University of Southern Denmark

Aims Better prediction of outcome after total hip arthroplasty (THA) is warranted. Systemic inflammation and central neuroinflammation are possibly involved in progression of osteoarthritis and pain. We explored whether inflammatory biomarkers in blood and cerebrospinal fluid (CSF) were associated with clinical outcome, and baseline pain or disability, 12 months after THA. Methods A total of 50 patients from the Danish Pain Research Biobank (DANPAIN-Biobank) between January and June 2018 were included. Postoperative outcome was assessed as change in Oxford Hip Score (OHS) from baseline to 12 months after THA, pain was assessed on a numerical rating scale, and disability using the Pain Disability Index. Multiple regression models for each clinical outcome were included for biomarkers in blood and CSF, respectively, including age, sex, BMI, and Kellgren-Lawrence score. Results Change in OHS was associated with blood concentrations of tumour necrosis factor (TNF), interleukin-8 (IL-8), interleukin-6 receptor (IL-6R), glycoprotein 130 (gp130), and IL-1β (R ² = 0.28, p = 0.006), but not with CSF biomarkers. Baseline pain was associated with blood concentrations of lymphotoxin alpha (LTα), TNFR1, TNFR2, and IL-6R (R ² = 0.37, p < 0.001) and CSF concentrations of TNFR1, TNFR2, IL-6, IL-6R, and IL-1Ra (R ² = 0.40, p = 0.001). Baseline disability was associated with blood concentrations of TNF, LTα, IL-8, IL-6, and IL-1α (R ² = 0.53, p < 0.001) and CSF concentrations of gp130, TNF, and IL-1β (R ² = 0.26, p = 0.002). Thus, preoperative systemic low-grade inflammation predicted 12-month postoperative outcome after THA, and was associated with preoperative pain and disability. Conclusion This study highlights the importance of systemic inflammation in osteoarthritis, and presents a possible path for better patient selection for THA in the future. Preoperative central neuroinflammation was associated with preoperative pain and disability, but not change in OHS after THA. Cite this article: Bone Joint Res 2024;13(12):741–749.

We consider problems in the functional analysis and evolution of combinatorial chemical reaction networks as rule-based, or three-level systems. The first level consists of rules, realized here as graph-grammar representations of reaction mechanisms. The second level consists of stoichiometric networks of molecules and reactions, modeled as hypergraphs. At the third level is the stochastic population process on molecule counts, solved for dynamics of population trajectories or probability distributions. Earlier levels in the hierarchy generate later levels combinatorially, and as a result constraints imposed in earlier and smaller layers can propagate to impose order in the architecture or dynamics in later and larger layers. We develop general methods to study rule algebras, emphasizing system consequences of symmetry; decomposition methods of flows on hypergraphs including the stoichiometric counterpart to Kirchhoff’s current decomposition and work/dissipation relations studied by Wachtel et al.; and the large-deviation theory for currents in a stoichiometric stochastic population process, deriving additive decompositions of the large-deviation function that relate a certain Kirchhoff flow decomposition to the extended Pythagorean theorem from information geometry. The latter result allows us to assign a natural probabilistic cost to topological changes in a reaction network of the kind produced by selection for catalyst-substrate specificity. We develop as an example a model of biological sugar-phosphate chemistry from a rule system published by Andersen et al. It is one of the most potentially combinatorial reaction systems used by biochemistry, yet one in which two ancient, widespread and nearly unique pathways have evolved in the Calvin-Benson cycle and the Pentose Phosphate pathway, which are additionally nearly reverses of one another. We propose a probabilistic accounting in which physiological costs can be traded off against the fitness advantages that select them, and which suggests criteria under which these pathways may be optimal.

Background Childhood obesity can have significant negative consequences for children’s wellbeing and long-term health. Prior school-based interventions to prevent child overweight and obesity have shown limited effects, highlighting the necessity for comprehensive approaches addressing complex drivers of childhood obesity. “Generation Healthy Kids” (GHK) is a multi-setting, multi-component intervention to promote healthy weight development, health and wellbeing in Danish children aged 6–11 years. This protocol describes the GHK main trial, which is a cluster-randomized trial evaluating effectiveness and implementation of the GHK intervention. Methods Twenty-four schools from the Capital, Zealand and Southern Denmark Regions are randomly allocated 1:1 to intervention or control. The intervention will run for two school years (18–20 months) from October 2023 to June 2025 and will include children in 1st–3rd grade (approx. n = 1,600). The intervention targets multiple settings, including families, schools, after-school clubs, and local communities. Within four focus areas–diet, physical activity, screen media use, and sleep habits–the intervention incorporates several fixed elements, including a school lunch program and three weekly sessions of physical activity at school. Furthermore, building on whole-systems thinking, the intervention encompasses co-created elements developed in collaboration with local stakeholders, e.g. municipalities, sports clubs and supermarkets. This part of the intervention emphasizes building local capacity and engagement to promote child health. Effectiveness data will be collected from participating children and families at baseline, and at the end of school year one (after 6–8 months) and school year two (after 18–20 months). The primary outcome is the change in fat mass, measured by air-displacement plethysmography, from baseline to end-of-study in the intervention group compared to the control group. This is supplemented with numerous secondary outcomes and other prespecified outcomes related to child health and wellbeing. Furthermore, thorough process evaluation will be performed. Discussion GHK combines evidence-based intervention elements targeting multiple settings with a whole-systems approach focusing on capacity building and stakeholder involvement. This novel approach holds promise as an innovative way to promote child health and wellbeing and prevent childhood obesity. Trial registration ClinicalTrials.gov: NCT05940675 (registered on 4 July 2023).

Objectives This study from Northern Vietnam aims to assess the association between social support and symptoms of depression among pregnant women screened for gestational diabetes mellitus (GDM). Methods A cross-sectional study was conducted among 823 pregnant women in Thai Binh, Vietnam. The women were screened for GDM and structured questionnaire were used to collect data on social support factors, GDM factors, and symptoms of depression. The diagnosis of GDM was based on the 2-hour 75-g OGTT according to WHO 2013 criteria. The Edinburg Postpartum Depression Scale (EPDS) with a cut-off of 10 and the Multidimensional Perceived Social Support Scale (MSPSS) were used to assess depression symptoms and perceived social support, respectively. Logistic regression analysis was conducted to measure the associations between social support, GDM-related factors, and symptoms of depression. The relationship between social support score and symptoms of depression was evaluated using Spearman’s correlation. The strength of the associations were measured by adjusted odds ratios (aOR) with 95% confidence intervals (CI). Results The prevalence rates of GDM and symptoms of depression were 22.2% (95%CI: 19.4–25.2) and 23.0% (95%CI: 20.1–26.0), respectively. Women who had moved away from their commune of birth and women who reported another person than their husband to be the primary person to confide in had increased odds of depression (aOR = 1.74; 95%CI:1.19–2.56 and aOR = 2.36; 95%CI:1.48–3.75, respectively). A reported lack of social support was strongly associated with increased odds of depression symptoms among both women with gestational diabetes mellitus (aOR = 6.16, 95% CI:2.35–16.12) and without gestational diabetes mellitus (aOR = 2.81; 95%CI: 1.67–4.75). When analysing the correlation between social support and depression symptoms, a negative correlation was found, with decreasing depression scores as the social support score increased. Conclusion The prevalence of symptoms of depression was high in our study, and women in Northern Vietnam who feel well-supported socially are less likely to report symptoms of depression. This finding applies both to women with and without GDM.

Background In the CONPET study, multiple myeloma patients with abnormal 18FDG positron emission/computed tomography scan after upfront autologous stem cell transplantation were treated with four cycles of carfilzomib–lenalidomide–dexamethasone (KRd). Side effect registrations show that carfilzomib might cause dyspnea, cough, respiratory tract infections, and heart failure. The aims were to investigate patient‐reported shortness of breath and dyspnea during KRd consolidation. Methods To assess shortness of breath, patients completed the Functional Assessment of Cancer Therapy—Pulmonary Symptom Index (FACT‐PSI) and the EORTC QLQ‐C30 to assess dyspnea. Shortness of breath was defined as decrease in FACT‐PSI score or starting/increasing diuretic drugs. Mixed effect logistic regression was used for the effect analysis. Linear mixed model and clinical relevance were used to investigate dyspnea. Results A total of 50 patients were included, median age 62 years (interquartile range 54–67). 17% reported shortness of breath at Day 15 Cycles 1–4 versus 11% at Day 1 Cycles 2–4, Cycle 4 Day 29, and 1 month posttreatment (p‐value 0.048). Compared with baseline, patients reported significant, and clinically relevant worsening in dyspnea during consolidation. Conclusion Our study confirmed earlier findings of carfilzomib causing shortness of breath during KRd administration and revealed dyspnea during consolidation compared to baseline. Trial Registration Clinicaltrials.gov: NCT03314636, EudraCT: 2017–000586‐72

Objective Rapid and accurate infection diagnosis is a prerequisite for appropriate antibiotic prescriptions in an ED. Accurately diagnosing acute infections can be difficult due to nonspecific symptoms and limitations of diagnostic testing. The accuracy of preliminary diagnoses, established on the initial clinical assessment, depends on a physician’s skills and knowledge. It has been scarcely studied, and knowledge of how infected patients present at EDs today is needed to improve it. Based on expert reference diagnoses and a current ED population, this study aimed to characterise adults presenting at EDs with suspected infection to distinguish between infections and non-infections and to investigate the accuracy of the preliminary infection diagnoses. Design This study was multicentre with a design that combined a cross-sectional study and a diagnostic study with a prospective enrolment. Setting Multicenter study including EDs at three Danish hospitals. Participants Adults admitted with a preliminary diagnosis of an infectious disease. Outcome measures Data were collected from medical records and participant interviews. The primary outcome was the reference diagnosis made by two medical experts on chart review. Univariate logistic regression analysis was performed to identify factors associated with infectious diseases. Results We included 954 patients initially suspected of having an infection, with 81% later having an infectious disease confirmed by experts. Parameters correlating to infection were fever, feeling unwell, male sex, high C-reactive protein, symptoms onset within 3 days, high heart rate, low oxygen saturation and abnormal values of neutrophilocytes and leucocytes. The three main conditions were community-acquired pneumonia (CAP) (34%), urinary tract infection (UTI) with systemic symptoms (21%) and cellulitis (10%). The sensitivity of the physician’s preliminary infection diagnoses was 87% for CAP, 74% for UTI and 77% for other infections. Conclusions Four out of five patients with a preliminary infection diagnosis, established on initial clinical assessment, were ultimately confirmed to have an infectious disease. The main infections included CAP, UTI with systemic symptoms and cellulitis. Physicians’ preliminary infection diagnoses were moderately in accordance with the reference diagnoses. Trial registration number NCT04661085 , NCT04681963 , NCT04667195 .

Purpose: This single-arm, pre–post pilot study assessed the feasibility and preliminary effectiveness of community-based group psychoeducation for informal caregivers (18+) of individuals with a range of mental illnesses in Denmark. The intervention was delivered by social work and healthcare professionals and aimed to improve well-being and prevent burnout. Keeping within the medical research council's framework for evaluating complex interventions, we focused on identifying key uncertainties. Method: Of 150 participants enrolled in the intervention, 84 and 56 completed pre- and postintervention questionnaires on demographics, acceptability, well-being, burnout, and coping. A convergent mixed methods design was applied, with quantitative and qualitative findings integrated at the reporting level. Results: The intervention demonstrated preliminary effectiveness in improving well-being but faced challenges in feasibility regarding participation rates and reach. Participants valued group processes, though some reported adverse effects. Conclusion: Future studies should address participation challenges and explore group dynamics before a full-scale evaluation.

Pickering interfacial biocatalysis (PIB), where biocatalysts stabilize emulsions through carrier coupling or polymer grafting, has emerged as a powerful platform for organic synthesis due to its ability to accommodate water‐insoluble substrates within enzymatic cascade reactions. PIB provides a large interfacial area for two‐phase reactions, reducing diffusional resistance and enhancing transformation efficiency. The performance of PIB relies heavily on enzyme‐particle conjugates, which serve a dual function: stabilizing the emulsion and acting as the active biocatalysts in the system. In this Concept, we discuss the latest advancements, current challenges, and future directions in the development of protein‐particle conjugates for PIB.

Opportunistic mobile predators can adapt their behaviour to specific foraging scenarios, allowing them to target diverse prey resources. An interesting example is the harbour porpoise (Phocoena phocoena), a marine mammal with a huge energy demand feeding on a large variety of fish, squid and shrimps. Little is known about the foraging behaviour of harbour porpoises, as observations of wild specimens are notoriously difficult to obtain. In this study, foraging was identified in almost 60% of videos from UAV recordings in Danish coastal waters during daylight hours. Observations reveal them to be flexible predators, foraging on both single fish and schools of fish, as well as individually and in groups of varying sizes. We argue that some of the observed behavioural adaptations and context‐dependent strategies for prey capture are based on information transfer and social learning. Our results provide unprecedented insights into the foraging behaviour of an opportunistic mammalian predator. Furthermore, this study highlights the importance of porpoises having access to coastal areas for energy acquisition, where they are in conflict with anthropogenic disturbances such as fisheries with the risk of bycatch.

Objectives Previous studies have indicated that maternal occupational psychosocial stressors may affect the risk of asthma in the offspring, but their results are inconsistent. Maternal occupational ergonomic strain is associated with predictors of fetal lung development, including preterm birth and low birthweight; however, it is not known, whether ergonomic strain during pregnancy is a risk factor for asthma in offspring. The aim was to investigate maternal psychosocial stressors and ergonomic strain during pregnancy relative to the risk of offspring asthma. Methods Live- and firstborn singletons (1996–2018) and their mothers were identified from Danish nationwide registers. Job code at time of conception was assigned to each mother and linked with exposure estimates from job exposure matrices (JEMs) of psychosocial stressors and ergonomic strain. Diagnoses of childhood asthma were retrieved from the Danish National Patient Register. Incidence rate ratios (IRR) of asthma were estimated using Poisson regression; adjusted for maternal asthma, age at conception, socioeconomic position, and body mass index, and calendar year. Results Maternal employment in occupations with low decision authority (IRR: 1.08, 95% CI 1.00–1.16) and high ergonomic strain (IRR: 1.09, 95% CI 1.02–1.16) was associated with increased risk of asthma among male offspring. Largely similar, but less consistent, associations were observed among female offspring due to low decision authority. Conclusion We found a minor increased risk of asthma among offspring whose mothers worked in an occupation with low decision authority or high ergonomic strain, most pronounced among male offspring.

Background Teriflunomide has been associated with an increased risk of hypertension. Real-world studies including adequate control groups are lacking. We hypothesized that patients with multiple sclerosis (MS) treated with teriflunomide would be at higher risk of developing hypertension than those treated with dimethyl fumarate. Methods We conducted a cohort study linking the Danish Multiple Sclerosis Registry with national health registries during a 10-year period. Teriflunomide ( N = 2656) and dimethyl fumarate ( N = 2237) exposure was defined by the first treatment record lasting ⩾ 3 months, at which time follow-up started. We included 4893 adult patients without hypertension at baseline. Hypertension was defined as an International Classification of Diseases 10th Revision code for hypertension and by dispensed prescription drugs identified by the respective Anatomical Therapeutic Chemical codes. We used multivariable-adjusted Cox regression. Results We found 40.6 (teriflunomide) and 13.1 (dimethyl fumarate) hypertension events per 1000 person-years. Compared to dimethyl fumarate-treated patients, patients treated with teriflunomide had a higher risk of developing hypertension (adjusted hazard ratio = 2.80; 95% confidence interval = 2.19–3.56). The number needed to harm was 16 and 9 at 3 and 5 years of follow-up, respectively. Conclusion We found an increased risk of hypertension in adult patients with MS treated with teriflunomide.

Shear strengthening of reinforced concrete beams using near-surface mounting (NSM) method with fiber-reinforced polymer (FRP) strips is more effective because of improved bond strength, better fire resistance and high maintainability. However, the surface preparation for NSM method is a difficult process where the beam–slab corner is not accessible by the rotary blade of the groove-making equipment. Consequently, the application of NSM method becomes more difficult to apply. Therefore, in this study, the effect of reducing in NSM length on the shear strength has been investigated by reinforcing only a part of the height, not the entire web of beam, referred to as the partial-length NSM method (PLNSM). Half scaled five RC T-beams were made and tested under symmetrical four-point static loading system. All except one was strengthened in shear in which the effect of reduced NSM length was balanced by inclining the partial-length NSM strips (IPLNSM). Furthermore, to mitigate the detrimental effect of reduced lengths of NSM strips, the retrofitting was enhanced by additional externally bonded reinforcement (EBR) method using CFRP sheets. The results showed that there was no significant negative effect of reduced NSM length on the strength of the strengthened specimens, and by providing inclined NSM strips, significant improvement in the strength was observed. Additionally, the hybrid approach combining the inclined partial length NSM (IPLNSM) and EBR method showed improvement in strength and deflection capacity. Lastly, when compared with the currently available design procedures, it was found that the available formulation can predict the design strength of PLNSM and IPLNSM reinforcement, thus making them a viable option for retrofitting reinforced concrete beams.

Type 2 diabetes (T2D) pathophysiology involves insulin resistance (IR) and inadequate insulin secretion. Current T2D management includes dietary adjustments and/or oral medications such as thiazolidinediones (TZDs). Carrots have shown to contain bioactive acetylenic oxylipins that are partial agonists of the peroxisome proliferator‐activated receptor γ (Pparg) that mimic the antidiabetic effect of TZDs without any adverse effects. TZDs exert hypoglycemic effects through activation of Pparg and through the regulation of the gut microbiota (GM) producing short‐chain fatty acids (SCFAs), which impact glucose and energy homeostasis, promote intestinal gluconeogenesis, and influence insulin signaling pathways. This study investigated the metabolic effects of carrot intake in a T2D mouse model, elucidating underlying mechanisms. Mice were fed a low‐fat diet (LFD), high‐fat diet (HFD), or adjusted HFD supplemented with 10% carrot powder for 16 weeks. Oral glucose tolerance tests were conducted at weeks 0 and 16. Fecal, cecum, and colon samples, as well as tissue samples, were collected at week 16 during the autopsy. Results showed improved oral glucose tolerance in the HFD carrot group compared to HFD alone after 16 weeks. GM analysis demonstrated increased diversity and compositional changes in the cecum of mice fed HFD with carrot relative to HFD. These findings suggest the potential effect of carrots in T2D management, possibly through modulation of GM. Gene expression analysis revealed no significant alterations in adipose or muscle tissue between diet groups. Further research into carrot‐derived bioactive compounds and their mechanisms of action is warranted for developing effective dietary strategies against T2D.

Background Existing evidence for associations of per- and polyfluoroalkyl substances (PFASs) with blood lipids, lipoproteins and apolipoproteins (apo), and coronary heart disease (CHD) risk is limited and inconsistent. This study aims to explore associations between plasma PFASs, blood lipoprotein subspecies defined by apolipoproteins, and CHD risk. Methods A case–control study of CHD was conducted in the Health Professionals Follow-Up Study (HPFS) and Nurses' Health Study (NHS). Among participants initially free of cardiovascular disease at blood collection in 1994 (HPFS) or 1990 (NHS), 101 participants who developed non-fatal myocardial infarction or fatal CHD were identified and confirmed. A healthy control was matched to each case for age, smoking status, and date of blood draw. Plasma levels of perfluorohexane sulfonic acid (PFHxS), perfluorooctanoic acid (PFOA), total perfluorooctane sulfonic acid (PFOS), branched PFOS (brPFOS), linear PFOS (nPFOS), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA) were measured. Conditional logistic regression and cubic spline regression models were used to examine associations between baseline PFASs and CHD risk. Linear regression models were applied to study PFAS associations with lipids and their subfractions. Results After multivariate adjustments, total PFOS, brPFOS and nPFOS were significantly associated with increased risk of developing CHD, and HRs (95% CIs) per log(ng/mL) increment of PFASs were 3.66 (1.36–9.89), 3.68 (1.55–8.76), and 3.01 (1.16–7.86), respectively. Significant positive dose–response relationships were identified for these PFASs (Plinearity = 0.01, 0.002, 0.02, respectively). Other PFASs were not associated with CHD risk. PFNA and PFDA were positively associated with total apoE levels among HDL particles with or without apoC-III. No associations were observed for other PFASs with blood lipid subspecies. Blood lipid subfractions did not explain the association between PFOS and CHD risk. Conclusions Plasma PFOS and its isomers were positively associated with CHD risk. These findings suggest that PFOS exposure causes public health risks that are greater than hitherto believed.

Objective: To explore if experience with hearing aid (HA) amplification affects speech-evoked cortical potentials reflecting comprehension abilities. Design: N400 and late positive complex (LPC) responses as well as behavioural response times to congruent and incongruent digit triplets were measured. The digits were presented against stationary speech-shaped noise 10 dB above individually measured speech recognition thresholds. Stimulus presentation was either acoustic (digits 1-3) or first visual (digits 1-2) and then acoustic (digit 3). Study sample: Three groups of older participants (N = 3 × 15) with (1) pure-tone average hearing thresholds <25 dB HL from 500-4000 Hz, (2) mild-to-moderate sensorineural hearing loss (SNHL) but no prior HA experience, and (3) mild-to-moderate SNHL and >2 years of HA experience. Groups 2-3 were fitted with test devices in accordance with clinical gain targets. Results: No group differences were found in the electrophysiological data. N400 amplitudes were larger and LPC latencies shorter with acoustic presentation. For group 1, behavioural response times were shorter with visual-then-acoustic presentation. Conclusion: When speech audibility is ensured, comprehension-related electrophysiological responses appear intact in individuals with mild-to-moderate SNHL, regardless of prior experience with amplified sound. Further research into the effects of audibility versus acclimatisation-related neurophysiological changes is warranted.

Alkyl phosphonates are important motifs in medicinal chemistry, yet their efficient synthesis by direct C(sp³)−H functionalization remains a challenge. Here, we report straightforward access to benzylic phosphonates by direct C(sp³)−H functionalization in a cross‐dehydrogenative‐coupling reaction between non‐specialized alkylarenes and unfunctionalized phosphites. Notably, the C−H substrates are used as the limiting reagents. The scope of benzylic C−H substrates is broad, and the mild reaction conditions allow for good functional group tolerance. Mechanistic studies indicate that the reaction proceeds via a radical pathway rather than the cationic pathway followed for specialized benzylic C−H substrates in previous methods.