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Ischemic heart disease (IHD) causes mortality and morbidity. High levels of occupational physical activity (OPA) increases IHD risk, and occupational lifting (OL) is suggested as a detrimental OPA exposure. This study investigated the association between accumulated OL throughout working life, and risk for IHD, and potential sex and hypertension differences. Data from Copenhagen Ageing and Midlife Biobank linked to register-based information on incident IHD during 9 years follow-up in the Danish National Patient Registry were included. The outcome was the odds of IHD from baseline (2009–2011) to end of follow-up (2018), among participants without IHD at baseline. Accumulated OL was assessed by linking occupational codes to a Job Exposure Matrix, creating a measure in ton-years (lifting 1,000 kg/day/year). Multivariable logistic regression tested associations between level of accumulated OL and IHD, among the 6,606 included individuals (68% men). During follow-up, 7.3% men and 3.6% women were hospitalized with IHD. Among all participants, the odds for IHD were 47% (OR 1.47, 95% CI 1.05–2.06) higher among those with ≥5 to <10 ton-years, 39% (OR 1.39, 95% CI 1.06–1.83) higher among those with ≥10 to <30 ton-years, and 62% (OR 1.62, 95% CI 1.18–2.22) higher among those with ≥30 ton-years, compared to no accumulated OL. However, these increased odds were in the same direction in the fully-adjusted model but statistically insignificant, ≥5 to <10 ton-years OR 1.28, 95% CI 0.88–1.88; ≥10 to <30 ton-years OR 1.20, 95% CI 0.85–1.69; and ≥30 ton-years OR 1.22, 95% CI 0.81–1.84. No statistically significant interactions, nor any associations, between OL and sex, or hypertension were seen.

Area regeneration of deprived neighborhoods is being used to reduce health inequality, socioeconomic deprivation and ethnic segregation. This quasi-experimental study examines if long-term graded exposure to urban regeneration is associated with primary healthcare-seeking behavior among residents. We compared general practitioner (GP) contacts from 2015-2020 in two adjacent, deprived social housing areas, one exposed to area regeneration. Populations were into Western and non-Western males and females aged 15 years and older (N = 3,960). Mean annual GP contact frequency for each group were estimated and a difference-in-difference (DiD) analysis was conducted with adjustments for propensity scores based on baseline characteristics. GP contact frequency increased for all groups across time with a systematically higher level and faster increase in the control groups. In particular, the mean difference between the exposed and control area for Western women increased from −4.67 to −5.76 annual contacts across the period. The mean differences in contact frequency increased for all groups but results of the DiD analyses were insignificant. In conclusion, an increasing gap in GP contact frequency, with the highest levels in the control area, was observed for all comparisons across time. More long-term research is needed to understand how the increasing gaps evolve.

BackgroundArea deprivation is associated with adverse mental health outcomes. In Denmark, urban regeneration is being used to dissolve concentrated socio-economic area deprivation and ethnic segregation. However, evidence on how urban regeneration affects mental health of residents is ambiguous partly due to methodological challenges. This study investigates if urban regeneration affects users of antidepressant and sedative medication among residents in an exposed and control social housing area in Denmark.MethodsUsing a longitudinal quasi-experimental design we measured users of antidepressant and sedative medication in one area undergoing urban regeneration compared with a control area. We measured prevalent and incident users from 2015 to 2020 among non-Western and Western women and men and used logistic regression to measure annual change in users over time. Analyses are adjusted for a covariate propensity score estimated using baseline socio-demographic characteristics and general practitioner contacts.ResultsUrban regeneration did not affect the proportion of prevalent nor incident users of antidepressant and sedative medication. However, levels were high in both areas compared with the national average. Descriptive levels of prevalent and incident users were generally lower among residents in the exposed area compared with the control area for most years and stratified groups confirmed by the logistic regression analyses.ConclusionUrban regeneration was not associated with users of antidepressant or sedative medication. We found lower levels of antidepressant and sedative medication users in the exposed area compared with the control area. More studies are needed to investigate the underlying reasons for these findings, and whether they could be related to underuse.

BackgroundPartnership break-up and living alone is associated with several negative health-related outcomes. Little is known about the association with physical functional ability in a life course perspective. The aim of this study is to investigate (1) the association between number of partnership break-ups and years living alone across 26 years of adult life respectively and objectively measured physical capability in midlife, (2) how the joint exposure of accumulated break-ups or years living alone respectively, and education relates to physical capability in midlife and (3) potential gender differences.MethodsLongitudinal study of 5001 Danes aged 48–62. Accumulated number of partnership break-ups and years living alone were retrieved from national registers. Handgrip strength (HGS) and number of chair rises (CR) were recorded as outcomes in multivariate linear regression analyses adjusted for sociodemographic factors, early major life events and personality.ResultsIncreasing number of years living alone was associated with poorer HGS and fewer CR. Concomitant exposure to short educational level and break-ups or long duration of time living alone respectively was associated with poorer physical capability compared with the groups with long educational level and no break-ups or few years lived alone.ConclusionAccumulated number of years living alone but not break-ups was associated with poorer physical functional ability. Joint exposure to a high number of years lived alone or break-ups respectively and having a short education was associated with the lowest levels of functional ability, which points towards an important target group for interventions. No gender differences were suggested.

BackgroundPartnership breakups and living alone are associated with several adverse health outcomes. The aim of this study, carried out in Denmark, is to investigate whether accumulated numbers of divorces/partnership breakups or years lived alone across 26 years of adult life are associated with levels of inflammation, and if vulnerability with regards to gender or educational level can be identified.Methods4835 participants from the Copenhagen Aging and Midlife Biobank (CAMB) aged 48–62 years were included. Data on accumulated numbers of partnership breakups and years living alone were retrieved from a national standardised annual register. Inflammatory markers interleukin 6 (IL-6) and high sensitivity C-reactive protein (hsCRP) were measured in blood samples. Multivariate linear regression analyses were adjusted for age, educational level, early major life events, body mass index, chronic diseases, medicinal intake affecting inflammation, acute inflammation and personality scores.ResultsFor men, an association was found between an increasing number of partnership breakups or number of years living alone and higher levels of inflammatory markers. No such association was found for women, and no evidence of partnership breakups and educational level having a joint effect was found for either gender.ConclusionThe findings suggest a strong association between years lived alone or accumulated number of partnership breakups and low-grade inflammation for middle-aged men, but not for women. Among those of either sex with a lower level of education, no specific vulnerability to accumulated years lived alone or number of breakups was identified.

BackgroundSocial inequality in ischaemic heart disease has been related to socioeconomic position in childhood, early adulthood and late adulthood. However, the impact of relative level of accumulated income periods across adult life course and the potential gender and age differences have not been investigated. The aim was to investigate the association between relative level of accumulated income across the life course and acute myocardial infarction (AMI) from age 60+ years and to study if the associations differ by gender and in different age groups (30–39 years, 40–49 years and 50–59 years).MethodsAll Danes born 1935–1954 (N=1 235 139) were followed up in registers for incident AMI (42 669 cases). The accumulated proportional deviation from median equivalised income (APDMEI) for each gender/age/calendar year strata was constructed and divided in quartiles. The associations were analysed by means of Cox’s proportional hazard models.ResultsAmong men, those in the lowest APDMEI quartile had an HR 1.40 (1.35–1.45) of AMI compared with the highest quartile. Those in the second and third highest quartiles had HR of 1.24 (1.20–1.28) and 1.14 (1.10–1.18), respectively. Among women, the lowest quartile had an HR of 1.78 (1.69–1.88), the second 1.45 (1.37–1.53) and the third 1.19 (1.13–1.26). The social gradient was similar across the different age groups.ConclusionThe risk of AMI increased with lower levels of relative accumulated income across the life course. While men generally had a higher risk of AMI, the social gradient was steeper in women. There was no indication of a specific sensitive age period for exposure to relative level of accumulated income.

Background: Social integration and perceived neighborhood environment are recognized as important social determinants of health. However, little is known about the association between social integration and perceived neighborhood environment among underrepresented population groups, such as residents in disadvantaged neighborhoods, in public health research. The aim of this study is to: 1) Describe the levels of social integration and 2) Investigate the association between social integration and neighborhood dissatisfaction and unsafety among middle-aged and older social housing residents. Methods: A multilingual face-to-face interviewer-administrated survey questionnaire was conducted among 206 residents aged 45 years and above (response rate: 34.1%) of various nationalities in disadvantaged socioeconomic positions in a social housing area in Denmark. The assessment of social integration was based on cohabitation status, frequency of face-to-face and non-face-to-face interaction with social relations and participation in local association activities. Neighborhood dissatisfaction measured the level of dissatisfaction with the neighborhood, and neighborhood unsafety assessed the level of unsafety being outdoors in the neighborhood. Descriptive statistics were conducted to illustrate respondent characteristics and the distribution of social integration among the study population. Logistic regression models were applied to analyze associations between social integration and neighborhood dissatisfaction and unsafety, adjusted for age, sex, country of origin, educational attainment and employment status. Results: In total, 23.8% of the respondents reported low levels of social integration. A medium level of social integration was associated with higher odds of neighborhood dissatisfaction (OR: 2.36; 95% CI: 1.04–5.38) compared to the highest level of integration. A low frequency of face-to-face interaction was associated with higher odds of neighborhood dissatisfaction (OR: 2.65; 95% CI: 1.16–6.06) and neighborhood unsafety (OR: 2.41; 95% CI: 1.04–5.57) compared to the highest frequency of face-to-face interaction. Conclusions: Almost one-fourth of respondents reported low levels of social integration. A medium level of social integration was associated with neighborhood dissatisfaction. A low frequency of face-to-face interaction was associated with neighborhood dissatisfaction and unsafety. The results suggest that targeted health promotion interventions designed to foster face-to-face interaction, hold potential to reduce neighborhood dissatisfaction and unsafety among residents in disadvantaged neighborhoods.

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 versusnonmetastatic 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, TGFβ 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.

Background:Little is known about the association between negative aspects of close social relations and development of ischaemic heart disease (IHD). We aim to address if the experience of worries/demands and conflicts with close social relations are related to risk of first-time hospitalization with IHD and whether emotional support can buffer this effect.Methods:A total of 8550 randomly selected men and women aged 36–52 years free of earlier IHD hospitalization at baseline in 2000 were followed prospectively for first-time hospitalization with IHD (ICD10: I21–25) through 2010 in the Danish National Patient Registry. Cox regression analysis was used to analyse data and all analyses were adjusted for age, gender, social class, cohabitation, and depressive symptoms.Results:Worries/demands from and conflicts with children were associated with IHD hospitalization in an exposure-dependent manner (p-trends 0.0001 and 0.03) with twice the risk among those most highly exposed, HRworries/demands= 2.05 (95% CI 0.91–4.54) and HRconflicts=1.90 (95% CI 1.00–3.61). ‘Always’ experiencing worries/demands from partner was also associated with a nearly twice the risk of IHD, whereas no association was found for conflicts with partner. High levels of worries/demands from or conflicts with family and friends were associated with a 40% higher risk of IHD.Conclusions:Negative aspects of close social relations are associated with higher risk of incident IHD hospitalization except for conflicts with partner. We found no clear evidence of a buffering effect of emotional support.

Plasma membrane proteins that are exposed on the cell surface have important biological functions, such as signaling into and out of the cells, ion transport, and cell-cell and cell-matrix interactions. The expression level of many of the plasma membrane proteins involved in these key functions is altered on cancer cells, and these proteins may also be subject to post-translational modification, such as altered phosphorylation and glycosylation. Additional protein alterations on cancer cells confer metastatic capacities, and some of these cell surface proteins have already been successfully targeted by protein drugs, such as human antibodies, that have enhanced survival of several groups of cancer patients. The combination of novel analytical approaches and subcellular fractionation procedures has made it possible to study the plasma membrane proteome in more detail, which will elucidate cancer biology, particularly metastasis, and guide future development of novel drug targets. The technical advances in plasma membrane proteomics and the consequent biological revelations will be discussed herein. Many of the advances have been made using cancer cell lines, but because the main goal of this research is to improve individualized treatment and increase cancer patient survival, further development is crucial to direct analysis of clinically relevant patient samples. These efforts include optimized specimen handling and preparation as well as improved proteomics platforms. Identification of potentially useful proteomics-based biomarkers must be validated in larger, well defined retrospective and prospective clinical studies, and these combined efforts should result in identification of biomarkers that will greatly improve early detection, prognosis, and prediction of treatment response.

Plasma membrane proteins that are exposed on the cell surface have important biological functions, such as signaling into and out of the cells, ion transport, and cell-cell and cell-matrix interactions. The expression level of many of the plasma membrane proteins involved in these key functions is altered on cancer cells, and these proteins may also be subject to post-translational modification, such as altered phosphorylation and glycosylation. Additional protein alterations on cancer cells confer metastatic capacities, and some of these cell surface proteins have already been successfully targeted by protein drugs, such as human antibodies, that have enhanced survival of several groups of cancer patients. The combination of novel analytical approaches and subcellular fractionation procedures has made it possible to study the plasma membrane proteome in more detail, which will elucidate cancer biology, particularly metastasis, and guide future development of novel drug targets. The technical advances in plasma membrane proteomics and the consequent biological revelations will be discussed herein. Many of the advances have been made using cancer cell lines, but because the main goal of this research is to improve individualized treatment and increase cancer patient survival, further development is crucial to direct analysis of clinically relevant patient samples. These efforts include optimized specimen handling and preparation as well as improved proteomics platforms. Identification of potentially useful proteomics-based biomarkers must be validated in larger, well defined retrospective and prospective clinical studies, and these combined efforts should result in identification of biomarkers that will greatly improve early detection, prognosis, and prediction of treatment response.

The spread of cancer cells from a primary tumor to form metastasis at distant sites is a complex multistep process. The cancer cell proteins and plasma membrane proteins in particular involved in this process are poorly defined, and a study of the very early events of the metastatic process using clinical samples or in vitro assays is not feasible. We have used a unique model system consisting of two isogenic human breast cancer cell lines that are equally tumorigenic in mice; but although one gives rise to metastasis, the other disseminates single cells that remain dormant at distant organs. Membrane purification and comparative quantitative LC-MS/MS proteomics identified 13 membrane proteins that were expressed at higher levels and three that were underexpressed in the metastatic compared with the non-metastatic cell line from a total of 1919 identified protein entries. Among the proteins were ecto-5'-nucleotidase (CD73), NDRG1, integrin β1, CD44, CD74, and major histocompatibility complex class II proteins. The altered expression levels of proteins identified by LC-MS/MS were validated using flow cytometry, Western blotting, and immunocyto- and immunohistochemistry. Analysis of clinical breast cancer biopsies demonstrated a significant correlation between high ecto-5'-nucleotidase and integrin β1 expression and poor outcome, measured as tumor spread or distant recurrence within a 10-year follow-up. Further the tissue analysis suggested that NDRG1, HLA-DRα, HLA-DRβ, and CD74 were associated with the ER–/PR–phenotype represented by the two cell lines. The study demonstrates a quantitative and comparative proteomics strategy to identify clinically relevant key molecules in the early events of metastasis, some of which may prove to be potential targets for cancer therapy.

The spread of cancer cells from a primary tumor to form metastasis at distant sites is a complex multistep process. The cancer cell proteins and plasma membrane proteins in particular involved in this process are poorly defined, and a study of the very early events of the metastatic process using clinical samples or in vitroassays is not feasible. We have used a unique model system consisting of two isogenic human breast cancer cell lines that are equally tumorigenic in mice; but although one gives rise to metastasis, the other disseminates single cells that remain dormant at distant organs. Membrane purification and comparative quantitative LC-MS/MS proteomics identified 13 membrane proteins that were expressed at higher levels and three that were underexpressed in the metastatic compared with the non-metastatic cell line from a total of 1919 identified protein entries. Among the proteins were ecto-5′-nucleotidase (CD73), NDRG1, integrin β1, CD44, CD74, and major histocompatibility complex class II proteins. The altered expression levels of proteins identified by LC-MS/MS were validated using flow cytometry, Western blotting, and immunocyto- and immunohistochemistry. Analysis of clinical breast cancer biopsies demonstrated a significant correlation between high ecto-5′-nucleotidase and integrin β1 expression and poor outcome, measured as tumor spread or distant recurrence within a 10-year follow-up. Further the tissue analysis suggested that NDRG1, HLA-DRα, HLA-DRβ, and CD74 were associated with the ER−/PR−phenotype represented by the two cell lines. The study demonstrates a quantitative and comparative proteomics strategy to identify clinically relevant key molecules in the early events of metastasis, some of which may prove to be potential targets for cancer therapy.

To disentangle the influences on health of selection processes related to genetic and rearing environmental factors from factors related to marriage benefits. We compared health status among same-sex male and female twin pairs who lived together during childhood and were discordant or concordant on adult marital status.

It has been hypothesized that areas with an unequal income distribution are less likely to invest in health and more likely to have a social environment that influences the development of ischaemic heart disease (IHD) METHODS: We used pooled data from two cohort studies conducted in Copenhagen to analyse the association between area income inequality and first admission to hospital or death from IHD in women and men while controlling for individual income and other IHD risk factors. A total of 11 685 women and 10 036 men, with initial health examinations between 1964 and 1992, were followed for a median of 13.8 years. Information on median income share at parish and municipality levels was obtained from population registers.

During the last decades, the prevalence of the allergic airway diseases, asthma and rhinitis, has increased worldwide. Introduction of environmental chemicals with adjuvant effect may play a role in this increase. In the present study, the adjuvant effects of di-n-butyl-, di-n-octyl-, di-iso-nonyl- and di-iso-decyl phthalate are studied in a screening model. Ovalbumin, used as the model antigen, was injected subcutaneously in the neck region of BALB/cJ mice with the selected phthalate in concentrations from 2–2000 μg/ml. Additionally, the mice were boosted once or twice with ovalbumin alone. Immunization with ovalbumin alone, the ovalbumin control group, served as the baseline for antibody production, whereas aluminium hydroxide served as the positive control. The levels of ovalbumin-specific IgE, IgG1 and IgG2a antibodies in sera were determined. Adjuvant effect was accepted to be present if a statistical increase in antibody production occurred in a test group as compared to an ovalbumin control group together with the fulfillment of dose-response relationships. Adjuvant effect varied strongly between the phthalates investigated. Phthalates with 8 or 9 carbon atoms in the alkyl side chains were the stronger adjuvants whereas phthalates with shorter or longer alkyl side chains possessed less adjuvant activity. Adjuvant effects were apparent either from the IgE or the IgG1 response or both, whereas no effect was seen on the IgG2a response. Additional studies with airborne exposure are required to establish whether the hazards also result in a significant risk for the development of allergy in man.

In a follow-up study of 70–95years old women and men (n = 911) we studied the association between change and stability in three structural aspects of social relations (contact frequency, contact diversity, cohabitation status) from 1986–1990 and mortality after the next four years in 1994. Women aged 70–74years who developed low contact frequencyor developed small contact diversityshowed significantly higher mortality, adjusted ORfreq: 3.78 (1.08–13.20), adjusted ORdiv: 3.79 (1.24–11.58). Women aged 70–74years with continuously low contact frequencyshowed an increased mortality compared to women constantly experiencing high contact frequency, adjusted OR: 2.75 (1.04–7.26). A tendency in the same direction for sustained small contact diversitywas found, adjusted OR: 1.98 (0.70–5.61). Among women aged 75+ years no impact of frequency and diversity was demonstrated, whereas continuously living alonewas a significant predictor of mortality, when compared to women continuously living with somebody, adjusted OR: 2.57 (1.29–5.09). In men, we found a significantly increased mortality among those who developed high contact frequency and developed large contact diversityORfreq: 3.91 (1.02–14.94) and ORdiv: 6.04 (1.30–28.03). In summary, we found rather larger age differences in the strength of the association between change in structural social relations and mortality. Furthermore, the associations seemed stronger among women than men, which may however mainly be explained by the small number of men in our cohort.

The purpose of this survey was to investigate the small-area variations in low birthweight within social services districts in Copenhagen and the relation of such variations to the socioeconomic characteristics of the district. The study was based on register data and included all live-born singleton births to women living in the city of Copenhagen from 1987-90. We found a statistically significant association between district and risk of newborns being small-for-gestational age (SGA). This association was independent of adjustment for maternal age and parity. Only part of the association was explained, though this was still significant, using an index summarizing the socioeconomic living conditions in the district. Splitting up the index into its four constituent components, however, showed that the association between SGA and district was primarily due to housing conditions in the districts. Mapping the districts demonstrated a clear tendency of clustering of the high-risk areas with poor socioeconomic conditions.

Background The aims of the present study are to analyse the association between marital status at age 24, 29, 34, and 39 years and subsequent mortality in a cohort of men born in 1953 (sensitive period); to study the impact of number of years married, number of years divorced/widowed, and number of marital break-ups on mortality (cumulative effect), and to examine whether these effects were independent of marital status at age 39 (proximity effect). Methods Prospective birth cohort study with follow-up of mortality from 1992 to 2002. Participants were 10 891 men born within the metropolitan area of Copenhagen, Denmark. Marital status in 1992 as well as start and termination of all previous marital status events from 1968 to 1992 were retrieved from the Danish Civil Registration System. Main outcome measures were hazard ratios (HR) for all-cause mortality from age 40 to 49 years. Results We found a strong protective effect of being married compared with never being married or divorced/widowed at every age. The association increased in strength with increasing age. Number of years divorced was associated with increased mortality risk in a dose-dependent manner at age 34 and 39 years. One or more marital break-ups was associated with higher mortality, whereas increasing number of years married was associated with lower mortality. Inclusion of current marital status attenuated the strength of the associations but most of them remained statistically significant. Conclusions Marital status and cumulated marital periods, especially cumulated periods divorced/widowed are strong independent predictors of mortality among younger males.