Extracellular glucose triggers metabolic reprogramming of cultured human bronchial epithelial cells and indirect fibroblast activation.

Glucose is essential for energy metabolism, and its usage can determine other cellular functions, depending on the cell type. In some pathological conditions, cells are exposed to high concentrations of glucose for extended periods. In this study, we investigated metabolic, oxidative stress, and cellular senescence pathways in human bronchial epithelial cells (HBECs) cultured in media with physiologically low (5 mm) and high (12.5 mm) glucose concentrations. HBECs exposed to 12.5 mm glucose showed increased glucose routing toward the pentose phosphate pathway, lactate synthesis, and glycogen, but not triglyceride synthesis. These metabolic shifts were not associated with changes in cell proliferation rates, oxidative stress, or cellular senescence pathways. Since hyperglycemia is associated with fibrosis in the lung, we asked whether HBECS could activate fibroblasts. Primary human lung fibroblasts cultured in media conditioned by 12.5 mm glucose-exposed HBECs showed a 1.3-fold increase in the gene expression of COL1A1 and COL1A2, along with twofold increased protein levels of smooth muscle cell actin and 2.4-fold of COL1A1. Consistently, HBECs cultured with 12.5 mm glucose secreted proteins associated with inflammation and fibrosis, such as interleukins IL-1ß, IL-10, and IL-13, CC chemokine ligands CCL2 and CCL24, and with extracellular matrix remodeling, such as metalloproteinases (MMP)-1, MMP-3, MMP-9, and MMP-13 and tissue inhibitors of MMPs (TIMP)-1 and -2. This study shows that HBECs undergo metabolic reprogramming and increase the secretion of profibrotic mediators following exposure to high concentrations of glucose, and it contributes to the understanding of the metabolic crosstalk of neighboring cells in diabetes-associated pulmonary fibrosis.

Small-Molecule Activation of Protein Phosphatase 2A Counters Bleomycin-Induced Fibrosis in Mice.

The activity of protein phosphatase 2A (PP2A), a serine-threonine phosphatase, is reduced in the lung fibroblasts of idiopathic pulmonary fibrosis (IPF) patients. The objective of this study was to determine whether the reactivation of PP2A could reduce fibrosis and preserve the pulmonary function in a bleomycin (BLM) mouse model. Here, we present a new class of direct small-molecule PP2A activators, diarylmethyl-pyran-sulfonamide, exemplified by ATUX-1215. ATUX-1215 has improved metabolic stability and bioavailability compared to our previously described PP2A activators. Primary human lung fibroblasts were exposed to ATUX-1215 and an older generation PP2A activator in combination with TGFß. ATUX-1215 treatment enhanced the PP2A activity, reduced the phosphorylation of ERK and JNK, and reduced the TGFß-induced expression of ACTA2, FN1, COL1A1, and COL3A1. C57BL/6J mice were administered 5 mg/kg ATUX-1215 daily following intratracheal instillation of BLM. Three weeks later, forced oscillation and expiratory measurements were performed using the Scireq Flexivent System. ATUX-1215 prevented BLM-induced lung physiology changes, including the preservation of normal PV loop, compliance, tissue elastance, and forced vital capacity. PP2A activity was enhanced with ATUX-1215 and reduced collagen deposition within the lungs. ATUX-1215 also prevented the BLM induction of Acta2, Ccn2, and Fn1 gene expression. Treatment with ATUX-1215 reduced the phosphorylation of ERK, p38, JNK, and Akt and the secretion of IL-12p70, GM-CSF, and IL1α in BLM-treated animals. Delayed treatment with ATUX-1215 was also observed to slow the progression of lung fibrosis. In conclusion, our study indicates that the decrease in PP2A activity, which occurs in fibroblasts from the lungs of IPF subjects, could be restored with ATUX-1215 administration as an antifibrotic agent.

Type 1 diabetes contributes to combined pulmonary fibrosis and emphysema in male alpha 1 antitrypsin deficient mice.

Type 1 diabetes (T1D) is a metabolic disease characterized by hyperglycemia and can affect multiple organs, leading to life-threatening complications. Increased prevalence of pulmonary disease is observed in T1D patients, and diabetes is a leading cause of comorbidity in several lung pathologies. A deficiency of alpha-1 antitrypsin (AAT) can lead to the development of emphysema. Decreased AAT plasma concentrations and anti-protease activity are documented in T1D patients. The objective of this study was to determine whether T1D exacerbates the progression of lung damage in AAT deficiency. First, pulmonary function testing (PFT) and histopathological changes in the lungs of C57BL/6J streptozotocin (STZ)-induced T1D mice were investigated 3 and 6 months after the onset of hyperglycemia. PFT demonstrated a restrictive pulmonary pattern in the lungs of STZ-injected mice, along with upregulation of mRNA expression of pro-fibrotic markers Acta2, Ccn2, and Fn1. Increased collagen deposition was observed 6 months after the onset of hyperglycemia. To study the effect of T1D on the progression of lung damage in AAT deficiency background, C57BL/6J AAT knockout (KO) mice were used. Control and STZ-challenged AAT KO mice did not show significant changes in lung function 3 months after the onset of hyperglycemia. However, histological examination of the lung demonstrated increased collagen accumulation and alveolar space enlargement in STZ-induced AAT KO mice. AAT pretreatment on TGF-ß-stimulated primary lung fibroblasts reduced mRNA expression of pro-fibrotic markers ACTA2, CCN2, and FN1. Induction of T1D in AAT deficiency leads to a combined pulmonary fibrosis and emphysema (CPFE) phenotype in male mice.

The Protective Role of Glutathione against Doxorubicin-Induced Cardiotoxicity in Human Cardiac Progenitor Cells.

This study investigated the protective effect of glutathione (GSH), an antioxidant drug, against doxorubicin (DOX)-induced cardiotoxicity. Human cardiac progenitor cells (hCPCs) treated with DOX (250 to 500 nM) showed increased viability and reduced ROS generation and apoptosis with GSH treatment (0.1 to 1 mM) for 24 h. In contrast to the 500 nM DOX group, pERK levels were restored in the group co-treated with GSH and suppression of ERK signaling improved hCPCs' survival. Similarly to the previous results, the reduced potency of hCPCs in the 100 nM DOX group, which did not affect cell viability, was ameliorated by co-treatment with GSH (0.1 to 1 mM). Furthermore, GSH was protected against DOX-induced cardiotoxicity in the in vivo model (DOX 20 mg/kg, GSH 100 mg/kg). These results suggest that GSH is a potential therapeutic strategy for DOX-induced cardiotoxicity, which performs its function via ROS reduction and pERK signal regulation.

StemRegenin-1 Attenuates Endothelial Progenitor Cell Senescence by Regulating the AhR Pathway-Mediated CYP1A1 and ROS Generation.

Endothelial progenitor cell (EPC)-based stem cell therapy is a promising therapeutic strategy for vascular diseases. However, continuous in vitro expansion for clinical studies induces the loss of EPC functionality due to aging. In this study, we investigated the effects of StemRegenin-1 (SR-1), an antagonist of aryl hydrocarbon receptor (AhR), on replicative senescence in EPCs. We found that SR-1 maintained the expression of EPC surface markers, including stem cell markers, such as CD34, c-Kit, and CXCR4. Moreover, SR-1 long-term-treated EPCs preserved their characteristics. Subsequently, we demonstrated that SR-1 showed that aging phenotypes were reduced through senescence-associated phenotypes, such as ß-galactosidase activity, SMP30, p21, p53, and senescence-associated secretory phenotype (SASP). SR-1 treatment also increased the proliferation, migration, and tube-forming capacity of senescent EPCs. SR-1 inhibited the AhR-mediated cytochrome P450 (CYP)1A1 expression, reactive-oxygen species (ROS) production, and DNA damage under oxidative stress conditions in EPCs. Furthermore, as a result of CYP1A1-induced ROS inhibition, it was found that accumulated intracellular ROS were decreased in senescent EPCs. Finally, an in vivo Matrigel plug assay demonstrated drastically enhanced blood vessel formation via SR-1-treated EPCs. In summary, our results suggest that SR-1 contributes to the protection of EPCs against cellular senescence.

Evaluating Novel Protein Phosphatase 2A Activators as Therapeutics for Emphysema.

The activity of PP2A (protein phosphatase 2A), a serine-threonine phosphatase, is reduced by chronic cigarette smoke (SM) exposure and α-1 antitrypsin (AAT) deficiency, and chemical activation of PP2A reduces the loss of lung function in SM-exposed mice. However, the previously studied PP2A-activator tricyclic sulfonamide compound DBK-1154 has low stability to oxidative metabolism, resulting in fast clearance and low systemic exposure. Here we compare the utility of a new more stable PP2A activator, ATUX-792, versus DBK-1154 for the treatment of SM-induced emphysema. ATUX-792 was also tested in human bronchial epithelial cells and a mouse model of AAT deficiency, Serpina1a-e-knockout mice. Human bronchial epithelial cells were treated with ATUX-792 or DBK-1154, and cell viability, PP2A activity, and MAP (mitogen-activated protein) kinase phosphorylation status were examined. Wild-type mice received vehicle, DBK-1154, or ATUX-792 orally in the last 2 months of 4 months of SM exposure, and 8-month-old Serpina1a-e-knockout mice received ATUX-792 daily for 4 months. Forced oscillation and expiratory measurements and histology analysis were performed. Treatment with ATUX-792 or DBK-1154 resulted in PP2A activation, reduced MAP kinase phosphorylation, immune cell infiltration, reduced airspace enlargements, and preserved lung function. Using protein arrays and multiplex assays, PP2A activation was observed to reduce AAT-deficient and SM-induced release of CXCL5, CCL17, and CXCL16 into the airways, which coincided with reduced neutrophil lung infiltration. Our study indicates that suppression of the PP2A activity in two models of emphysema could be restored by next-generation PP2A activators to impact lung function.

Relationship Between Resilience, Community Participation, and Successful Aging Among Older Adults in South Korea: Mediating Role of Community Participation.

A high level of resilience is positively related to successful aging. However, interventions to increase resilience in older adults are not yet available. This study aimed to examine the mediating role of community participation in the relationship between resilience and successful aging. Data from 284 individuals aged 60 years and above were analyzed in this cross-sectional study. The pathways among resilience, community participation, and successful aging were statistically significant after controlling for sociodemographic characteristics, depression, disability, and chronic disease. The analysis revealed a partial mediating effect of community participation (unstandardized estimate = .01, p < .01), explaining 16.4% of the total effect of resilience on successful aging. Promoting community participation may be beneficial for enhancing successful aging in community-dwelling older adults. Further studies to examine the causal relationship between community participation and successful aging and to develop community services are recommended to use community resources as means to support successful aging.

The Mediating Role of Social Participation in Motoric Cognitive Risk and its Relation to Depression and Loneliness in Older Adults.

BACKGROUND: Motoric cognitive risk syndrome (MCR) reduces the quality of life, independence, and social interaction in older adults. Social participation is a potentially modifiable factor that benefits cognitive and mental health. This study explored the mediating roles of social participation between MCR and depression and between MCR and loneliness. METHODS: We performed a secondary analysis of data from the 2015-2016 National Social Life, Health, and Aging Project. Slow gait speed and cognitive decline were used to assess MCR. Mediation analysis was applied to two models, both of which used MCR as an exposure and social participation as a mediator. The outcomes were depression and loneliness for each model, respectively. RESULTS: Among 1,697 older adults, 196 (11.6%) had MCR. The mediating role of social participation was statistically significant in both models. The indirect effect (ß=0.267, p=0.001) of MCR on depression through social participation comprised 11.97% of the total effect (ß=2.231, p<0.001). The indirect effect (ß=0.098, p=0.001) of MCR on loneliness through social participation was 19.48% of the total effect (ß=0.503, p<0.001). CONCLUSION: Interventions to increase social participation may reduce depression and loneliness of older adults with MCR.

Pediatric Eosinophilic Esophagitis: Searching for Serologic Markers.

OBJECTIVE: Eosinophilic esophagitis (EoE) is a Th2 disease that presently is diagnosed and followed by clinical symptoms in the presence of endoscopic biopsies documenting elevated esophageal eosinophilia. To simplify clinical care, multiple studies have attempted to identify a disease specific serologic marker. None have been successful. The goal of this study was to employ custom designed Luminex multiplex bead assays to identify a reliable serologic marker for EoE. METHODS: Luminex assays were employed to measure serum levels of 11 analytes associated with EoE (IL-5, lL13, periostin, eotaxin-3, thymic stromal lymphopoietin, and immunoglobulins) in a cohort of pediatric patients consisting of active EoE (n=30), EoE in remission (n=13), and controls (n=34). RESULTS: No analyte was found to be elevated or depressed in active EoE compared to the other groups. Additionally, among the cohort with active EoE, none of the 11 analytes correlated with peak esophageal eosinophilia, endoscopic features of EoE quantitatively defined by an EoE validated endoscopic reference score (EREFS), or esophageal thickness as determined by endosonography. CONCLUSION: This is the largest prospective survey of heterogeneous markers studied in a consecutive cohort to determine whether they could diagnose or follow EoE. Although none were identified in this cohort, Luminex provides a rapid, economical tool to simultaneously screen multiple sera for proteins that are increased or decreased in disease states.

Mechanisms Linking COPD to Type 1 and 2 Diabetes Mellitus: Is There a Relationship between Diabetes and COPD?

Chronic obstructive pulmonary disease (COPD) patients frequently suffer from multiple comorbidities, resulting in poor outcomes for these patients. Diabetes is observed at a higher frequency in COPD patients than in the general population. Both type 1 and 2 diabetes mellitus are associated with pulmonary complications, and similar therapeutic strategies are proposed to treat these conditions. Epidemiological studies and disease models have increased our knowledge of these clinical associations. Several recent genome-wide association studies have identified positive genetic correlations between lung function and obesity, possibly due to alterations in genes linked to cell proliferation; embryo, skeletal, and tissue development; and regulation of gene expression. These studies suggest that genetic predisposition, in addition to weight gain, can influence lung function. Cigarette smoke exposure can also influence the differential methylation of CpG sites in genes linked to diabetes and COPD, and smoke-related single nucleotide polymorphisms are associated with resting heart rate and coronary artery disease. Despite the vast literature on clinical disease association, little direct mechanistic evidence is currently available demonstrating that either disease influences the progression of the other, but common pharmacological approaches could slow the progression of these diseases. Here, we review the clinical and scientific literature to discuss whether mechanisms beyond preexisting conditions, lifestyle, and weight gain contribute to the development of COPD associated with diabetes. Specifically, we outline environmental and genetic confounders linked with these diseases.

Association Between Social Participation and Cognitive Function in Community-Dwelling Adults.

Social participation is associated with cognitive function; however, their causal relationships have not been reported yet. This study was designed to examine the autoregressive effects and bidirectional causal relationship between social participation and cognitive function. In this secondary longitudinal data analysis, we enrolled 4,834 Korean adults. A cross-lagged panel model with fixed effects was used to examine the causal relationships between social participation and cognitive function. Both participation (unstandardized coefficient = .370, p < .001) and cognitive function (unstandardized coefficient = .151, p < .001) had positive autoregressive effects over time. Participation had a cross-lagged effect on cognitive function (unstandardized coefficient = .061, p < .001). However, the cross-lagged effects of cognitive function on participation were not statistically significant (unstandardized coefficient = .051, p = .312). Various health-care programs that promote social participation and improve cognitive function must be established. Additional studies are required to confirm the causal effects of cognitive function on participation.

LRP1 loss in airway epithelium exacerbates smoke-induced oxidative damage and airway remodeling.

The LDL receptor-related protein 1 (LRP1) partakes in metabolic and signaling events regulated in a tissue-specific manner. The function of LRP1 in airways has not been studied. We aimed to study the function of LRP1 in smoke-induced disease. We found that bronchial epithelium of patients with chronic obstructive pulmonary disease and airway epithelium of mice exposed to smoke had increased LRP1 expression. We then knocked out LRP1 in human bronchial epithelial cells in vitro and in airway epithelial club cells in mice. In vitro, LRP1 knockdown decreased cell migration and increased transforming growth factor ß activation. Tamoxifen-inducible airway-specific LRP1 knockout mice (club Lrp1-/-) induced after complete lung development had increased inflammation in the bronchoalveolar space and lung parenchyma at baseline. After 6 months of smoke exposure, club Lrp1-/- mice showed a combined restrictive and obstructive phenotype, with lower compliance, inspiratory capacity, and forced expiratory volume0.05/forced vital capacity than WT smoke-exposed mice. This was associated with increased values of Ashcroft fibrotic index. Proteomic analysis of room air exposed-club Lrp1-/- mice showed significantly decreased levels of proteins involved in cytoskeleton signaling and xenobiotic detoxification as well as decreased levels of glutathione. The proteome fingerprint created by smoke eclipsed many of the original differences, but club Lrp1-/- mice continued to have decreased lung glutathione levels and increased protein oxidative damage and airway cell proliferation. Therefore, LRP1 deficiency leads to greater lung inflammation and damage and exacerbates smoke-induced lung disease.

Effects of healthcare access and financial status on self-rated health among adults living alone in South Korea.

Assessments of the overall health status of people living alone are important for developing health promotion programs and delivering appropriate health services. In the context of universal social health insurance system of South Korea, the relationship between failure to access health-care and self-rated health among adults living alone has given little attention. In addition, the influence of objective financial status on self-rated health in adults living alone has not explored so far. The sample of the present study comprised 4,852 adults who participated in the cross-sectional 2015 Korea National Health and Nutrition Examination Survey. The main finding was that the unmet health-care needs resulting from the inability to access health-care services during the previous 12 months was independently associated with fair or poor self-rated health, especially for women living alone. Having an income below the subsistence level was significantly associated with fair or poor self-rated health among women living alone. The findings of this study demonstrate the need for policies enabling appropriate delivery of health-care services, especially for women living alone. It is necessary to provide community-based monitoring programs related to general health for women living alone with a household income below the minimum cost-of-living.

Subjective memory complaints and social participation among older adults: results from the health and retirement study.

Objectives:This study aims to examine whether subjective memory complaints (SMC) contribute to social participation among older adults.Method:The study sample was 4,713 community-dwelling older adults aged 65 years and older from four waves (2010, 2012, 2014, 2016) of the Health and Retirement Study. Hierarchical linear modeling analysis was used to examine the association of SMC with social participation after controlling for factors influencing social participation. Demographic factors (i.e. age, gender, and perceived socioeconomic status) were entered in block 1, health-related factors (i.e. health conditions, perceived health, instrumental activities of daily living, memory-immediate and delayed, and depressive symptoms) were entered in block 2, environmental factors (i.e. perceived social support and strain from spouse, child, family, and friend) were entered in block 3, and SMC was entered in block 4.Results:The result showed that factors significantly contributing to social participation are age (standardized ß = -0.08, p < 0.01), perceived socioeconomic status (ß = 0.16, p < 0.001), perceived health (ß = 0.15, p < 0.001), instrumental activities of daily living (ß = 0.12, p < 0.001), memory-immediate and delayed (ß = 0.09, p < 0.001; ß = 0.08, p < 0.001, respectively), social support from spouse and friend (ß = 0.04, p < 0.05; ß = 0.13, p < 0.001, respectively), social strain from friend (ß = 0.07, p < 0.001), and SMC (ß = -0.05, p < 0.001). The demographic factors explained 9.5%, health-related factors explained 8.5%, environmental factors explained 2.4%, and SMC explained 0.1% of the variance in social participation.Conclusion: This finding suggests that SMC may contribute to social participation in older adults.Supplemental data for this article can be accessed online at https://doi.org/10.1080/13607863.2021.1961123 .

Cystine and Methionine Deficiency Promotes Ferroptosis by Inducing B-Cell Translocation Gene 1.

Ferroptosis is a type of programmed necrosis triggered by iron-dependent lipid peroxidation. We investigated the role of B-cell translocation gene 1 (BTG1) in cystine and methionine deficiency (CST/Met (-))-mediated cell death. CST/Met (-) depleted reduced and oxidized glutathione in hepatocyte-derived cells, increased prostaglandin-endoperoxide synthase 2 expression, and promoted reactive oxygen species accumulation and lipid peroxidation, as well as necrotic cell death. CST/Met (-)-mediated cell death and lipid peroxidation was specifically inhibited by pretreatment with ferroptosis inhibitors. In parallel with cell death, CST/Met (-) blocked global protein translation and increased the expression of genes associated with the integrated stress response. Moreover, CST/Met (-) significantly induced BTG1 expression. Using a BTG1 promoter-harboring reporter gene and siRNA, activating transcription factor 4 (ATF4) was identified as an essential transcription factor for CST/Met (-)-mediated BTG1 induction. Although knockout of BTG1 in human HAP1 cells did not affect the accumulation of reactive oxygen species induced by CST/Met (-), BTG1 knockout significantly decreased the induction of genes associated with the integrated stress response, and reduced lipid peroxidation and cell death in response to CST/Met (-). The results demonstrate that CST/Met (-) induces ferroptosis by activating ATF4-dependent BTG1 induction.

Impact of Social Network Size and Contact Frequency on Resilience in Community-Dwelling Healthy Older Adults Living Alone in the Republic of Korea.

The aim of this study was to investigate the characteristics of social health and its association with resilience among older adults living alone excluded from the public care service due to their relatively good health. For this cross-sectional study, we surveyed older adults aged between 65 and 80 years using questionnaires to measure the social health status and levels of resilience of the participants. We conducted a hierarchical regression analysis to confirm the association between resilience and social network. Finally, data from 266 community-dwelling older adults were analyzed. We discovered that participants had social networks with a mean score on the Lubben Social Network Scale 18.13 ± 7.98, which means they were socially isolated. The network size (standardized ß = -0.149, p < 0.05) and contact frequency (standardized ß = 0.136, p < 0.05) correlated positively with higher levels of resilience. A hierarchical model accounted for 48.0% of the variance in resilience. The results suggested that interventions by the public health service to protect social health are needed for older adults living alone even when they are physically, emotionally, and cognitively healthy. In addition, smaller network size and higher frequency of contacts may be considered to strengthen resilience, which is a protective factor in social health.

Development of a rabbit monocyte activation test as an alternative to the rabbit pyrogen test and its application in the analysis of plasma-derived products.

The rabbit pyrogen test (RPT) is a safety test conducted as a part of mandatory requirements of regulatory agencies. RPT is currently performed for routine quality control (QC) by manufacturers and for national lot release of biological products, such as plasma-derived products. However, RPT involves the use of many rabbits, counter to the international efforts to minimize the use of animals in research. Furthermore, pyrogen amount cannot be discerned from the test results and the results may be considerably affected by various factors. Therefore, a need exists for substituting RPT with in vitro assays. As a viable alternative to RPT, we here established a rabbit monocyte activation test (RMAT) based on the human MAT in the European Pharmacopoeia. RMAT uses rabbit peripheral blood mononuclear cells as the source of monocytes instead of live animals. The test detected endotoxin, lipoteichoic acid, peptidoglycan, and zymosan with high sensitivity, showing high correlation with the in vivo RPT results. The results of RMAT and RPT testing of non-pyrogenic plasma-derived products were also consistent. Furthermore, RMAT showed satisfactory recovery rates in an interference test with product samples and spiked-in pyrogens. We conclude that RMAT could replace the existing RPT for routine QC.

Therapeutic Potential of Alpha-1 Antitrypsin in Type 1 and Type 2 Diabetes Mellitus.

Alpha-1 antitrypsin (AAT) has established anti-inflammatory and immunomodulatory effects in chronic obstructive pulmonary disease but there is increasing evidence of its role in other inflammatory and immune-mediated conditions, like diabetes mellitus (DM). AAT activity is altered in both developing and established type 1 diabetes mellitus (T1DM) as well in established type 2 DM (T2DM). Augmentation therapy with AAT appears to favorably impact T1DM development in mice models and to affect ß-cell function and inflammation in humans with T1DM. The role of AAT in T2DM is less clear, but AAT activity appears to be reduced in T2DM. This article reviews these associations and emerging therapeutic strategies using AAT to treat DM.

Effects of occupational balance on subjective health, quality of life, and health-related variables in community-dwelling older adults: A structural equation modeling approach.

Occupational balance is an important variable associated with health and quality of life. This study aimed to investigate the influence of occupational balance on health, quality of life, and other health-related variables using structural equation modeling. We analyzed data from 208 adults over 55 years old. Mean age of the participants was 70.21 years (SD 7.22). The research model for analysis was based on the results of previous studies addressing occupational balance and related variables such as stress, leisure satisfaction, life satisfaction, subjective health, quality of life, and participation. General fit indices of the final model were acceptable (x2/df = 1.708, p < .001, RMSEA = .058, TLI = .923, CFI = .929, and SRMR = .067). Although the size of effect was small to medium (.157-.249), occupational balance was identified as an independent variable directly or indirectly affecting subjective health, quality of life, and health-related variables in the final model. Our results showed that it is possible to improve subjective health and quality of life by promoting better occupational balance. Further studies developing an intervention program based on occupational balance are required to confirm the feasibility of the intervention and its effect on older adults' health and quality of life in real-life circumstances.

Standardization of the first Korean national reference standard for snake (Gloydius brevicaudus) antivenom.

In 2017, the second national reference standard (NRS) for Gloydius snake venom was established to replace the first NRS for Gloydius snake venom. In connection with the second venom NRS, a candidate for the first NRS for Gloydius snake antivenom was produced in 2017. In this study, the qualification of the candidate was estimated and the potency was determined by a collaborative study. The potency (anti-lethal titer and anti-hemorrhagic titer) of the candidate was determined by measuring the capability of the antivenom to neutralize the lethal and hemorrhagic effects of the second NRS for Gloydius snake venom, which was calibrated against the regional reference standard for Gloydius snake antivenom established in 2006. Two Korean facilities contributed data from 20 independent assays. Subsequently, one foreign national control research laboratories participated in this collaborative study. The general common potency of the anti-lethal and anti-hemorrhagic titers was obtained from the results of a total of 25 tests performed at three facilities. According to the results of the present study, the candidate preparation showed good quality and is judged to be suitable to serve as the first NRS for Gloydius snake antivenom with the following potency: an anti-lethal titer of 3100 unit (U) (95% confidence interval 2991-3276 U) and anti-hemorrhagic titer of 3000 U (95% confidence interval 2849-3159 U). In conclusion, the first NRS for Gloydius snake antivenom was established in this study. This reference standard will be used routinely for quality control of a snake antivenom product by manufacturer in Korea, which also can be used for national quality control, including a national lot-release test of the snake antivenom product.