Validity of self-reported use of antihypertensives and lipid modifying agents: Results from the population-based HUNT Study.

In the absence of biomarkers, the true biological footprint of migraine remains incompletely understood. It could perhaps be best characterized using machine learning models of multimodal data. The aim of this study was to (1) develop diagnostic models of migraine using multimodal data and (2) identify data-driven migraine phenotypes. This was a cross-sectional machine learning analysis of demographics, self-reported clinical and headache data, and genome-wide genotype data from the Trøndelag Health Study (data collected 1995-1997 and 2006-2008). All participants who were genotyped and completed the headache questionnaire were included. First, predictive machine learning models were developed using genotype data and general clinical data (excluding headache data) to diagnose individuals with migraine vs headache-free controls. Models were optimized on a training set and evaluated on a held-out test set, scored with the area under the receiver operating characteristic curve (AUC). Second, unsupervised models were trained on the headache data and the most predictive features from the diagnostic models to identify subgroups. The subgroups were compared using genome-wide association analyses, conventional polygenic risk scores (PRSs), and machine learning-based genetic risk scores. A total of 43,197 individuals were included in the diagnostic models, and 12,185 individuals were included in the data-driven phenotyping (mean [SD] age 49.1 [16.7] years; 51.7% women). The top-performing diagnostic model was a light gradient boosting machine, with a test set AUC of 0.80 (95% CI 0.78-0.81). Two main clusters were identified, one with 1,425 individuals, 94% of whom met diagnostic criteria for migraine, and another with 10,760 individuals, whereof 71% had nonmigraine headaches. The former was subclustered into 4 relatively distinct groups: one with only men, one with prominent neck pain, one with more musculoskeletal pain, anxiety and depression, and one with "classic" migraine. The groups were better discriminated by machine learning-based genetic risk scores compared with PRSs. Migraine can accurately be diagnosed from nonheadache data, suggesting that it is biologically describable by combinations of clinical, genetic, and environmental data. Data-driven phenotyping with such data identifies migraine subgroups with distinct phenotypic and genotypic signals, possibly not captured by current diagnostic criteria-but with potential implications for management.

This study aimed to investigate the associations of adolescents' self-reported family financial stress, registry-based parental household income and parental education with adolescent anxiety and depression symptoms. Additionally, we adjust these associations for parental anxiety and depression symptoms and examine potential secular changes in these associations. Family linkage study, using two cross-sectional population-based health studies, the Young-HUNT study and the HUNT study. Registry-based data from Statistics Norway (SSB). Northern part of Trøndelag County, Norway. Adolescent (aged 13-19 years) participating in The Young-HUNT3 Survey (2006-2008, n=8199) and The Young-HUNT4 Survey (2017-2019, n=8066) and their parents participating in The HUNT3 Survey (2006-2008, n=50 800) and the HUNT4 Survey (2017-2019, n=56 042). Adolescent anxiety and depression symptoms were assessed by a short version of the Hopkins Symptom Checklist (HSCL), the five-item HSCL-5. Self-reported family financial stress was measured using a single-item question. Parental anxiety and depression were assessed by the 14-item Hospital Anxiety and Depression Rating Scale (total HADS score). Parental income and parental education were obtained from SSB. We use a multilevel mixed-effects generalised linear model. Adolescents who perceived their family financial stress as worse than others reported a higher SCL-5 total score compared with those with self-perceived average financial stress. The relative differences ranged from 1.16 (95% CI 1.09 to 1.23) in boys to 1.24 (95% CI 1.17 to 1.31) in girls. In contrast, little or no association was found between parental registry-based income or educational level and adolescents' mean SCL-5 total scores. Adjusting for parental HADS scores did not alter the estimates. With a few exceptions for girls, there was no evidence for a secular change in these associations. Self-perceived family financial stress, but not registry-based parental income and education, was associated with elevated anxiety and depression symptom levels in adolescents, and findings were essentially the same in Young-HUNT3 and Young-HUNT4. These findings underscore the importance of incorporating multiple measures of socioeconomic status when investigating socioeconomic inequalities in adolescent mental health.

While cross-sectional studies suggest that physical activity (PA) is associated with a lower risk of sarcopenia, the long-term PA patterns remain poorly characterized. We aimed to examine whether PA patterns across mid- to late adulthood are associated with sarcopenia in older age. We included 4702 individuals (mean age 76.4 ± 5.0 years, 53% female) from the HUNT4 (Trøndelag Health Study) 70+ cohort with PA data across three prior waves (HUNT1-3). PA was categorized as active or inactive at each time point (1984-86, 1995-97, 2006-08) according to the World Health Organization 2020 guidelines. Sarcopenia at HUNT4 (2017-19) was defined according to the European Working Group on Sarcopenia (EWGSOP2) criteria as probable (low strength) or confirmed (low strength and low muscle mass). Logistic regression analyses were used to examine associations between long-term PA patterns and sarcopenia. PA showed a clear inverse dose-response relationship with sarcopenia, with stronger associations for confirmed than probable sarcopenia. Compared with persistent inactivity, being active at all three time points was associated with 78% lower odds of confirmed sarcopenia at HUNT4 (OR 0.22, 95% CI: 0.08-0.66). Participants active at two and one time points had 40% (OR 0.60, 0.38-0.95) and 26% (OR 0.74, 0.55-1.00) lower odds, respectively. Associations varied by PA pattern, with lower odds observed among those becoming active (OR 0.57, 0.39-0.84) but not among those becoming inactive. Long-term PA shows a clear dose-response relationship with sarcopenia risk in later life. While sustained activity across adulthood confers the greatest benefit, initiating PA even later in life remains associated with lower odds of sarcopenia.

Impacts of HLA-DR3DQ2 and HLA-DR4DQ8 haplotypes singly and combined on autoimmunity, phenotype and comorbidity in patients with Latent Autoimmune Diabetes in the adult. Results from the HUNT and ESTRID studies.

Some evidence suggests that higher serum TSH may be part of normal aging, but studies are limited to a 13-year follow-up. We examined TSH changes over a 22-year follow-up across the adult lifespan. Longitudinal analyses of the population-based HUNT Study, Norway, with TSH measurements from 1995-1997, 2006-2008, and 2017-2019, and linkage to the Norwegian Prescribed Drug Registry. In individuals without thyroid medication or overt thyroid dysfunction, we estimated (1) geometric mean serum TSH by age, integrating cross-sectional and longitudinal measurements using linear mixed models, (2) percentiles of the TSH distribution by age, and (3) within-individual TSH change during follow-up, expressed by geometric mean ratios (GMR) reflecting the fold change in geometric mean TSH. We included 127 483 TSH measurements among 80 284 participants, of whom 36 886 had ≥2 measurements and 11 749 had ∼22-year follow-up. When integrating all cross-sectional and longitudinal measurements, mean TSH was higher at older age in men, while the association with age was weaker and less consistently observed in women. When examining within-individual change, mean TSH increased modestly by 0.13 mIU/L (GMR 1.09; 95%CI 1.07, 1.10) over 22 years in men, but not in women (GMR 0.97; 95%CI 0.96, 0.98). This increase was stronger at 0.5 mIU/L in men aged ≥70 years at baseline (GMR 1.32; 95%CI 1.15, 1.48). The TSH distribution widened at older age in both sexes. Mean serum TSH increased with age in older men, but showed only modest or no age-related change in younger men and in women. The wider TSH distribution at older age supports the need for age-specific TSH reference ranges.

Celiac disease (CeD) occurs in genetically predisposed individuals who are exposed to dietary gluten proteins. Genome-wide association studies have found CeD to be associated with a genetic predisposition to shorter telomere length. It was therefore of interest to measure leukocyte telomere length in a large cohort of patients with CeD. This study was population-based and included a defined cohort of patients with CeD in the Trøndelag Health Study. Leukocyte telomere length was measured by quantitative polymerase chain reaction (PCR) in patients and controls 1:2 matched for age, sex, alcohol, and tobacco use. The study population consisted of 58.7% women, with mean age 43 (SD 14.5) years, where half were never smokers, and the majority consumed little or no alcohol. Telomer length in 1,077 patients with CeD did not differ significantly from 2,147 matched controls, 10.39 kb (SD 2.21) vs 10.52 kb (SD 2.25), P = 0.088. In a mixed linear model, we found higher age and alcohol consumption, but not tobacco use or sex, to be associated with shorter telomere length. The telomere length did not differ between patients with newly diagnosed and known CeD. This large population-based study provides evidence that CeD is not associated with clinically meaningful telomere shortening.

Apolipoprotein E (APOE) genotype and cardiovascular risk are both associated with dementia, but their separate and joint contributions remain uncertain. We examined the independent and combined associations of APOE genotype and cardiovascular disease (CVD) risk with incident dementia in a Norwegian populationbased cohort. In this prospective cohort study, baseline data were obtained from the second Trøndelag Health Study (HUNT2, 1995-97), with follow-up through linkage to specialist health-care records and the Norwegian Cause of Death Registry through Dec 31, 2023. We included 22,108 participants aged 50 years or older who were free of CVD, diabetes, and dementia at baseline. APOE genetic risk and cardiovascular risk based on SCORE2 were each classified into three categories. Adjusted hazard ratios (HRs) for incident dementia were estimated using Cox models. During a median follow-up of 22.0 years, 3,714 incident dementia events occurred. Compared with low APOE genetic risk, adjusted HRs were 1.25(95% CI1.10-1.41) for intermediate risk and 3.09(2.73-3.49) for high risk. Compared with low-to-moderate CVD risk, adjusted HRs were 1.19(1.07-1.32) for high risk and 1.36(1.19-1.55) for very high risk. In joint analyses, the highest risk was observed in participants with high APOE genetic risk and very high cardiovascular risk (HR 3.78, 2.85-5.01). Higher cardiovascular risk was more clearly associated with dementia in participants without high APOE genetic risk, whereas dementia risk was consistently elevated across cardiovascular risk categories among those with high APOE genetic risk. There was no clear evidence of multiplicative interaction (p=0.059). APOE genotype and cardiovascular risk were independently associated with incident dementia, with highest risk among individuals with both high genetic and cardiovascular risk.

Reduced cardiorespiratory fitness (CRF) is associated with chronic pain, but longitudinal population-based evidence is limited. Whether CRF can prevent pain worsening or promote improvement is unclear. This study investigated (1) the cross-sectional association between estimated CRF (eCRF) and chronic pain, (2) the longitudinal association between eCRF and changes in pain severity over 11 years, and (3) whether changes in eCRF are associated with changes in pain severity. Data were collected from the Trøndelag Health Study (HUNT) in Norway. Cross-sectional analyses included 18,837 adults from HUNT3 (2006-08), and longitudinal analyses followed participants to HUNT4 (2017-19), stratified by baseline pain status: no or mild (n = 11,517) or moderate/severe chronic pain (n = 5312). Cardiorespiratory fitness was estimated using a validated nonexercise algorithm and categorized into sex- and age-specific quintiles. Logistic regression estimated odds ratios with 95% confidence intervals. Cross-sectionally, higher eCRF was associated with lower odds of chronic pain, with the largest difference between the highest and the lowest quintiles (women: OR 0.56, 95% CI 0.49-0.64; men: OR 0.64, 95% CI 0.53-0.78). Longitudinally, among participants with no or mild pain, both high baseline eCRF and maintained high eCRF were associated with lower odds of pain worsening. Among those with chronic pain, maintaining or increasing eCRF was associated with greater odds of pain reduction, whereas high baseline eCRF showed a nonsignificant trend in the same direction. Higher eCRF was associated with lower odds of chronic pain and with more favorable changes in pain severity in the general population.

The central theme of this article basically resides in the relationship established by indigenous peoples between their hunting practices and the forest. Indigenous ways of connecting ‘hunting’ and ‘forest’ necessarily pass through other modes of knowing, only marginally – if it all – dependent on vision. On the contrary, sounds, smells and even dreams are, for many South American indigenous collectives, more trustworthy indices than what the eye sees. This article divides into two parts. In the first, I set out the main ideas related to the anthropological study of hunting in Amazonia at a conceptual level. In the second, shifting toward an anthropology of hunting as lived experience, I develop a reflection based on my own fieldwork with the Awa-Guajá, arriving, finally, at an anthropological (and ecological) critique of the threats to which indigenous territories are now exposed.

BackgroundEpigenetic clocks, developed using blood DNA methylation data, can be used to estimate biological ages and pace of aging. We aimed to identify potential determinants of the pace of aging, estimated using blood DNA methylation, and to investigate the association between the pace of aging and all-cause mortality in a population-based Norwegian cohort with repeated DNA methylation measurements.MethodsThis study included 140 cancer-free controls from a lung cancer nested case-control study within the Trøndelag Health Study (HUNT). DNA methylation was measured in blood samples in both HUNT2 (1995–97) and HUNT3 (2006–08), 11 years apart. The pace of aging was estimated using two established measures of biological age, DNAmPhenoAge and DNAmGrimAge2, and two direct measures of pace of aging, DunedinPoAm and DunedinPACE, all derived from blood DNA methylation data. All-cause mortality was followed up until 2023.ResultsThere was a moderate to excellent reliability of the repeated measurements, with intraclass correlation coefficient (ICC) values ranged from 0.69–0.91. University education appeared to be associated with a slower pace of aging, while smoking and obesity were associated with a faster pace. A one-standard deviation increase in the pace of aging, as measured by DNAmGrimAge2, was associated with a hazard ratio (HR) of 2.42 (95% confidence interval (CI) 1.25 to 4.68) for all-cause mortality in HUNT2, and a HR of 2.30 (95% CI 1.22 to 4.33) in HUNT3 after adjustment for the established risk factors.ConclusionsThe pace of aging, as estimated using blood DNA methylation, appears to be an independent predictor of all-cause mortality. This measure may reflect the combined influence of genetic, lifestyle, and environmental factors on individual aging trajectories.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13148-026-02070-8.

Background The long-term disease course of Ulcerative Colitis (UC) remains incompletely understood. This study aimed to characterize the longitudinal changes of disease extent and severity in UC in a population-based cohort Methods Incident UC cases were identified among adult participants (≥20 years) in the Trøndelag Health Study (HUNT) and validated thorough hospital records. Participation in a HUNT survey enabled access to hospital records, allowing verification of the diagnosis and detailed assessment of the disease course. Cases were followed from diagnosis, until the end of follow-up on 1 April 2024. Longitudinal changes in disease extent and severity were assessed using the validated Montreal Classification. Kaplan-Meier methods and Cox proportional hazard regression were used to estimate progression rates and hazard ratios (HRs) with 95% Confidence Intervals (CIs). Results The study included 736 UC cases with a median follow-up of 5.3 years (interquartile range 1.5–11.8). Progression in disease extent occurred most frequently during the first three years after diagnosis. Cases presenting with proctitis had the highest annual risk of progressing in extent (7.5%), compared to those with left-sided colitis (3%). After 10 years, the proportion with proctitis declined from 43% to 24%, whereas the proportion of left-sided colitis and extensive colitis increased from 36% to 44% and 21% to 32%, respectively. Male sex was associated with a significantly lower risk of progression in extent compared to females (HR 0.56 95%CI 0.36–0.88). Men also showed a tendency towards a lower risk of developing more severe disease, although this did not reach statistical significance (HR 0.71, 95% CI 0.78–1.04). After 10 years, the proportion of patients experiencing severe disease increased from 24% to 45%. Patients diagnosed in the most recent time-period (2010–2023) had a significantly higher hazard of developing more severe disease during follow-up compared with those diagnosed before 2002 (HR 2.13 95% CI 1.13–4.03). Age at diagnosis and smoking status were not associated with changes in disease extent or severity. Conclusion Cases with UC demonstrated progression in disease extent over time. Disease severity followed a relapsing-remitting course, but with an increasing proportion of cases developing more severe disease during follow-up. Cases diagnosed after 2010 also showed a tendency towards a more severe disease course. Female sex was associated with a higher risk of progression in extent and having episodes of severe disease during follow-up.

BackgroundChronic kidney disease (CKD) prevalence and prognosis are currently based exclusively on glomerular functions, but the kidney tubule possesses numerous additional functions with pathophysiological and prognostic value. Tubular secretion is also critical for toxin and drug elimination but has not been well described in healthy individuals and corresponding reference ranges have not been established.Material and methodsAmong participants from the Norwegian population-based HUNT3 study we identified a healthy subset by excluding those reporting poor general health, or smoking, diabetes, cardiovascular disease, treated hypertension, severe, and CKD (eGFR <60mL/min/1.73m2). We measured 12 well-characterized markers of tubular secretion in blood and urine using liquid chromatography mass spectrometry (LC-MS). Tubular secretory function was reported for each marker as urine/plasma-ratio (UPR, with and without indexing to urine creatinine and osmolality), clearance, and fractional excretion.ResultsWe included 636 healthy participants (295 men) with mean age 47years (SD 14). Less than 3.2% of participants in age and sex subgroups fell outside the upper and lower limits of a common reference interval, so partitioning for age and sex was not necessary. Median urine/plasma ratio indexed for creatinine (UPRcreat) ranged from 3 to 87uM/uM·mmol, and plasma clearance ranged from 35 to 976mL/min. Phenylacetylglutamine, isovalerylglycine, 2-methylsuccinic acid, and hippuric acid demonstrated the highest UPRcreat values (87, 75, 72, and 61uM/uM·mmol, respectively). We also measured 1,7-dimethyluric acid, kynurenic acid, adipic acid, suberic acid, cinnamoylglycine, 1,2,7-trimethyluric acid, indoxyl sulfate, and p-cresol sulfate. Reference intervals based on 2.5th and 97.5th percentiles were similar across age and sex.ConclusionThis study quantifies reference ranges of endogenous tubular secretory solutes among a population of community dwelling healthy adults.

The single-nucleotide polymorphism (SNP) rs1800693 in the tumor necrosis factor receptor 1 (TNFR1) gene leads to the formation of a protein-mimicking effect of TNF-α inhibitors, which are agents used to treat sarcoidosis. We investigated the association between rs1800693 and disease progression in two populations with non-Lofgren sarcoidosis (nLS). We genotyped two nLS cohorts (Ruhrlandklinik, Germany, n = 108, and the HUNT study, Norway, n = 393), and two control groups with (n = 313) and without (n = 2414) COPD for rs1800693 (A/G polymorphism). Pulmonary function tests at inclusion and at the end of follow-up were compared according to genotype. The mean follow-up times were 6.5 (German) and 7.9 (Norwegian) years. German AA patients had an absolute decline in %pred FVC (-8.5, 95% CI -3.4, -13.6) and DLco (-4.9, 95% CI -0.1, -9.7). In AG/GG (G+), the absolute decline in FVC was less pronounced (-3.9, 95% CI -1.1, -6.8), and DLco was stable. In the Norwegian patients, the decrease in lung function was similar between the AA and G+ groups. Compared with homozygous GG, homozygous AA was associated with a lower FVC %pred at baseline (-5.7, 95% CI -0.2, -11.6) and at the end of follow-up (-7.0, 95% CI -0.1, -14.0). Genotype was not associated with lung function in either control group. TNFR1 rs1800693 might be associated with lung function impairment and decline in non-Lofgren sarcoidosis patients.

Using data on Norwegian adolescents, this study aimed to explore changes in mental health, quality of life, somatic health complaints and loneliness from before and one year into the COVID-19 pandemic, also considering the changes according to socioeconomic position (SEP). The study involved a cross-sectional comparative design with data from Young-HUNT4 (2017-2019) (n = 4347) and Young-HUNT COVID (May/June 2021) (n = 2033), aged 16-19 years. Additionally, longitudinal changes from Young-HUNT4 (n = 1565), aged 13-15 years, with follow-up in Young-HUNT COVID were explored. The impact of SEP was investigated through regression analyses and investigating prevalence changes in high and low SEP groups. In the cross-sectional comparison, boys and girls reported higher levels of loneliness and mental distress (boys only) into the pandemic compared to before, while general health and quality of life remained stable. Longitudinally, all factors changed adversely except for general health in boys. Comparing younger (13-15 years) with older (16-19 years) adolescents from Young-HUNT4, demonstrated the same adverse pattern as in the longitudinal sample. Poor health, poor quality of life and loneliness were more prevalent in the low compared to the high SEP group. In the low SEP group, mental distress, poor general health and life quality worsened in boys while improved in girls during the study period. Except for mental distress in boys, general health and life quality did not deteriorate in the study period, although loneliness increased in both sexes. In the low SEP group, girls seemed to cope better than boys where health and well-being even improved.

Exploring longitudinal associations between farmer self-reported psychological and physical job demands, and the welfare of their livestock. The HUNT Study, Norway.

The incidence of cancer-associated venous thromboembolism (CAT) has risen in recent decades, underscoring the need for novel risk biomarkers and mechanistic insights. MicroRNAs (miRNAs) have emerged as promising biomarkers for various diseases, with elevated miRNA-145-5p (miR-145-5p) levels linked to reduced venous thromboembolism (VTE) risk. We aimed to investigate the association between plasma miR-145-5p levels and risk of future VTE related to (CAT) and unrelated to cancer (non-CAT). Plasma miR-145-5p levels were measured in a case cohort derived from the Trøndelag Health Study (HUNT3; N = 50 807). The study included 455 VTEs (95 CATs), occurring during 9 years of follow-up, and 1740 randomly sampled age-weighted subcohort participants. VTEs were classified as CAT if they occurred within 1 year before or 2 years after a cancer diagnosis. Multivariable adjusted hazard ratios (HRs) for CAT and non-CAT were estimated using weighted Cox regression, with cancer modeled as a time-varying covariate. Increasing miR-145-5p levels were associated with lower risk of CAT (HR per 1 SD, 0.70; 95% CI, 0.52-0.96) and non-CAT (HR, 0.81; 95% CI, 0.72-0.91). Individuals in the highest miR-145-5p quartile had lower risk of both CAT (HR, 0.55; 95% CI, 0.25-1.20) and non-CAT (HR, 0.48; 95% CI, 0.33-0.69) than those in the lowest quartile. High plasma miR-145-5p levels were associated with lower risk of CAT and non-CAT, suggesting that miR-145-5p has the potential to serve as a risk biomarker for CAT.

To evaluate and compare the predictive value of eight dementia risk scores for late-life cognitive function and cognitive decline; ANU-ADRI, CAIDE, CogDrisk, LIBRA, LIBRA2, UKBDRS(-APOE), and a Lancet commission-based risk score. Using Norwegian Trøndelag Health Study (HUNT) data, we calculated risk scores from lifestyle and health data of 7221 dementia-free participants (mean age: 76.8 years, 54.1% female) collected in HUNT3 (2006-2008). Cognitive function was assessed using the Montreal Cognitive Assessment scale (MoCA) 11 years later in HUNT4 70+, and reassessed in 4716 participants 4 years thereafter. Associations between continuous risk scores or risk score tertiles, cognition and cognitive decline were examined using linear mixed-effects models. Logistic regression models were used to test associations between risk scores and a ≥ 3-point decline in MoCA scores. All risk scores were significantly associated with cognitive function and cognitive decline. Associations with cognitive function ranged from UKBDRS β per 1SD=-1.61(95%CI:-1.72,-1.51) to CAIDE (β=-0.74;95%CI:-0.82,-0.67), and with yearly cognitive decline from Lancet (β=-0.23;95%CI:-0.27,-0.18) to CAIDE (β=-0.04;95%CI:-0.07,-0.02). High-low risk group differences in cognitive function were largest for CogDrisk (β=-3.04;95%CI:-3.27,-2.81), LIBRA (β=-3.04;95%CI:-3.27,-2.80) and lowest for CAIDE (β=-1.65;95%CI:-1.86,-1.44). High-risk groups showed the steepest decline for UKBDRS-APOE (β=-0.43;95%CI:-0.52,-0.34), Lancet (β=-0.39;95%CI:-0.48,-0.30), and LIBRA (β=-0.38;95%CI:-0.47,-0.28). All scores predicted ≥3-point decline modestly: AUCs were highest for UKBDRS (AUC=0.61;95%CI:0.60,0.63), UKBDRS-APOE (0.61;95%CI:0.60,0.63), CogDrisk (0.60;95%CI:0.58,0.62), and Lancet (0.60;95%CI:0.58,0.61), but none outperformed a model including age and education alone (0.61;95%CI:0.60,0.63). Risk scores captured meaningful gradients in cognition and decline but offered limited discriminatory accuracy beyond demographics, supporting their use for prevention-oriented risk profiling rather than prediction.

Psoriasis is recognized as a systemic inflammatory disease associated with metabolic dysregulation. Understanding these metabolic changes may reveal biomarkers to elucidate disease mechanisms and predict comorbidities. While previous studies have identified psoriasis-associated metabolites, findings are often limited by sample sizes and lack validation. To identify circulating metabolites associated with psoriasis, including disease severity and psoriatic arthritis. Further, we investigated whether the metabolic signature was disease-specific compared to other immune-mediated inflammatory diseases (IMIDs). We performed a cross-sectional analysis of 470,352 White/European individuals from the UK Biobank (n=453,428) and HUNT (n=16,924). Nuclear Magnetic Resonance spectroscopy was used to quantify metabolite levels, covering lipoprotein fractions and subfractions, fatty acids, and small-molecular metabolites. For each metabolite, we performed multivariable linear regression adjusting for age, sex, BMI, smoking status, and use of lipid-lowering medications. The metabolomic profile of psoriasis was largely consistent across the two populations. In the model adjusted for age and sex, 123 metabolic measures were associated with psoriasis. After full adjustment, only Glycoprotein acetyls (GlycA) remained associated with psoriasis (coefficient [95% CI]: 0.09 [0.07-0.11] in UK Biobank and 0.11 [0.06-0.17] in HUNT). In HUNT, severe psoriasis exhibited more pronounced metabolic alterations compared to non-severe psoriasis. Across both populations, phenylalanine levels were highly elevated in psoriatic arthritis compared to cutaneous psoriasis (0.44 [0.29-0.60] in UK Biobank and 0.47 [0.28-0.67] in HUNT). In comparisons across IMIDs, atopic dermatitis and cutaneous-limited psoriasis exhibited milder metabolic alterations, and psoriasis in HUNT showed a distinct lipoprotein profile. This large-scale study confirms metabolic alterations in individuals with psoriasis and highlights phenylalanine as a potential biomarker for joint involvement in psoriasis. The distinct metabolomic profile of psoriasis relative to other IMIDs suggests a potentially unique systemic profile. These findings offer a foundation for advancing biomarker research and mechanistic studies for psoriasis.

Introduction This study investigates the intersection of indigenous knowledge systems (IKS) and entrepreneurial practices in hunting and gathering communities on the Wild Coast, South Africa. Indigenous groups face mounting pressure to preserve cultural traditions while engaging in modern economic systems. Examining how IKS aligns with entrepreneurial strategies is critical for advancing sustainable and inclusive livelihoods.Materials and Methods A qualitative design was employed, using five focus group discussions with six participants each (n = 30). Participants were purposively sampled to reflect diversity in gender, age and livelihood experience. Discussions explored cultural practices, economic activities and visions for the future. Data were transcribed, coded and analysed thematically to identify key patterns.Results Six interrelated themes emerged: connection to nature—survival strategies remain anchored in ecological stewardship. cultural practices and traditions—hunting, gathering and rituals reinforce community identity. Economic challenges and opportunities—participants cited limited resources and market access but identified eco-tourism and niche value chains as promising. knowledge sharing and education—oral traditions and intergenerational transfer of knowledge ensure cultural continuity. Resilience and adaptability—communities creatively adapt traditional practices to modern contexts. future aspirations and visions—participants seek to blend cultural heritage with entrepreneurial opportunities for long-term sustainability.Conclusion The findings underscore the enduring value of IKS in shaping entrepreneurial practices that are both sustainable and culturally grounded. Integrating traditional knowledge with modern development opportunities, particularly eco-tourism and community-based enterprises offers viable pathways for economic empowerment. Supportive policies are needed to facilitate equitable market access and preserve cultural heritage. Strengthening collaboration between indigenous communities, policymakers and external stakeholders is essential for creating resilient local economies that respect cultural identity and environmental values.