and daytime sleepiness 36.1%. Insomnia, sleepiness, depression, and occupational stress were significantly associated with fatigue. Ward nurses who cared for COVID-19 patients within the past month had significantly higher occupational stress related to organizational climate than those who had not provided care, and ICU nurses who cared for COVID-19 patients had significantly higher job insecurity-related occupational stress. Nurses have a high prevalence of fatigue and depression during the pandemic. Thus, insomnia, sleepiness, depression, and occupational stress must be reduced to lower nurses' fatigue. Caring for COVID-19 patients was not significantly associated with fatigue, but there were significant differences in occupational stress between nurses who provided such care and those who did not. Work environment-specific strategies are needed to reduce nurses' occupational stress during the pandemic.

Social Frailty among Community-Dwelling Older Adults during the COVID-19 Pandemic in Korea: A Cross-Sectional Study.

Social frailty among older adults has become a growing concern from a public health perspective in the context of the coronavirus disease 2019 (COVID-19) pandemic. This study's aim was to investigate the influence of various aspects of social frailty in community-dwelling older adults during the COVID-19 pandemic. This study carried out a secondary analysis of data collected from the 2020 National Survey of Older Koreans and performed multinomial logistic regression analysis to identify the predictive factors of social frailty. The affected factors for the social frailty group were health conditions (depression), behavioral and metabolic risk factors (exercise, nutritional status, current smoking status, drinking frequency), intrinsic capacity (cognitive functions, activities of daily living), and digital literacy (use of smartphone or tablet PCs). Since multidimensional factors could affect older adults' social frailty, comprehensive strategies are urgently needed to reduce their rate of social frailty.