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BackgroundDeep learning has shown potential in various scientific domains but faces challenges when applied to complex, high-dimensional multi-omics data. Alzheimer's Disease (AD) is a neurodegenerative disorder that lacks targeted therapeutic options. This study introduces the Circular-Sliding Window Association Test (c-SWAT) to improve the classification accuracy in predicting AD using serum-based metabolomics data, specifically lipidomics.MethodsThe c-SWAT methodology builds upon the existing Sliding Window Association Test (SWAT) and utilizes a three-step approach: feature correlation analysis, feature selection, and classification. Data from 997 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) served as the basis for model training and validation. Feature correlations were analyzed using Weighted Gene Co-expression Network Analysis (WGCNA), and Convolutional Neural Networks (CNN) were employed for feature selection. Random Forest was used for the final classification.FindingsThe application of c-SWAT resulted in a classification accuracy of up to 80.8% and an AUC of 0.808 for distinguishing AD from cognitively normal older adults. This marks a 9.4% improvement in accuracy and a 0.169 increase in AUC compared to methods without c-SWAT. These results were statistically significant, with a p-value of 1.04 × 10ˆ-4. The approach also identified key lipids associated with AD, such as Cer(d16:1/22:0) and PI(37:6).InterpretationOur results indicate that c-SWAT is effective in improving classification accuracy and in identifying potential lipid biomarkers for AD. These identified lipids offer new avenues for understanding AD and warrant further investigation.FundingThe specific funding of this article is provided in the acknowledgements section.

Abstract Background Presence of autoantibodies against α-synuclein (α-syn AAb) in serum of the general population has been widely reported. That such peripheral factors may be involved in central nervous system pathophysiology was demonstrated by detection of immunoglobulins (IgGs) in cerebrospinal fluid and brain of Parkinson’s disease (PD) patients. Thus, blood-borne IgGs may reach the brain parenchyma through an impaired blood-brain barrier (BBB). Findings The present study aims to evaluate the patho-physiological impact of α-syn AAbs on primary brain cells, i.e., on spontaneously active neurons and on astrocytes. Exposure of neuron-astrocyte co-cultures to human serum containing α-syn AAbs mediated a dose-dependent reduction of spontaneous neuronal activity, and subsequent neurodegeneration. Removal specifically of α-syn AAbs from the serum prevented neurotoxicity, while purified, commercial antibodies against α-syn mimicked the neurodegenerative effect. Mechanistically, we found a strong calcium flux into neurons preceding α-syn AAbs-induced cell death, specifically through NMDA receptors. NMDA receptor antagonists prevented neurodegeneration upon treatment with α-syn (auto)antibodies. α-syn (auto)antibodies did not affect astrocyte survival. However, in presence of α-syn, astrocytes reacted to α-syn antibodies by secretion of the chemokine RANTES. Conclusion These findings provide a novel basis to explain how a combination of BBB impairment and infiltration of IgGs targeting synuclein may contribute to neurodegeneration in PD and argue for caution with α-syn immunization therapies for treatment of PD.

Abstract Proteins exert their function through protein–protein interactions. In Drosophila, G protein-coupled receptors like rhodopsin (Rh1) interact with a G protein to activate visual signal transduction and with arrestins to terminate activation. Also, membrane proteins like Rh1 engage in protein–protein interactions during folding within the endoplasmic reticulum, during their vesicular transport and upon removal from the cell surface and degradation. Here, we expressed a Rh1-TurboID fusion protein (Rh1::TbID) in Drosophila photoreceptors to identify in vivo Rh1 interaction partners by biotin proximity labeling. We show that Rh1::TbID forms a functional rhodopsin that mediates biotinylation of arrestin 2 in conditions where arrestin 2 interacts with rhodopsin. We also observed biotinylation of Rh1::TbID and native Rh1 as well as of most visual signal transduction proteins. These findings indicate that the signaling components in the rhabdomere approach rhodopsin closely, within a range of ca. 10 nm. Furthermore, we have detected proteins engaged in the maturation of rhodopsin and elements responsible for the trafficking of membrane proteins, resembling potential interaction partners of Rh1. Among these are chaperons of the endoplasmic reticulum, proteins involved in Clathrin-mediated endocytosis as well as previously unnoticed contributors to rhodopsin transportation, such as Rab32, Vap33, or PIP82.

Abstract Aim To explore and compare Danish health‐care professionals’ attitudes and knowledge towards pain management of children. Methods The cross‐sectional study was carried out using the Pediatric Pain Knowledge and Attitudes Questionnaire. The questionnaire was distributed to all health care professionals caring for children in three hospital settings, including nurses and physicians in departments of pediatric, emergency, and anesthesia and medical laboratory technologists. Results The study was conducted in 2020 and 765 health care professionals participated. Within the six main categories included in the questionnaire, there were significant differences between nurses and physicians in three subcategories: view on the care of children in pain, using drugs to relieve pain, and the four mandatories. Comparing nurses with medical laboratory technicians, there were significant differences in the subcategory "view on the care of children in pain." Comparing types of clinical departments, there were significant differences in the subcategories’ view on the care of children in pain, using drugs to relieve pain, and the four mandatories. Overall, we found that the participating health professionals did not have a uniform understanding of pain management and therefore might treat children differently. Conclusion The present study highlights the need to align health care professionals’ knowledge regarding pain assessment and management of children, as well as the need to develop and test interventions that support the use of knowledge in practice.

The popularity of new mobility services (NMS), like car sharing, urban bikes or e-scooters, is increasing in many urban areas. In comparison to traditional supply-oriented public transport with defined timetables and transportation routes, NMS are demand-responsive services aiming to meet the ad-hoc needs of users. NMS have started to influence the way people move in urban areas, and they also have an impact on public transport operators which begin to offer their own NMS or integrate the services of established NMS operators. This article investigates the changes implied by NMS for the enterprise architecture (EA) of public transport operators. The paper presents and evaluates an EA approach for integrating demand-responsive services into traditional supply-oriented public transport. We propose a partial enterprise architecture as an extension of the established ITVU core model, which is an established reference model in the public transportation domain. Although EA management is recognised as relevant for public transport companies, there is a lack of such an extension addressing NMS integration. The contribution of this article are to (1) offer an overview of the state of research in enterprise architectures for public transport, (2) make a case study for illustrating the challenges and requirements of NMS integration, (3) provide a first version of the partial (core) reference EA for integration of NMS including an initial evaluation.

Introduction Management of an endoscopically resected malignant colorectal polyps can be challenging due to the risk of residual tumour and lymphatic spread. International studies have shown, that of those choosing surgical management instead of surveillance strategy, there are between 54% and 82% of bowel resections without evidence of residual tumour or lymphatic spread. As surgical management entails risks of complications and surveillance strategy entails risks of residual tumour or recurrence, a clinical dilemma arises when choosing a management strategy. Shared decision-making is a concept that can be used in preference-sensitive decision-making to facilitate patient involvement and empowerment to facilitate active patient participation in the decision-making process.Methods and analysis This study protocol describes our clinical multi-institutional, non-randomised, interventional phase II study at Danish surgical departments planned to commence in the second quarter of 2024. The aim of this study is to examine whether shared decision-making and using a patient decision aid in consultations affect patients’ choice of management, comparing with retrospective data. The secondary aim is to investigate patients’ experiences, perceived involvement, satisfaction, decision conflict and other outcomes using questionnaire feedback directly from the patients.Ethics and dissemination There are no conflicts of interest for principal or local investigators in any of the study sites. All results will be published at Danish and international meetings, and in English language scientific peer-reviewed journals. Our study underwent evaluation by the Regional Committees on Health Research Ethics for Southern Denmark (file number 20232000-47), concluding that formal approval was not required for this kind of research.Trial registration number NCT05776381.

The authors report a systematic analyses of blood biomarkers for metabolism against the whole spectrum of diseases in 100,000 individuals and reveals a prominent role of numerous metabolic biomarkers as risk markers beyond heart disease and diabetes.

OBJECTIVES: This study aimed to assess if, during the second wave of the COVID-19 pandemic, healthcare workers had increased severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection rates, following close contact with patients, co-workers and persons outside work with COVID-19. METHODS: A follow-up study of 5985 healthcare workers from Denmark was conducted between November 2020 and April 2021 and provided day-to-day information on COVID-19 contacts. SARS-CoV-2 infection was defined by the first positive polymerase chain reaction (PCR) test ever. Data was analyzed in multivariable Poisson regression models. RESULTS: The SARS-CoV-2 infection rates following close contact 3–7 days earlier with patients, co-workers and persons outside work with COVID-19 were 153.7, 240.8, and 728.1 per 100 000 person-days, respectively. This corresponded with age, sex, month, number of PCR tests and mutually adjusted incidence rate ratios of 3.17 [40 cases, 95% confidence interval (CI) 2.15–4.66], 2.54 (10 cases, 95% CI 1.30–4.96) and 17.79 (35 cases, 95% CI 12.05–26.28). The risk of SARS-CoV-2 infection was thus lower, but the absolute numbers affected was higher following COVID-19 contact at work than COVID-19 contact off work. CONCLUSIONS: Despite strong focus on preventive measures during the second wave of the pandemic, healthcare workers were still at increased risk of SARS-CoV-2 infection when in close contact with patients or co-workers with COVID-19. There is a need for increased focus on infection control measures in order to secure healthcare workers’ health and reduce transmission into the community during ongoing and future waves of SARS-CoV-2 and other infections.

As the adoption of battery electric buses (BEBs) in public transportation systems grows, the need for precise energy consumption forecasting becomes increasingly important. Accurate predictions are essential for optimizing routes, charging schedules, and ensuring adequate operational range. This paper introduces an innovative forecasting methodology that combines a propulsion and auxiliary energy model with a novel concept, the environment generator. This approach addresses the primary challenge in electric bus energy forecasting: estimating future environmental conditions, such as weather, passenger load, and traffic patterns, which significantly impact energy demand. The environment generator plays a crucial role by providing the energy models with realistic input data. This study validates various models with different levels of model complexity against real-world operational data from a case study of over one year with 16 electric buses in Göttingen, Germany. Our analysis thoroughly examines influencing factors on energy consumption, like altitude, temperature, passenger load, and driving patterns. In order to comprehensively understand energy demands under varying operational conditions, the methodology integrates data-driven models and physical simulations into a modular and highly accurate energy predictor. The results demonstrate the effectiveness of our approach in providing more accurate energy consumption forecasts, which is essential for efficient electric bus fleet management. This research contributes to the growing body of knowledge in electric vehicle energy prediction and offers practical insights for transit authorities and operators in optimizing electric bus operations.

The formation of branched microtubule networks in mitotic spindles depends on the augmin complex. Zupa, Würtz et al. elucidate the molecular architecture and conformational plasticity of the augmin complex using integrative structural biology, providing structural insights into microtubule branching.

During spring 2021, AZD1222 and BNT162b2 were used as prime and BNT162b2 as booster COVID-19 vaccines in Denmark. We obtained self-reported information on systemic reactogenicity day-by-day during two weeks for 2862 healthcare workers vaccinated with heterologous AZD1222 + BNT162b2 or homologous BNT162b2 + BNT162b2 regimens and compared prevalences of symptoms with unvaccinated healthcare workers. We found comparable systemic reactogenicity during the first week in the two vaccine regimens and no reactogenicity during the second week. Most of the symptoms returned to a level equal to the control population four days after booster vaccination.

The human microtubule nucleator γ-TuRC is composed of more than thirty subunits, including actin. Here the authors reveal the structural mechanism of modular γ-TuRC assembly and show a functional role of actin in microtubule nucleation.

Abstract Wild-type cultivations are of invaluable relevance for industrial biotechnology when it comes to the agricultural or food sector. Here, genetic engineering is hardly applicable due to legal barriers and consumer’s demand for GMO-free products. An important pillar for wild-type cultivations displays the genus Bacillus. One of the challenges for Bacillus cultivations is the global ComX-dependent quorum sensing system. Here, molecular process control can serve as a tool to optimize the production process without genetic engineering. To realize this approach, quantitative knowledge of the mechanism is essential, which, however, is often available only to a limited extent. The presented work provides a case study based on the production of cyclic lipopeptide surfactin, whose expression is in dependence of ComX, using natural producer B. subtilis DSM 10 T. First, a surfactin reference process with 40 g/L of glucose was performed as batch fermentation in a pilot scale bioreactor system to gain novel insights into kinetic behavior of ComX in relation to surfactin production. Interestingly, the specific surfactin productivity did not increase linearly with ComX activity. The data were then used to derive a mathematic model for the time course of ComX in dependence of existing biomass, biomass growth as well as a putative ComX-specific protease. The newly adapted model was validated and transferred to other batch fermentations, employing 20 and 60 g/L glucose. The applied approach can serve as a model system for molecular process control strategies, which can thus be extended to other quorum sensing dependent wild-type cultivations.

Summary: Background: The direct effects of general adiposity (body mass index (BMI)) and central adiposity (waist-to-hip-ratio (WHR)) on circulating lipoproteins, lipids, and metabolites are unknown. Methods: We used new metabolic data from UK Biobank (N=109,532, a five-fold higher N over previous studies). EDTA-plasma was used to quantify 249 traits with nuclear-magnetic-resonance spectroscopy including subclass-specific lipoprotein concentrations and lipid content, plus pre-glycemic and inflammatory metabolites. We used univariable and multivariable two-stage least-squares regression models with genetic risk scores for BMI and WHR as instruments to estimate total (unadjusted) and direct (mutually-adjusted) effects of BMI and WHR on metabolic traits; plus effects on statin use and interaction by sex, statin use, and age (proxy for medication use). Findings: Higher BMI decreased apolipoprotein B and low-density lipoprotein cholesterol (LDL-C) before and after WHR-adjustment, whilst BMI increased triglycerides only before WHR-adjustment. These effects of WHR were larger and BMI-independent. Direct effects differed markedly by sex, e.g., triglycerides increased only with BMI among men, and only with WHR among women. Adiposity measures increased statin use and showed metabolic effects which differed by statin use and age. Among the youngest (38-53y, statins-5%), BMI and WHR (per-SD) increased LDL-C (total effects: 0.04-SD, 95%CI=-0.01,0.08 and 0.10-SD, 95%CI=0.02,0.17 respectively), but only WHR directly. Among the oldest (63-73y, statins-29%), BMI and WHR directly lowered LDL-C (-0.19-SD, 95%CI=-0.27,-0.11 and -0.05-SD, 95%CI=-0.16,0.06 respectively). Interpretation: Excess adiposity likely raises atherogenic lipid and metabolite levels exclusively via adiposity stored centrally, particularly among women. Apparent effects of adiposity on lowering LDL-C are likely explained by an effect of adiposity on statin use. Funding: UK Medical Research Council; British Heart Foundation; Novo Nordisk; National Institute for Health Research; Wellcome Trust; Cancer Research UK

Objective: Our study aimed to compare symptoms day by day for non-hospitalized individuals testing positive and negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: In total, 210 positive-test and 630 negative-test healthcare workers in the Central Denmark Region were followed for up to 90 days after testing, between April and June, 2020. Their daily reported COVID-19-related symptoms were compared graphically and by logistic regression. Results: Thirty per cent of the positive-test and close to 0% of the negative-test participants reported a reduced sense of taste and smell during all 90 days (adjusted odds ratio [aOR] 86.07, 95% CI 22.86–323). Dyspnea was reported by an initial 20% of positive-test participants, declining to 5% after 30 days, without ever reaching the level of the negative-test participants (aOR 6.88, 95% CI 2.41–19.63). Cough, headache, sore throat, muscle pain, and fever were temporarily more prevalent among the positive-test participants; after 30 days, no increases were seen. Women and older participants were more susceptible to long-lasting COVID-19 symptoms. Conclusion: The prevalence of long-lasting reduced sense of taste and smell is highly increased in mild COVID-19 patients. This pattern is also seen for dyspnea at a low level, but not for cough, sore throat, headache, muscle pain, or fever.

Mit dem Ziel, zukünftige Lehrkräfte besser auf ihre vielfältigen Beratungsaufgaben im Schulalltag vorzubereiten und Inklusion qualifiziert und innovativ mitzugestalten (Lindmeier & Lindmeier, 2018), wird ein phasenübergreifendes Beratungscurriculum für Förderschullehrer*innen nach dem systemischen Ansatz (Weinhardt, 2020) entwickelt und erprobt (60 Studierende à 2 Kohorten, viereinhalb Jahre, drei Ausbildungsphasen). Professionelle sonderpädagogische Beratungskompetenz erfordert in inklusiven schulischen Settings neben der Beratung von Kolleg*innen, Eltern und Schüler*innen insbesondere eine intensive, fortlaufende (Selbst-)Reflexion (Lindmeier & Lindmeier, 2018). Dieser fortlaufende Entwicklungs- und Reflexionsprozess bildet durch reflexive Professionalisierung im Wechsel mit reflektierender Professionalität den Kern der Ausbildung zu sonderpädagogischer Beratungskompetenz im Projekt „Sonderpädagogische Beratung in der inklusiven Schule“ (SoBiS). Die Ausbildungsinhalte werden in regelmäßiger Kooperation mit den Beteiligten aller Phasen – Universität, Studienseminar, Pädagogisches Landesinstitut – der Förderschullehrer*innenbildung abgestimmt sowie dynamisch fortentwickelt. Die Didaktik des Curriculums und die Evaluation sehen einen Design-Based Research Ansatz vor (Reinmann, 2018, Benner, 2018). Quantitativ wird u.a. ein Fragebogen zur Beratungskompetenzentwicklung eingesetzt; qualitativ wird iterativ-zirkulär vorgegangen (Ochs & Schweitzer, 2015). Als Erhebungsinstrumente kommen hierbei unter anderem Gruppendiskussionen und schriftliche Reflexionen von Einzelcoachings zum Einsatz.

Pleiotropy and genetic correlation are widespread features in genome-wide association studies (GWAS), but they are often difficult to interpret at the molecular level. Here, we perform GWAS of 16 metabolites clustered at the intersection of amino acid catabolism, glycolysis, and ketone body metabolism in a subset of UK Biobank. We utilize the well-documented biochemistry jointly impacting these metabolites to analyze pleiotropic effects in the context of their pathways. Among the 213 lead GWAS hits, we find a strong enrichment for genes encoding pathway-relevant enzymes and transporters. We demonstrate that the effect directions of variants acting on biology between metabolite pairs often contrast with those of upstream or downstream variants as well as the polygenic background. Thus, we find that these outlier variants often reflect biology local to the traits. Finally, we explore the implications for interpreting disease GWAS, underscoring the potential of unifying biochemistry with dense metabolomics data to understand the molecular basis of pleiotropy in complex traits and diseases.

The Scrambled Sentences Task (SST) is a robust measure of interpretational processes in psychopathology. However, there is little evidence of its utility in measuring dysfunctional appraisals (DAs) of potentially traumatic events. We developed a novel SST for trauma-related DAs and examined its psychometric properties including convergent validity (correlations with PTSD-related symptoms and self-reported DAs), divergent validity (e.g., symptoms of depression and eating disorders), and retest reliability via an online study. Our sample (T1: N = 214, T2: N = 145) included participants who reported a potentially traumatic life event still eliciting distress. We found high correlations between the SST, PTSD-related symptoms ( r = .37-.51), and self-report measures of DAs ( r = .41-.58), indicating good convergent validity. Internal consistency (split-half = .78-.90) and retest reliability (ICC(3,1) = .73-.81) were also good. However, moderate to large correlations with symptoms of other disorders ( r = .17-.58) indicated limited divergent validity. Finally, the SST explained unique variance in PTSD-related symptoms above self-report measures of DAs. The results demonstrate the promise of the SST as a valid and reliable tool to assess DAs in the context of potentially traumatic life events. Further research should investigate the transdiagnostic role of trauma-related DAs in psychopathology and the relationship between the SST and self-report measures of DAs.

In human nutrition, bovine milk is an essential source of bioavailable vitamin B12 and B12-binding proteins, including transcobalamin. In this study, we estimated genetic parameters for milk content of vitamin B12 and transcobalamin using milk samples from 341 and 663 Danish Holstein cows, respectively. Additionally, we conducted whole-genome association analysis to identify SNP and genes associated with vitamin B12 and transcobalamin. Our results indicated moderate to high heritability for vitamin B12 (0.37 ± 0.18) and transcobalamin (0.61 ± 0.13) content in the Danish Holstein. With a significance threshold of –log10 P-value > 5.87, significant associations were detected between SNP in Bos taurus autosome (BTA)17 and the log-transformed transcobalamin content of milk; no significant association was detected for vitamin B12. The significant region in BTA17 was imputed to full sequence for further fine mapping, and the SNP with the most significant associations to transcobalamin were assigned to the transcobalamin 2 (TCN2) gene.

Background: Fabry disease (FD) is a lysosomal storage disorder resulting in systemic accumulation of globotriaosylceramide (Gb3) causing multi-organ dysfunction. The audiologic involvement in FD has been neglected in previous studies; while not a lethal aspect of the disease, hearing loss can have a significantly negative impact on quality of life. Objective: To investigate hearing loss from baseline through 16 years follow-up of the Danish FD cohort and to compare audiometric data to other clinical variables. Methods: Data was collected prospectively and assessed retrospectively during a period of 16 years from 83 patients (age: 9–72 years; sex: 29 males and 54 females). 55 patients underwent treatment. Air conduction thresholds was assessed at six frequencies between 0.25 and 8 kHz bilaterally. Data was analyzed using multilinear models. Results: Mean follow-up period for patients undergoing a FD specific treatment was 7.8 years (0–12.8 years, SD 3.8 years, n = 55). Hearing thresholds for FD patients deviated from healthy individuals at all frequencies for both sexes (p

This study reviews the European evidence on the impact of professional development (PD) of pre-school educators on child outcomes. A meta-analysis investigates how PD of pre-school educators in formal pre-school centers in Europe affects child outcomes. The European studies are quite recent and limited in numbers, and our results show a significant positive effect of PD on child outcomes with an overall effect size of 0.35 (with a 95% confidence interval from 0.20 to 0.51). The magnitude is slightly smaller than corresponding results based on US studies, but indicates a general positive effect of PD on child outcomes.

From previous research it is well known that victimization can have various short- and long-term consequences resulting in a need for support to cope with the victimization. Research also shows, however, that not all victims of crime seek or receive support. One cause of this might be the conditions and constraints that affect professionals' matching of support services with individual victims' needs. The purpose of the present conceptual paper is to discuss how professionals can co-produce support services with the individual victim and if needed engage suitable external organizations for the purpose of adapting support services to the individual victim's needs, while also considering the complex field of constraints that professionals need to navigate during this process. The paper makes two main contributions. First, it conceptualizes the complex field of constraints as consisting of five sets of conditions (mandatory, local, professional, support-user, and inter-organizational conditions), which professionals must navigate during the co-production of victim support services. Second, the paper suggests a seven-step process of how professionals can navigate this complex field during co-production of victim support services' activities with the individual victim, and potentially those of external organizations as well. [ABSTRACT FROM AUTHOR]

The nucleation of microtubules from αβ-tubulin subunits is mediated by γtubulin complexes, which vary in composition across organisms. Here, authors present the cryo-EM structure of the heterotetrameric γ-tubulin small complex (γ-TuSC) from C. albicans at near-atomic resolution.

Summary: Background: Ticagrelor was introduced in Denmark in 2011 after randomised data showed its superiority over clopidogrel for patients with acute coronary syndrome (ACS). We assessed the effectiveness and safety of ticagrelor implementation in ACS patients undergoing percutaneous coronary intervention (PCI). Methods: We identified PCI-treated ACS patients in Western Denmark who redeemed a P2Y12 inhibitor prescription within 14 days. Using Danish health registries, 1-year outcomes were compared before (2007-2010) and after (2012-2015) introduction of ticagrelor. Outcomes were MACE (death, myocardial infarction, and ischaemic stroke) and hospitalisation for bleeding. Inverse probability of treatment weights were used to estimate weighted incidence rate ratios (wIRRs). Findings: We included 14,450 patients; 7,102 were treated in the earlier time period (99·9% clopidogrel) and 7,348 in the later time period (87·8% ticagrelor). Ticagrelor implementation was not associated with a clinically relevant difference in 1-year risk of MACE with 413 events in the ticagrelor period vs. 424 events in the clopidogrel period (cumulative incidence percentage [CIP] 5·6% vs. 6·0%; wIRR 1·06, 95% CI 0·92-1·22). The 1-year risk of bleeding was also similar between groups with 335 bleedings requiring hospitalisation in the ticagrelor period vs. 309 events in the clopidogrel period (CIP 4·6% vs. 4·4%; wIRR 1·05, 95% CI 0·89-1·23). Results were robust in patients above and below 70 years of age. Interpretation: Implementation of ticagrelor was not associated with changes in risks of ischaemic or bleeding events in Danish PCI-treated ACS patients.

OBJECTIVES: The number of dinucleotide repeats (GT)_n modulate expression of heme oxygenase 1 (HMOX1), a stress response gene. Multiple repeats might affect chronic obstructive pulmonary disease (COPD) susceptibility. We aimed to investigate the association of this polymorphism with COPD and its interaction with occupational exposures (vapor, gas, dust, or fumes). METHODS: This population-based cross-sectional study included 4703 Danes, aged 45–84 years. HMOX1 (GT)_n was genotyped and grouped as short: ≤26, medium: 27–32 and long: ≥33 alleles. COPD was defined by the lower limit of normal (2.5^th FEV_1/FVC and FEV_1 centiles). Occupational exposure was defined as ever exposed to vapor, gas, dust, or fume in expert-selected jobs. Associations were analyzed by adjusted mixed logistic regression. RESULTS: The population included 6% with COPD, 48% who had smoked ≥10 pack-years, and 46% with occupational exposure. HMOX1 was genotyped in 4423 participants. The adjusted odds ratio (OR) for the association between HMOX1 long allele and COPD was 1.75 [95% confidence interval (CI) 1.18–2.60]. An interaction was evident between HMOX1 long allele and occupational exposure, OR 2.38 (95% CI 1.04–5.46), versus HMOX1 short/medium without exposure. Analyses were replicated in another cohort, aged 20–44 years, N=1168, including 3% with COPD, 25% who had smoked ≥10 pack-years and 20% with occupational exposure. No associations were seen between COPD and HMOX1 long allele here. CONCLUSIONS: Long alleles in HMOX1 alone and in interaction with occupational exposure seem to be associated with COPD. Failure to replicate data may be due to premature age for COPD development and low occupational exposure prevalence. We propose this long allele may be a genetic contributor to the COPD pathogenesis.

Background Peripheral artery disease (PAD) and coronary artery disease (CAD) represent atherosclerosis in different vascular beds. We used detailed metabolic biomarker profiling to identify common and discordant biomarkers and clarify pathophysiological differences for these vascular diseases. Methods and Results We used 5 prospective cohorts from Finnish population (FINRISK 1997, 2002, 2007, and 2012, and Health 2000; n=31 657; median follow‐up time of 14 years) to estimate associations between >200 metabolic biomarkers and incident PAD and CAD. Metabolic biomarkers were measured with nuclear magnetic resonance, and disease events were obtained from nationwide hospital records. During the follow‐up, 498 incident PAD and 2073 incident CAD events occurred. In age‐ and sex‐adjusted Cox models, apolipoproteins and cholesterol measures were robustly associated with incident CAD (eg, hazard ratio [HR] per SD for higher apolipoprotein B/A‐1 ratio, 1.30; 95% CI, 1.25–1.36), but not with incident PAD (HR per SD for higher apolipoprotein B/A‐1 ratio, 1.04; 95% CI, 0.95–1.14; Pheterogeneity0.05). Lower proportion of polyunsaturated fatty acids relative to total fatty acids, and higher concentrations of monounsaturated fatty acids, glycolysis‐related metabolites, and inflammatory protein markers were strongly associated with incident PAD, and many of these associations were stronger for PAD than for CAD (Pheterogeneity

Introduction: The fishing- and the seafood processing industries are the largest industrial sectors in Greenland. Despite this, only a few cases of occupational diseases in this industry have been reported to the Danish Labor Market Insurance. Occupational asthma and allergy are well-known occupational diseases in the seafood processing industry worldwide and underreporting of occupational diseases in Greenland is suspected.Objective: The aim of the current study was to examine the associations between job exposures and occupational asthma and rhino conjunctivitis in workers in the Greenlandic seafood processing industry and to compare the prevalence of sensitization by type and degree of exposure to snow crab, shrimp, fish, and the fish parasite, Anisakis simplex.Methods: Data from 382 Greenlandic seafood processing workers were collected during 2016–2018. Data included questionnaire answers, lung function measurements, skin prick tests, and blood samples with ImmunoCAP. For all analyses, p < 0.05 was considered the level of significance.Results: 5.5% of the workers had occupational asthma and 4.6% had occupational rhino conjunctivitis. A large proportion of the workers were sensitized to allergens specific to the workplace; 18.1% to snow crab, 13.6% to shrimp, 1.4% to fish, and 32.6% to the fish parasite, A. simplex. We found a dose-response relationship between the risk of being sensitized to snow crab and A. simplex and years of exposure to the allergens in the seafood processing industry.Conclusion: This study showed that a considerable proportion of workers in the Greenlandic seafood processing industry had occupational asthma and rhino conjunctivitis. Additionally, the study showed high sensitization levels toward snow crab, shrimp, and the fish parasite, A. simplex. This supports the hypothesis of a considerable degree of underreporting of occupational allergic airway disease in the Greenlandic seafood processing industry. Prospectively, it is important to inform workers, leaders, and health care professionals of the health problems and the law on worker's compensation, and to initiate preventive actions at factory and trawler level.