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We investigated the effects of 35 inflammatory cytokines on respiratory outcomes, including COVID-19, asthma (atopic and non-atopic), chronic obstructive pulmonary disease (COPD), and pulmonary function indices, using Mendelian randomization and colocalization analyses. The emerging associations were further explored using observational analyses in the UK Biobank. We found an inverse association between genetically predicted macrophage colony stimulating factor (MCSF), soluble intercellular adhesion molecule-1 (sICAM), and soluble vascular cell adhesion molecule-1 with risk of COVID-19 outcomes. sICAM was positively associated with atopic asthma risk, whereas tumor necrosis factor-alfa showed an inverse association. A positive association was shown between interleukin-18 and COPD risk (replicated in observational analysis), whereas an inverse association was shown for interleukin-1 receptor antagonist (IL-1ra). IL-1ra and monocyte chemotactic protein-3 were positively associated with lung function indices, whereas inverse associations were shown for MCSF and interleukin-18 (replicated in observational analysis). Our results point to these cytokines as potential pharmacological targets for respiratory traits., Competing Interests: The authors declare the following competing interests: Salomaa Veikko was funded by the Finnish Foundation for Cardiovascular Research and by the Juho Vainio Foundation. Salomaa Veikko has received an honorarium from Sanofi for consulting and has ongoing research collaboration with Bayer Ltd. (All outside the present study). These companies had no role in study design, data collection and analysis, decision to publish, or preparation of the article. Sirpa Jalkanen, Marko Salmi: Financial support for cytokine analyses has come from the Finnish Academy. Abril Izquierdo and Martin Tobin were supported for the present article by Wellcome Trust grants (WT202849/Z/16/Z, WT225221/Z/22/Z) and the National Institute of Health and Care Research (NIHR) Leicester Biomedical Research Center. Martin Tobin has also received an NIHR Senior Investigator Award and had a funded research collaboration with Orion Pharma (the latter outside the scope of this work). Markku Timonen has received payment for one lecture for Otsuka Pharmaceutical and payment for two lectures for H. Lundbeck A/S. Marjo-Ritta Jarvelin is partly funded by the Medical Research Council (MR/S019669/1). James Yarmolinsky is supported by a Cancer Research UK Population Research Postdoctoral Fellowship (C68933/A28534). The remaining authors have no competing interests to declare., (© 2024 The Author(s).)

Evening chronotype is known to be associated with various chronic diseases and cardiovascular risk factors. Metabolic syndrome is a group of conditions that together raise the risk of coronary heart disease, diabetes, stroke, and other serious health problems. Only a few studies have been published on the association between chronotype and metabolic syndrome in unselected population data, with conflicting results. The aim of this study was to evaluate the association between chronotype and metabolic syndrome at population level by using unselected Northern Finland Birth cohort 1966 (NFBC1966) database. The study population consists of participants with NFBC66 ( n = 5,113, 57% female) at the age of 46 yr old. Chronotype was determined with shortened Morningness-Eveningness Questionnaires and expressed as morning (44%), intermediate (44%), and evening types (12%). Metabolic syndrome was determined according to the definition of International Diabetes Federation. One-way ANOVA, Kruskal-Walli's test, and χ 2 tests were used to compare the chronotype groups, followed by logistic regression analysis (adjusted with alcohol consumption, smoking, marital status, level of education, and leisure-time physical activity). In women, the prevalence of metabolic syndrome was statistically significantly higher in the evening type group: 23, 24, and 34% for morning, intermediate, and evening groups, respectively ( P < 0.001). In logistic regression analysis, evening chronotype was associated with higher risk of having metabolic syndrome (OR 1.5; CI 95% 1.2 to 2.0). In this population-based birth cohort study, the evening chronotype was independently associated with higher prevalence of metabolic syndrome in women. NEW & NOTEWORTHY Only a few studies have been conducted on the association between chronotype and metabolic syndrome in unselected population data, with conflicting results. In this population-based cohort study of 5,113 participants, the evening chronotype associated with metabolic syndrome in women when there was no such association in men. The result supports a previous South Korean population study of 1,620 participants, in which the association was also found in women, but not in men.

Background: Reflective capacity is a prerequisite for transformative learning. It is regarded as an essential skill in professional competence in the field of medicine. Our aim was to investigate the reflective capacity and the objects of action (themes) which revealed reflective writing of medical students during a general practice/family medicine course., Methods: Second-year medical students were requested to write learning diaries during a compulsory course in general practice/family medicine consisting of the principles of the physician-patient relationship. The course included a group session supervised by a clinical lecturer and a 3-day training period in a local health centre. We conducted data-driven content analysis of the learning diaries. In the learning diaries, student observations were most commonly directed to events during the training period and to group sessions. Occasionally, observation was directed at inner experience., Results: The following themes were related to reflective writing: feelings towards the end of life, demanding situations in practice, physician's attitude to patient, student's inner experiences, and physician's well-being. The entries indicated different types of reflective capacity. Three subgroups were identified: 'simple reporting,' 'reflective writing,' and 'advanced reflective writing.', Conclusion: Professional growth requires the development of reflective capacity, as it is essential for successful patient care and better clinical outcomes. To develop and enhance the reflective capacity of medical students during their education, the curriculum should provide frequent opportunities for students to assess and reflect upon their various learning experiences., (© 2024. The Author(s).)

Background: Due to rapid urbanization, there is a need to better understand the relative roles of residential environment and physical activity in depression. We aimed to investigate whether neighbourhood characteristics are related to the presence of depressive symptoms and whether the association is modified by physical activity., Methods: This cross-sectional study used the 46-year-old follow-up data (n = 5489) from the Northern Finland Birth Cohort 1966. Data on depressive symptoms, measured by Beck Depression Inventory-II, and self-reported and accelerometer-measured physical activity were included. Neighbourhood characteristics, population density, distance to the closest grocery store, bus stops and cycle/pedestrian paths, distance to the nearest parks and forests, residential greenness and level of urbanicity were calculated using Geographic Information System methods based on participants' home coordinates., Results: According to ordinal logistic regression analyses adjusted for physical activity at different intensities and individual covariates, living in a neighbourhood with higher population density and urbanicity level were associated with a higher risk of experiencing more severe depressive symptoms. Higher residential greenness was associated with a lower risk of experiencing more severe depressive symptoms after adjustment for self-reported light and moderate-to-vigorous physical activity, accelerometer-measured moderate-to-vigorous physical activity and individual covariates. Both higher self-reported and accelerometer-measured physical activity were independently associated with a lower risk of more severe depressive symptoms., Conclusions: Both residential environment and physical activity behaviour play an important role in depressive symptoms; however, further research among populations of different ages is required. Our findings can be utilized when designing interventions for the prevention of depression., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Public Health Association.)

Purpose: Individuals with depression exhibit significantly higher levels of systemic inflammation than those without depression, particularly among those with atypical depression. However, this association has been less convincing at the population level among individuals without a formal depression diagnosis but with suggestive symptoms. Our aim was to clarify this association., Materials and Methods: In a large birth cohort sample of the Finnish general population, we examined the cross-sectional association between high-sensitivity C-reactive protein (hsCRP) levels in venous blood samples and atypical/non-atypical depressive symptoms using the Beck Depression Inventory-II to screen 5443 middle-aged participants., Results: As expected, depressive symptoms associated to elevated hsCRP-levels compared to non-depressed. Participants with the atypical subtype of depressive symptoms ( n  = 84) had an odds ratio (OR) of 2.59 (95% CI 1.40-4.81) for elevated hsCRP levels compared to the non-depressed group. Similarly, our findings indicate that participants with non-atypical symptoms ( n  = 440) also showed an OR of 1.42 (95% CI 1.05-1.92) when compared to the non-depressed group ( n  = 4919)., Conclusions: These results provide additional support for previous research linking depression and inflammation and add to the field with a unique and sizeable study population. Furthermore, the current results support the notion that different types of depressive symptoms may be associated with inflammatory markers in slightly different ways.

Background: The association between rosacea and psychiatric comorbidity has been reported previously. However, there is a lack of general population studies about this subject area., Objectives: The aim of this study was to the association between rosacea with depressive and anxiety symptoms at the population level., Methods: A clinical whole-body examination was performed by dermatologists for 1,932 subjects belonging to the Northern Finland Birth Cohort 1966 Study during the 46-year follow-up survey. The presence of depressive and anxiety symptoms was gathered by using validated Hopkins Symptom Checklist-25 (HSCL-25) included in the self-administered questionnaires. Binary logistic regression analysis was used to identify associations between rosacea and psychological symptoms., Results: Rosacea was found in dermatological evaluation in 15.1% of the study subjects (n = 292). In logistic regression analyses, after adjusting for confounding factors, those with rosacea had 1.6-fold (OR 1.55, 95% CI: 1.02-2.32) risk for psychiatric symptoms according to HSCL-25 when compared with controls. In separate analyses of the HSCL-25 depression subscale, the risk was increased, especially for depressive symptoms (OR 1.56, 95% CI: 1.10-2.18)., Conclusions: Patients with rosacea seem to have increased risk for depressive and anxiety symptoms in general population. Physicians treating patients with rosacea should pay more attention to the psychosocial health of patients., (© 2023 S. Karger AG, Basel.)

Objective: To leverage large scale genetic association data to investigate the interplay between circulating cytokines and cardiometabolic traits, and thus identifying potential therapeutic targets., Design: Bi-directional Mendelian randomisation study., Setting: Genome-wide association studies from three Finnish cohorts (Northern Finland Birth Cohort 1966, Young Finns Study, or FINRISK study), and genetic association summary statistics pooled from observational studies for expression quantitative trait loci and cardiometabolic traits., Participants: Data for 47 circulating cytokines in 13 365 individuals from genome-wide association studies, summary statistic data for up to 21 735 individuals on circulating cytokines, summary statistic gene expression data across 49 tissues in 838 individuals, and summary statistic data for up to 1 320 016 individuals on cardiometabolic traits., Interventions: Relations between circulating cytokines and cardiovascular, anthropometric, lipid, or glycaemic traits (coronary artery disease, stroke, type 2 diabetes mellitus, body mass index, waist circumference, waist to hip ratio, systolic blood pressure, glycated haemoglobin, high density lipoprotein cholesterol, low density lipoprotein cholesterol, total cholesterol, triglycerides, C reactive protein, glucose, fasting insulin, and lifetime smoking)., Main Outcome Methods: Genetic instrumental variables that are biologically plausible for the circulating cytokines were generated. The effects of cardiometabolic risk factors on concentrations of circulating cytokines, circulating cytokines on other circulating cytokines, and circulating cytokines on cardiometabolic outcomes were investigated., Results: Genetic evidence (mendelian randomisation P<0.0011) suggests that higher body mass index, waist circumference, smoking, higher concentrations of lipids, and systolic blood pressure increase circulating concentrations of several inflammatory cytokines and C reactive protein. Evidence for causal relations (mendelian randomisation P<0.0011) were noted between circulating cytokines, including a key role of vascular endothelial growth factor on influencing the concentrations of 10 other cytokines. Both mendelian randomisation (P<0.05) and colocalisation (posterior probability >0.5) suggested that coronary artery disease risk is increased by higher concentrations of circulating tumour necrosis factor related apoptosis-inducing ligand (TRAIL), interleukin-1 receptor antagonist (IL1RA), and macrophage colony-stimulating factor (MCSF)., Conclusion: This study offers insight into inflammatory mediators of cardiometabolic risk factors, cytokine signalling cascades, and effects of circulating cytokines on different cardiometabolic outcomes., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: DG is employed part-time by Novo Nordisk and has received consultancy fees from Policy Wisdom. VS has received honoraria from Novo Nordisk and Sanofi for consultations and travel support from Novo Nordisk. He also has ongoing research collaboration with Bayer Ltd. GKH reports institutional research support from Aegerion, Amgen, AstraZeneca, Eli Lilly, Genzyme, Ionis, Kowa, Pfizer, Regeneron, Roche, Sanofi, and The Medicines Company; speaker’s bureau and consulting fees from Amgen, Aegerion, Sanofi, and Regeneron (fees paid to the academic institution); and part-time employment at Novo Nordisk, outside of the submitted work. These declarations are all unrelated to this study., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Background: Previously Cloninger's temperament traits have been researched as a risk factor for depression mostly in cross-sectional studies. In these studies, especially high harm avoidance has been associated with an increased risk of depression. The main objective of this study was to investigate how temperament traits affect the risk of the onset of depression in a previously mentally healthy adult population., Methods: This study includes a follow-up period of 23 years from the age of 31 until 54 in the Northern Finland Birth Cohort 1966 Study. Temperament was measured at the 31-year follow-up using Temperament and Character Inventory (TCI). The outcome of the study was depressive disorder diagnosis during the follow-up in both sexes. To be able to take correlations between temperament traits we also did an analysis using temperament clusters., Results: Our sample size was 3999 individuals, out of which 240 were diagnosed with depression. For women an increase in the TCI score for novelty seeking (NS), harm avoidance (HA) or persistence (P) increased the risk of depression during the follow-up. For men only HA was a significant predictor of depression. An increase in reward dependence (RD) was found to reduce the risk of psychotic depression. In the analysis using the temperament clusters, the cluster including shy and pessimistic individuals was associated with risk for depression diagnosis in men., Conclusions: This prospective general population-based cohort study added to previous knowledge of high HA being a risk factor for depression, but it also found new associations such as higher P and NS., (Copyright © 2022. Published by Elsevier Inc.)

Pruritus has an extensive impact on functional, social and psychosocial behaviour. The association between pruritus and psychological well-being has mostly been studied among selected patient groups, whereas population-based studies are lacking. The aim of this study was to determine the association between pruritus and insomnia, quality of life, depression and anxiety at the population level in the general population. A cross-sectional population-based study was conducted in 2012 to 2013. Study subjects (n = 6,809) belonging to the Northern Finland Birth Cohort 1966 Study participated in a large follow-up study at the age of 45-47 years. They completed an extensive health questionnaire including questions on pruritus and several previously validated questionnaires regarding symptoms of psychosocial well-being. Pruritus affected 19.9% of the study subjects weekly, being more common in women than in men (p < 0.001). A significant association was found between both localized and generalized pruritus and symptoms of insomnia, depression, anxiety and decreased quality of life. The association was seen even in those with mild psychological symptoms/insomnia, and it affected both sexes. The severity of psychological symptoms increased with increasing frequency of pruritus. In conclusion, pruritus has a multiple effect on psychosocial well-being. Physicians should consider possible psychosocial symptoms in patients with pruritus.

Background: Low levels of physical activity (PA) and high sedentary time (ST) are common in older adults and lack of PA is a risk factor for cardiovascular disease (CVD). Knowledge about associations with accelerometer-measured PA, ST and CVD risk in older adults is insufficient. This study examines the associations of accelerometer-measured PA and ST with cardiovascular risk measured using the Framingham risk score (FRS) and all-cause mortality in older adults., Methods: A population-based sample of 660 (277 men, 383 women) older people (mean age 68.9) participated in the Oulu45 cohort study from 2013‒2015. PA and ST were measured with wrist-worn accelerometers at baseline for two weeks. Ten-year CVD risk (%) was estimated with FRS. The data for all-cause mortality were identified from the Digital and Population Data Services Agency, Finland after an average of 6.2 years follow-up. The associations between moderate to vigorous physical activity (MVPA), light physical activity (LPA), ST and FRS were analyzed using the multivariable linear regression analysis. Associations between LPA, ST and mortality were analyzed using the Cox proportional-hazard regression models., Results: Each 10 min increase in MVPA (β = -0.779, 95% CI -1.186 to -0.371, p < 0.001) and LPA (β = -0.293, 95% CI -0.448 to -0.138, p < 0.001) was negatively associated with FRS while a 10 min increase in ST (β = 0.290, 95% CI 0.158 to 0.421, p < 0.001) was positively associated with FRS. After adjustment for waist circumference, only ST was significantly associated with FRS. Each 10 min increase in LPA was associated with 6.5% lower all-cause mortality risk (HR = 0.935, 95% CI 0.884 to 0.990, p = 0.020) and each 10 min increase in ST with 5.6% increased mortality risk (HR = 1.056, 95% CI 1.007 to 1.108, p = 0.025)., Conclusion: A higher amount of daily physical activity, at any intensity level, and avoidance of sedentary time are associated with reduced cardiovascular disease risk in older people. Higher time spent in light physical activity and lower sedentary time are associated with lower all-cause mortality., (© 2022. The Author(s).)

Competing Interests: Conflicts of interest Dr Kauppi has received educational grants from Novartis, LEO Pharma, Sanofi Genzyme, AbbVie, and Janssen-Cilag and honoraria from Sanofi Genzyme for speaking. Dr Tasanen has received educational grants from Novartis and Pfizer and honoraria from Novartis, AbbVie, Janssen-Cilag, Sanofi Genzyme, and Lilly for consulting and/or speaking. Dr Huilaja has received educational grants from Takeda, Janssen-Cilag, Novartis, AbbVie, and LEO Pharma; received honoraria from Sanofi Genzyme, Novartis, AbbVie, and UCB Pharma for consulting and/or speaking; and is an investigator for AbbVie. Dr Timonen and Author Jokelainen have no conflicts of interest to declare.

The purpose of this study was to examine and compare the associations between albuminuria and fasting (FPG), 1 h post-load (1 h PG) and 2 h post-load plasma glucose (2 h PG) in an oral glucose tolerance test (OGTT). A total of 496 people free of known diabetes (mean age 72 years) participated in the examinations including the OGTT with plasma glucose measurements at 0, 1, and 2 h and levels of HbA1c. Albuminuria was determined by the urinary albumin-to-creatinine ratio and was defined as ≥3.0 mg/mmol. Compared with those without albuminuria, participants with albuminuria had significantly higher 1 h PG and 2 h PG levels, but not FPG or HbA1c levels. An elevated 1 h PG increased the estimated odds ratio of albuminuria more than three times in people with prediabetic 1 h PG (8.6-11.5 mmol/L: OR 3.60; 95% CI 1.70-7.64) and diabetic 1 h PG (≥11.6 mmol/L: OR 3.05; 95% CI 1.29-7.23). After adjusting for blood pressure and age, the association of elevated 1 h PG with albuminuria remained significant. Prediabetic or diabetic FPG, 2 h PG, or HbA1c did not have a statistically significant association with albuminuria. These findings suggest that 1 h PG seems to be the best glycemic parameter and is useful in recognizing persons with an elevated risk of early kidney disease due to hyperglycemia.