Age-specific findings on lifestyle and trajectories of cognitive function from the Korean Longitudinal Study of Aging.

OBJECTIVES: Few longitudinal studies have explored age-related differences in the relationship between lifestyle factors and cognitive decline. This study investigated lifestyle factors at baseline that slow the longitudinal rate of cognitive decline in young-old (55-64 years), middle-old (65-74 years), and old-old (75+ years) individuals. METHODS: We conducted an 11-year follow-up that included 6,189 older adults from the Korean Longitudinal Study of Aging, which is a cohort study of community-dwelling older Koreans. Lifestyle factors, including physical activity, social activity (SA), smoking, and alcohol consumption were assessed at baseline. Cognitive function was measured at 2-year intervals over 11 years. Latent growth modeling and multi-group analysis were performed. RESULTS: The influence of lifestyle factors on the rate of cognitive decline differed by age. Smoking at baseline (-0.05; 95% confidence interval [CI], -0.11 to -0.00, per study wave) accelerated cognitive decline in young-old individuals, whereas frequent participation in SA at baseline (0.02; 95% CI, 0.01 to 0.03, per study wave) decelerated cognitive decline in middle-old individuals. None of the lifestyle factors in this study decelerated cognitive decline in old-old individuals. CONCLUSIONS: Cognitive strategies based on modifiable lifestyle factors such as smoking cessation in young-old individuals and frequent SA participation in middle-old age individuals may have great potential for preventing cognitive decline. Because the influence of lifestyle factors varied by age group, age-specific approaches are recommended to promote cognitive health.

Measurement Properties of the Stroke-Predischarge Occupational Therapy Assessment.

There is no comprehensive predischarge occupational therapy assessment tool in South Korea. The objective of this study was to determine Stroke-Predischarge Occupational Therapy Assessment (S-POTA) validity and reliability. Twenty-seven occupational therapists (OTs) assessed 97 patients with stroke. Concurrent validity was evaluated by comparing S-POTA scores with stroke-specific quality of life (SS-QOL). Discriminant validity was evaluated by comparing S-POTA scores between outpatient and readmitted groups, and a receiver operating characteristic analysis was conducted. The test-retest was conducted twice in 20 patients, and the inter-rater test was conducted with two OTs per patient. S-POTA positively correlated with SS-QOL. S-POTA rating differs significantly across outpatients and readmitted groups. All S-POTA areas under curve values ranged from .70 to .85, and cut-off points were derived. Cronbach's α for internal consistency was .953, the intraclass correlation coefficient for test-retest was .990, and .987 for inter-rater reliability. The results suggest S-POTA is a reliable tool for efficient implementation of discharge planning.

Predictive factors associated with trajectory of job satisfaction of workers with physical disabilities: A latent growth curve analysis.

BACKGROUND: Job satisfaction is a highly useful factor in maintaining a successful work life for the disabled. OBJECTIVE: This study aimed to evaluate how job satisfaction among workers with physical disabilities evolves over time, and to identify predictive factors that influence the trajectory of job satisfaction. METHODS: A longitudinal data analysis using the three-year databases of the 2016-2018 Employment Panel Survey for the Disabled (n = 693). A latent growth curve model analysis was conducted to determine the trajectory of the job satisfaction among workers with physical disabilities, as well as the predictive factors affecting it. RESULTS: Job satisfaction among workers with physical disabilities increased over time, and there were substantial individual differences in the trajectory of the job satisfaction. The significant predictors for the job satisfaction over the three years were degree of disability, computer usage ability, employment support services, and experience of discrimination. Gender, educational background, interpersonal relationship/organizational adaptability, convenience facilities for the disabled, job suitability, disability acceptability, and self-esteem had a considerable impact on the intercept of the job satisfaction, but not on the slope. CONCLUSION: The findings would inform healthcare providers to establish mid-to-long-term vocational rehabilitation intervention plans that could increase the job satisfaction among workers with physical disabilities.

Analysis of differentially expressed long non-coding RNAs in LPS-induced human HMC3 microglial cells.

BACKGROUND: Long non-coding RNAs (lncRNAs) are emerging as key modulators of inflammatory gene expression, but their roles in neuroinflammation are poorly understood. Here, we identified the inflammation-related lncRNAs and correlated mRNAs of the lipopolysaccharide (LPS)-treated human microglial cell line HMC3. We explored their potential roles and interactions using bioinformatics tools such as gene ontology (GO), kyoto encyclopedia of genes and genomes (KEGG), and weighted gene co-expression network analysis (WGCNA). RESULTS: We identified 5 differentially expressed (DE) lncRNAs, 4 of which (AC083837.1, IRF1-AS1, LINC02605, and MIR3142HG) are novel for microglia. The DElncRNAs with their correlated DEmRNAs (99 total) fell into two network modules that both were enriched with inflammation-related RNAs. However, treatment with the anti-inflammatory agent JQ1, an inhibitor of the bromodomain and extra-terminal (BET) protein BRD4, neutralized the LPS effect in only one module, showing little or even enhancing effect on the other. CONCLUSIONS: These results provide insight into, and a resource for studying, the regulation of microglia-mediated neuroinflammation and its potential therapy by small-molecule BET inhibitors.

The bromodomain inhibitor JQ1 up-regulates the long non-coding RNA MALAT1 in cultured human hepatic carcinoma cells.

The epigenetic reader, bromodomain-containing 4 (BRD4), is overexpressed in hepatocellular carcinoma (HCC), and BRD4 inhibition is considered as a new therapeutic approach. The BRD inhibitor JQ1 is known to inhibit the enrichment of BRD4 at enhancer sites. Gene network analyses have implicated long non-coding RNAs (lncRNAs) in the effects of JQ1, but the precise molecular events remain unexplored. Here, we report that in HepG2 cells, JQ1 significantly reduced various proliferation-related lncRNAs, but up-regulated the known liver tumor marker, MALAT1. Using ChIP-sequencing data, ChIP-qPCR, luciferase reporter assays, and chromatin conformation capture (3C), we characterized the MALAT1 gene locus. We found that JQ1 elicited a rearrangement of its chromatin looping conformation, which involved the putative enhancers E1, E2, E3, the gene body, and the promoter. We further found that the forkhead box protein A2 (FOXA2) binds to E2 and the promoter; suppression of FOXA2 expression resulted in MALAT1 up-regulation and increased cell proliferation. These results suggest that the inhibition of MALAT1 may improve the effect of BET inhibitors as an anti-cancer therapy and that FOXA2 would be a suitable target for that approach.

Comprehensive transcriptome profiling of BET inhibitor-treated HepG2 cells.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and poor prognosis. Emerging evidence suggests that epigenetic alterations play a crucial role in HCC, suggesting epigenetic inhibition as a promising therapeutic approach. Indeed, the bromodomain and extra-terminal (BET) inhibitors inhibit the proliferation and invasion of various cancers but still lack a strong mechanistic rationale. Here, we identified the differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs) in human HCC cell line HepG2 treated with the BET inhibitors, JQ1, OTX015, or ABBV-075. We analyzed the correlation between DEmRNAs and DElncRNAs in common for the three inhibitors based on their expression profiles and performed functional annotation pathway enrichment analysis. Most of these shared DEmRNAs and DElncRNAs, including some novel transcripts, were downregulated, indicating decreased proliferation/adhesion and increased apoptosis/inflammation. Our study suggests that BET proteins play a crucial role in regulating cancer progression-related genes and provide a valuable resource for novel putative biomarkers and therapeutic targets in HCC.

Targeting of noncoding RNAs encoded by a novel MYC enhancers inhibits the proliferation of human hepatic carcinoma cells in vitro.

The proto-oncogene MYC is important for development and cell growth, however, its abnormal regulation causes cancer. Recent studies identified distinct enhancers of MYC in various cancers, but any MYC enhancer(s) in hepatocellular carcinoma (HCC) remain(s) elusive. By analyzing H3K27ac enrichment and enhancer RNA (eRNA) expression in cultured HCC cells, we identified six putative MYC enhancer regions. Amongst these, two highly active enhancers, located ~ 800 kb downstream of the MYC gene, were identified by qRT-PCR and reporter assays. We functionally confirmed these enhancers by demonstrating a significantly reduced MYC expression and cell proliferation upon CRISPR/Cas9-based deletion and/or antisense oligonucleotide (ASO)-mediated inhibition. In conclusion, we identified potential MYC enhancers of HCC and propose that the associated eRNAs may be suitable targets for HCC treatment.

Applying Latent Profile Analysis to Identify Lifestyle Profiles and Their Association with Loneliness and Quality of Life among Community-Dwelling Middle- and Older-Aged Adults in South Korea.

This study aimed to examine the multi-faceted lifestyle profiles of community-dwelling middle- and older-aged adults based on their physical activity, participation in various activities, and nutrition. It identified the association of lifestyle profiles with demographic variables, quality of life, and mental health. The analysis included 569 participants (mean age = 60.2; SD = 4.3). Latent profile analysis identified three distinctive lifestyle profiles: "inactive and unbalanced" (36.4%), "basic life maintenance" (54.6%), and "active and balanced" (9.1%). Sex (p < 0.001), age (p < 0.001), and regular medication intake (p < 0.01) were statistically significantly different among the three profiles. Of the "inactive and unbalanced" lifestyle group, 63.3% of it was comprised of by females, and a relatively large distribution was aged over 65. In the "basic life maintenance" subgroup, males showed a relatively large distribution, and 92.6% of participants were aged 55-64. People with active and balanced lifestyles demonstrated high quality of life levels (p < 0.001) and low loneliness levels (p < 0.01). Multinomial logistic regression revealed a statistically significant positive association between lifestyle profiles and quality of life (p < 0.001) as well as mental health (p < 0.01). Therefore, health promotion that considers multi-faceted lifestyle factors would need to improve health and quality of life among community-dwelling middle- and older-aged adults in South Korea.

BET inhibitor suppresses migration of human hepatocellular carcinoma by inhibiting SMARCA4.

Hepatocellular carcinoma (HCC) is one of the most prevalent and poorly responsive cancers worldwide. Bromodomain and extraterminal (BET) inhibitors, such as JQ1 and OTX-015, inhibit BET protein binding to acetylated residues in histones. However, the physiological mechanisms and regulatory processes of BET inhibition in HCC remain unclear. To explore BET inhibitors' potential role in the molecular mechanisms underlying their anticancer effects in HCC, we analyzed BET inhibitor-treated HCC cells' gene expression profiles with RNA-seq and bioinformatics analysis. BET inhibitor treatment significantly downregulated genes related to bromodomain-containing proteins 4 (BRD4), such as ACSL5, SLC38A5, and ICAM2. Importantly, some cell migration-related genes, including AOC3, CCR6, SSTR5, and SCL7A11, were significantly downregulated. Additionally, bioinformatics analysis using Ingenuity Knowledge Base Ingenuity Pathway Analysis (IPA) revealed that SMARCA4 regulated migration response molecules. Furthermore, knockdown of SMARCA4 gene expression by siRNA treatment significantly reduced cell migration and the expression of migration-related genes. In summary, our results indicated that BET inhibitor treatment in HCC cell lines reduces cell migration through the downregulation of SMARCA4.

The BET inhibitor attenuates the inflammatory response and cell migration in human microglial HMC3 cell line.

Microglia, resident macrophages of the brain that act as primary immune cells, play essential roles in innate immunity and neuroinflammatory pathologies. Microglial cells are rapidly activated in response to infection and inflammation/injury, associated with the expression of proinflammatory genes and secretion of cytokines. The bromodomain and extra-terminal (BET) inhibitor JQ1 has been shown to be an epigenetic agent that reduces inflammation. In this study, we investigated the mechanisms underlying the anti-inflammatory and anti-migratory functions of JQ1 and the genes targeted by JQ1 in lipopolysaccharide (LPS)-activated human microglial clone 3 (HMC3) cells using RNA-sequencing (RNA-seq). We analyzed the pattern of inflammation-related genes (chemokines, cytokines, and interferon-stimulated genes) and migration-related genes with JQ1 treatment from differentially expressed genes analysis in HMC3 cells. We found that LPS-induced IRF1 directly regulated inflammation- and migration-related genes and that JQ1 significantly reduced IRF1 and its target genes. Additionally, IRF1 attenuation significantly downregulated target genes and inhibited microglial migration. Our data suggest that the BET inhibitor JQ1 can modulate the inflammatory response and migration through the regulation of LPS-induced IRF1 in human microglia.

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.

Effects of a Cognitive-Functional Intervention Method on Improving Executive Function and Self-Directed Learning in School-Aged Children with Attention Deficit Hyperactivity Disorder: A Single-Subject Design Study.

BACKGROUND: School-aged children with attention deficit hyperactivity disorder (ADHD) face many difficulties with self-directed learning because of their poor executive function. This leads to secondary problems such as learning disabilities and depression, so the role of intervention to improve executive function in school-aged children with ADHD is important. OBJECTIVE: The present study is aimed to investigate how cognitive-functional (Cog-Fun) intervention affected executive function of school-aged children with ADHD and the sustainability of these effects. To investigate the effects of changes in the executive function of school-aged children with ADHD through Cog-Fun intervention in self-directed learning. METHOD: A single-subject A-B-A research design was employed in this study. Three children aged 9-10 years who were diagnosed with ADHD were selected. A total of 17 experimental sessions were conducted. The Cog-Fun intervention program was implemented during the intervention phase. To measure dependent variables, Behavior Rating Inventory of Executive Function (BRIEF) and Homework Problems Checklist (HPC) were used. Significant changes in executive function assessed by the Children's Color Trails Test (CCTT) and Stroop test were analyzed through two-standard deviation band analysis. Additionally, video clips of task performance were analyzed to examine qualitative performance changes in self-directed learning. RESULT: All three participants presented statistically significant changes with a number of near-misses of CCTT and color words score of Stroop test during the intervention. T-scores of the Global Executive Composite (GEC) decreased after the intervention, indicating improvement in executive function. The follow-up period revealed retention of the improved executive function. Additionally, self-directed learning improved in all participants after the implementation Cog-Fun intervention. CONCLUSION: The study supports the effectiveness of Cog-Fun intervention in improving executive function in school-aged children with ADHD and confirmed that the improvement of executive function ultimately leads to the improvement of self-directed learning performance.

Impact of Family-Centered Early Intervention in Infants with Autism Spectrum Disorder: A Single-Subject Design.

OBJECTIVE: Autism spectrum disorder is a neurodevelopmental disorder that affects communication, social skills, and behavior and can present in early childhood. The present study is aimed at investigating the effects of family-centered early intervention on the quality of social interaction and social interaction skills in infants with suspected autism spectrum disorder using a single-subject design. METHOD: As a single-subject design study, evaluations were conducted at baseline phase A, intervention phase B, baseline phase A', and follow-up phase. The family-centered early intervention program was implemented during the intervention phase. Family-centered early intervention programs included home environmental modification, play video recording and training, task and feedback, related information training, and question and answer. The Modified Checklist for Autism in Toddlers, Revised, with Follow-Up and Evaluation of Social Interaction was used for evaluation. RESULT: Three participants completed the study. After applying the family-centered early intervention program, the quality of social interaction and social interaction skills of all participants improved. In addition, the risk of autism spectrum disorder in all participants was reduced. CONCLUSION: Family-centered early intervention was confirmed to have a positive effect on the improvement of social interaction skills in infants with suspected autism spectrum disorder.

The Development of Leisure Participation Assessment Tool for the Elderly.

OBJECTIVES: This study is aimed at developing multidimensional leisure participation assessment tool for the elderly to achieve quantitative and qualitative assessment of leisure participation and leisure exploration. METHODS: This study collected preliminary items through literature review, statistical office data, and survey of the elderly's leisure activities and considered the list of leisure activities as assessment items by conducting a Delphi survey. Reliability was verified through internal consistency and test-retest reliability. The assessment tool was finally confirmed using content validity and discriminant validity. RESULTS: A total of 81 leisure items classified into 8 categories and 22 subcategories were obtained through data collection and Delphi survey. Cronbach's α value was 0.939, and Intraclass Correlation Coefficient was 0.941. A content validity test was confirmed by validating that I-CVI was 0.78 or more and the S-CVI was 0.95. According to the result of discriminant validity, there was a difference in the number of participating leisure activities and leisure activities with participation intention by age. CONCLUSION: The leisure participation assessment tool for the elderly developed in this study can obtain information on the overall view of the leisure of the elderly by measuring leisure exploration, leisure participation, and interference factor affecting leisure participation.

Development and Validation of the Activities of Daily Living Short Form for Community-Dwelling Korean Stroke Survivors.

This study developed and validated a short form (SF) using activities of daily living (ADL) outcome measures from the Korea National Health and Nutrition Examination Survey (KNHANES) that can minimize survey administration burden for clinicians. This study utilized secondary data from the 2005 KNHANES with 422 community-dwelling stroke survivors. The KNHANES data were collected from April to June 2005 in South Korea. We created a 7-item SF from the 17 ADL questions in the survey using item response theory (IRT) methodologies. The precision and validity of the SF were compared to the full questionnaire of ADL items and the EuroQol-5D total score. Among the 17 ADL questions, 14 questions demonstrated unidimensional construct validity. Using IRT methodologies, a set of 7 items were selected from the full bank. The 7-item SF demonstrated good psychometric properties: high correlation with the full bank ( r = .975, p < .001), good internal consistency (Cronbach's α = .93), and a high correlation with the EuroQol-5D total score ( r = .678, p < .001). These findings indicate that a well-developed SF can precisely measure ADL performance capacity for stroke survivors compared to the full item bank, which is expected to reduce the administration burden of the KNHANES.

The effects of mental practice combined with modified constraint-induced therapy on corticospinal excitability, movement quality, function, and activities of daily living in persons with stroke.

PURPOSE: Studies on to what extent the combined therapy of modified constraint-induced movement therapy and mental practice is more effective than modified constraint-induced movement therapy alone are lacking. This study aims to compare the effects of the combined therapy with modified constraint-induced movement therapy alone on corticospinal excitability, quality of the movement of the affected upper extremity, upper motor functions, and performance of the affected arm in daily life of hemiplegic stroke patients. METHODS: The participants comprised 14 people who had suffered stroke and were randomly divided into two groups. All participants participated in modified constraint-induced movement therapy, while only the experimental group partook in additional mental practice. Both groups were tested for corticospinal excitability, quality of movement, hand function, and activities of daily living. RESULTS: Both groups showed significant improvement in the movement quality of reaching and performance of activities of daily living. In the experimental group, functional improvement of the upper limb was also observed. The improvements in corticospinal excitability, upper extremity function, and performance in daily activities were significantly greater in the experimental group compared to the control group. CONCLUSIONS: This study confirmed that the combined therapy produces more effective improvement in corticospinal excitability, upper limb function, and performance in daily activities. The combined therapy of mental practice and modified constraint-induced movement therapy could be used as a clinically useful intervention. Implications for rehabilitation Modified constraint-induced movement therapy could be used as an intervention method for people with stroke to make improvements in the quality of movement and performance in activities of daily livings with the affected side. With additional mental practice, upper extremity functions improve, and changes in neurological, functional and performance in daily lives are greater compared to modified constraint-induced movement therapy without mental practice. Impact of mental practice has on rehabilitation should not be underestimated.

Comparison of Cognitive Orientation to daily Occupational Performance and conventional occupational therapy on occupational performance in individuals with stroke: A randomized controlled trial.

BACKGROUND: Cognitive Orientation to daily Occupational Performance (CO-OP) approach based on cognitive strategy in occupational therapy. OBJECTIVES: To investigate the effects of CO-OP approach on occupational performance in individuals with hemiparetic stroke. METHODS: This study was designed as a 5-week, randomized, single-blind. Forty-three participants who had a diagnosis of first stroke were enrolled in this study. The participants were randomly assigned to the experimental group (n = 20) or the control group (n = 23). The experimental group conducted CO-OP approach while the control group conducted conventional occupational therapy based on occupational performance components. This study measured Canadian Occupational Performance Measure (COPM) and Performance Quality Rating Scale (PQRS). Outcome measurements were performed at baseline and post-intervention. RESULTS: After training, the scores of COPM and PQRS in trained task were significantly higher for the score in the experimental group than the control group. In addition, the non-trained task was significantly higher for the score in the experimental group than the control group in COPM and the PQRS. CONCLUSIONS: This study suggests that the CO-OP approach is beneficial effects on the occupational performance to improvement in individuals with hemiparetic stroke, and have positive effects on generalization and transfer of acquired skills.

The effects of virtual reality-based bilateral arm training on hemiplegic children's upper limb motor skills.

BACKGROUND: Hemiplegic cerebral palsy is a neurological symptom appearing on the unilateral arm and leg of the body that causes affected upper/lower limb muscle weakening and dysesthesia and accompanies tetany and difficulties in postural control due to abnormal muscle tone, and difficulties in body coordination. OBJECTIVES: The purpose of this study was to examine the impact of virtual reality-based bilateral arm training on the motor skills of children with hemiplegic cerebral palsy, in terms of their upper limb motor skills on the affected side, as well as their bilateral coordination ability. METHODS: The research subjects were three children who were diagnosed with hemiplegic cerebral palsy. The research followed an ABA design, which was a single-subject experimental design. The procedure consisted of a total of 20 sessions, including four during the baseline period (A1), 12 during the intervention period (B), and four during the baseline regression period (A2), For the independent variable bilateral arm training based on virtual reality, Nintendo Wii game was played for 30 minutes in each of the 12 sessions. For the dependent variables of upper limb motor skills on the affected side and bilateral coordination ability, a Wolf Motor Function Test (WMFT) was carried out for each session and the Pediatric Motor Activity Log (PMAL) was measured before and after the intervention, as well as after the baseline regression period. To test bilateral coordination ability, shooting baskets in basketball with both hands and moving large light boxes were carried out under operational definitions, with the number of shots and time needed to move boxes measured. The results were presented using visual graphs and bar graphs. RESULTS: The study's results indicated that after virtual reality-based bilateral arm training, improvement occurred in upper limb motor skills on the affected sides, and in bilateral coordination ability, for all of the research subjects. Measurements of the effects of sustained therapy after completion of the intervention, during the baseline regression period, revealed that upper limb motor skills on the affected side and bilateral coordination ability were better than in the baseline period for all subjects. CONCLUSION: This study confirmed that for children with hemiplegic with cerebral palsy, bilateral arm training based on virtual reality can be an effective intervention method for enhancing the upper limb motor skills on the affected side, as well as bilateral coordination ability.

Effects of Task-Oriented Training as an Added Treatment to Electromyogram-Triggered Neuromuscular Stimulation on Upper Extremity Function in Chronic Stroke Patients.

The purpose of the present study was to investigate the effects of electromyogram-triggered neuromuscular stimulation (EMG-stim) combined with task-oriented training (TOT) on upper extremity function in chronic stroke patients. Twenty chronic stroke patients were randomly assigned to either the intervention (n = 10) or control (n = 10) group. The intervention group conducted TOT with EMG-stim on the wrist and finger extensor of the affected arm for 30 minutes per day, 5 days per week, for 4 weeks. The control group was provided EMG-stim for 20 minutes per day for the same duration. The intervention group exhibited significant improvement relative to the control group in muscle activation, motor recovery (Fugl-Meyer assessment) and dexterity (Box and Block Test) (p < 0.05). Significant differences in hand function between the groups were detected in the writing of short sentences and in stacking checkers (p < 0.05). It is concluded that EMG-stim in combination with TOT may be better than EMG-stim alone for the treatment of arm paresis in stroke patients. Further research with a larger sample is recommended to examine neurologic changes or cerebral cortex reorganization. Copyright © 2016 John Wiley & Sons, Ltd.