100 ancient genomes show repeated population turnovers in Neolithic Denmark.

Major migration events in Holocene Eurasia have been characterized genetically at broad regional scales1-4. However, insights into the population dynamics in the contact zones are hampered by a lack of ancient genomic data sampled at high spatiotemporal resolution5-7. Here, to address this, we analysed shotgun-sequenced genomes from 100 skeletons spanning 7,300 years of the Mesolithic period, Neolithic period and Early Bronze Age in Denmark and integrated these with proxies for diet (13C and 15N content), mobility (87Sr/86Sr ratio) and vegetation cover (pollen). We observe that Danish Mesolithic individuals of the Maglemose, Kongemose and Ertebølle cultures form a distinct genetic cluster related to other Western European hunter-gatherers. Despite shifts in material culture they displayed genetic homogeneity from around 10,500 to 5,900 calibrated years before present, when Neolithic farmers with Anatolian-derived ancestry arrived. Although the Neolithic transition was delayed by more than a millennium relative to Central Europe, it was very abrupt and resulted in a population turnover with limited genetic contribution from local hunter-gatherers. The succeeding Neolithic population, associated with the Funnel Beaker culture, persisted for only about 1,000 years before immigrants with eastern Steppe-derived ancestry arrived. This second and equally rapid population replacement gave rise to the Single Grave culture with an ancestry profile more similar to present-day Danes. In our multiproxy dataset, these major demographic events are manifested as parallel shifts in genotype, phenotype, diet and land use.

Risk of long COVID and associated symptoms after acute SARS-COV-2 infection in ethnic minorities: A nationwide register-linked cohort study in Denmark.

BACKGROUND: Ethnic minorities living in high-income countries have been disproportionately affected by Coronavirus Disease 2019 (COVID-19) in terms of infection rates, hospitalisations, and deaths; however, less is known about long COVID in these populations. Our aim was to examine the risk of long COVID and associated symptoms among ethnic minorities. METHODS AND FINDINGS: We used nationwide register-based cohort data on individuals diagnosed with COVID-19 aged ≥18 years (n = 2,287,175) between January 2020 and August 2022 in Denmark. We calculated the risk of long COVID diagnosis and long COVID symptoms among ethnic minorities compared with native Danes using multivariable Cox proportional hazard regression and logistic regression, respectively. Among individuals who were first time diagnosed with COVID-19 during the study period, 39,876 (1.7%) were hospitalised and 2,247,299 (98.3%) were nonhospitalised individuals. Of the diagnosed COVID-19 cases, 1,952,021 (85.3%) were native Danes and 335,154 (14.7%) were ethnic minorities. After adjustment for age, sex, civil status, education, family income, and Charlson comorbidity index, ethnic minorities from North Africa (adjusted hazard ratio [aHR] 1.41, 95% confidence interval [CI] [1.12,1.79], p = 0.003), Middle East (aHR 1.38, 95% CI [1.24,1.55], p < 0.001), Eastern Europe (aHR 1.35, 95% CI [1.22,1.49], p < 0.001), and Asia (aHR 1.23, 95% CI [1.09,1.40], p = 0.001) had significantly greater risk of long COVID diagnosis than native Danes. In the analysis by largest countries of origin, the greater risks of long COVID diagnosis were found in people of Iraqi origin (aHR 1.56, 95% CI [1.30,1.88], p < 0.001), people of Turkish origin (aHR 1.42, 95% CI [1.24,1.63], p < 0.001), and people of Somali origin (aHR 1.42, 95% CI [1.07,1.91], p = 0.016). A significant factor associated with an increased risk of long COVID diagnosis was COVID-19 hospitalisation. The risk of long COVID diagnosis among ethnic minorities was more pronounced between January 2020 and June 2021. Furthermore, the odds of reporting cardiopulmonary symptoms (including dyspnoea, cough, and chest pain) and any long COVID symptoms were higher among people of North African, Middle Eastern, Eastern European, and Asian origins than among native Danes in both unadjusted and adjusted models. Despite including the nationwide sample of individuals diagnosed with COVID-19, the precision of our estimates on long COVID was limited to the sample of patients with symptoms who had contacted the hospital. CONCLUSIONS: Belonging to an ethnic minority group was significantly associated with an increased risk of long COVID, indicating the need to better understand long COVID drivers and address care and treatment strategies in these populations.

Heritability of cancers in Japanese population: Estimation from recent cohort data.

Cancers are genetically categorized into common diseases showing a so-called multifactorial inheritance except for rare familial cancers. And as a measure to estimate the strength of genetic factors in the multifactorial diseases, heritability (h2) is generally used. However, there have been few reports on the estimation of heritability for cancers. We calculated the heritability from the incidence in subject population and the familial recurrence rate in first-degree relatives of the affected for cancers quoting the data from a large-scale prospective cohort study by Hidaka et al. published in 2020. This is the first report for heritability of any cancers in Japanese population. The results showed that heritability of overall cancers in Japanese population is 0.064, which is much lower than Nordic population reported by Mucci et al. that was 0.33. For individual cancers, stomach cancer (h2 = 0.14), colorectum cancer (0.006), lung cancer (0.08) and uterine cancer (0.16) accounted for half of the total patients, and each heritability tends to be lower than previously reported for the European descent. The results of this study suggest that heritability of cancers varies greatly by ethnicity. And these results should be important in terms of cancer genetics and in the genetic counseling for cancers.

N-terminal pro-B-type natriuretic peptide levels vary by ethnicity and are associated with insulin sensitivity after gestational diabetes mellitus.

BACKGROUND: Individuals of South Asian origin have a greater risk of cardiovascular disease after gestational diabetes mellitus (GDM) than European individuals. B-type natriuretic peptide (BNP) and the amino-terminal fragment of its prohormone (NT-proBNP) are commonly used for heart failure screening and diagnosis, but biologically BNP exerts several beneficial cardiovascular effects primarily by counteracting the renin-angiotensin-aldosterone-system. We asked whether ethnic differences in circulating NT-proBNP levels could be explained by the differences in cardiometabolic and inflammatory risk markers? METHODS: We examined 162 South Asian and 107 Nordic women in Norway 1-3 years after GDM with a clinical examination, fasting blood samples and an oral glucose tolerance test. We measured the levels of NT-proBNP, high-sensitivity cardiac troponin T, high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), leptin, adiponectin and markers of insulin sensitivity, such as the Matsuda insulin sensitivity index (ISI). Finally, we tried to identify which independent covariate best mediated the ethnic differences in NT-proBNP. RESULTS: The mean (SD) age was 35.3 (4.5) years, BMI 29.1 (6.0) kg/m2, waist-height ratio 0.60 (0.08) and 164 women (61%) had prediabetes/diabetes. Notably, South Asian women had lower levels of NT-proBNP than Nordic women in both the normoglycemic and prediabetes/diabetes groups (median (IQR) 26  (15-38)  vs. 42 (22-66) ng/L, p < 0.001). Higher NT-proBNP levels were associated with greater insulin sensitivity in both South Asian and Nordic women (p = 0.005 and p < 0.001). South Asian women had higher levels of hsCRP (median (IQR) 2.2 (1.1-4.4) vs. 1.2 (0.3-4.2) mg/L), IL-6 (2.3 (1.5-3.2) vs. 1.5 (1.5-2.5) pg/mL), leptin (1647 (1176-2480) vs. 1223 (876-2313) pmol/L), and lower adiponectin levels (7.2 (5.3-9.3) vs. 10.0 (7.2-13.5) mg/L) and Matsuda ISI (2.4 (1.7-3.7) vs. 4.2 (2.9-6.1), pall<0.01) than Nordic women. Even after adjusting for these differences, higher NT-proBNP levels remained associated with insulin sensitivity (22% higher NT-proBNP per SD Matsuda ISI, p = 0.015). Insulin sensitivity and adiponectin mediated 53% and 41% of the ethnic difference in NT-proBNP. CONCLUSIONS: NT-proBNP levels are lower in South Asian than in Nordic women after GDM. Lower NT-proBNP levels correlate with impaired insulin sensitivity. Lower NT-proBNP levels in South Asian women could, therefore, be attributed to impaired insulin sensitivity rather than total body fat.

The Danish Aging and Cognition (DanACo) cohort.

BACKGROUND: With aging populations worldwide, identification of predictors of age-related cognitive decline is becoming increasingly important. The Danish Aging and Cognition Cohort (DanACo) including more than 5000 Danish men was established to investigate predictors of age-related cognitive decline from young adulthood to late mid-life. CONSTRUCTION AND CONTENT: The DanACo cohort was established through two separate data collections with identical designs involving a follow-up examination in late mid-life of men for whom intelligence test scores were available from their mandatory conscription board examination. The cohort consists of 5,183 men born from 1949 through 1961, with a mean age of 20.4 years at baseline and a mean age of 64.4 years at follow-up. The baseline measures consisted of height, weight, intelligence test score and educational level collected at the conscription board examination. The follow-up assessment consisted of a re-administration of the same intelligence test and a comprehensive questionnaire covering socio-demographic factors, lifestyle, and health-related factors. The data were collected in test sessions with up to 24 participants per session. Using the unique personal identification number assigned to all Danes, the cohort has been linked to data from national administrative and health registers for prospectively collected data on socioeconomic and health-related factors. UTILITY AND DISCUSSION: The DanACo cohort has some major strengths compared to existing cognitive aging cohorts such as a large sample size (n = 5,183 men), a validated global measure of cognitive ability, a long retest interval (mean 44.0 years) and the availability of prospectively collected data from registries as well as comprehensive questionnaire data. The main weakness is the low participation rate (14.3%) and that the cohort consists of men only. CONCLUSION: Cognitive decline is a result of a summary of factors across the life-course. The DanACo cohort is characterized by a long retest interval and contains data on a wealth of factors across adult life which is essential to establish evidence on predictors of cognitive decline. Moreover, the size of the cohort ensures sufficient statistical power to identify even relatively weak predictors of cognitive decline.

Adult offspring and their socioeconomic resources for development and survival of stroke: A Swedish and Danish nationwide register-based study.

AIMS: To explore the relationships between adult offspring's socioeconomic resources and the development of stroke and survival after stroke among older adults in Denmark and Sweden. METHODS: The study included 1,464,740 Swedes and 835,488 Danes who had turned 65 years old between 2000 and 2015. Multivariable Cox proportional hazard regression models were used to analyse incident stroke and survival after stroke until 2020. RESULTS: Lower level of offspring's education, occupation and income were associated with higher hazards of stroke among both men and women in Sweden and Denmark. Associations with offspring's education, occupation and income were most consistent for death after the acute phase and for educational level. From one to five years after stroke and compared with a high educational level of offspring, low and medium educational level were associated with 1.34 (95% confidence interval (CI): 1.11; 1.62) and 1.18 (95% CI: 1.10; 1.27) as well as 1.26 (95% CI: 1.06; 1.48) and 1.14 (1.07; 1.21) times higher hazard of death in Swedish women and men, respectively. The corresponding estimates in the Danish population were 1.36 (1.20; 1.53) and 1.10 (1.01; 1.20) for women and 1.23 (95% CI: 1.11; 1.32) and 1.13 (95% CI: 1.05; 1.21) for men. CONCLUSIONS: Adult offspring socioeconomic resources are, independently of how we measure them and of individual socioeconomic characteristics, associated with development of stroke in old age in both Denmark and Sweden. The relationships between offspring socioeconomic resources and death after stroke are present especially after the acute phase and most pronounced for educational level as a measure of offspring socioeconomic resources.

Does losing family members in midlife matter for late-life mental and cognitive health? A longitudinal study of older Swedes spanning 30 years.

OBJECTIVES: Mental and cognitive health is crucial to ensure well-being in older age. However, prolonged periods of stress, grief, and bereavement might compromise mental health balance, leading to profound changes. This study investigated the sex-stratified associations between midlife bereavement experiences (e.g. sibling loss, spousal loss, and multiple losses) and late-life depression (LLD) and cognitive impairment. METHOD: Linked data from the Swedish Level-of-Living Survey and the Swedish Panel Study of Living Conditions of the Oldest Old (SWEOLD) were used. Multiple logistic regressions were performed to examine the associations between midlife bereavement and LLD (n = 1078) and cognitive impairment (n = 995), separately. RESULTS: Sibling loss and multiple losses in midlife were associated with lower odds of LLD, especially among women. Among men, sibling loss in midlife was associated with lower odds of cognitive impairment, while the experience of two losses among women suggested an increased (but non-significant) risk of cognitive impairment. Interaction analyses did not show significant effects between bereavement and gender on LLD and cognitive impairment. CONCLUSION: Midlife bereavement might have gendered implications on LLD and cognitive impairment, but associations need to be confirmed by well-powered studies. Further research is warranted to elucidate the association between multiple midlife losses and reduced LLD risk.

Prostate Cancer Screening With PSA, Kallikrein Panel, and MRI: The ProScreen Randomized Trial.

Importance: Prostate-specific antigen (PSA) screening has potential to reduce prostate cancer mortality but frequently detects prostate cancer that is not clinically important. Objective: To describe rates of low-grade (grade group 1) and high-grade (grade groups 2-5) prostate cancer identified among men invited to participate in a prostate cancer screening protocol consisting of a PSA test, a 4-kallikrein panel, and a magnetic resonance imaging (MRI) scan. Design, Setting, and Participants: The ProScreen trial is a clinical trial conducted in Helsinki and Tampere, Finland, that randomized 61 193 men aged 50 through 63 years who were free of prostate cancer in a 1:3 ratio to either be invited or not be invited to undergo screening for prostate cancer between February 2018 and July 2020. Interventions: Participating men randomized to the intervention underwent PSA testing. Those with a PSA level of 3.0 ng/mL or higher underwent additional testing for high-grade prostate cancer with a 4-kallikrein panel risk score. Those with a kallikrein panel score of 7.5% or higher underwent an MRI of the prostate gland, followed by targeted biopsies for those with abnormal prostate gland MRI findings. Final data collection occurred through June 31, 2023. Main Outcomes and Measures: In descriptive exploratory analyses, the cumulative incidence of low-grade and high-grade prostate cancer after the first screening round were compared between the group invited to undergo prostate cancer screening and the control group. Results: Of 60 745 eligible men (mean [SD] age, 57.2 [4.0] years), 15 201 were randomized to be invited and 45 544 were randomized not to be invited to undergo prostate cancer screening. Of 15 201 eligible males invited to undergo screening, 7744 (51%) participated. Among them, 32 low-grade prostate cancers (cumulative incidence, 0.41%) and 128 high-grade prostate cancers (cumulative incidence, 1.65%) were detected, with 1 cancer grade group result missing. Among the 7457 invited men (49%) who refused participation, 7 low-grade prostate cancers (cumulative incidence, 0.1%) and 44 high-grade prostate cancers (cumulative incidence, 0.6%) were detected, with 7 cancer grade groups missing. For the entire invited screening group, 39 low-grade prostate cancers (cumulative incidence, 0.26%) and 172 high-grade prostate cancers (cumulative incidence, 1.13%) were detected. During a median follow-up of 3.2 years, in the group not invited to undergo screening, 65 low-grade prostate cancers (cumulative incidence, 0.14%) and 282 high-grade prostate cancers (cumulative incidence, 0.62%) were detected. The risk difference for the entire group randomized to the screening invitation vs the control group was 0.11% (95% CI, 0.03%-0.20%) for low-grade and 0.51% (95% CI, 0.33%-0.70%) for high-grade cancer. Conclusions and Relevance: In this preliminary descriptive report from an ongoing randomized clinical trial, 1 additional high-grade cancer per 196 men and 1 low-grade cancer per 909 men were detected among those randomized to be invited to undergo a single prostate cancer screening intervention compared with those not invited to undergo screening. These preliminary findings from a single round of screening should be interpreted cautiously, pending results of the study's primary mortality outcome. Trial Registration: ClinicalTrials.gov Identifier: NCT03423303.

Mental health of Scandinavians during the first lockdown in the COVID-19 pandemic: Psychosocial resources and coping strategies as protective or risk factors for anxiety and depression.

BACKGROUND: The COVID-19 pandemic was a global health and economic crisis. In the early phase of the pandemic, studies found that populations were reporting lower levels of mental well-being and high levels of distress and worry. This study investigated potential protective and risk factors such as sociodemographics and psychological factors such as adaptation/coping. METHODS: Two convenience samples from Norway and Denmark were recruited during the early phase of the first lockdown in May 2020 using snowball sampling primarily by social media. Measures included the Patient Health Questionnaire-4 (PHQ-4) for screening anxiety and depression, COVID-19 distress, and coping strategies applied during the lockdown. Descriptive analyses were applied as well as bivariate correlations for associations between coping and mental health measures. RESULTS: Levels of anxiety and depression were not alarmingly high, but being young, single, and female constituted a higher risk for poorer mental health. Applying positive reframing strategies was negatively associated with poor mental health and high COVID-19 stress, whereas distraction coping strategies were positively correlated with poor mental health and high COVID-19 stress. CONCLUSION: Applying positive reframing as a coping strategy may constitute a protective factor for mental health in the early phase of a crisis such as a pandemic. This knowledge may inform public health agencies on how to promote mental health in similar situations in the future. However, longitudinal and qualitative studies are needed to investigate the long-term effects of the different coping strategies applied.

Family financial socialization during emerging adulthood: Insights from a cross-lagged panel model.

The present study tested the Gudmunson and Danes (2011) family financial socialization model (FFSM) using three waves of longitudinal data gathered from a college cohort of emerging adults in the United States. Specifically, we aimed to test the validity of this model in emerging adulthood (Aim 1), to verify whether the effect of the parent's socialization on a child's end financial outcome is mediated by intermediary financial outcomes (Aim 2), and to verify whether the effects found when testing the FFSM are stable across time points (Aim 3). Our findings indicate that of eight paths in the model between family socialization processes and financial socialization outcomes, seven paths were significant, thereby lending support for the validity of FFSM in emerging adulthood (Aim 1). Second, we found no mediation effects of parental financial socialization on emerging adult financial behavior and well-being via the internalization of parents' beliefs, values, and practices (Aim 2). We offer plausible explanations for this result. Last, we verified that the financial socialization processes and their effects are generally invariant across the beginning, the middle, and the end of the emerging adulthood (Aim 3). We interpret our findings in the context of the extant literature on emerging adults' transition to adult independence and provide insights for practice. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Adverse childhood experiences, sexual risk-taking and non-consensual sexual experiences in a nationally representative study of 15-29-year-old Danes.

BACKGROUND: Adverse childhood experiences (ACEs) have been linked with risky health-related behaviors and poor health. OBJECTIVE: This study aimed to investigate associations of ACEs with a broad panel of sexual risk-taking behaviors and non-consensual sexual experiences among young people in Denmark. PARTICIPANTS AND SETTING: Baseline questionnaire data from 15 to 29-year-old participants in the nationally representative cohort study Project SEXUS were used in combination with data from Danish national registers to include a total of 13,132 individuals. METHODS: In logistic regression analyses, confounder-adjusted odds ratios (aORs) with 95 % confidence intervals (CIs) were obtained for associations of five ACE categories (Household challenges, Loss or threat of loss, Material deprivation, Abuse, and Neglect) and a cumulative ACE score with measures of sexual risk-taking and non-consensual sexual experiences. RESULTS: Statistically significant associations were observed between ACEs and multiple sexual risk-taking behaviors and non-consensual sexual experiences with particularly increased odds among individuals with a history of Abuse, Neglect, or an ACE score of 3 or more. Specifically, Abuse was associated with having received payment for sex (women: aOR 5.38; 95 % CI 2.73-10.61; men: aOR 2.11; 95 % CI 1.22-3.64), with having paid for sex (men: aOR 1.88; 95 % CI 1.41-2.51), and with having been the victim of a sexual assault after age 18 years (women: aOR 3.33; 95 % CI 2.36-4.68). CONCLUSIONS: In this Danish study, multiple measures of sexual risk-taking and non-consensual sexual experiences were markedly more common among young people with ACEs than in those without ACEs. This knowledge should be considered in future initiatives to promote sexual health among young people.

Prosocial Behaviour and Antibiotic Resistance: Evidence from a Discrete Choice Experiment.

INTRODUCTION: The health of a community depends on the health of its individuals; therefore, individual health behaviour can implicitly affect the health of the entire community. This is particularly evident in the case of infectious diseases. Because the level of prosociality in a community might determine the effectiveness of health programmes, prosocial behaviour may be a crucial disease-control resource. This study aimed to extend the literature on prosociality and investigate the role of altruism in antibiotic decision making. METHODS: A discrete choice experiment was conducted to assess the influence of altruism on the general public's preferences regarding antibiotic treatment options. The survey was completed by 378 Swedes. Latent class analysis models were used to estimate antibiotic treatment characteristics and preference heterogeneity. A three-class model resulted in the best model fit, and altruism significantly impacted preference heterogeneity. RESULTS: Our findings suggest that people with higher altruism levels had more pronounced preferences for treatment options with lower contributions to antibiotic resistance and a lower likelihood of treatment failure. Furthermore, altruism was statistically significantly associated with sex, education, and health literacy. CONCLUSIONS: Antibiotic awareness, trust in healthcare systems, and non-discriminatory priority setting appear to be structural elements conducive to judicious and prosocial antibiotic behaviour. This study suggests that prosocial messages could help to decrease the demand for antibiotic treatments.

Performance of a 74-Microhaplotype Assay in Kinship Analyses.

Microhaplotypes (MHs) consisting of multiple SNPs and indels on short stretches of DNA are new and interesting loci for forensic genetic investigations. In this study, we analysed 74 previously defined MHs in two of the populations that our laboratory provides with forensic genetic services, Danes and Greenlanders. In addition to the 229 SNPs that originally made up the 74 MHs, 66 SNPs and 3 indels were identified in the two populations, and 45 of these variants were included in new definitions of the MHs, whereas 24 SNPs were considered rare and of little value for case work. The average effective number of alleles (Ae) was 3.2, 3.0, and 2.6 in Danes, West Greenlanders, and East Greenlanders, respectively. High levels of linkage disequilibrium were observed in East Greenlanders, which reflects the characteristics of this population that has a small size, and signs of admixture and substructure. Pairwise kinship simulations of full siblings, half-siblings, first cousins, and unrelated individuals were performed using allele frequencies from MHs, STRs and SNPs from Danish and Greenlandic populations. The MH panel outperformed the currently used STR and SNP marker sets and was able to differentiate siblings from unrelated individuals with a 0% false positive rate and a 1.1% false negative rate using an LR threshold of 10,000 in the Danish population. However, the panel was not able to differentiate half-siblings or first cousins from unrelated individuals. The results generated in this study will be used to implement MHs as investigative markers for relationship testing in our laboratory.

The clinical and economic burden of illness in the first two years after ostomy creation: a nationwide Danish cohort study.

BACKGROUND: Living with an ostomy is often associated with costly complications. This study examined the burden of illness the first two years after ostomy creation. METHODS: Data from Danish national registries included all adult Danes with an ostomy created between 2002 and 2014. RESULTS: Four cohorts consisted, respectively, of 11,385 subjects with a colostomy and 4,574 with an ileostomy, of which 1,663 subjects had inflammatory bowel disease (IBD) and 1,270 colorectal cancer as cause of their ileostomy. The healthcare cost was significantly higher for cases versus matched controls for all cohorts. In the first year, the total healthcare cost per person-year was €27,962 versus €4,200 for subjects with colostomy, €29,392 versus €3,308 for subjects with ileostomy, €15,947 versus €2,216 when IBD was the underlying cause, and €32,438 versus €4,196 when it was colorectal cancer. Healthcare costs decreased in the second year but remained significantly higher than controls. Hospitalization and outpatient services were primary cost drivers, with ostomy-related complications comprising 8-16% of hospitalization expenses. CONCLUSION: Compared to controls, subjects with an ostomy bear a significant health and financial burden attributable to ostomy-related complications, in addition to the underlying disease, emphasizing the importance of better ostomy care to enhance well-being and reduce economic strain.

Case-Fatality Rate in Parkinson's Disease: A Nationwide Registry Study.

BACKGROUND: Patients with Parkinson's disease (PD) may have an increased risk of mortality, but robust estimates are lacking. OBJECTIVE: To compare mortality rates nationally between patients with PD and controls. METHODS: The case-fatality rates of Finnish PD patients diagnosed in 2004-2018 (n = 23,688; 57% male, mean age at diagnosis = 71 years) and randomly selected sex- and age-matched control subjects (n = 94,752) were compared using data from national registries. The median follow-up duration was 5.8 years (max 17 years). RESULTS: The case-fatality rate in patients with PD was higher than that in matched controls (HR 2.29; 95% CI 2.24-2.33; P < 0.0001). Excess fatality among PD patients was already present at 1 year from diagnosis and then plateaued at 29% at 12 years after diagnosis. The long-term relative hazard of death in PD patients vs. matched controls did not differ based on sex. Patients with early-onset PD (age at diagnosis <50 years old) had the highest relative hazard of death (HR 3.36) compared to matched control subjects, and the relative hazard decreased with higher age at diagnosis. The seven-year excess risk of death decreased during the study period, especially in men. In patients with PD, male sex, increasing age, and increasing comorbidity burden were associated with an increased risk of death. CONCLUSIONS: An increased risk of death among PD patients was evident from early on. The increase in risk was greatest among young-onset patients. The excess risk in early PD declined during the study period, particularly in men. The reasons for this are unknown.

General and orofacial symptoms associated with acute and long COVID in 80- and 90-year-old Swedish COVID-19 survivors.

OBJECTIVES: To describe acute and long COVID-19 symptoms among older elderly Swedes and to find predictive factors for the development symptoms associated with acute and long COVID. MATERIAL AND METHODS: A questionnaire about general and oral health was mailed to all 80-year-olds (born 1942, n = 6299) and 90-year-olds (born 1932, n = 1904) in two Swedish counties. Participants reporting COVID-19 were asked to complete an additional questionnaire. RESULTS: Overall response rate was 66 % (n = 5375). Affirmative responses to having been sick/tested positive for COVID-19 were reported by 577 persons. Response rate to the COVID-19 questionnaire was 49 %. The majority (88 %) reported some general symptoms during the acute stage while 44 % reported orofacial symptom/s. Reporting of any form of long-COVID general symptoms was 37 and 35 % for orofacial symptoms. Predictive factors for contracting COVID-19 (based on self-report from 2017) were living in elderly housing/senior care facility (OR 1.6, CI 1.0-2.3), large number (>10) of weekly social contacts (OR 1.5, CI 1.3-1.9), being married (OR 1.4, CI 1.1-1.7) and high school/university education (OR 1.3 CI 1.1-1-6). The highest odds ratio for general symptoms of long-COVID were a single complete denture (OR 5.0, CI 2.0-12.3), reporting bad breath (OR 3.7, CI 1.9-7.2) and daytime dry mouth (OR 2.2, CI 1.1-4.2). Regarding long-COVID orofacial symptoms, the highest risk factors were bad breath (OR 3.8, CI 1.9-7.5) and a single complete denture in one jaw (OR 3.4, CI 1.2-9.8). CONCLUSION: Long-COVID general and orofacial symptoms are common among older elderly COVID-19 survivors CLINICAL SIGNIFICANCE: Oral microorganisms may be responsible for development of long-COVID symptoms. Health personnel managing COVID-19 patients should carefully examine dental status, especially in those having acrylic-based removable dentures, for oral signs and symptoms. If found, rigorous oral hygiene procedures should be carried out including cleaning/disinfection of the denture.

Quantifying the relative importance of genetics and environment on the comorbidity between mental and cardiometabolic disorders using 17 million Scandinavians.

Mental disorders are leading causes of disability and premature death worldwide, partly due to high comorbidity with cardiometabolic disorders. Reasons for this comorbidity are still poorly understood. We leverage nation-wide health records and near-complete genealogies of Denmark and Sweden (n = 17 million) to reveal the genetic and environmental contributions underlying the observed comorbidity between six mental disorders and 15 cardiometabolic disorders. Genetic factors contributed about 50% to the comorbidity of schizophrenia, affective disorders, and autism spectrum disorder with cardiometabolic disorders, whereas the comorbidity of attention-deficit/hyperactivity disorder and anorexia with cardiometabolic disorders was mainly or fully driven by environmental factors. In this work we provide causal insight to guide clinical and scientific initiatives directed at achieving mechanistic understanding as well as preventing and alleviating the consequences of these disorders.

Effects of a carbohydrate-reduced high-protein diet delivered with meal kits to Danish people with type 2 diabetes: protocol for a 12-month randomised controlled trial.

INTRODUCTION: The cornerstone in the management of type 2 diabetes (T2D) is lifestyle modification including a healthy diet, typically one in which carbohydrate provides 45%-60% of total energy intake (E%). Nevertheless, systematic reviews and meta-analyses of trials with low carbohydrate diets (which are increased in protein and/or fat) for T2D have found improved glycaemic control in the first months relative to comparator diets with higher carbohydrate content. Studies lasting ≥1 year are inconclusive, which could be due to decreased long-term dietary adherence. We hypothesise that glucometabolic benefits can be achieved following 12 months of carbohydrate-restricted dieting, by maximising dietary adherence through delivery of meal kits, containing fresh, high-quality ingredients for breakfast, dinner and snacks, combined with nutrition education and counselling. METHODS AND ANALYSIS: This protocol describes a 12-month investigator-initiated randomised controlled, open-label, superiority trial with two parallel groups that will examine the effect of a carbohydrate-reduced high-protein (CRHP) diet compared with a conventional diabetes (CD) diet on glucometabolic control (change in glycated haemoglobin being the primary outcome) in 100 individuals with T2D and body mass index (BMI) >25 kg/m2. Participants will be randomised 1:1 to receive either the CRHP or the CD diet (comprised 30/50 E% from carbohydrate, 30/17 E% from protein and 40/33 E% from fat, respectively) for 12 months delivered as meal kits, containing foods covering more than two-thirds of the participants' estimated daily energy requirements for weight maintenance. Adherence to the allocated diets will be reinforced by monthly sessions of nutrition education and counselling from registered clinical dietitians. ETHICS AND DISSEMINATION: The trial has been approved by the National Committee on Health Research Ethics of the Capital Region of Denmark. The trial will be conducted in accordance with the Declaration of Helsinki. Results will be submitted for publication in international peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER: NCT05330247. PROTOCOL VERSION: The trial protocol was approved on 9 March 2022 (study number: H-21057605). The latest version of the protocol, described in this manuscript, was approved on 23 June 2023.

Gastrointestinal symptom burden in diabetic autonomic and peripheral neuropathy - A Danes cohort study.

OBJECTIVE: We investigated associations between gastrointestinal symptoms - evaluated as a combined weighted symptom score (CWSS) - Diabetic autonomic neuropathy (DAN), and distal symmetrical polyneuropathy (DSPN) in type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS: Cross-sectional study in a tertiary outpatient clinic. CWSS was calculated based on questionnaires: gastroparesis composite symptom index (GCSI) and gastrointestinal symptom rating score (GSRS). DAN and DSPN were addressed using the composite autonomic symptom score 31 (COMPASS-31) questionnaire, cardiac autonomic reflex tests (CARTs), electrochemical skin conductance (ESC), vibration perception threshold (VPT), Michigan Neuropathy Screening Instrument (MNSI), pain- and thermal sensation. Analyses were adjusted for age, sex, diabetes duration, smoking, LDL-cholesterol, HbA1C and systolic blood pressure. Type 1 and type 2 diabetes were evaluated separately. RESULTS: We included 566 with type 1 diabetes and 377 with type 2 diabetes. Mean ± SD age was 58 ± 15 years and 565 (59.9 %) were women. A high CWSS was present in 143 (25 %) with type 1 and 142 (38 %) with type 2 diabetes. The odds of DAN by COMPASS-31 (p < 0.001) were higher in the high score group. For type 1 diabetes, odds of cardiac autonomic neuropathy were higher in the high CWSS group. The odds of DSPN by VPT and MNSI in type 1 diabetes, and by ESC, VPT and pain sensation in type 2 diabetes were higher in the high CWSS group. CONCLUSIONS: A high symptom score was associated with neuropathy by COMPASS-31 and vibration perception. Gastrointestinal symptom burden associated inconsistently with other neuropathy tests between diabetes types.

Genetic Characterization of Intimin Gene (eae) in Clinical Shiga Toxin-Producing Escherichia coli Strains from Pediatric Patients in Finland.

Shiga toxin (Stx)-producing Escherichia coli (STEC) infections cause outbreaks of severe disease in children ranging from bloody diarrhea to hemolytic uremic syndrome (HUS). The adherent factor intimin, encoded by eae, can facilitate the colonization process of strains and is frequently associated with severe disease. The purpose of this study was to examine and analyze the prevalence and polymorphisms of eae in clinical STEC strains from pediatric patients under 17 years old with and without HUS, and to assess the pathogenic risk of different eae subtypes. We studied 240 STEC strains isolated from pediatric patients in Finland with whole genome sequencing. The gene eae was present in 209 (87.1%) strains, among which 49 (23.4%) were from patients with HUS, and 160 (76.6%) were from patients without HUS. O157:H7 (126, 60.3%) was the most predominant serotype among eae-positive STEC strains. Twenty-three different eae genotypes were identified, which were categorized into five eae subtypes, i.e., γ1, ß3, ε1, θ and ζ3. The subtype eae-γ1 was significantly overrepresented in strains from patients aged 5-17 years, while ß3 and ε1 were more commonly found in strains from patients under 5 years. All O157:H7 strains carried eae-γ1; among non-O157 strains, strains of each serotype harbored one eae subtype. No association was observed between the presence of eae/its subtypes and HUS. However, the combination of eae-γ1+stx2a was significantly associated with HUS. In conclusion, this study demonstrated a high occurrence and genetic variety of eae in clinical STEC from pediatric patients under 17 years old in Finland, and that eae is not essential for STEC-associated HUS. However, the combination of certain eae subtypes with stx subtypes, i.e., eae-γ1+stx2a, may be used as risk predictors for the development of severe disease in children.