Regulation of embryonic haematopoietic multipotency by EZH1.

All haematopoietic cell lineages that circulate in the blood of adult mammals derive from multipotent haematopoietic stem cells (HSCs). By contrast, in the blood of mammalian embryos, lineage-restricted progenitors arise first, independently of HSCs, which only emerge later in gestation. As best defined in the mouse, 'primitive' progenitors first appear in the yolk sac at 7.5 days post-coitum. Subsequently, erythroid-myeloid progenitors that express fetal haemoglobin, as well as fetal lymphoid progenitors, develop in the yolk sac and the embryo proper, but these cells lack HSC potential. Ultimately, 'definitive' HSCs with long-term, multilineage potential and the ability to engraft irradiated adults emerge at 10.5 days post-coitum from arterial endothelium in the aorta-gonad-mesonephros and other haemogenic vasculature. The molecular mechanisms of this reverse progression of haematopoietic ontogeny remain unexplained. We hypothesized that the definitive haematopoietic program might be actively repressed in early embryogenesis through epigenetic silencing, and that alleviating this repression would elicit multipotency in otherwise lineage-restricted haematopoietic progenitors. Here we show that reduced expression of the Polycomb group protein EZH1 enhances multi-lymphoid output from human pluripotent stem cells. In addition, Ezh1 deficiency in mouse embryos results in precocious emergence of functional definitive HSCs in vivo. Thus, we identify EZH1 as a repressor of haematopoietic multipotency in the early mammalian embryo.

Therapeutic potential of FLT4-targeting peptide in acute myeloid leukemia.

Previously, we found that dysfunctional natural killer (NK) cells with low interferon gamma (IFN-γ) were restored in acute myeloid leukemia (AML) by the FLT4 antagonist MAZ51. Here, we developed 12 peptides targeting FLT4 for clinical application and examined whether they restored the frequency of lymphocytes, especially T cells and NK cells, and high IFN-γ expression, as MAZ51 treatment did in our previous study. Although clinical data from using peptides are currently available, peptides targeting FLT4 to modulate immune cells have not been fully elucidated. In this study, we focus on novel peptide 4 (P4) from the intracellular domain of FLT4 because it had dominant negative activity. Similar to MAZ51, high IFN-γ levels were expressed in AML-mononuclear cells exposed to P4. Additionally, T and NK cell levels were restored, as were high IFN-γ levels, in a leukemic environment when P4 was treated. Interestingly, the regulatory T cells were significantly decreased by P4, implying the role of peptide in tumor niche. Overall, we demonstrated the therapeutic value of functionally modulating lymphocytes using a peptide targeting FLT4 and proposed the development of advanced therapeutic approaches against AML by using immune cells.

FLT4 as a marker for predicting prognostic risk of refractory acute myeloid leukemia.

Treating patients with refractory acute myeloid leukemia (AML) remains challenging. Currently there is no effective treatment for refractory AML. Increasing evidence has demonstrated that refractory/relapsed AML is associated with leukemic blasts which can confer resistance to anticancer drugs. We have previously reported that high expression of Fms-related tyrosine kinase 4 (FLT4) is associated with increased cancer activity in AML. However, the functional role of FLT4 in leukemic blasts remains unknown. Here, we explored the significance of FLT4 expression in leukemic blasts of refractory patients and mechanisms involved in the survival of AML blasts. Inhibition or absence of FLT4 in AML blasts suppressed homing to bone marrow of immunocompromised mice and blocked engraftment of AML blasts. Moreover, FLT4 inhibition by MAZ51, an antagonist, effectively reduced the number of leukemic cell-derived colony-forming units and increased apoptosis of blasts derived from refractory patients when it was co-treated with cytosine arabinoside under vascular endothelial growth factor C, its ligand. AML patients who expressed high cytosolic FLT4 were linked to an AML-refractory status by internalization mechanism. In conclusion, FLT4 has a biological function in leukemogenesis and refractoriness. This novel insight will be useful for targeted therapy and prognostic stratification of AML.

Haematopoietic stem and progenitor cells from human pluripotent stem cells.

A variety of tissue lineages can be differentiated from pluripotent stem cells by mimicking embryonic development through stepwise exposure to morphogens, or by conversion of one differentiated cell type into another by enforced expression of master transcription factors. Here, to yield functional human haematopoietic stem cells, we perform morphogen-directed differentiation of human pluripotent stem cells into haemogenic endothelium followed by screening of 26 candidate haematopoietic stem-cell-specifying transcription factors for their capacity to promote multi-lineage haematopoietic engraftment in mouse hosts. We recover seven transcription factors (ERG, HOXA5, HOXA9, HOXA10, LCOR, RUNX1 and SPI1) that are sufficient to convert haemogenic endothelium into haematopoietic stem and progenitor cells that engraft myeloid, B and T cells in primary and secondary mouse recipients. Our combined approach of morphogen-driven differentiation and transcription-factor-mediated cell fate conversion produces haematopoietic stem and progenitor cells from pluripotent stem cells and holds promise for modelling haematopoietic disease in humanized mice and for therapeutic strategies in genetic blood disorders.

Thermal resistance of Escherichia coli O157:H7 in laboratory media, milk, and beef extracts during non-isothermal processing at various heating rates.

This study investigated the effect of non-isothermal treatments with different heating rates (HRs) on inactivating Escherichia coli O157:H7 in various heating media. E. coli O157:H7 in phosphate-buffered saline (pH 7; PBS), Luria-Bertani broth with (LBS) or without (LB) 1% NaCl, milk, 3% beef extract (beef3%), and 30% beef extract (beef30%) were inactivated under non-isothermal conditions (up to 50 - 60 °C) using various HRs between 1.32 and 10.78 °C/min. After treatment with an HR of 1.32 °C/min to a target temperature of 60 °C, the reduction level of E. coli O157:H7 were 6.49, 2.28, 1.20, 1.30, 5.55 and 5.02 log CFU/mL in PBS, LB, LBS, milk, beef3%, and beef30%, respectively. Contrastingly, E. coli O157:H7 treated in PBS, LB, milk, beef3%, and beef30% with an HR of 10.78 °C/min to the same target temperature were completely inactivated to not-detectable level. Moreover, E. coli O157:H7 treated at 10.63 °C/min exhibited more severe morphological injuries than those at 2.23 °C/min. Interestingly, inactivation through non-isothermal treatment is potentially involved in either ribonucleic acid or lipid synthesis, as E. coli O157:H7 treated at 10.63 °C/min for 3.5 min less recovered on TSA with rifampicin and streptomycin. These observations highlight the ability of the E. coli O157:H7 to survive for long periods at a potentially sub-lethal temperature, which may be enhanced concomitantly with a decrease in the HR of the non-isothermal treatment.

A nanobody targeting the LIN28:let-7 interaction fragment of TUT4 blocks uridylation of let-7.

The LIN28:pre-let-7:TUTase ternary complex regulates pluripotency and oncogenesis by controlling processing of the let-7 family of microRNAs. The complex oligouridylates the 3' ends of pre-let-7 molecules, leading to their degradation via the DIS3L2 exonuclease. Previous studies suggest that components of this complex are potential therapeutic targets in malignancies that aberrantly express LIN28. In this study we developed a functional epitope selection approach to identify nanobody inhibitors of the LIN28:pre-let-7:TUT4 complex. We demonstrate that one of the identified nanobodies, Nb-S2A4, targets the 106-residue LIN28:let-7 interaction (LLI) fragment of TUT4. Nb-S2A4 can effectively inhibit oligouridylation and monouridylation of pre-let-7g in vitro. Expressing Nb-S2A4 allows maturation of the let-7 species in cells expressing LIN28, highlighting the therapeutic potential of targeting the LLI fragment.

Clinical Course of Patients With Mediastinal Lymph Node Tuberculosis and Risk Factors for Paradoxical Responses.

BACKGROUND: Paradoxical responses (PR) occur more frequently in lymph node tuberculosis (LNTB) than in pulmonary tuberculosis and present difficulties in differential diagnosis of drug resistance, new infection, poor patient compliance, and adverse drug reactions. Although diagnosis of mediastinal LNTB has become much easier with the development of endosonography, limited information is available. The aim of this study was to investigate the clinical course of mediastinal LNTB and the risk factors associated with PR. METHODS: Patients diagnosed with mediastinal LNTB via endosonography were evaluated retrospectively between October 2009 and December 2019. Multivariable logistic regression was applied to evaluate the risk factors associated with PR. RESULTS: Of 9,052 patients who underwent endosonography during the study period, 158 were diagnosed with mediastinal LNTB. Of these, 55 (35%) and 41 (26%) concurrently had pulmonary tuberculosis and extrapulmonary tuberculosis other than mediastinal LNTB, respectively. Of 125 patients who completed anti-tuberculosis treatment, 21 (17%) developed PR at a median of 4.4 months after initiation of anti-tuberculosis treatment. The median duration of anti-tuberculosis treatment was 6.3 and 10.4 months in patients without and with PR, respectively. Development of PR was independently associated with age < 55 years (adjusted odds ratio [aOR], 5.72; 95% confidence interval [CI], 1.81-18.14; P = 0.003), lymphocyte count < 800/µL (aOR, 8.59; 95% CI, 1.60-46.20; P = 0.012), and short axis diameter of the largest lymph node (LN) ≥ 16 mm (aOR, 5.22; 95% CI, 1.70-16.00; P = 0.004) at the time of diagnosis of mediastinal LNTB. CONCLUSION: As PR occurred in one of six patients with mediastinal LNTB during anti-tuberculosis treatment, physicians should pay attention to patients with risk factors (younger age, lymphocytopenia, and larger LN) at the time of diagnosis.

A time-dependent subdistribution hazard model for major dental treatment events in cancer patients: a nationwide cohort study.

BACKGROUND: Dental care in cancer patients tends to be less prioritized. However, limited research has focused on major dental treatment events in cancer patients after the diagnosis. This study aimed to examine dental treatment delays in cancer patients compared to the general population using a national claims database in South Korea. METHOD: The Korea National Health Insurance Service-National Sample Cohort version 2.0, collected from 2002 to 2015, was analyzed. Treatment events were considered for stomatitis, tooth loss, dental caries/pulp disease, and gingivitis/periodontal disease. For each considered event, time-dependent hazard ratios and associated 95% confidence intervals were calculated by applying a subdistribution hazard model with time-varying covariates. Mortality was treated as a competing event. Subgroup analyses were conducted by type of cancer. RESULTS: The time-dependent subdistribution hazard ratios (SHRs) of stomatitis treatment were greater than 1 in cancer patients in all time intervals, 2.04 within 30 days after cancer diagnosis, and gradually decreased to 1.15 after 5 years. The SHR for tooth loss was less than 0.70 within 3 months after cancer diagnosis and increased to 1 after 5 years. The trends in SHRs of treatment events for other dental diseases were similar to those observed for tooth loss. Subgroup analyses by cancer type suggested that probability of all dental treatment event occurrence was higher in head and neck cancer patients, particularly in the early phase after cancer diagnosis. CONCLUSION: Apart from treatments that are associated with cancer therapy, dental treatments in cancer patients are generally delayed and cancer patients tend to refrain from dental treatments. Consideration should be given to seeking more active and effective means for oral health promotion in cancer patients.

Multiple mechanisms disrupt the let-7 microRNA family in neuroblastoma.

Poor prognosis in neuroblastoma is associated with genetic amplification of MYCN. MYCN is itself a target of let-7, a tumour suppressor family of microRNAs implicated in numerous cancers. LIN28B, an inhibitor of let-7 biogenesis, is overexpressed in neuroblastoma and has been reported to regulate MYCN. Here we show, however, that LIN28B is dispensable in MYCN-amplified neuroblastoma cell lines, despite de-repression of let-7. We further demonstrate that MYCN messenger RNA levels in amplified disease are exceptionally high and sufficient to sponge let-7, which reconciles the dispensability of LIN28B. We found that genetic loss of let-7 is common in neuroblastoma, inversely associated with MYCN amplification, and independently associated with poor outcomes, providing a rationale for chromosomal loss patterns in neuroblastoma. We propose that let-7 disruption by LIN28B, MYCN sponging, or genetic loss is a unifying mechanism of neuroblastoma development with broad implications for cancer pathogenesis.

Efficacy of Internet-Based Acceptance and Commitment Therapy for Depressive Symptoms, Anxiety, Stress, Psychological Distress, and Quality of Life: Systematic Review and Meta-analysis.

BACKGROUND: Acceptance and commitment therapy (ACT) is an empirically supported transdiagnostic approach that involves mindfulness processes and behavior change processes for valued living. OBJECTIVE: This systematic review and meta-analysis of randomized controlled trials (RCTs) aimed to assess the efficacy of internet-based ACT (iACT) for depressive symptoms, anxiety, stress, psychological distress, and quality of life (QoL). METHODS: PubMed, CINAHL, PsycINFO, and SCOPUS databases were searched to identify relevant RCTs published up to June 5, 2021. The included RCTs were assessed using the Cochrane Collaboration risk-of-bias tool. The use of either a random effects model or fixed effects model was determined using I2 statistic values for heterogeneity. Subgroup analyses were conducted according to the type of control group, the use of therapist guidance, delivery modes, and the use of targeted participants, when applicable. RESULTS: A total of 39 RCTs met the inclusion criteria. Meta-analyses found small effects of iACT on depressive symptoms, anxiety, stress, psychological distress, and QoL at the immediate posttest and follow-up. There was no significant effect of iACT on stress at follow-up. Subgroup analyses showed small to medium effects of iACT on all the outcomes at the immediate posttest and follow-up compared with the passive control groups. In contrast, subgroup analyses that compared iACT with active control groups found no differences between groups on stress, psychological distress, and QoL at the immediate posttest or on depressive symptoms, anxiety, and stress at follow-up. In addition, subgroup analyses conducted according to the use of therapist guidance, delivery modes, and the use of targeted participants found no statistically significant subgroup differences among studies in all the outcomes, except for the subgroup difference among studies according to the use of targeted participants for depressive symptoms at the immediate posttest (ie, a statistically significant, larger effect of iACT when studies targeted people with depressive symptoms). The overall risk of bias across the studies was unclear. CONCLUSIONS: The findings of this study contribute to the body of evidence regarding the effects of iACT on depressive symptoms, anxiety, stress, psychological distress, and QoL and may be applicable in any population, as ACT is a transdiagnostic approach. Few studies have compared iACT with active control conditions, especially for stress and psychological distress at the immediate posttest and follow-up. In addition, the active control conditions varied among the included studies. Further high-quality studies are needed to better understand whether iACT is comparable or superior to other evidence-based interventions, such as cognitive behavioral therapy, in decreasing depressive symptoms, anxiety, stress, and psychological distress and improving QoL.

The Effects of Internet-Based Acceptance and Commitment Therapy on Process Measures: Systematic Review and Meta-analysis.

BACKGROUND: Acceptance and commitment therapy (ACT) is based on a psychological flexibility model that encompasses 6 processes: acceptance, cognitive defusion, self-as-context, being present, values, and committed action. OBJECTIVE: This systematic review and meta-analysis of randomized controlled trials (RCTs) aimed to examine the effects of internet-based ACT (iACT) on process measures. METHODS: A comprehensive search was conducted using 4 databases. The quality of the included RCTs was assessed using the Cochrane Collaboration Risk of Bias Tool. A random-effects or fixed-effects model was used. Subgroup analyses for each outcome were conducted according to the type of control group, use of therapist guidance, delivery modes, and use of targeted participants, when applicable. RESULTS: A total of 34 RCTs met the inclusion criteria. This meta-analysis found that iACT had a medium effect on psychological flexibility and small effects on mindfulness, valued living, and cognitive defusion at the immediate posttest. In addition, iACT had a small effect on psychological flexibility at follow-up. The overall risk of bias across studies was unclear. CONCLUSIONS: Relatively few studies have compared the effects of iACT with active control groups and measured the effects on mindfulness, valued living, and cognitive defusion. These findings support the processes of change in iACT, which mental health practitioners can use to support the use of iACT.

Effects of mindfulness-and acceptance-based interventions on quality of life, coping, cognition, and mindfulness of people with multiple sclerosis: a systematic review and meta-analysis.

This systematic review and meta-analysis of randomized controlled trials (RCTs) examined effects of mindfulness- and acceptance-based interventions (MABIs) on quality of life (QoL), coping, cognition, and mindfulness among people with multiple sclerosis (MS). Four electronic databases were searched to 3 July 2020. Data was combined in a random-effects meta-analysis model. Eighteen RCTs met the eligibility criteria. Meta-analyses at the immediate posttest found: moderate effects of MABIs on QoL, coping, and attention; and a large effect on memory. A large effect of MABIs on QoL was found at follow-up. There was no significant effect of MABIs on mindfulness. Relatively fewer studies in outcomes other than QoL were found, and the overall risk of bias across the included 18 RCTs was unclear. Future high-quality studies with follow-up evaluations are needed to support effects of MABIs on QoL, coping, cognition, and mindfulness in people with MS and examine intervention features that increase and maintain effects.

Effects of mindfulness-based interventions on psychological distress and mindfulness in incarcerated populations: A systematic review and meta-analysis.

BACKGROUND: As incarcerated populations report significantly higher prevalence rates for psychological distress than community populations, it is important to have an evidence-based perspective on what reduces psychological distress among people in prison or jail. AIMS: To examine effects of mindfulness-based interventions (MBIs) on psychological distress, including anxiety, depressive symptoms, stress and overall psychological distress, and on mindfulness in incarcerated populations. METHODS: This systematic review and meta-analysis of randomised controlled trials (RCTs) involved a comprehensive search within the PubMed, CINAHL, PsycINFO, and SCOPUS databases to identify relevant RCTs. The quality of the included RCTs was assessed using the Cochrane Collaboration risk of bias tool. Depending on I2 statistic values for heterogeneity, either a random effects model or fixed effects model was used. Subgroup analyses for each outcome were conducted to see whether effects differed when compared MBIs to active control groups, provided with other comparable interventions, or passive control groups, provided with no intervention (i.e., treatment as usual [TAU] control groups or waiting list controls). RESULTS: Thirteen RCTs met the eligibility criteria. Meta-analyses showed moderate effects of MBIs on depressive symptoms and overall psychological distress, large effects on stress, and small effects on anxiety and mindfulness. The overall risk of bias across studies was unclear. Fewer studies were conducted to compare effects of MBIs to other interventions than TAU. CONCLUSIONS: Future high-quality studies comparing MBIs to other active interventions are needed to understand better whether the former are comparable or superior to other evidence-based treatments in decreasing distress and improving mindfulness in incarcerated populations and/or in which circumstances one may be preferable to the other.

Mindfulness-Based Interventions for Older Adults with Dementia or Mild Cognitive Impairment: A Meta-Analysis.

OBJECTIVES: This systematic review and meta-analysis examined the effects of mindfulness-based interventions (MBIs) on psychological symptoms, cognitive functions, and quality of life in older adults with dementia or mild cognitive impairment (MCI). METHODS: A comprehensive search was conducted within four databases to identify relevant randomized controlled trials (RCTs). Heterogeneity was assessed using the I2 statistic. Depending on I2 statistic values, either a random effects model or fixed effects model was used. RESULTS: 10 RCTs published in 11 articles met the eligibility criteria. The present meta-analysis study found no significant effect of MBIs on depressive symptoms, anxiety, quality of life, memory, and overall cognitive functions compared to control groups. CONCLUSIONS: Future high-quality studies involving different types of MBIs are needed to better understand the effects of MBIs on psychological symptoms, quality of life, and cognitive functions in older adults with MCI and dementia and examine effective intervention features. CLINICAL IMPLICATIONS: There is insufficient evidence to determine whether or not practitioners should be routinely providing MBIs to older adults with MCI and dementia due to the lack of studies currently.

A Quasi-experimental Study Measuring the Effectiveness of Two Empathy Enhancement Programs on Caregivers Working with Older Adults Living Alone.

Objectives: This quasi-experimental study assessed the effectiveness of two empathy enhancement programs on direct care workers of older adults living alone in South Korea.Methods: A total of 104 direct care workers participated in either a simulation-based program or a lecture-based program. Data were collected prior to and 2 weeks after the program implementation using self-reported questionnaires.Results: The lecture-based group had significantly higher levels of empathy compared to the simulation-based group. Pretest-posttest differences were found in the lecture-based group only, including higher levels of empathy and caring efficacy and lower levels of secondary traumatic stress and burnout.Conclusions: More studies are needed to identify helpful components of empathy enhancement programs to direct care workers working with older adults living alone. Also, a further randomized controlled trial study is needed to assess programs' effectiveness on older adults living alone and direct care workers.Clinical implications: A lecture-based empathy enhancement program can increase levels of empathy and caring efficacy of direct care workers working with older adults and decrease care workers' levels of burnout and stress. Training for direct care workers of older adults is needed to improve the empathy of direct care workers while reducing their stress and burnout.

Acceptance and Commitment Therapy (ACT) Guided Online for Distressed Caregivers of Persons Living with Dementia.

OBJECTIVES: This study examined the effects of a guided online acceptance and commitment therapy (ACT) intervention on distressed family caregivers of persons living with dementia and explored the experiences of these caregivers in the ACT intervention. METHODS: Seven family caregivers experiencing psychological distress individually participated in 10 ACT videoconference sessions guided by a trained coach. Quantitative data, such as psychological distress, burden, and ACT processes, were collected at pretest and posttest and analyzed using the Wilcoxon signed-rank test. Individual interviews were conducted at posttest and analyzed using interpretative phenomenological analysis. RESULTS: Statistically significant reductions were found in depressive symptoms, anxiety, stress, and burden (p < .05) with medium effect sizes. ACT sessions helped caregivers gain renewed strength by: being equipped with resources to use under distress throughout the caregiving journey; being more self-compassionate and taking care of one's self; and being more patient with relatives with dementia. CONCLUSIONS: Findings contribute to the limited evidence in guided online ACT for caregivers of persons living with dementia. Further studies with a larger sample size are needed to evaluate the efficacy of guided online ACT. CLINICAL IMPLICATIONS: Guided online ACT may reduce depressive symptoms, anxiety, stress, and burden of family caregivers of persons living with dementia.

Mindfulness- and Acceptance-Based Interventions for Symptom Reduction in Individuals With Multiple Sclerosis: A Systematic Review and Meta-Analysis.

OBJECTIVE: To examine the effects of mindfulness- and acceptance-based interventions (MABIs) on reducing symptoms in individuals with multiple sclerosis (MS). DATA SOURCES: A comprehensive search was conducted within the PubMed, CINAHL, PsycINFO, and SCOPUS databases for articles published from inception to July 3, 2020. STUDY SELECTION: Randomized controlled trials (RCTs) were included if MABIs were provided to individuals with MS exclusively, with reported pre-and posttest results in symptoms of depression, anxiety, stress, fatigue, or pain. DATA EXTRACTION: Characteristics of the included RCTs and data for meta-analysis were extracted. The quality of the included RCTs was assessed using the Cochrane Collaboration risk of bias tool. DATA SYNTHESIS: A random effects model with the inverse variance method was used with effect size reported as standardized mean difference. Heterogeneity was assessed using the I2 statistic. RESULTS: Twenty-three RCTs met the eligibility criteria. Meta-analyses found large effects of MABIs on reducing depressive symptoms, anxiety, stress, and pain, as well as a moderate effect of MABIs on reducing fatigue at the immediate posttest. Large effects of MABIs on reducing depressive symptoms, anxiety, and stress at follow-up were also found, whereas a moderate effect on reducing fatigue was found at follow-up. There was no significant effect of MABIs on reducing pain at follow-up. CONCLUSIONS: Fewer studies were included in meta-analyses for pain at the immediate posttest and follow-up and stress and fatigue at follow-up. The overall risk of bias was unclear. Future high-quality studies with follow-up evaluations are needed to support effects of MABIs on reducing symptoms in individuals with MS and examine intervention features that increase and maintain effects.

A factorial randomized controlled trial to examine separate and combined effects of a simulation-based empathy enhancement program and a lecture-based education program on family caregivers of people with dementia.

OBJECTIVES: The present study was a 2 × 2 factorial randomized controlled trial that examined if a simulation-based empathy enhancement program and a lecture-based education program, together or separately, improved outcomes of family caregivers of people with dementia. METHOD: A total of 101 participants were randomly assigned to simulation-based education only, lecture-based education only, simulation-based education plus lecture-based education, or treatment as usual. Data were analyzed using a two-way analysis of covariance while controlling for pretest results, kinship, and gender. RESULTS: Statistically significant interaction effects between the simulation program and the lecture program were found in the levels of well-being and helplessness. The lecture program accompanied by the simulation program led to higher level of well-being in terms of happiness and lower level of helplessness than the lecture program alone. Caregivers with the lecture program provided led to less frequent use of dysfunctional coping strategies than those with no lecture program provided. Caregivers with the simulation program provided led to more frequent use of emotion-focused coping strategies than those with no simulation program provided. CONCLUSIONS: Findings of the present study support benefits of combined of and separate simulation-based and lecture-based programs on family caregivers of people with dementia in important outcomes affecting quality of care and quality of lives in families of people with dementia. Further studies are needed to identify intervention components that can improve empathy of family caregivers of people with dementia and be embedded into a multicomponent program tailored better to families in different needs.

Leisure-time physical activity, coping and life satisfaction among Korean individuals with physical disabilities.

A few studies explored the relationships among leisure-time physical activity (LTPA), coping, and life satisfaction among individuals with physical disabilities. This study aims to investigate how LPTA contributes to coping and life satisfaction among Korean individuals with physical disabilities. Using a purposive sampling strategy, a total of 351 people with physical disabilities participated in this study. The results of this study find that participation in LTPA leads to the development of active coping strategies that contribute to increased life satisfaction. This study suggests that encouraging LTPA participation can be a critical task to healthcare providers working with individuals with physical disabilities.

Effectiveness of a community-based integrated service model for older adults living alone: A nonrandomized prospective study.

OBJECTIVE: Older adults living alone face physical, emotional, and social health problems, and prefer to age in place (AIP) in their homes. A community-based integrated model for AIP is needed and few studies have identified its impact on older adults living alone. METHODS: This was a non-randomized prospective study. Participants were 877 community-dwelling older adults living alone, aged above 65 years, in S* city in South Korea. The intervention group (n = 331) received a community-based integrated service (CBIS) model based on AIP for six months from October 2019 to April 2020. RESULTS: Scores on frailty (ß = -0.377, p < .001), loneliness (ß = -1.897, p = .018), and health-related quality of life (ß = 4.299, p = .021) significantly improved in the intervention group. Among the intervention group, loneliness scores significantly improved among participants aged under 80 years than those aged over 80 years. CONCLUSION: The CBIS model improved frailty, loneliness, and quality of life in community-dwelling older adults living alone.