Salivary Cortisol and Melatonin, Sleep, and Behavioral Patterns in Older Adults Living With Dementia.

BACKGROUND: Over half of the older adults living with dementia have behavioral and psychological symptoms of dementia (BPSD), including sleep disturbance; however, little is known about physiological markers. Salivary cortisol and melatonin have been identified as potential biomarkers of BPSD, with evidence suggesting a relationship between these biomarkers and various behavioral factors, as well as sleep and activity patterns. OBJECTIVES: The aim of this study was to investigate the time-dependent changes in salivary cortisol and melatonin levels in older adults with dementia, their relationship with the sleep-wake cycle, and their correlation with BPSD symptoms and behavioral factors. METHODS: This observational study conducted in Seoul and Gyeonggi-do, South Korea, used data from 172 older adults with dementia, measuring sleep and activity patterns for 2 weeks using a wearable device, in addition to administering questionnaires for neuropsychiatric and psychological symptoms-the Neuropsychiatric Inventory, Cohen-Mansfield Agitation Inventory, and Cornell Scale for Depression in Dementia. Salivary cortisol and melatonin levels were measured at four time points and divided into four groups based on a dual-trajectory model. Differences among the groups were analyzed using one-way analysis of variance. RESULTS: The participants showed normal but heterogeneous patterns of salivary cortisol and melatonin levels. Dual-trajectory pattern analysis showed that higher levels of melatonin during the daytime were correlated with poor nighttime sleep efficiency and decreased disinhibited behaviors, and higher levels of cortisol at all four time points were associated with decreased physical activity. DISCUSSION: Measuring and analyzing periodic changes in cortisol and melatonin levels can predict various behavioral symptoms (e.g., sleep disturbances, activity counts, and disinhibition) in older adults with dementia. A study with an experimental design is needed to discover the direct physiological interactions between cortisol, melatonin, and these symptoms.

Long-term care facilities' response to the COVID-19 pandemic: An international, cross-sectional survey.

AIMS: To (i) assess the adherence of long-term care (LTC) facilities to the COVID-19 prevention and control recommendations, (ii) identify predictors of this adherence and (iii) examine the association between the adherence level and the impact of the pandemic on selected unfavourable conditions. DESIGN: Cross-sectional survey. METHODS: Managers (n = 212) and staff (n = 2143) of LTC facilities (n = 223) in 13 countries/regions (Brazil, Egypt, England, Hong Kong, Indonesia, Japan, Norway, Portugal, Saudi Arabia, South Korea, Spain, Thailand and Turkey) evaluated the adherence of LTC facilities to COVID-19 prevention and control recommendations and the impact of the pandemic on unfavourable conditions related to staff, residents and residents' families. The characteristics of participants and LTC facilities were also gathered. Data were collected from April to October 2021. The study was reported following the STROBE guidelines. RESULTS: The adherence was significantly higher among facilities with more pre-pandemic in-service education on infection control and easier access to information early in the pandemic. Residents' feelings of loneliness and feeling down were the most affected conditions by the pandemic. More psychological support to residents was associated with fewer residents' aggressive behaviours, and more psychological support to staff was associated with less work-life imbalance. CONCLUSIONS: Pre-pandemic preparedness significantly shaped LTC facilities' response to the pandemic. Adequate psychological support to residents and staff might help mitigate the negative impacts of infection outbreaks. IMPACT: This is the first study to comprehensively examine the adherence of LTC facilities to COVID-19 prevention and control recommendations. The results demonstrated that the adherence level was significantly related to pre-pandemic preparedness and that adequate psychological support to staff and residents was significantly associated with less negative impacts of the pandemic on LTC facilities' staff and residents. The results would help LTC facilities prepare for and respond to future infection outbreaks. PATIENT OR PUBLIC CONTRIBUTION: No Patient or Public Contribution.

Effects of registered nurses' staffing levels, work environment and education levels on nursing home residents' quality of life and nurse outcomes.

AIMS AND OBJECTIVES: To examine the effects of registered nurse staffing levels, work environment and education levels on the residents' quality of life and nurses' job dissatisfaction, burnout and turnover intention. BACKGROUND: Registered nurse staffing status and work environment are suboptimal in nursing homes worldwide. Nursing home care aims to maximise residents' quality of life. However, evidence on the impact of registered nurse staffing levels, work environment and education levels on the residents' quality of life and nurse outcomes in nursing homes is limited. DESIGN: This is a cross-sectional observational study. METHODS: A total of 513 residents and 117 registered nurses from 39 nursing homes in South Korea participated in surveys. The main measures included registered nurses' staffing levels, work environment, education levels, residents' quality of life, registered nurses' job dissatisfaction, burnout and turnover intention. We analysed data using the generalised estimating equations and reported the study using the STROBE checklist. RESULTS: Overall, the residents' quality-of-life score was 13.7 ± 2.6 (out of 17). Residents in nursing homes with a higher number of registered nurses or with work environment evaluated as 'mixed' or 'better' (compared with 'poor') had a higher quality of life. Regarding nurse outcomes, 74.4% of the registered nurses were dissatisfied with their current jobs, 12.0% had burnout and 18.8% had a turnover intention. Registered nurses working in 'mixed' or 'better' work environment were less likely to have job dissatisfaction. Registered nurses' education levels did not have a statistically significant effect on the resident and nurse outcomes. CONCLUSIONS: Registered nurse staffing levels and work environment should be considered important for improving residents' quality of life and nurses' job satisfaction. RELEVANCE TO CLINICAL PRACTICE: Regulation and policy reforms are needed to increase the registered nurse staffing levels and to create a good work environment in nursing homes. PATIENT OR PUBLIC CONTRIBUTION: Nursing home residents and registered nurses participated in the surveys of this study. Registered nurses facilitated resident recruitment by identifying and introducing the study to residents who were eligible for study participation. TRIAL REGISTRATION: Not applicable.

The development and evaluation of a self-efficacy enhancement program for older adults with mild cognitive impairment.

OBJECTIVE: The aims of this study were to develop a self-efficacy enhancement program and to evaluate its effect on cognitive function, dementia knowledge, self-efficacy, depression, and dementia preventive behaviors in older adults (age ≥ 65 years) with mild cognitive impairment (MCI). METHODS: This equivalent control group pretest-posttest study was conducted at a tertiary hospital in Seoul, South Korea. Older adults with MCI were randomly allocated to an experimental (EG, n = 16) or control group (CG, n = 16). The EG underwent an 8-week intervention (weekly 60-min session) utilizing self-efficacy enhancement strategies; the CG received usual care. The intervention was comprised of physical, cognitive, and emotional activities and was followed by 4-week maintenance during which both groups engaged in self-learning at home with a dementia preventive guidebook. Outcome data were evaluated at the pretest and 8, 10, and 12 weeks later. This study adhered to the CONSORT guidelines. RESULTS: There were significant differences in cognitive function, dementia knowledge, self-efficacy, and dementia preventive behaviors, but not in depression between the two groups over the time. Regarding cognitive function subdomains, significant differences were observed in visuospatial/executive, attention, language, and delayed recall. CONCLUSION: The integrated intervention consisting of physical, cognitive, and emotional activities was effective in improving cognitive function, dementia knowledge, self-efficacy, and dementia preventive behaviors. This suggests that this program can be utilized as an educational program to prevent dementia in older adults with MCI in dementia support centers, public health centers, clinics, and hospitals. TRIAL REGISTRATION: KCT0006094 in the Clinical Research Information Service. Retrospectively registered 23 April 2021, https://cris.nih.go.kr/cris/search/listDetail.do.

Trajectories of depressive symptoms among community-dwelling Korean older adults: findings from the Korean longitudinal study of aging (2006-2016).

BACKGROUND: Depression among older adults is an important public health concern associated with increased risk of suicide and decreased physical, cognitive, and social functioning. This study identified trajectories of depressive symptoms and investigated predictive variables of group-based trajectory modeling among Korean community-dwelling older adults. METHODS: Participants comprised 2016 community-dwelling Korean adults over 65 years. Data from the years 2006-2016 of the Korean Longitudinal Study of Aging, a nationally representative panel survey that has been conducted every two years since 2006, were used. We employed a group-based trajectory modeling analysis to identify depressive symptom trajectories. Multinomial logistic regression analysis was conducted to identify predictors of each class of depressive symptoms. RESULTS: Five depressive symptom trajectory groups were identified: Group 1, "None" (28.9%); Group 2, "Slowly worsening" (24.3%); Group 3, "Rapidly worsening" (17.5%); Group 4 "Improving" (12.4%); and Group 5, "Persistently severe" (16.9%). Older adults followed five distinct depressive symptom trajectories over 10 years. Mini-Mental State Examination scores, number of chronic diseases, educational level, and social activity were predictors associated with increasing depressive symptoms. CONCLUSIONS: This study showed that many older adults living in the community have depressive symptoms. To prevent and treat depression and aid successful mental health aging among older adults, the development of interventions should be tailored to target specific needs for each symptom trajectory. It is necessary to develop community-based interventions and strategies to identify and prevent depressive symptom trajectories among older adults.

Predictors of patient safety activities among registered nurses and nurse aides in long-term care facilities: cross-sectional study.

BACKGROUND: In Korea, nurse aides (NAs) are legally permitted as substitutes for registered nurses (RNs) in long-term care (LTC) facilities, even though they have very different levels of education and qualification standards. Many studies in hospitals have shown better hospital nurse staffing, more educated nurses, and improved nurse work environments have been associated with lower hospital mortality and length of stay. There is research showing that a higher percentage of RNs with a bachelor's degree corresponded to lower incidence rates of pressure ulcers in Korean LTC facilities. This study aimed to explore the factors that influence patient safety activities of the RNs and NAs working in LTC facilities and to identify the relationship between patient safety culture (PSC) and patient safety activities. METHODS: This study is a descriptive cross-sectional survey. The study participants were conveniently collected from 88 RNs and 71 NAs who worked at 33 LTC facilities for more than three months. The patient safety activities tool was developed by the researchers for residents of LTC facilities based on the tools developed by Park et al. (2012) for hospital nurses and the patient safety goals of the Joint Commission. The questionnaires were collected by email or mobile application and kept confidential. Data were analyzed using descriptive statistics, independent t-test, one-way ANOVA, Pearson correlation coefficients, and multiple regression analysis. RESULTS: The mean scores of PSC and patient safety activities were 4.03 ± 0.51 points and 4.29 ± 0.49 points out of 5, respectively. There was significant correlation between PSC and patient safety activities (r = .23, p = .004). Factors influencing patient safety activities among RNs and NAs in LTC facilities were RNs (ß = .377, p < .001), organizational system of PSC (ß = .314, p < .010), and work shift type (fixed night shift, on-call, 24-h shift) (ß = -.264, p = .004), which explained about 36.0% of total variance (F = 5.69, p < .001). CONCLUSION: The findings indicate that it is necessary to mandate RNs instead of NAs to enhance residents' safety in LTC facilities. Additionally, the importance of an organizational safety system and effective working shift types to prevent residents' safety accidents in LTC facilities is indicated.

Non-pharmacological interventions using information and communication technology for behavioral and psychological symptoms of dementia: A systematic review and meta-analysis protocol.

AIM: To review and examine the effectiveness of non-pharmacological interventions on behavioural and psychological symptoms of dementia using information and communication technology. DESIGN: This is a systematic review and meta-analysis. METHODS: The databases including PubMed, CINAHL with Full Text (EBSCOhost), PsycINFO, Embase, and the Cochrane Library will be searched for all published studies. Studies will be screened and selected with criteria described in PICOS format. Risk of bias will be assessed by the National Institute for Health and Clinical Excellence checklist. Data will be extracted from eligible studies and used to perform a meta-analysis examining the overall effects and effects on individual outcomes. Additionally, we will conduct meta-regression to examine the association between explanatory variables and behavioural and psychological symptoms. This study has been funded since June 2020. DISCUSSION: This study will be the first to reveal the effects of non-pharmacological interventions using information and communication technology on behavioural and psychological symptoms of dementia. Furthermore, this study will provide updated and valid evidence of interventions using this for managing behavioural and psychological symptoms of dementia. IMPACT: Although non-pharmacological interventions using information and communication technology for older adults living with dementia are continuously developing, their direct effect remains unclear. This study will evaluate the effectiveness of these interventions on behavioural and psychological symptoms of dementia and provide the evidence to implement these interventions among older adults living with dementia. Thus, caregivers and nursing staff can manage behavioural and psychological symptoms of dementia more effectively by incorporating information and communication technology.

Transitional care from hospital to home for frail older adults: A systematic review and meta-analysis.

Frail older adults are vulnerable to hospitalization and transitional care is needed to maintain care continuity; however, there exists no review regarding transitional care focusing on frailty. This study aimed to investigate transitional care for frail older adults and its effectiveness. Search terms were (P) frail older adults; (I) transitional care initiated before discharge; (C) usual care; (O) all health outcomes. Fourteen trials were identified. The most measured outcome was readmission (n = 13), followed by mortality (n = 9), function (n = 7), quality of life (n = 5), and self-rated health (n = 5). Statistical significance effects were reported in the followings: n = 6, readmission; n = 0, mortality; n = 3, function; n = 2, quality of life; and n = 4, self-rated health. The meta-analysis demonstrated that transitional care reduced readmission at six months but not other time points nor mortality or quality of life. The intervention effectiveness was inconclusive; therefore, an evidence-based yet novel approach is necessary to establish an adequate transitional care intervention for frail older adults.

Factors associated with retention intention of Registered Nurses in Korean nursing homes.

AIM: To identify the factors associated with retention intention among Registered Nurses in South Korean nursing homes. BACKGROUND: Although nurses are not mandatory personnel, Korean nursing homes employ Registered Nurses. INTRODUCTION: Determining the factors related to Registered Nurses' retention intention is important for their job stability and ensure provision of quality care. METHODS: This mixed-methods study employed a sequential explanatory design. A self-reported questionnaire survey was conducted between May 1 and July 3, 2019, with 155 Registered Nurses providing direct care from 37 nursing homes. In-depth qualitative interviews were conducted with 10 participants from August 1 to September 30, 2019. Data were analyzed using multilevel analysis for quantitative study and thematic analysis for qualitative study. RESULTS: The participants' average age was 48.48 years. Personal factors related to retention intention were Registered Nurses' role, educational level, and job satisfaction. Institutional factors were ownership, number of beds, and working environment. The qualitative study revealed five themes: "Satisfaction with meaningful relationships," "Potential for professional growth," "Nursing service accompanied by emotional labor," "Poor working environments in nursing homes," and "Unprotected nursing expertise." DISCUSSION: A nursing home's work environment is related to the Registered Nurses' retention intention. Most Registered Nurses in Korea received low wages, lacked access to career management programs, and experienced emotional labor. CONCLUSION: This study highlighted the personal and institutional factors related to retention intention among Registered Nurses in South Korean nursing homes. IMPLICATIONS FOR NURSING AND NURSING POLICY: A law that designates Registered Nurses as an essential nursing home workforce is required. Further, nursing homes should increase the number of Registered Nurses to improve working conditions and thereby job satisfaction. It is also necessary to foster a working environment that facilitates professional development opportunities and job clarity.

Nurses in advanced roles as a strategy for equitable access to healthcare in the WHO Western Pacific region: a mixed methods study.

BACKGROUND: The Western Pacific region constitutes one-quarter of the world's population and has diverse health needs. While dialogue on and promotion of advanced practice nurses are ongoing, this study investigated the current responsibilities of nurses in advanced roles, future healthcare needs, and the implications of these components for nurses' professional development within the Western Pacific region. METHODS: This study employed three phases, a descriptive survey on the current status of nurses in advanced roles in the Western Pacific region, followed by a Delphi survey, and exploratory interviews. A total of 55 national experts with clinical, academic, and/or government-related backgrounds from 18 countries participated from December 2017 - December 2018. The descriptive survey via email to identify the status of nurses in advanced roles and a working definition was developed. This formed the basis for the Delphi survey, which identified key barriers and challenges for enhancing the development of nurses in advanced roles within the country (round 1) and for the region (rounds 2 and 3). Lastly, semi-structured individual interviews were conducted to identify strategies for establishing nurses in advanced roles to improve equitable access to healthcare. RESULTS: Thirty-seven roles and characteristics were identified and categorized for nurses performing advanced roles. Emergency care, critical care, elderly health, child health, and rural/remote communities were identified as fields with particular need for nurses in advanced roles in the Western Pacific region. Providing effective services, influencing government leadership, and advocating for health system sustainability were deemed necessary to improve equitable healthcare access. We found that nurses in advanced roles are not limited to clinical tasks within the hospital but are poised for active participation in primary healthcare, education/teaching, professional leadership, quality management, and research. CONCLUSIONS: Demand for nurses in advanced roles is high in the Western Pacific region and 15 items were identified across five core strategic areas to enhance development of nurses in advanced roles. Governmental-level recommendations include establishing legislative protection, improving systems for remuneration, strengthening supportive channels, and conducting national needs assessments.

Factors Associated With Behavioral and Psychological Symptoms of Dementia: Prospective Observational Study Using Actigraphy.

BACKGROUND: Although disclosing the predictors of different behavioral and psychological symptoms of dementia (BPSD) is the first step in developing person-centered interventions, current understanding is limited, as it considers BPSD as a homogenous construct. This fails to account for their heterogeneity and hinders development of interventions that address the underlying causes of the target BPSD subsyndromes. Moreover, understanding the influence of proximal factors-circadian rhythm-related factors (ie, sleep and activity levels) and physical and psychosocial unmet needs states-on BPSD subsyndromes is limited, due to the challenges of obtaining objective and/or continuous time-varying measures. OBJECTIVE: The aim of this study was to explore factors associated with BPSD subsyndromes among community-dwelling older adults with dementia, considering sets of background and proximal factors (ie, actigraphy-measured sleep and physical activity levels and diary-based caregiver-perceived symptom triggers), guided by the need-driven dementia-compromised behavior model. METHODS: A prospective observational study design was employed. Study participants included 145 older adults with dementia living at home. The mean age at baseline was 81.2 (SD 6.01) years and the sample consisted of 86 (59.3%) women. BPSD were measured with a BPSD diary kept by caregivers and were categorized into seven subsyndromes. Independent variables consisted of background characteristics and proximal factors (ie, sleep and physical activity levels measured using actigraphy and caregiver-reported contributing factors assessed using a BPSD diary). Generalized linear mixed models (GLMMs) were used to examine the factors that predicted the occurrence of BPSD subsyndromes. We compared the models based on the Akaike information criterion, the Bayesian information criterion, and likelihood ratio testing. RESULTS: Compared to the GLMMs with only background factors, the addition of actigraphy and diary-based data improved model fit for every BPSD subsyndrome. The number of hours of nighttime sleep was a predictor of the next day's sleep and nighttime behaviors (odds ratio [OR] 0.9, 95% CI 0.8-1.0; P=.005), and the amount of energy expenditure was a predictor for euphoria or elation (OR 0.02, 95% CI 0.0-0.5; P=.02). All subsyndromes, except for euphoria or elation, were significantly associated with hunger or thirst and urination or bowel movements, and all BPSD subsyndromes showed an association with environmental change. Age, marital status, premorbid personality, and taking sedatives were predictors of specific BPSD subsyndromes. CONCLUSIONS: BPSD are clinically heterogeneous, and their occurrence can be predicted by different contributing factors. Our results for various BPSD suggest a critical window for timely intervention and care planning. Findings from this study will help devise symptom-targeted and individualized interventions to prevent and manage BPSD and facilitate personalized dementia care.

Behaviors of care providers and resistiveness to oral care of persons living with dementia.

Since care providers' behavior could be related to resistiveness to care (RTC) among persons living with dementia, developing care providers' behavioral strategies to reduce or prevent RTC is required. This study examined whether care providers' person-centered or task-centered behaviors were related to RTC. A secondary data analysis was conducted using 70 videos of 23 persons living with dementia who received routine oral care in long-term care settings. Data were analyzed using linear mixed models. Among task-centered behaviors, "physically controlling" significantly increased RTC. For person-centered behaviors, "cooperatively negotiating" increased RTC, while "assessing comfort" decreased RTC. Care providers need to consider the comfort or needs of persons living with dementia rather than physically controlling them in oral care situations. These findings may offer insight into the context of RTC occurrences to provide more comfortable oral care for persons living with dementia.

Empagliflozin dilates the rabbit aorta by activating PKG and voltage-dependent K+ channels.

We investigated the vasodilatory effects of empagliflozin (a sodium-glucose co-transporter 2 inhibitor) and the underlying mechanisms using rabbit aorta. Empagliflozin induced vasodilation in a concentration-dependent manner independently of the endothelium. Likewise, pretreatment with the nitric oxide synthase inhibitor L-NAME or the SKca inhibitor apamin together with the IKca inhibitor TRAM-34 did not impact the vasodilatory effects of empagliflozin. Pretreatment with the adenylyl cyclase inhibitor SQ22536 or a guanylyl cyclase inhibitor ODQ or a protein kinase A (PKA) inhibitor KT5720 also did not alter the vasodilatory response of empagliflozin. However, the vasodilatory effects of empagliflozin were significantly reduced by pretreatment with the protein kinase G (PKG) inhibitor KT5823. Although application of the ATP-sensitive K+ (KATP) channel inhibitor glibenclamide, large-conductance Ca2+-activated K+ (BKCa) channel inhibitor paxilline, or inwardly rectifying K+ (Kir) channel inhibitor Ba2+ did not impact the vasodilatory effects of empagliflozin, pretreatment with the voltage-dependent K+ (Kv) channel inhibitor 4-AP reduced the vasodilatory effects of empagliflozin. Pretreatment with DPO-1 (Kv1.5 channel inhibitor), guangxitoxin (Kv2.1 channel inhibitor), or linopirdine (Kv7 channel inhibitor) had little effect on empagliflozin-induced vasodilation. Application of nifedipine (L-type Ca2+ channel inhibitor) or thapsigargin (sarco-endoplasmic reticulum Ca2+-ATPase pump inhibitor) did not impact empagliflozin-induced vasodilation. Therefore, empagliflozin induces vasodilation by activating PKG and Kv channels.

Association of Nurse Staffing With Nosocomial Infections of Very Low-Birth-Weight Infants.

Prior studies have reported inconsistent findings regarding the relationship between nurse staffing and nosocomial infections in very low-birth-weight (VLBW) infants. Little is known about whether similar associations occur in Korea. The purpose of this study was to identify the nurse staffing of neonatal intensive care units (NICUs) in Korea and to verify the association between nurse staffing and nosocomial infections among VLBW infants in NICUs. We selected 4654 VLBW infants admitted to 52 hospitals. Nosocomial infections were defined as incidence of bloodstream infection, urinary tract infection (UTI), or rotavirus infection. The average number of NICU patients per nurse was 4.51(minimum-maximum: 2.38-8.16). Hospitals with a higher number of patients per nurse exhibited a significant increased UTI rate (P = .005) and rotavirus infection rate (P = .025) in the univariate analysis. After adjusting for all patient and hospital characteristics, UTI significantly increased with increasing number of patients per nurse (odds ratio [OR] = 1.79; 95% confidence interval, 1.29-2.47), while bloodstream infection (OR = 0.93; 95% confidence interval, 0.79-1.09) and rotavirus infection (OR = 1.14; 95% confidence interval, 0.92-1.41) were not significant. These findings revealed that a nurse staffing in NICUs is an important factor for preventing UTI among VLBW infants.

Effects of registered nurse staffing on quality of care and resident outcomes in nursing homes.

Few studies focus on Registered Nurse (RN) staffing and resident health outcomes in Korean nursing homes. This study aimed to investigate the effects of RN staffing on quality of care and resident outcomes in South Korean nursing homes. The study was a secondary data analysis of 5679 participants from the National Health Insurance Service. A mixed-effect linear model and multinomial logistic regression model assessed resident outcomes and quality of care, respectively. The number of RNs significantly affected patient mortality. The overall evaluation rating for quality of care in nursing homes increased as the number of RNs increased. Level of RN staffing in nursing homes influenced health management and quality of care for residents. A variety of efforts are needed to strengthen the workforce of RNs in nursing homes, including enacting a law for safe RN staffing and converting the evaluation of nursing home quality into health outcomes.

Interprofessional global health competencies of South Korean health professional students: educational needs and strategies.

BACKGROUND: There is growing recognition of the importance of educating health professional students to enhance their competence in collaborating with individuals from other health professions in the area of global health. This study aimed to identify the performance levels in interprofessional global health competencies (IGHC) of health professional students, their educational needs, and the strategies for successfully developing IGHC. METHODS: This study used a mixed methods design involving an online survey followed by focus group interviews. A sample of 325 fourth-year undergraduate students from 14 health-related majors completed a self-report online survey (38.8% response rate). The performance of IGHC was measured on a five-point Likert scale using the IGHC items developed by the Consortium of Universities for Global Health. Additionally, 12 senior students and five professors in global health-related majors participated in focus group interviews. The students' educational needs and priorities were analysed using the Borich needs assessment and the Locus for Focus model. RESULTS: The participants' IGHC mean score was 3.11 (SD = 0.55) and differed by previous global health activity experiences (t = - 2.10, p = .037). Nine competencies in six domains using the Locus for Focus model were identified as a priority for global health education. Suggested strategies to enhance IGHC included establishing IGHC education in formal curricula, developing value-based content and outcomes, and engaging students in learning activities. CONCLUSIONS: It is necessary to design an interprofessional pre-departure course to achieve the priority IGHC and to organise learning activities where there is cooperation in problem solving while applying the expertise of each major within resource-limited settings. This study supports future health professional education that should foster enhanced roles and scopes of practice as changing agents to assure the achievement of sustainable development goals.

Succinate induces hepatic fibrogenesis by promoting activation, proliferation, and migration, and inhibiting apoptosis of hepatic stellate cells.

Liver fibrosis is a progressive pathological process that accompanies wound healing; however, therapeutics for reversing hepatic fibrosis are unavailable. Activation of hepatic stellate cells (HSCs) play a critical role in liver fibrosis. Recent reports showed that succinate and its receptor, G-protein coupled receptor 91 (GPR91), act as signaling molecules during the activation of HSCs. However, the role of succinate in proliferation, apoptosis, and migration of HSCs has not been studied. In this study, we determined whether succinate regulates proliferation, apoptosis, and migration of HSCs and induces liver fibrosis in a mouse model. Succinate treatment not only induced activation of HSCs, but also increased the proliferation and migration of LX-2 HSCs and inhibited apoptosis. To investigate whether succinate causes hepatic fibrosis, 100 mg/kg succinate or control PBS was administered by intraperitoneal injection to mice once a day for four weeks. There were significant molecular changes such as increased α-SMA and collagen type 1 production and increased production of inflammatory cytokines such as IL-6 and TNF-α, but not TGF-ß, in the succinate-treated group compared to the control group. However, no morphological changes were observed in Masson's trichrome staining. In conclusion, the present study demonstrated that succinate induces activation, proliferation, and migration of HSCs and attenuates apoptosis in LX-2 HSCs. Therefore, inhibition of succinate accumulation may be an effective method for reversing liver fibrosis by controlling HSC survival and growth.

Metformin ameliorates activation of hepatic stellate cells and hepatic fibrosis by succinate and GPR91 inhibition.

BACKGROUND: Chronic liver disease is becoming a major cause of morbidity and mortality worldwide. During liver injury, hepatic stellate cells (HSCs) trans-differentiate into activated myofibroblasts, which produce extracellular matrix. Succinate and succinate receptor (G-protein coupled receptor91, GPR91) signaling pathway has now emerged as a regulator of metabolic signaling. A previous study showed that succinate and its specific receptor, GPR91, are involved in the activation of HSCs and the overexpression of α-smooth muscle actin (α-SMA). Metformin, a well-known anti-diabetic drug, inhibits hepatic gluconeogenesis in the liver. Many studies have shown that metformin not only prevented, but also reversed, steatosis and inflammation in a nonalcoholic steatohepatitis (NASH) animal model. However, the role of metformin in HSC activation and succinate-GPR91 signaling has not been clarified. METHODS: The immortalized human HSCs, LX-2 cells, were used for the in vitro study. For the in vivo study, male C57BL/J6 mice were randomly divided into 3 groups and were fed with a methionine-choline-deficient diet (MCD diet group) as a nonalcoholic steatohepatitis (NASH) mouse model with or without 0.1% metformin for 12 weeks, or were fed a control methionine-choline-sufficient diet (MCS diet group). RESULTS: In our study, metformin and 5-aminoimidazole-4-carboxamide 1-ß-d-ribofuranoside (AICAR), which is an analog of adenosine monophosphate, were shown to suppress α-SMA expression via enhanced phosphorylation of AMP-activated protein kinase (AMPK) and inhibition of succinate-GPR91 signaling in activated LX-2 cells induced by palmitate- or succinate. Metformin and AICAR also reduced succinate concentration in the cell lysates when LX-2 cells were treated with palmitate. Moreover, metformin and AICAR reduced interleukin-6 and, transforming growth factor-ß1 production in succinate-treated LX-2 cells. Both metformin and AICAR inhibited succinate-stimulated HSC proliferation and cell migration. Mice fed a MCD diet demonstrated increased steatohepatitis and liver fibrosis compared to that of mice fed control diet. Metformin ameliorated steatohepatitis, liver fibrosis, inflammatory cytokine production and decreased α -SMA and GPR91expression in the livers of the MCD diet-fed mice. CONCLUSION: This study shows that metformin can attenuate activation of HSCs by activating the AMPK pathway and inhibiting the succinate-GPR91 pathway. Metformin has therapeutic potential for treating steatohepatitis and liver fibrosis.

Exposure to far-infrared ray attenuates methamphetamine-induced impairment in recognition memory through inhibition of protein kinase C δ in male mice: Comparison with the antipsychotic clozapine.

We have previously demonstrated that repeated treatment with methamphetamine (MA) results in a recognition memory impairment via upregulation of protein kinase C (PKC) δ and downregulation of the glutathione peroxidase-1 (GPx-1)-dependent antioxidant system. We also demonstrated that far-infrared ray (FIR) attenuates acute restraint stress via induction of the GPx-1 gene. Herein, we investigated whether exposure to FIR modulates MA-induced recognition memory impairment in male mice, and whether cognitive potentials mediated by FIR require modulation of the PKCδ gene, extracellular signal-regulated kinase (ERK) 1/2, and glutathione-dependent system. Repeated treatment with MA significantly increased PKCδ expression and its phosphorylation out of PKC isoenzymes (i.e., PKCα, PKCßI, PKCßII, PKCζ, and PKCδ expression) in the prefrontal cortex of mice. Exposure to FIR significantly attenuated MA-induced increase in phospho-PKCδ and decrease in phospho-ERK 1/2. In addition, FIR further facilitated the nuclear factor E2-related factor 2 (Nrf2)-dependent glutathione synthetic system. Moreover, L-buthionine-(S, R)-sulfoximine, an inhibitor of glutathione synthesis, counteracted the FIR-mediated phospho-ERK 1/2 induction and memory-enhancing activity against MA insult. More important, positive effects of FIR are comparable to those of genetic depletion of PKCδ or the antipsychotic clozapine. Our results indicate that FIR protects against MA-induced memory impairment via activations of the Nrf2-dependent glutathione synthetic system, and ERK 1/2 signaling by inhibition of the PKCδ gene.

Exposure to Far Infrared Ray Protects Methamphetamine-Induced Behavioral Sensitization in Glutathione Peroxidase-1 Knockout Mice via Attenuating Mitochondrial Burdens and Dopamine D1 Receptor Activation.

Evidence indicates that stress conditions might lead to drug dependence. Recently, we have demonstrated that exposure to far infrared ray (FIR) attenuates acute restraint stress via induction of glutathione peroxidase-1 (GPx-1) gene. We investigated whether FIR affects methamphetamine (MA)-induced behavioral sensitization and whether FIR-mediated pharmacological activity requires interaction between dopamine receptor and GPx-1 gene. We observed that MA treatment significantly increased GPx-1 expression in the striatum of wild-type (WT) mice. Interestingly, exposure to FIR potentiated MA-induced increase in GPx-1 expression. This phenomenon was also observed in animals receiving MA with dopamine D1 receptor antagonist SCH23390. However, dopamine D2 receptor antagonist sulpiride did not affect MA-induced GPx-1 expression. FIR exposure or SCH23390, but not sulpiride, significantly attenuated MA-induced behavioral sensitization. Exposure to FIR significantly attenuated MA-induced dopamine D1 receptor expression, c-Fos induction and oxidative burdens. FIR-mediated antioxidant effects were also more pronounced in mitochondrial- than cytosolic-fraction. In addition, FIR significantly attenuated against MA-induced changes in mitochondrial superoxide dismutase and mitochondrial GPx activities, mitochondrial transmembrane potential, intramitochondrial Ca2+ level, mitochondrial complex-I activity, and mitochondrial oxidative burdens. The attenuation by FIR was paralleled that by SCH23390. Effects of FIR or SCH23390 were more sensitive to GPx-1 KO than WT mice, while SCH23390 treatment did not exhibit any additive effects on the protective activity mediated by FIR, indicating that dopamine D1 receptor constitutes a molecular target of FIR. Our result suggests that exposure to FIR ameliorates MA-induced behavioral sensitization via possible interaction between dopamine D1 receptor and GPx-1 gene.