A novel hepatocyte ketone production assay to help the selection of nutrients for the ketogenic diet treatment of epilepsy.

The classic ketogenic diet is an effective treatment option for drug-resistant epilepsy, but its high fat content challenges patient compliance. Optimizing liver ketone production guided by a method comparing substrates for their ketogenic potential may help to reduce the fat content of the diet without loss in ketosis induction. Here, we present a liver cell assay measuring the ß-hydroxybutyrate (ßHB) yield from fatty acid substrates. Even chain albumin-conjugated fatty acids comprising between 4 and 18 carbon atoms showed a sigmoidal concentration-ßHB response curve (CRC) whereas acetate and omega-3 PUFAs produced no CRC. While CRCs were not distinguished by their half-maximal effective concentration (EC50), they differed by maximum response, which related inversely to the carbon chain length and was highest for butyrate. The assay also suitably assessed the ßHB yield from fatty acid blends detecting shifts in maximum response from exchanging medium chain fatty acids for long chain fatty acids. The assay further detected a dual role for butyrate and hexanoic acid as ketogenic substrate at high concentration and ketogenic enhancer at low concentration, augmenting the ßHB yield from oleic acid and a fatty acid blend. The assay also found propionate to inhibit ketogenesis from oleic acid and a fatty acid blend at low physiological concentration. Although the in vitro assay shows promise as a tool to optimize the ketogenic yield of a fat blend, its predictive value requires human validation.

Loneliness and regular sports participation among people of Turkish and Moroccan origin and native Dutch people in the Netherlands. A longitudinal study.

OBJECTIVE: Sports participation is lower in people of Turkish and Moroccan origin in the Netherlands than in native Dutch people. Addressing this inequality calls for better insights into antecedents of sports participation in different ethnic groups. Theorists suggested that loneliness may hamper sports participation, and levels of loneliness are high among people of Turkish and Moroccan origin. This study assessed the longitudinal association between loneliness and regular sports participation among Turkish origin, Moroccan origin and native Dutch people. METHODS: Data are from Turkish origin (n = 394), Moroccan origin (n = 387) and native Dutch (n = 1663) people who participated in Wave 1 (2008-2010) and Wave 2 (2013) of the Netherlands Longitudinal Lifecourse Study. Regular sports participation at follow-up was regressed on loneliness at baseline in logistic regression models adjusted for baseline sports participation and a range of confounders. Models were stratified by ethnic group. RESULTS: Turkish and Moroccan origin people had lower rates of regular sports participation and higher levels of loneliness than native Dutch people. Loneliness at baseline was negatively associated with sports participation at follow-up for people of Turkish and Moroccan origin. No evidence of a longitudinal association between loneliness and sports participation among native Dutch people was found. CONCLUSIONS: The demonstrated positive longitudinal association between loneliness and regular sports participation in people of Turkish and Moroccan origin potentially opens new ways to encourage physical activity in these groups. An integrated approach to addressing loneliness and physical inactivity among people with a non-western migration background may benefit the realization of both goals.

The contribution of parity to ethnic differences in mothers' body mass index in the Netherlands: A Blinder-Oaxaca decomposition approach.

Women of Turkish and Moroccan origin in the Netherlands are relatively likely to have an unhealthy bodyweight. This study sheds light on how ethnic differences in parity, i.e., the number of times a female carried pregnancies to a viable gestational age, contribute to body mass index (BMI) differences between Turkish-born and Moroccan-born mothers aged 35 + and their native Dutch counterparts. We applied a Blinder-Oaxaca decomposition approach to pooled data from four migrant surveys based on national probability samples (n = 2,532). Unlike conventional mediation analyses, the Blinder-Oaxaca approach recognizes that the association between parity and bodyweight may vary across different groups. Our results indicated that Turkish-born and Moroccan-born mothers in the Netherlands had more children and a higher BMI than native Dutch mothers. Regression analyses moreover showed that the parity-BMI gradient was steeper for Turkish-born mothers than for native Dutch mothers. Decomposition using the Blinder-Oaxaca approach indicated that the higher number of children of Turkish-born and Moroccan-born mothers compared to native Dutch mothers contributed substantially to the higher mean BMI in the former groups. The steeper parity-BMI gradient in Turkish-born mothers further amplified the contribution of parity to the higher mean BMI of Turkish-born mothers as compared to native Dutch mothers. Future research is needed to assess to which extent the steep parity-BMI gradient in Turkish-born mothers can be explained by relatively strong barriers to a healthy lifestyle that Turkish-born mothers of a larger number of children may face due to a relatively strongly gendered division of household and childrearing tasks.

Changes in work conditions and well-being among healthcare professionals in long-term care settings in the Netherlands during the COVID-19 pandemic: a longitudinal study.

BACKGROUND: Healthcare professionals working in long-term care facilities reported heavy job demands and a lack of job resources during the 2019 coronavirus disease (COVID-19) pandemic. However, how job demands and resources in these facilities changed during the pandemic, and how possible changes affected professionals' work-related well-being, remains unclear. Thus, we explored changes in job demands and resources in the face of surging COVID-19 infection rates, and investigated associations of these changes with changes in burnout and work engagement, among healthcare professionals working in long-term care facilities in the Netherlands. METHODS: This longitudinal study was conducted with healthcare professionals working in five long-term care facilities in the Netherlands. Data were collected in early and late 2021, when infection rates in long-term care facilities were low and high (mean, 29.1 and 275.4 infections/day), respectively. In total, 173 healthcare professionals completed the validated Job Demands and Resources Questionnaire, Copenhagen Burnout Inventory, and Utrecht Work Engagement Scale at both timepoints. We performed paired-samples t tests to examine changes in job demands and resources, and fixed-effects linear regression analyses to examine associations of within-person changes in job demands and resources with those in burnout and work engagement. RESULTS: Healthcare professionals perceived increased workloads, associated with increased burnout and decreased work engagement during the study period. Within-person increases in perceived collegial support were associated positively with work engagement and negatively with burnout symptoms. CONCLUSIONS: Healthcare professionals in long-term care facilities perceived increased workloads in the wake of surging infection rates during the COVID-19 pandemic, resulting in increased burnout and decreased work engagement. These changes in burnout and work engagement were also perceived in response to declining collegial support. Efforts to protect the work-related well-being of healthcare professionals working in long-term care facilities in the pandemic context that focus on workload reduction and the promotion of collegial support may be most beneficial.

Towards Standardisation of a Diffuse Midline Glioma Patient-Derived Xenograft Mouse Model Based on Suspension Matrices for Preclinical Research.

Diffuse midline glioma (DMG) is an aggressive brain tumour with high mortality and limited clinical therapeutic options. Although in vitro research has shown the effectiveness of medication, successful translation to the clinic remains elusive. A literature search highlighted the high variability and lack of standardisation in protocols applied for establishing the commonly used HSJD-DIPG-007 patient-derived xenograft (PDX) model, based on animal host, injection location, number of cells inoculated, volume, and suspension matrices. This study evaluated the HSJD-DIPG-007 PDX model with respect to its ability to mimic human disease progression for therapeutic testing in vivo. The mice received intracranial injections of HSJD-DIPG-007 cells suspended in either PBS or Matrigel. Survival, tumour growth, and metastases were assessed to evaluate differences in the suspension matrix used. After cell implantation, no severe side effects were observed. Additionally, no differences were detected in terms of survival or tumour growth between the two suspension groups. We observed delayed metastases in the Matrigel group, with a significant difference compared to mice with PBS-suspended cells. In conclusion, using Matrigel as a suspension matrix is a reliable method for establishing a DMG PDX mouse model, with delayed metastases formation and is a step forward to obtaining a standardised in vivo PDX model.

Longitudinal health behaviour patterns among adults aged ≥50 years in China and their associations with trajectories of depressive symptoms.

OBJECTIVES: Against the background of the growing recognition of the need for a holistic perspective on health behaviour, we aim to identify longitudinal patterns of multiple health behaviours, and to assess associations of such patterns with depressive symptoms among older people in China. METHODS: Using three waves of China Health and Retirement Longitudinal Study data (n = 8439), we performed latent class growth analyses (LCGAs) to identify longitudinal patterns of multiple health behaviours. Random-effects models were estimated to assess associations between health behaviour patterns and depressive symptoms. RESULTS: The best fitting LCGA model had seven classes: (1) connected active non-smokers (average posterior probability: 21.8%), (2) isolated active non-smokers (24.7%), (3) isolated inactive non-smokers (17.0%), (4) isolated active smokers (14.5%), (5) connected active smokers (12.2%), (6) increasingly connected and active non-smokers (5.4%), and (7) moderately connected inactive smokers (4.4%). Depressive symptoms were highest in the four classes with lower probabilities of social participation across waves. No evidence was found of change over time in depressive symptomatology gaps between people with different health behaviour trajectories. CONCLUSION: Health behaviour patterns characterized by consistently low social participation were associated with raised depressive symptomatology, suggesting that focusing on social participation may benefit later-life mental health promotion strategies.

Social integration and mental health of Somali refugees in the Netherlands: the role of perceived discrimination.

BACKGROUND: We assess whether social integration is associated with mental health among Somali refugees in the Netherlands, and how this association is shaped by perceived discrimination. METHODS: We performed linear regression and formal mediation analyses on Survey Integration Minorities data (n = 417) to assess whether the effects of two facets of social integration - Dutch language proficiency and informal contacts with natives - on mental health were mediated or suppressed by perceived discrimination. RESULTS: Dutch language proficiency was positively associated with mental health, but also with perceived discrimination. Informal contact with natives was not significantly associated with mental health or perceived discrimination. There was marginally significant evidence (p < .1) that perceived discrimination suppressed the positive association between Dutch language proficiency and mental health. DISCUSSION: Greater Dutch language proficiency appears to be beneficial for Somali refugees' mental health, but this effect may partly be cancelled by the associated stronger experiences of discrimination.

Gender differences in bodyweight change following COVID-19 lockdown measures in the Netherlands: a prospective longitudinal study.

BACKGROUND: The current study aimed to prospectively assess bodyweight change following the implementation of lockdown measures to contain the COVID-19 pandemic in the Netherlands and to explore the potentially moderating role of gender in this association. DESIGN: Using Dutch DNB Household Survey panel data collected between 1993 and 2020, we estimated fixed-effects regression models of bodyweight change. Models were stratified by gender and formal tests of gender differences in coefficient estimates were performed. PARTICIPANTS: 4365 women and 4583 men aged 18-65 were included in the study. The total number of observations was 41 330. OUTCOME MEASURES: The outcome of interest was self-reported bodyweight in kilograms. Additional analyses were performed using body mass index (self-reported weight in kilograms divided by self-reported height in metres squared) as the outcome. RESULTS: The implementation of Dutch lockdown measures in 2020 was associated with bodyweight gain of approximately 800 g in working-age women compared with the 3 prior years. Bodyweight gain in 2020 relative to the prior years was significantly stronger for women than for men (F(4, 8947)=3.9, p<0.01). No evidence of bodyweight gain in working-age men was found. CONCLUSION: Results indicate that bodyweight gain following COVID-19 lockdown measures in the Netherlands was more pronounced among women than among men. Although necessary to contain the COVID-19 pandemic, lockdown measures may contribute to a different public health challenge in the rising prevalence of overweight and obesity.

Turkish and Moroccan Dutch women's views of using a self-sampling kit for human papillomavirus testing as a tool for cervical cancer screening: What are the barriers and the motivators?

OBJECTIVE: This study explores barriers and motivators to use self-sampling kits for human papillomavirus testing for cervical cancer screening as perceived by Dutch women of Turkish and Moroccan origin living in the Netherlands. METHODS: A total of 11 in-depth semi-structured interviews were conducted and structured according to the theory of planned behavior. RESULTS: Findings suggest that self-sampling may lift important barriers hampering traditional cervical cancer screening, such as those related to shame and chastity. However, self-sampling raises its own barriers too. Most importantly, some women fear that self-sampling may harm virginity. Some women also do not feel confident about their ability to properly use the self-sampling kit, but fears about the inability to properly use it often fade away upon having seen the self-sampling kit. Moreover, results show that knowledge about cervical cancer and its origin is limited, which may undermine women's willingness to participate in a screening program. CONCLUSIONS: These results suggest that communication strategies to encourage using self-sampling kits among women of Turkish and Moroccan origin could benefit from culturally sensitive approaches, for example, by placing emphasis on issues such as virginity and chastity. Consistent with a recent advice of the Health Council of the Netherlands, the kit could furthermore be sent to eligible women as a standard procedure, rather than upon request. This could reduce hassle and doubts about women's ability to use the self-sampling kit. Finally, educating women about the importance of screening to prevent cervical cancer is needed to foster informed decision-making.

Positive and negative ageing perceptions account for health differences between older immigrant and native populations in the Netherlands.

BACKGROUND: This study assessed the extent to which persistent differences in self-rated health (SRH) between older immigrants and natives are attributable to negative and positive ageing perceptions. METHODS: The study was conducted with three population groups in Rotterdam, the Netherlands: native Dutch people aged ≥70 years (n = 1150), Turkish immigrants aged ≥65 years (n = 680) and Moroccan immigrants aged ≥65 years (n = 292). To assess participants' internal ageing representations, we used the short Aging Perceptions Questionnaire, which distinguishes negative (consequences, chronic and cyclical timeline awareness, and emotional representations) and positive (positive consequences, positive and negative control) dimensions and has been validated in native and immigrant populations. We analysed differences in ageing perceptions between immigrants and natives and the associations of ageing perceptions with SRH. We used Karlson-Holm-Breen decomposition to assess ageing perceptions' mediation of the relationship between migration background and SRH. RESULTS: Older immigrants had stronger negative and weaker positive ageing perceptions (excepting the positive consequences of ageing) than did Dutch natives. Ageing perceptions mediated the relationship between migration background and SRH. SRH differences between Turkish immigrants and native Dutch older persons were explained mainly by differences in negative consequences and cyclical timeline awareness. SRH differences between Moroccan immigrants and native Dutch older persons were attributable mainly to differences in negative consequences and positive control. CONCLUSIONS: Differences in positive and negative ageing perceptions between older immigrants and natives in the Netherlands largely explained SRH differences between these population groups.

The impact of an additional nurse assistant during evening shifts on nurses' perceptions of job demands, job resources and well-being.

AIM: Workloads and other job demands jeopardize nurses' well-being, especially during evening shifts when there are less resources than during the day. The current study aims to shed light on how the addition of a nurse assistant to ward staffing during evening shifts has an impact on nurses' perceptions of job demands, job resources, and well-being. DESIGN: We performed a pre-post pilot study, whereby we compared nurses' perceptions of job demands, job resources, and well-being before and after the addition of a nurse assistant to ward staffing during evening shifts. METHODS: All nurses at the ward of a top-clinical hospital (N = 28) completed a baseline and follow-up survey including validated measures on job demands (workload and physical demands), job resources (autonomy and task clarity), and well-being (recovery from work and sleep problems). RESULTS: Compared with baseline, nurses reported fewer job demands (lower workloads and fewer physical demands) and sleep problems at follow-up. No statistically significant changes in job resources (autonomy and task clarity) and recovery difficulties were found. CONCLUSIONS: We found preliminary evidence that the addition of a nurse assistant during evening shifts could reduce workloads, physical demands, and sleep problems among nurses. IMPACT: This study highlighted that heavy job demands and sleep problems associated with evening shifts may be addressed by adding a nurse assistant to the nursing team. Future studies with larger samples and a control group are needed to provide better estimates of the magnitude of the beneficial effects and of the cost-effectiveness of an intervention of this kind.

Early-Life Circumstances, Health Behavior Profiles, and Later-Life Health in Great Britain.

Objectives: Drawing on UK Household Longitudinal Study data, this study assessed a pathway from early-life disadvantage to suboptimal later-life health via health behavior. Methods: Latent class analysis was used to identify distinct smoking, nutrition, alcohol, and physical activity health behavior profiles. Mediation analyses were performed to assess indirect effects of early-life disadvantage via health behavior on allostatic load, an objective measure of physiological wear and tear. Results: Four health behavior profiles were identified: (1) broadly healthy and high alcohol consumption, (2) low smoking and alcohol consumption, healthy nutrition, and physically inactive, (3) broadly unhealthy and low alcohol consumption, and (4) broadly moderately unhealthy and high alcohol consumption. Having grown up in a higher socioeconomic position family was associated with lower later-life allostatic load. This was partly attributable to health behavioral differences. Discussion: Growing up under disadvantageous socioeconomic circumstances may initiate a chain of risk by predisposing people to health behavior profiles associated with poorer later-life health.

Is having more children beneficial for mothers' mental health in later life? Causal evidence from the national health and aging trends study.

OBJECTIVES: Members of the baby boom cohorts had fewer children than their parents. Given that adult children are an important source of social support in later life, this may have implications for the mental health of new cohorts of older people. This study investigates whether having additional children protects white mothers aged 65 and older against mental health problems. METHOD: Data are from Wave 1 and Wave 5 of the National Health and Aging Trends Study (n = 3,845). An instrumental variable approach exploiting the preference for mixed-sex offspring is used to estimate the causal effect of additional children on the risk of elevated depression and anxiety symptomatology. RESULTS: The estimated instrumental variable model shows that additional children reduce the risk of suboptimal mental health among white mothers aged 65 and older. CONCLUSION: Results suggest that declines in higher-order births may put new cohorts of older women at increased risk of suboptimal mental health.

The causal effect of number of children on later-life overweight and obesity in parous women. An instrumental variable study.

Many older women in Europe are overweight or obese. One of the factors linked to overweight and obesity among older women is childbearing. However, results of observational studies on the association between women's number of children and excess weight should be interpreted with caution, because they may be prone to bias due to residual confounders or reverse causation. We use data of women aged 50 and older with at least two births from seven waves the Survey of Health, Ageing and Retirement in Europe (n = 113,932) collected between 2004 and 2020. We adopt an instrumental variable approach that exploits the well-established preference for mixed-sex offspring to estimate the causal effect of number of children on older parous women's body mass index (BMI) and their risk of overweight (BMI >= 25 kg/m2) and obesity (BMI >= 30 kg/m2). The instrumental variable models provided evidence for a causal positive effect of having 3 + children as opposed to 2 children on mothers' body mass index, overweight (BMI >= 25 kg/m2) risk and obesity (BMI >= 30 kg/m2) risk. Predicted BMI was 1.8 kg/m2 higher for mothers with 3 + children than for mothers with 2 children, and their predicted probability of overweight and obesity was 18.3 and 8.6 percentage points higher, respectively. Results remained virtually unchanged after adjusting for age, educational attainment, country and wave of data collection.

Gray divorce and mental health in the United Kingdom.

The number of older people who experience marital break-up has increased in many Western countries. However, limited empirical attention has been given to the study of the consequences of later-life divorce or separation. Previous studies on gray divorce are often cross-sectional and tend to capture a mix of short- and long-term effects of divorce and possibly selection effects into divorce. Drawing on data from nine waves of the UK Household Longitudinal Study (2009/2010-2017/2018), we analyze the effect of marital break-up on the mental health of 909 adults aged 50 or over to test the crisis model and the chronic strain model of divorce. We use fixed effects linear regression models to account for time-invariant confounders and distinguish between pre- and post-divorce effects. Our results indicate that older adults' depressive symptoms (GHQ) increase in the years before and upon union dissolution. After separation, depressive symptoms decrease and return to approximately previous baseline levels. Our analyses on heterogeneity in the effects of gray divorce show that post-divorce adjustment is faster for childless adults than for parents. We find no evidence that adjustment after gray divorce is slower for women than for men, or for persons who already experienced a prior union dissolution than for those who separate for the first time. The results are consistent with the crisis model of divorce but in contrast with the chronic strain model of divorce. Older adults are able to adjust to marital break-up, and their fertility histories tend to moderate the negative effect of later-life divorce on mental health.

Prenatal famine exposure and mental health in later midlife.

OBJECTIVES: Maternal malnutrition during pregnancy may have long-lasting effects on offspring's mental health. We investigate the effect of prenatal exposure to the Dutch famine (mid November 1944 to late April 1945) on mental health in later mid-life. METHODS: Data are from the Netherlands Kinship Panel Study (n = 642). We use difference-in-difference analyses to compare mental health in later midlife (measured with the MHI-5 index) across three cohorts ('pre-famine cohort', 'famine cohort', 'post-famine cohort') and across two regions (famine affected cities vs. rest of the country). RESULTS: In the affected cities, we find poorer mental health for the famine cohort than for the pre-famine and post-famine cohorts. In the non-affected rest of the country, no significant mental health differences between birth cohorts were found. The mental health differences between birth cohorts differ significantly between the affected cities and the rest of the Netherlands. CONCLUSION: Our analyses link prenatal famine exposure to poorer mental health in later midlife. This suggests that in utero malnutrition has a long-lasting detrimental effect on mental health.

Number of Children, Partnership Status, and Later-life Depression in Eastern and Western Europe.

Objectives: To investigate associations between number of children and partnership with depressive symptoms among older Europeans and assess whether associations are greater in Eastern than Western countries. We further analyze whether associations are mediated by provision and receipt of emotional and financial support. Methods: Using cross-sectional data for five Eastern (Bulgaria, Czech Republic, Georgia, Romania, and Russia) and four Western European countries (Belgium, France, Norway, and Sweden) (n = 15,352), we investigated variation in depressive symptoms using linear regression. We fitted conditional change score models for depressive symptoms using longitudinal data for four countries (Bulgaria, Czech Republic, Georgia, and France) (n = 3,978). Results: Unpartnered women and men had more depressive symptoms than the partnered. In Eastern, but not Western, European countries childlessness and having one compared with two children were associated with more depressive symptoms. Formal tests indicated that partnership and number of children were more strongly associated with depressive symptoms in Eastern than Western Europe. Discussion: Availability of close family is more strongly associated with older people's depressive symptoms in Eastern than Western Europe. The collapse of previous state supports and greater economic stress in Eastern Europe may mean that having a partner and children has a greater psychological impact than in Western countries.

Parental health limitations, caregiving and loneliness among women with widowed parents: longitudinal evidence from France.

We investigate how daughters' feelings of loneliness are impacted when widowed parents develop health limitations, and when daughters take on personal care tasks in response. Using longitudinal data from daughters of widowed parents drawn from the French Family and Intergenerational Relationships Study (ERFI, 1485 observations nested in 557 daughters), we assess (a) whether health limitations of widowed parents are associated with daughters' feelings of loneliness regardless of whether or not daughters provide personal care and (b) whether there is an effect of care provision on loneliness that cannot be explained by parental health limitations. Fixed effect regression analyses show that widowed parents' health limitations were associated with raised feelings of loneliness among their daughters. No significant additional effect of providing personal care to a widowed parent was found. Prior research on the impact of health limitations of older parents on the lives of their adult-children has focused mostly on issues related to informal caregiving. Our findings suggest that more attention to the psychosocial impact of parental health limitations-net of actual caregiving-on adult children's lives is warranted.

Gender differences in the correlates of loneliness among Japanese persons aged 50-70.

OBJECTIVE: This study aimed to explore gender differences in the correlates of loneliness among Japanese persons aged 50-70. METHODS: Logistic regression models were estimated on cross-sectional Japanese Generations and Gender Survey data of 4057 persons aged 50-70. Loneliness was measured as having a score of 2 or higher on the shortened De Jong Gierveld loneliness scale. RESULTS: For more than half of the respondents, De Jong Gierveld loneliness scores exceeded the threshold of 2. Loneliness was more prevalent among men than among women. Living without a spouse or partner was more strongly associated with loneliness for men than for women. Childlessness was more strongly associated with loneliness for women than for men. CONCLUSION: A large proportion of Japanese people between 50 and 70, particularly men, are lonely. Programs aimed at reducing loneliness should acknowledge that antecedents of loneliness differ between women and men.

Care Ideals in the Netherlands: Shifts between 2002 and 2011.

Our study's premise was that normative care beliefs can inform the current care policy debate. We conducted latent class regression analyses on two waves of Netherlands Kinship Panel Study data (n = 4,163) to distinguish care ideals that captured multiple dimensions of normative care beliefs simultaneously. We also assessed how these care ideals have shifted in the early twenty-first century. We distinguished four care ideals: warm-modern (family and state jointly responsible for caring, egalitarian gender roles), cold-modern (large state responsibility, restricted family responsibility, egalitarian gender roles), traditional (restricted state responsibility, large family responsibility, moderately traditional gender roles), and cold-traditional (large state responsibility, restricted family responsibility, traditional gender roles). Between 2002 and 2011, there has been a shift away from warm-modern care ideals and towards cold-modern care ideals. This is remarkable, because Dutch policy makers have increasingly encouraged family members to take on an active role in caring for dependent relatives.