Social relations and health in an ethnically diverse social housing area selected for large structural changes compared to municipal levels: a Danish survey study.

BACKGROUND: This study aims to describe demographics, social relations and health in an ethnically diverse social housing area selected to undergo large structural changes and compare it to the surrounding municipality. Furthermore, to explore the association between social relations and self-rated health (SRH) and the interaction with country of origin in both populations. METHODS: Data sources include a multilingual interviewer-driven survey study in a social housing area (N = 209) and a municipal health survey (N = 1,638) among residents aged 45 + years. Information on social relations include contact frequency with and support from family, friends, and neighbors. Descriptive and multivariate logistic regression analyses adjusted for age, sex, and country of origin are presented, as well as joint effect analyses of social relations and country of origin on SRH. RESULTS: In the social housing area, 38.8% of the respondents reported poor SRH compared to 19.5% in the municipality. In both study populations low contact frequency was associated with poor SRH, however insignificantly in the social housing area compared to the municipality sample, OR = 1.50 (0.65-3.46) vs. OR = 2.42 (1.70-3.45). Joint exposure to having non-Western background and low contact frequency was strongly associated with poor SRH in the social housing area, OR = 6.28 (1.80-21.89) but less so in the municipality, OR = 3.67 (1.55-8.69). The same tendency was seen regarding low support from social relations. CONCLUSIONS: This study provides insight to a population that is generally underrepresented in survey studies. In the social housing area, approximately twice as many reported poor SRH compared to the municipality data. In both populations, low contact frequency and low support were associated with poor SRH. Residents with weak social relations and non-Western origin simultaneously were more likely to report poor SRH in the social housing area specifically but less so in the municipality, indicating a higher vulnerability among the residents in the social housing area.

Monitoring process-related impurities in biologics-host cell protein analysis.

During biologics development, manufacturers must demonstrate clearance of host cell impurities and contaminants to ensure drug purity, manufacturing process consistency, and patient safety. Host cell proteins (HCPs) are a major class of process-related impurities and require monitoring and documentation of their presence through development and manufacturing. Even in residual amounts, they are known to affect product quality and efficacy as well as patient safety. HCP analysis using enzyme-linked immunosorbent assay (HCP-ELISA) is the standard technique, due to its simple handling, short analysis time, and high sensitivity for protein impurities. Liquid chromatography mass spectrometry (LC-MS) is an orthogonal method for HCP analysis and is increasingly included in regulatory documentation. LC-MS offers advantages where HCP-ELISA has drawbacks, e.g., the ability to identify and quantify individual HCPs. This article summarizes the available knowledge about monitoring HCPs in biologics and presents the newest trends in HCP analysis with current state-of-the-art HCP measurement tools. Through case studies, we present examples of HCP control strategies that have been used in regulatory license applications, using an MS-based coverage analysis and HCP-ELISA and LC-MS for HCP quantification. This provides novel insight into the rapid evolving strategy of HCP analysis. Improvements in technologies to evaluate HCP-ELISA suitability and the implementation of orthogonal LC-MS methods for HCP analysis are important to rationally manipulate, engineer, and select suitable cell lines and downstream processing steps to limit problematic HCPs.

Use of candles and risk of cardiovascular and respiratory events in a Danish cohort study.

Burning candles at home emit small particles and gases that pollute indoor air. Exposure to fine particles in outdoor air has been convincingly linked to cardiovascular and respiratory events, while the associations with fine and ultrafine particles from candle burning remain unexplored. We examined the association between the use of candles and incident cardiovascular and respiratory events. We collected data on 6757 participants of the Copenhagen Aging and Midlife Biobank cohort recruited in 2009 and followed them up for the first hospital contact for incident cardiovascular and respiratory events until 2018. We investigated an association between the self-reported frequency of candle use in wintertime and cardiovascular and respiratory events, using Cox regression models adjusting for potential confounders. During follow-up, 1462 and 834 were admitted for cardiovascular and respiratory events, respectively. We found null associations between candle use and a hospital contact due to cardiovascular and respiratory events, with hazard ratios (HRs) and 95% confidence intervals (CI) of 0.97 (95% CI: 0.84, 1.11) and 0.98 (95% CI: 0.81, 1.18), respectively, among those using candles >4 times/week compared with <1 time/week. For cause-specific cardiovascular diseases, HRs were 1.10 (95% CI: 0.85, 1.43) for ischemic heart disease and 1.18 (95% CI: 0.77, 1.81) for myocardial infarction. For chronic obstructive pulmonary disease, HR was 1.26 (95% CI: 0.81, 1.97). We found no statistically significant associations between candle use and the risk of cardiovascular and respiratory events. Studies with improved exposure assessments are warranted.

Do changes in frailty, physical functioning, and cognitive functioning predict mortality in old age? Results from the Longitudinal Aging Study Amsterdam.

BACKGROUND: The ability to accurately predict survival in older adults is crucial as it guides clinical decision making. The added value of using various health indicators as well as changes in these indicators for predicting mortality remains unclear. The aim of this study was to investigate whether changes in health indicators such as frailty and physical performance improve mortality predictions in old age. METHODS: This is a population based prospective cohort study on 995 community-dwelling people aged 68-92 years from the Longitudinal Aging Study Amsterdam. Two measurements at a three-year interval (1995/1996 and 1998/1999) were available for the frailty index, frailty phenotype, grip strength, walking speed, and Mini-Mental State Examination (MMSE). Cox regression was used to analyze mortality risks associated with the current health status and changes in health, with mortality data up to 2017. The extent to which these health indicators improved mortality predictions compared to models with age and sex only was assessed by the area under the receiver operating characteristic curve (AUC). RESULTS: The AUC of age and sex for five-year mortality was 72.8% (95% CI 69.0 - 76.5) and was the lowest in the oldest old (age > 80.5 years). The added AUC of the current status of health indicators ranged from 0.7 to 3.3%. The added AUC of the three-year change was lower, ranging from -0.0 to 1.1%, whereas the added AUC of three-year change and current status combined was similar to current status alone, ranging from 0.6 to 3.2%. Across age, the added AUC of current status was highest in the oldest old, however there was no such pattern using three-year change. Overall, the frailty index appeared to improve mortality predictions the most, followed by the frailty phenotype, MMSE, grip strength, and walking speed. CONCLUSIONS: Current health status improved mortality predictions better than changes in health. Its contribution was highest in the oldest old, but the added value to models with age and sex only was limited.

Challenges and lessons learnt from conducting a health survey in an ethnically diverse population.

Aim: To document the challenges of developing and executing an interviewer-driven survey questionnaire in an ethnically diverse and deprived social housing area undergoing reconstruction in Denmark. Methods: The survey was initially planned to be conducted in three waves (before, during and after reconstruction of the housing area), based on a questionnaire covering health, wellbeing and social relations. The first two waves took place in 2018 and 2019 (invited n=~600 per wave) and the third wave will be conducted once the reconstruction is finalised. The approach to the third wave is under revision by the research team. The questionnaire was translated from Danish into the seven most common languages in the housing area. A bilingual interview team went door to door interviewing residents. Field notes were collected systematically during each wave to document the process. Results: The response rates were 35% (n=209) and 22% (n=132) for waves 1 and 2, respectively. There was an overall decrease in response rates between waves 1 and 2 for all language groups, but particularly for Arabic and Turkish-speaking men. The most frequently stated reasons for non-participation included illness and language barriers. The key lessons learnt were that overcoming linguistic and cultural barriers to conducting research among residents in this social housing area requires time and resources. Conclusions: Several challenges are associated with conducting a survey in ethnically diverse and deprived social housing areas. Documenting the challenges and learning from experience are both important, in order to include this hard-to-reach population in health research.

Social relations and contact with general practitioner in a middle-aged Danish population: a prospective register- and survey-based cohort study.

BACKGROUND: Findings about the relationship between individuals' social relations and general practitioner (GP) contact are ambiguous as to whether weak social relations are associated with an increased or decreased consultation pattern. Furthermore, social relations may affect GP contact differently for men compared to women, between socioeconomic groups and according to perceived need. The overall aim of the study is to examine the association between functional aspects of social relations, perceived emotional and instrumental social support, the tendency to consult a GP and the frequency of GP contact. METHODS: The study comprised 6911 individuals aged 49-61 at baseline from the Copenhagen Aging and Midlife Biobank (CAMB). We conducted a two-part regression to explore the association between perceived emotional and instrumental social support and GP contact (tendency and frequency), controlling for age, sex, occupational social class, cohabitation status and number of morbidities. RESULTS: Results show no overall effect of the perceived social support aspects of social relations on GP contact independent of health-related needs. CONCLUSIONS: Our results do not support that perceived social support, reflecting functional aspects of social relations, are associated with general practitioner contact among middle-aged people. TRIAL REGISTRATION: The study has been registered and approved by the Danish Data Protection Agency and the local ethical committee (approval No.H-A-2008-126 and No. 2013-41-1814).

Undertaking graphic facilitation to enable participation in health promotion interventions in disadvantaged neighbourhoods in Denmark.

This study reports on a health promotion intervention (HPI), where graphic facilitation (GF) was used as an innovative method to enable participation in a co-design process in a multi-ethnic and disadvantaged neighbourhood in Denmark. The aim was to enable middle-aged and older residents to participate in the research process of planning and evaluating the HPI, as well as in the activities it constituted. GF was used to document statements and inputs from residents through visual meeting minutes and resident experiences with coronavirus disease 2019 (COVID-19) lockdown were drawn by a graphic facilitator. We use the ladder of participation as a framework to unfold the participation enabled by GF. During the HPI, data were produced through ethnographic field studies in and outside the neighbourhood and in design workshops with residents. The study finds that GF helped in reaching a target group difficult to engage in research and that the engagement of a graphic facilitator shifted the power-balance between the researchers and the residents, redistributing expertise. Carrying out GF in a HPI is a collaborative endeavour and in addition to research competences, it requires the artistic and relational skills of a graphic facilitator. The co-created process of the visual minutes and COVID-19 experiences created a sense of ownership and encouraged the residents to reflect on their interaction with the researchers. The redistribution of expertise was conditioned by the power dynamics present and GF helped unfold these dynamics. This is especially important in an HPI engaging socio-economically vulnerable populations.

This study reports on graphic facilitation as an innovative method to enable participation in health promotion interventions. It investigates how engagement from the target group was achieved. The study is set in an ethnically diverse and disadvantaged neighbourhood. Residents 45 years+ were invited to participate in two phases of HPI activities. In Phase I, a resident committee planned and evaluated four social outings aiming to build and strengthen social relations among the residents. A graphic facilitator was part of the process, visually documenting the residents' inputs and facilitating a transparent and visual engagement process. In Phase II, seven residents participated in interviews about their experiences during coronavirus disease 2019 lockdown. The graphic facilitator transformed the interviews into an illustrative book communicating their experiences, and posters communicating expedient health behaviour during the pandemic. The graphic facilitation method made it possible to engage a heterogeneous group of residents and helped overcome language barriers. We conclude that it is a relevant method to use when engaging people unfamiliar to research and in risk of suffering from various health problems. The method is suitable for redistributing power and actively including everyday experiences as testimonies of expertise, thereby creating a sense of ownership among the participants.

Loneliness, Social Isolation, and Chronic Disease Outcomes.

BACKGROUND: Research suggests that loneliness and social isolation (SI) are serious public health concerns. However, our knowledge of the associations of loneliness and SI with specific chronic diseases is limited. PURPOSE: The present prospective cohort study investigated (a) the longitudinal associations of loneliness and SI with four chronic diseases (cardiovascular disease [CVD], chronic obstructive pulmonary disease [COPD], diabetes mellitus Type 2 [T2D], and cancer), (b) the synergistic association of loneliness and SI with chronic disease, and (c) baseline psychological and behavioral explanatory factors. METHODS: Self-reported data from the 2013 Danish "How are you?" survey (N = 24,687) were combined with individual-level data from the National Danish Patient Registry on diagnoses in a 5 year follow-up period (2013-2018). RESULTS: Cox proportional hazard regression analyses showed that loneliness and SI were independently associated with CVD (loneliness: adjusted hazard ratio (AHR) = 1.20, 95% confidence interval [CI; 1.03, 1.40]; SI: AHR = 1.23, 95% CI [1.04, 146]) and T2D (loneliness: AHR =1.90, 95% CI [1.42, 2.55]; SI: AHR = 1.59, 95% CI [1.15, 2.21]). No significant associations were found between loneliness or SI and COPD and cancer, respectively. Likewise, loneliness and SI did not demonstrate a synergistic effect on chronic disease. Multiple mediation analysis indicated that loneliness and SI had an indirect effect on CVD and T2D through both baseline psychological and behavioral factors. CONCLUSION: Loneliness and SI were independently associated with a diagnosis of CVD and T2D within a 5 year follow-up period. The associations of loneliness and SI with CVD and T2D were fully explained by baseline psychological and behavioral factors.

Smartphone interactions and mental well-being in young adults: A longitudinal study based on objective high-resolution smartphone data.

Aims: To investigate the effects of objectively measured smartphone interactions on indicators of mental well-being among men and women in a population of young adults. Methods: A total of 816 young adults (mean±SD age 21.6±2.6 years; 77% men) from the Copenhagen Network Study were followed with objective recordings of smartphone interactions from calls, texts and social media. Participants self-reported on loneliness, depressive symptoms and disturbed sleep at baseline and in a four-month (interquartile range 75-163 days) follow-up survey. Multiple linear regression was used to analyse the association between smartphone interactions and mental well-being separately for men and women. Results: A higher number of smartphone interactions was associated with lower levels of loneliness at baseline and the same pattern appeared for depressive symptoms, although this was less pronounced. A high level of smartphone interaction was associated with lower levels of disturbed sleep for men, but not for women. In follow-up analyses, a high versus low level of smartphone interaction was associated with an increase in loneliness and depressive symptoms over time for women, but not for men. Conclusions: Smartphone interactions are related to better mental well-being, which may be attributed to the beneficial effects of an underlying social network. Over time, accommodating a large network via smartphone communication might, however, have negative effects on mental well-being for women.

Changes and correlations in height from 7 to 69 years of age across the birth years of 1930 to 1989.

OBJECTIVES: The aims of this study were to describe changes in height during childhood and to investigate potential changes in the proportion of children attaining final height in childhood and in correlations between child and adult height across birth cohorts. METHODS: We included 363 059 children (179 906 girls) from the Copenhagen School Health Records Register, who were born between 1930 and 1989, with height measurements at ages 7, 10, or 13 years. Linkages to data resources containing adult height values between ages 18 and 69 years were possible for a subpopulation of 96 133 individuals (23 051 women). Birth years were categorized as 1930 to 1939, 1940 to 1949, and 1950 to 1989. Descriptive height statistics were estimated by birth years and birth cohorts. Height correlations were examined using sex- and age-specific partial Pearson correlation analyses and meta-regression techniques. RESULTS: Across 60 birth years, mean child heights at age 7 increased by 2.9 cm in girls and 3.0 cm in boys, and adult heights increased as well. The proportions of children attaining final height by age 13 remained low across the birth cohorts; nonetheless, there was a significant increase from 0.7% to 1.5% in girls only (P < .0001). Both child-child and child-adult height correlations were strong and remained relatively stable across birth cohorts. CONCLUSIONS: Mean child and adult height increased during the study period, but the proportion of children attaining final height at age 13 remained low. Child-child and child-adult height correlations were largely unchanged across birth cohorts.

Midlife Forgetfulness and Risk of Dementia in Old Age: Results from the Danish Working Environment Cohort Study.

BACKGROUND: Despite the current evidence of a high prevalence of forgetfulness in middle-aged individuals, and the evidence of a link between midlife memory complaints and biological changes in the brain, no previous study has yet investigated midlife forgetfulness in relation to risk of dementia in old age. AIMS: We investigated whether midlife forgetfulness was an indicator of an increased risk of dementia in old age. METHODS: We used data from 3,136 employed men and women who participated in the Danish Work Environment Cohort Study in 1990. These data were linked to Danish national registers. Participants were asked whether their closest relative had ever told them that they were forgetful. Incidence rate ratios (IRR) were estimated using Poisson regression analysis. RESULTS: At baseline, 749 (24%) study participants were categorized as forgetful, and 86 (2.7%) participants were diagnosed with dementia during a total of 31,724 person-years at risk. After adjusting for sociodemographic factors, comorbidities, and work-related factors, midlife forgetfulness was associated with a higher risk of dementia (IRR = 1.82; 95% CI: 1.12-2.97). CONCLUSIONS: This study is the first to investigate midlife forgetfulness and dementia, and the results suggest that midlife forgetfulness is an early indicator of an increased risk of dementia in old age.

The joint effect of unemployment and cynical hostility on all-cause mortality: results from a prospective cohort study.

BACKGROUND: It is hypothesised that hostility accentuates the association between stressful conditions and health. This study aims to test this hypothesis by analysing the joint effect of unemployment and hostility on all-cause mortality among men and women. METHODS: The population was 3677 men and 4138 women from the Danish workforce who participated in a survey in 2000. The joint exposure variable was defined as 1) employed, not hostile, 2) unemployed, not hostile, 3) hostile and employed, 4) unemployed and hostile. Outcome was defined as all-cause mortality between 2000 and 2014. Data was analysed with Cox proportional hazards models with age as the underlying time scale. The interaction between unemployment and hostility was studied using the synergy index. RESULTS: Compared to employed non-hostile men, men who were both hostile and unemployed were at markedly higher risk of premature death with a hazard ratio (HR) of 3.19 (95% CI 2.22-4.69). A similar picture was found for hostile and unemployed women, with a HR of 1.97 (95% CI 1.24-3.12). However, the mortality in men and women exposed to both did not exceed what was expected from the combination of their individual effects. Hence, we did not find that hostility enhances the association between unemployment and all-cause mortality. CONCLUSION: Men and women exposed to both unemployment and hostility were at markedly high risk of premature mortality. However, this study did not support the hypothesis that the deleterious health effect of the combination of unemployment and hostility exceeds their individual effects.

Cumulative physical workload and mobility limitations in middle-aged men and women: a population-based study with retrospective assessment of workload.

PURPOSE: To assess the association between exposure to physical workload throughout working life and risk of mobility limitations in midlife in a population-based Danish cohort. METHODS: The study was cross-sectional with a retrospective exposure assessment, and data were from a questionnaire used in the Copenhagen Aging and Biobank. Cumulative physical workload was estimated by combining information about the participants' employments and data from a job exposure matrix. Daily amount of lifting was standardised in ton-years (lifting 1000 kg/day/year) and grouped in 5 exposure groups (no/minor (1-2 ton-years)/low (3-10 ton-years)/moderate (11-20 ton-years)/high exposure (> 20 ton-years)). The outcome was self-reports of mobility limitations (running 100 m, walking 400 m, and climbing stairs to the 2nd floor) in midlife. The association between exposure and outcome was analysed using logistic regression models. RESULTS: We included 4996 men and 2247 women, mean age 56 years. 21% of men and 10% of women were in the highest exposure-group (> 20 ton-years). Higher cumulative exposure was associated with higher odds for mobility limitations. Exposure to more than 20 ton-years compared to no exposure increased the odds for limitations in walking, age-adjusted odds ratio (OR) 3.2 (95% CI: 2.4-4.3) for men, 2.3 (1.4-3.8) for women. Corresponding results for running: 2.5 (2.2-3.0) for men, 1.6 (1.2-2.2) for women, and for limitations in climbing stairs: 4.2 (3.3-5.2) for men, 1.7 (1.2-2.4) for women. Results were attenuated when confounders were added. CONCLUSIONS: Exposure to physical workload throughout working life is associated with higher odds for mobility limitations in midlife.

Prolonged or serious conflicts at work and incident dementia: a 23-year follow-up of the Copenhagen City Heart Study.

PURPOSE: Only a few studies have investigated the impact of negative aspects of social relations on cognitive function, and they have shown mixed results. Conflicts at work are part of the negative aspects of social relations, but the impact of experiencing conflicts at work has not yet been investigated as a risk factor for dementia. Therefore, we investigated whether experiencing prolonged or serious conflicts with a supervisor or colleagues at work was associated with incident dementia in old age. METHODS: We analyzed data of 6,436 men and women from the third survey of the Copenhagen City Heart Study. At baseline in 1991-1994, the participants reported whether they had ever had a prolonged or serious conflict at work. The participants were followed until 2014. We used Poisson regression to estimate incidence rate ratios (IRR) and their 95% confidence intervals (CI). RESULTS: After adjusting for potential confounders, the IRR for dementia was 1.53 (95% CI 0.77-3.03) among participants who had reported having prolonged or serious conflicts both with a supervisor and colleagues compared with participants who had never had such conflicts. In separate analyses stratified by sex, the IRRs were 2.14 (95% Cl 0.97-4.71) for men and 0.98 (95% Cl 0.29-3.32) for women. CONCLUSIONS: Our findings did not support an overall association between experiencing prolonged or serious conflicts at work and incident dementia. However, because of the large differences in the point estimates for men and women, future research could aim at investigating potential sex differences regarding the association between conflicts at work and dementia.

Education and Cognitive Aging: Accounting for Selection and Confounding in Linkage of Data From the Danish Registry and Survey of Health, Ageing and Retirement in Europe.

Earlier studies report inconsistent associations between education and cognitive aging. We assessed the association, accounting for selective dropout due to death or dementia, and, in a subsample, accounting for confounding by early-life intelligence. Data from the Danish component of the Survey of Health, Ageing and Retirement in Europe (n = 3,400) were linked to registry data (education records, dementia diagnoses, and mortality) and the Danish Conscription Database (youth intelligence measurements for 854 men). Word recall and verbal fluency were assessed up to 4 times over 10 years (2004-2013) and combined by averaging the z scores. We fitted a joint model linking a time-to-event model for dementia or death to a linear mixed-effects model for cognitive change. Rate of cognitive decline was slower among people with high education compared with low education (ß = 0.112, 95% confidence interval (CI): 0.056, 0.170). Adjusting for youth intelligence did not attenuate the association between education and cognitive decline (crude ß = 0.136, 95% CI: 0.028, 0.244 vs. adjusted ß = 0.145, 95% CI: 0.022, 0.269). The results suggest that higher education may slow cognitive decline in later life. In this sample, results changed little when accounting for selective attrition and confounding by intelligence.

Loneliness and objectively measured physical capability in middle-aged adults.

Background: Loneliness is associated with poor functional ability in older people. Little is known about this association in the middle-aged. The aim is to investigate if perceived loneliness is associated with lower physical capability among middle-aged men and women and if the associations of loneliness with physical capability interact with socioeconomic position and cohabitation status. Methods: 5224 participants from Copenhagen Aging and Midlife Biobank (CAMB) aged 49-62 years (mean age 54) were included. Handgrip strength (measured by a dynamometer) and maximal number of chair rises in 30 s was recorded. Multivariate linear regression analyses were adjusted for age, occupational social class, cohabitation status, morbidity and personality traits. Results: No association was found between loneliness and physical capability. For example estimates for handgrip strength in 'often' lonely men and women compared with the 'not lonely' were 1.2 kg (95% CI - 0.5;2.9)/1.0 kg (-0.7;2.6). Low occupational social class was associated with poorer physical capability, and living alone was associated with poorer handgrip strength in men [-2.4 kg (95% CI - 3.2;-1.5)] and poorer chair rise test in women [-0.8 rises (95% CI - 1.6;-0.1)]. There was no support for interactions. Conclusion: In contrast to earlier studies among older people, no association between loneliness and physical capability was found in this cohort of middle-aged men and women. Loneliness may not yet have resulted in detectable differences in physical capability in this age group. Further research is needed to clarify if, and at what point in the life course loneliness begins to affect physical capability.

NADH-Cytochrome b5 Reductase 3 Promotes Colonization and Metastasis Formation and Is a Prognostic Marker of Disease-Free and Overall Survival in Estrogen Receptor-Negative Breast Cancer.

Metastasis is the main cause of cancer-related deaths and remains the most significant challenge to management of the disease. Metastases are established through a complex multistep process involving intracellular signaling pathways. To gain insight to proteins central to specific steps in metastasis formation, we used a metastasis cell line model that allows investigation of extravasation and colonization of circulating cancer cells to lungs in mice. Using stable isotopic labeling by amino acids in cell culture and subcellular fractionation, the nuclear, cytosol, and mitochondria proteomes were analyzed by LC-MS/MS, identifying a number of proteins that exhibited altered expression in isogenic metastatic versus nonmetastatic cancer cell lines, including NADH-cytochrome b5 reductase 3 (CYB5R3), l-lactate dehydrogenase A (LDHA), Niemann-pick c1 protein (NPC1), and nucleolar RNA helicase 2 (NRH2). The altered expression levels were validated at the protein and transcriptional levels, and analysis of breast cancer biopsies from two cohorts of patients demonstrated a significant correlation between high CYB5R3 expression and poor disease-free and overall survival in patients with estrogen receptor-negative tumors (DFS: p = .02, OS: p = .04). CYB5R3 gene knock-down using siRNA in metastasizing cells led to significantly decreased tumor burden in lungs when injected intravenously in immunodeficient mice. The cellular effects of CYB5R3 knock-down showed signaling alterations associated with extravasation, TGFß and HIFα pathways, and apoptosis. The decreased apoptosis of CYB5R3 knock-down metastatic cancer cell lines was confirmed in functional assays. Our study reveals a central role of CYB5R3 in extravasation/colonization of cancer cells and demonstrates the ability of our quantitative, comparative proteomic approach to identify key proteins of specific important biological processes that may also prove useful as potential biomarkers of clinical relevance. MS data are available via ProteomeXchange with identifier PXD001391.

Parental break-ups and stress: roles of age & family structure in 44 509 pre-adolescent children.

Background: Parental break-up is wide spread, and the effects of parental break-up on children's well-being are known. The evidence regarding child age at break-up and subsequent family arrangements is inconclusive. Aim: to estimate the effects of parental break-up on stress in pre-adolescent children with a specific focus on age at break-up and post-breakup family arrangements. Methods: We used data from the Danish National Birth Cohort. Participants included 44 509 children followed from birth to age 11. Stress was self-reported by children at age 11, when the children also reported on parental break-up and post break-up family arrangements. Results: Twenty-one percent of the children had experienced a parental break-up at age 11, and those who had experienced parental break-up showed a higher risk of stress (OR:1.72, 95%CI:1.55;1.91) regardless of the child's age at break-up. Children living in a new family with stepparents (OR = 1.63, 95%CI:1.38;1.92), or shared between the parents (OR = 1.48, 95%CI:1.26;1.75) reported higher stress than children of intact families. Single parent families reported markedly higher stress levels than children in intact families (OR = 2.18, 95%CI:1.90;2.50) and all other family types. Children who were satisfied with their living arrangements post-break-up reported the same stress level as children living in intact families (OR = 1.01, 95%CI:0.86;1.18). Conclusion: Children who experience parental break-up have higher stress levels, also many years after the break-up, and those living in a single parent household post break-up seem to be most vulnerable. Living arrangements post-breakup should be further investigated as a potential protective factor.

Understanding the relation between socioeconomic position and inflammation in post-menopausal women: education, income and occupational prestige.

Background: The role of occupational prestige, a direct measure of the perceived status of job and job holder, in inflammation is unknown. To contribute to understanding the pathways by which socioeconomic position (SEP) is associated with inflammation, we aimed to estimate the direct effects of education, income and occupational prestige on C-reactive protein (CRP) and to describe the relationship between these markers and CRP. Methods: The study was based on 2026 post-menopausal women enrolled in the Women's Health Initiative-Observational Study. Occupational prestige was determined by linking a text description of longest held occupation with a social status item from the Occupational Information Network. Path analysis was employed to estimate direct and mediated effects. Results: The study suggests that higher levels of education, income, and occupational prestige are associated with 8% (95% CI as percentage change -12, -4), 5% [95% CI (-8, -2) and 4% (95% CI - 7, -1)] lower levels of CRP, respectively. The inverse association between education and CRP was explained by the effect of education on income and occupational prestige. The effect of occupational prestige on CRP was independent of mediators in the model. Conclusions: The findings indicate that education may work to influence CRP primarily through increasing income and occupational prestige and provides evidence that occupational prestige captures a unique aspect of SEP.

Social relations and healthcare utilisation among middle-aged and older people: study protocol for an implementation and register-based study in Denmark.

BACKGROUND: While previous research establishes an association between social relations, health and use of healthcare services among older people, how to implement this knowledge in real-life settings has received much less attention. This study will explore the relationship between social relations, health and use of healthcare services in a Danish mid-life population sample. In addition, the study will explore individual and contextual factors affecting the implementation of a group-based life story intervention aimed at establishing and strengthening social relations among older people at nursing homes in Denmark. METHODS/DESIGN: A combined quantitative register-based approach and a qualitative implementation approach will be applied in this study. First, we will quantitatively analyse the relationship between social relations, health status and use of healthcare services among middle-aged people in Denmark by linking survey data on social relations, loneliness, self-perceived health and disease status from the Copenhagen Aging and Midlife Biobank (CAMB) (n = 7191) with national registries through the Public Health Database on use of healthcare services and demographic and socioeconomic factors. Second, we will qualitatively analyse individual and contextual factors affecting the implementation process of the group-based life story intervention based on semi-structured interviews (n = 16), observations and field notes with and among intervention stakeholders, i.e., participants and group leaders facilitating the intervention. DISCUSSION: The results of this study are expected to improve knowledge about mechanisms through which social relations are associated with health status and use of healthcare services and to inform the implementation of future interventions targeting social relations among older people at nursing homes. TRIAL REGISTRATION: The study has been registered and approved by the Danish Data Protection Agency. Seperate approvals have been attained for the qualitative data (Approval No. SUND-2016-08), and for the quantitative data in the CAMB database which has also received approval from the local ethical committee (approval No.H-A-2008-126 and No. 2013-41-1814, respectively).