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Abstract Background Worldwide, peers support has been shown to play a crucial role in supporting people with mental illness in their personal recovery process and return to everyday life. Qualitiative studies underpinning the mechanisms of change in peer support has been reviewed. However, the findings are primeraly based on the perspectives of peer support workers employed in mental health services. Thus, qualitiative studies elucidating the mechanisms of change from the recipient perspective in mental health service independent civil society settings are higly needed to further contribute to the evidence of peer support. The ‘Paths to every day life’ (PEER) is evaluated in a randomized trial and is substantiated by qualitative studies investigating the experiences of PEER from the perspectives of the recipients and the facilitators of peer support. The purpose of this qualitative study underpinned by critical realism was to substantiate the PEER intervention program theory by gaining deeper insight into the change mechanisms and elaborate how, when, and under what circumstances the peer support groups potentially had or did not have an impact on personal recovery from the perspectives of the recipients of peer support. Methods Eleven individuals were interviewed at the end of the ten-week group course. The semi-structured realist-inspired interviews were audio recorded and transcribed verbatim. The analysis was guided by reflective thematic analysis and through an abductive framework based on the program theory. Data were coded and analysed in Nvivo software. Results Four overarching themes were identified that informed and nuanced the program theory: 1) Connectedness as a prerequisite for engagement; 2) A sense of hope by working out new paths to recovery; 3) Seeing new sides of oneself; and 4) Sprout for change. Conclusions This study substantiates the program theory and the quantitative results of the PEER trial by elaborating on mechanisms that were felt to be essential for the personal recovery process from the perspectives of the recipients of the group-based peer support. In addition, the study points out that the opportunities to act in everyday life depended on individual context and where the group participants were on their recovery journey. Trial registration ClinicalTrials.gov identifier: NCT04639167.

Abstract Background Diabetes-related lower extremity complications such as diabetic foot ulcer (DFU) are a global disability burden. Treatment and care for patients with DFU call for a multisectoral approach that incorporates interdisciplinary care pathways. We aimed to explore the interplay between patients with DFU and healthcare professionals in cross-sectoral settings that address treatment and care and to determine “what works, for whom, and under what circumstances”. Method The study was designed as a realistic evaluation. The data were generated from September 2022 to March 2023 and drew upon approximately 60 h of participant observation of 14 patients during the treatment and care of DFUs in their homes (primary care) and/or at outpatient clinics (wound specialist clinics in a hospital setting) in a Danish cross-sectoral setting. The Standards for Reporting Qualitative Research (SRQR) were applied in this study. Results We identified three illuminating themes that described the interplay between patients with DFU and related healthcare professionals representing both primary and secondary health care systems: (1) humour is a relationship-enhancing element between nurses and patients; (2) support from patients’ coping strategies promotes patient-centeredness and collaboration; and (3) patients and professionals occupy unnegotiated identity roles. Conclusion Our study led to a refined programme theory developed through the realistic evaluation process that allows us to propose an answer to the problem of “what works, for whom, and under what circumstances”. The interplay between patients with DFU and healthcare professionals in a cross-sectoral setting for treatment and care is characterised by the use of humour as a relation-enhancing element and by improving support for patient coping strategies, which encourages healthcare professionals to promote health literacy. Future research should examine strategies for negotiating identity roles between patients with DFU and healthcare professionals to enhance collaboration, patient health literacy, and health promotion in cross-sectoral healthcare settings.

Abstract Background Bilateral blood pressure (BP) measurement is important in cardiovascular prevention for identifying systolic interarm BP difference (IAD) and hypertension. We investigated sex-stratified IAD prevalence and its associations and coexistence with screen-detected peripheral atherosclerosis and hypertension. Furthermore, we determined the proportion misclassified as non-hypertensive when using the lower versus the higher reading arm. Methods This sub-study formed part of the Viborg Screening Program (VISP), a cross-sectorial population-based cardiovascular screening programme targeting 67-year-old Danes. VISP includes screening for peripheral atherosclerosis (lower extremity arterial disease and carotid plaque), abdominal aortic aneurysm, hypertension, diabetes mellitus, and cardiac disease. Self-reported comorbidities, risk factors, and medication use were also collected. Among 4,602 attendees, 4,517 (82.1%) had eligible bilateral and repeated BP measurements. IAD was defined as a systolic BP difference ≥ 10 mmHg. IAD-associated factors (screening results and risk factors) were estimated by logistic regression; proportional coexistence was displayed by Venn diagrams (screening results). Results We included 2,220 women (49.2%) and 2,297 men (50.8%). IAD was more predominant in women (26.8%) than men (21.0%) (p

Abstract Background Nonspecific discharge diagnoses after acute hospital courses represent patients discharged without an established cause of their complaints. These patients should have a low risk of adverse outcomes as serious conditions should have been ruled out. We aimed to investigate the mortality and readmissions following nonspecific discharge diagnoses compared to disease-specific diagnoses and assessed different nonspecific subgroups. Methods Register-based cohort study including hospital courses beginning in emergency departments across 3 regions of Denmark during March 2019–February 2020. We identified nonspecific diagnoses from the R- and Z03-chapter in the ICD-10 classification and excluded injuries, among others—remaining diagnoses were considered disease-specific. Outcomes were 30-day mortality and readmission, the groups were compared by Cox regression hazard ratios (HR), unadjusted and adjusted for socioeconomics, comorbidity, administrative information and laboratory results. We stratified into short (3–

Abstract Background In epilepsy, the ictal phase leads to cerebral hyperperfusion while hypoperfusion is present in the interictal phases. Patients with Alzheimer’s disease (AD) have an increased prevalence of epileptiform discharges and a study using intracranial electrodes have shown that these are very frequent in the hippocampus. However, it is not known whether there is an association between hippocampal hyperexcitability and regional cerebral blood flow (rCBF). The objective of the study was to investigate the association between rCBF in hippocampus and epileptiform discharges as measured with ear-EEG in patients with Alzheimer’s disease. Our hypothesis was that increased spike frequency may be associated with increased rCBF in hippocampus. Methods A total of 24 patients with AD, and 15 HC were included in the analysis. Using linear regression, we investigated the association between rCBF as measured with arterial spin-labelling MRI (ASL-MRI) in the hippocampus and the number of spikes/sharp waves per 24 h as assessed by ear-EEG. Results No significant difference in hippocampal rCBF was found between AD and HC (p-value = 0.367). A significant linear association between spike frequency and normalized rCBF in the hippocampus was found for patients with AD (estimate: 0.109, t-value = 4.03, p-value

Abstract The prevalence of hyperthyroidism and hypothyroidism and associated risk factors are unknown in liver transplant recipients. We aimed to determine the prevalence of hyperthyroidism and hypothyroidism and associated risk factors in liver transplant recipients and to compare it with controls from the general population. As part of the Danish Comorbidity in Liver Transplant Recipients (DACOLT) Study, all Danish liver transplant recipients over the age of 20 were invited for measurements of concentrations of thyrotropin and thyroid hormones. The prevalence of hyperthyroidism and hypothyroidism was compared to age- and sex-matched controls from the Copenhagen General Population Study. Using logistic regression adjusted for age, sex, smoking, and body-mass index, we investigated potential risk factors. We recruited 489 liver transplant recipients and 1808 controls. Among liver transplant recipients, 14 (2.9%) had hyperthyroidism compared with 21 (1.2%) of controls (adjusted odds ratio [aOR] 2.24, 95% confidence interval [CI] 1.05–4.75, P = 0.04), while 42 (5.7%) had hypothyroidism compared with 139 (7.7%) of controls (aOR 0.68, 95% CI 0.43–1.08, P = 0.10). Female sex, and autoimmune hepatitis and primary sclerosing cholangitis as causes of transplantation were associated with hyperthyroidism after adjustments. Age, female sex, and autoimmune liver diseases as cause of transplantation were associated with hypothyroidism after adjustments. DACOLT is registered in ClinicalTrials.gov (NCT04777032).

BackgroundFraction of exhaled nitric oxide with an expiratory flow of 50 mL/s (FENO50) is a biomarker of eosinophilic airway inflammation. Liver transplant recipients have an increased risk of pulmonary infections, but little is known about the burden of chronic pulmonary diseases in this group. We aimed to assess the prevalence of elevated FENO50 in liver transplant recipients and compare it to controls from the general population.MethodsFENO50 was measured in 271 liver transplant recipients from The Danish Comorbidity in Liver Transplant Recipients (DACOLT) study and 1,018 age- and sex-matched controls from The Copenhagen General Population Study (CGPS). Elevated FENO50 was defined as ≥25 or ≥50 parts per billion (ppb). The analyses were adjusted for known and suspected confounders.ResultsThe median age of the liver transplant recipients was 55 years (interquartile range (IQR) 46–64), and 58% were men. The liver transplant recipients had a higher median FENO50 than the controls [16 ppb (IQR 10–26) vs. 13 ppb (IQR 8–18.), p < 0.001]. Furthermore, the liver transplant recipients had a higher prevalence of elevated FENO50 (for FENO50 ≥25 ppb 27% vs. 11%, p < 0.001 and ≥50 ppb 4% vs. 2%, p = 0.02). The results were similar after adjusting for age, sex, smoking status, use of airway medication, and blood eosinophil counts [the adjusted odds ratio (OR) for FENO50 ≥25 ppb was 3.58 (95% CI: 2.50–5.15, p < 0.0001) and the adjusted OR for FENO50 ≥50 ppb was 3.14 (95% CI: 1.37–7.20, p = 0.007)].ConclusionThe liver transplant recipients had elevated FENO50, implying increased eosinophilic airway inflammation. The clinical impact of this finding needs further investigation.

Abstract Background Neuron-derived extracellular vesicles (NDEVs) in blood may be used to derive biomarkers for the effects of exercise in Alzheimer’s disease (AD). For this purpose, we studied changes in neuroprotective proteins proBDNF, BDNF, and humanin in plasma NDEVs from patients with mild to moderate AD participating in the randomized controlled trial (RCT) of exercise ADEX. Methods proBDNF, BDNF, and humanin were quantified in NDEVs immunocaptured from the plasma of 95 ADEX participants, randomized into exercise and control groups, and collected at baseline and 16 weeks. Exploratorily, we also quantified NDEV levels of putative exerkines known to respond to exercise in peripheral tissues. Results NDEV levels of proBDNF, BDNF, and humanin increased in the exercise group, especially in APOE ε4 carriers, but remained unchanged in the control group. Inter-correlations between NDEV biomarkers observed at baseline were maintained after exercise. NDEV levels of putative exerkines remained unchanged. Conclusions Findings suggest that the cognitive benefits of exercise could be mediated by the upregulation of neuroprotective factors in NDEVs. Additionally, our results indicate that AD subjects carrying APOE ε4 are more responsive to the neuroprotective effects of physical activity. Unchanged NDEV levels of putative exerkines after physical activity imply that exercise engages different pathways in neurons and peripheral tissues. Future studies should aim to expand upon the effects of exercise duration, intensity, and type in NDEVs from patients with early AD and additional neurodegenerative disorders. Trial registration The Effect of Physical Exercise in Alzheimer Patients (ADEX) was registered in ClinicalTrials.gov on April 30, 2012 with the identifier NCT01681602. Graphical abstract

Hyperpolarization with the dissolution dynamic nuclear polarization (dDNP) technique yields > 10,000-fold signal increases for NMR-active nuclei (e.g. 13C). Hyperpolarized 13C-labeled metabolic tracer molecules thus allow real-time observations of biochemical pathways in living cellular systems without interfering background. This methodology lends itself to the direct observation of altered intracellular reaction chemistry imparted for instance by drug treatment, infections, or other diseases. A reoccurring challenge for longitudinal cell studies of mammalian cells with NMR and dDNP-NMR is maintaining cell viability in the NMR spectrometer. 3D cell culture methods are increasing in popularity because they provide a physiologically more relevant environment compared to 2D cell cultures. Based on such strategies a mobile 3D culture system was devised. The clinical drug etoposide was used to treat cancer cells (HeLa) and the resulting altered metabolism was measured using hyperpolarized [1–13C]pyruvate. We show that sustaining the cell cultivation in cell incubators and only transferring the cells to the NMR spectrometer for the few minutes required for the dDNP-NMR measurements is an attractive alternative to cell maintenance in the NMR tube. High cell viability is sustained, and experimental throughput is many doubled.

Introduction: Impaired quality of life (QoL) and premature death in patients with primary non-affective psychotic disorders is related to lifestyle-induced comorbidities. Current municipal health-promoting treatment and care do not embrace the challenges of living with psychotic disorders. Aim: This cross-sectional study aimed to identify the proportion of outpatients diagnosed with primary psychotic disorders who need health-promoting treatment and care, and who receive municipal health-promoting interventions. Methods: Of 206 eligible invited outpatients from three psychiatric services clinics in Southern Denmark, 165 participated. Demographic and health characteristics, and use of alcohol, cannabis, drugs, and cigarettes were identified via a screening tool. Blood test information, body measurements, and medication status were extracted from the outpatients’ medical records. The need for health promotion was assessed based on body mass index (BMI), and use of alcohol, cannabis, drugs, and cigarettes. Results: Seventy-three percent of outpatients needed health promotion, of whom 61 % were not offered municipal health-promoting treatment and care. Thirty-six percent had one or more somatic comorbidities, including diabetes mellitus (15 %) and cardiovascular disease (10 %); 41 % smoked a mean (SD) of 19 (10) cigarettes daily. Mean (SD) BMI was 34 (8) kg/m2 for women and 29 (7) kg/m2 for men. Conclusion: The majority of outpatients with non-affective psychotic disorders need health-promoting interventions, but only about 40 % of these patients receive such municipal health-promoting treatment and care. Future studies should clarify the impact of these interventions on the health status, QoL, and life expectancy of these patients.

Abstract Accurate large‐scale soil moisture (SM) maps are crucial for catchment‐scale hydrological models used for water resource management and warning systems for droughts, floods, and wildfires. SM can be mapped by mobile cosmic‐ray neutron (CRN) systems of moderated detectors at homogeneous landscapes of similar soil and vegetation. In this study, we present a new approach for mobile CRN detection to perform to its full potential, where CRN measurements can also be converted to SM at heterogeneous landscapes. The approach is based solely on thermal and epithermal neutron datasets obtained from mobile dual‐spectra CRN detection, combined with theoretical developments using a particle transport model. For each measurement point, the land cover type is identified using the thermal‐to‐epithermal (T/E) ratio, and the relevant neutron‐count‐to‐soil‐moisture conversion function is estimated from CRN stations located at the main land cover types in the catchment. With this approach, the requirement of collecting 100+ soil samples for each point along the survey route is omitted. We use this T/E‐dependent approach to obtain SM maps from 12 CRN surveys and compare it with a simple approach where only the conversion function from the agricultural site is used. SM by the simple approach is comparable to the estimates of the agricultural stations of a capacitance sensor network, while the estimates of the T/E‐dependent approach also compare well with the heathland and forest stations. With accurate SM estimates for all landcover types, the average error is reduced from 0.089 to 0.038 when comparing CRN SM with space‐borne Soil Moisture Active Passive Mission estimates.

ABSTRACT Staphylococcus aureus (S. aureus) represents a major clinical challenge due to its explicit capacity to select mutations that increase antibiotic resistance and immune evasion. However, the molecular mechanisms are poorly defined, especially for adaptive immunity. Cancer immunotherapy targeting programmed cell death protein 1 (PD-1) enhances T-cell activity and is emerging for the treatment of certain viral infections, while its potential against bacterial infections remains elusive. We show that an S. aureus clpP mutant, selected during clinical antibiotic therapy, inhibits T-cell activity by directly interacting with PD-1 on human T cells. Specificity of the interaction was confirmed using recombinant PD-1, as well as PD-1 overexpressing and knock out cells. Moreover, the PD-1-binding S. aureus inhibited intracellular calcium mobilization, T-cell proliferation, CD25 expression, and IL-2 secretion, while the key effects were alleviated by antibody-mediated PD-1 blockade using an engineered IgG1-based anti-PD-1 antibody. Our results suggest that clpP mutant S. aureus directly targets PD-1 to evade immune activation and that therapeutic targeting of PD-1 may be used against certain staphylococcal infections. IMPORTANCE Therapies that target and aid the host immune defense to repel cancer cells or invading pathogens are rapidly emerging. Antibiotic resistance is among the largest threats to human health globally. Staphylococcus aureus (S. aureus) is the most common bacterial infection, and it poses a challenge to the healthcare system due to its significant ability to develop resistance toward current available therapies. In long-term infections, S. aureus further adapt to avoid clearance by the host immune defense. In this study, we discover a new interaction that allows S. aureus to avoid elimination by the immune system, which likely supports its persistence in the host. Moreover, we find that blocking the specific receptor (PD-1) using antibodies significantly relieves the S. aureus-imposed inhibition. Our findings suggest that therapeutically targeting PD-1 is a possible future strategy for treating certain antibiotic-resistant staphylococcal infections.

IntroductionWith no cure or effective treatment, the prevalence of patients with Alzheimer’s disease (AD) is expected to intensify, thereby increasing the social and financial burden on society. Light-based 40 Hz brain stimulation is considered a novel treatment strategy for patients with AD that may alleviate some of this burden. The clinical trial ALZLIGHT will utilize a novel Light Therapy System (LTS). The LTS uses Invisible Spectral Flicker for non-invasive induction of 40 Hz neural activity. This protocol describes a trial evaluating the efficacy and safety of a light-based 40 Hz brain stimulation in patients with mild-to-moderate AD.Methods62 patients with mild-to-moderate AD will participate in a randomized, double-blinded, placebo-controlled, parallel-group, and single-center trial. The participants will partake in an enrollment period of 1 month, an intervention period of 6 months, and a 1.5-month post-interventional follow-up period. Prior to the baseline measurement (week 0), the patients will be randomized to either active or placebo intervention from baseline (week 0) to post-intervention follow-up (week 26).DiscussionThis protocol describes a randomized, double-blinded, placebo-controlled clinical trial that may increase the understanding of the effect of gamma oscillations in the human brain and how it could be utilized as a novel and important tool for the treatment of AD. The effect is measured through a large, multidisciplinary assessment battery.Clinical trial registration:www.ClinicalTrials.gov, (NCT05260177). Registered on March 2, 2022.

Notch signaling is crucial for pancreatic cell fate choice. With mathematical modeling and experiments, Xu et al. provides new insights into how different Notch ligands and Hes1 oscillation guide the spatial-temporal dynamics of cell differentiation.

OBJECTIVES: The aim of this study was to analyze whether individuals reporting exposure to workplace bullying had a higher risk of suicidal behavior, including both suicide attempt and death by suicide, than those not reporting such exposure. METHODS: Using a prospective cohort study design, we linked data from nine Danish questionnaire-based surveys (2004–2014) to national registers up to 31 December 2016. Exposure to workplace bullying was measured by a single item. Suicide attempts were identified in hospital registers and death by suicide in the Cause of Death Register. Among participants with no previous suicide attempts, we estimated hazard ratios (HR) and 95% confidence intervals (CI), adjusting for sex, age, marital status, socioeconomic status, and history of psychiatric morbidity. RESULTS: The sample consisted of 98 330 participants (713 798 person-years), 63.6% were women, and the mean age was 44.5 years. Of these participants, 10 259 (10.4%) reported workplace bullying. During a mean follow-up of 7.3 years, we observed 184 cases of suicidal behavior, including 145 suicide attempts, 35 deaths by suicide and 4 cases that died by suicide after surviving a suicide attempt. The fully-adjusted HR for the association between workplace bullying and suicidal behavior was 1.65 (95% CI 1.06–2.58). The HR for suicide attempts and death by suicide were 1.65 (1.09–2.50) and 2.08 (0.82–5.27), respectively. Analyses stratified by sex showed a statistically significant association between workplace bullying and suicidal behavior among men but not women. CONCLUSIONS: The results suggest that exposure to workplace bullying is associated with an elevated risk of suicidal behavior among men.

Abstract Background The number of people struggling with vulnerability to mental health difficulties is increasing worldwide, and there is a need for new interventions, to prevent more people from developing serious mental illnesses. In recent years, peer support has been suggested as a key element in creating person-centered interventions in mental health services. However, the evidence for peer support is not yet established. We aim to investigate the effect of a 10-week peer-support intervention “Paths to EvERyday life” (PEER) added to service as usual (SAU) versus SAU alone in a Danish municipality setting. Methods A two-armed, investigator-initiated, multi-municipal, parallel-group superiority trial to investigate the effectiveness of the PEER intervention added to SAU compared to SAU alone. A total of 284 participants will be recruited from the municipal social services in the participating municipalities and by self-referrals and randomly assigned to (1) the PEER intervention added to SAU or (2) SAU. The primary outcome is a self-assessed personal recovery (Questionnaire about the process of recovery (QPR-15)) at end of the intervention. The secondary outcomes are self-assessed empowerment (Empowerment Scale Rogers (ESR)), quality of life (The Manchester Short Assessment of Quality of life (MANSA)), and functioning (Work and Social Adjustment Scale (WSAS)). Discussion This trial will test a new community-based peer-support intervention, and if the intervention proves to be effective, the goal is that future integration of this intervention will improve individual recovery and mental health and reduce the societal burden of individuals seeking municipal social support and/or mental health services. Trial registration ClinicalTrials.gov NCT04639167. Registered on Nov. 19, 2020.

Background: In patients with Alzheimer's disease (AD) without clinical seizures, up to half have epileptiform discharges on long-term in-patient electroencephalography (EEG) recordings. Long-term in-patient monitoring is obtrusive, and expensive as compared to outpatient monitoring. No studies have so far investigated if long-term outpatient EEG monitoring is able to identify epileptiform discharges in AD. Our aim is to investigate if epileptiform discharges as measured with ear-EEG are more common in patients with AD compared to healthy elderly controls (HC). Methods: In this longitudinal observational study, 24 patients with mild to moderate AD and 15 age-matched HC were included in the analysis. Patients with AD underwent up to three ear-EEG recordings, each lasting up to two days, within 6 months. Results: The first recording was defined as the baseline recording. At baseline, epileptiform discharges were detected in 75.0% of patients with AD and in 46.7% of HC (p-value = 0.073). The spike frequency (spikes or sharp waves/24 h) was significantly higher in patients with AD as compared to HC with a risk ratio of 2.90 (CI: 1.77–5.01, p

Abstract Background As people living with HIV (PLWH) are growing older, there is increased incidence of metabolic diseases, including type 2 diabetes mellitus, for which insulin resistance is a key determinant. In this study, we aimed to investigate risk factors associated with insulin resistance in PLWH. Methods We included well-treated PLWH without hepatitis co-infection, and with available fasting serum insulin and plasma glucose (n = 643) from the Copenhagen Comorbidity in HIV Infection Study. Insulin resistance was calculated using the homeostasis model assessment of insulin resistance (HOMA-IR). We investigated the association between risk factors and high HOMA-IR in a logistic regression model adjusted for age, sex, abdominal obesity, smoking status, and origin. When including use of thymidine analogues and/or didanosine in the model, we also adjusted for time with HIV. Results Median (IQR) age of PLWH was 52 years (46–61), and 87% (n = 557) were male. Median (IQR) HOMA-IR was 1.86 (1.23–3.14) mmol/L × mU/L. Risk factors significantly associated with high HOMA-IR included older age, BMI ≥ 25, abdominal obesity, waist circumference, use of thymidine analogues and/or didanosine, time with HIV, and CD4+ nadir

Abstract Background Monocytes play an important role in inflammation, and monocytosis and monocyte activation are features of chronic inflammation. We aimed to investigate if HIV status was associated with monocyte count and monocyte activation and to assess the relationship between monocyte count and monocyte activation markers and HIV-related factors. Methods Persons living with HIV (PLWH) with measured monocyte count and sCD14 and sCD163 were included from the Copenhagen Comorbidity in HIV infection (COCOMO) study and matched 1:5 on sex and age with uninfected controls. In addition, 74 uninfected individuals from COCOMO with measured sCD14 and sCD163 were included. Identical protocols and equipment were used to determine monocyte counts and monocyte activation in PLWH and uninfected controls. Linear regression adjusted for age, sex, smoking and waist-to-hip-ratio was used to analyze the association between possible risk factors and monocyte outcomes. Results We included 871 PLWH and 4355 uninfected controls. PLWH had − 0.021 [− 0.031 − 0.011] × 109/L) lower monocyte count than uninfected controls, and in adjusted analyses HIV status was independently associated with − 0.035 [− 0.045, − 0.025] × 109/L lower monocyte count. In contrast, PLWH had higher sCD163 and sCD14 concentrations than uninfected controls. After adjustment, HIV-status was associated with higher sCD14 and sCD163 concentrations (588 [325, 851] ng/ml, and 194 [57, 330] ng/ml, respectively). Conclusion PLWH had lower monocyte counts than controls, but the absolute difference was small, and any clinical impact is likely limited. In contrast, concentrations of monocyte activation markers, previously implicated as drivers of non-AIDS comorbidity, were higher in PLWH than in controls.

Multiomics technologies improve the biological understanding of health status in people living with HIV on antiretroviral therapy (PWH). Still, a systematic and in-depth characterization of metabolic risk profile during successful long-term treatment is lacking. Here, we used multi-omics (plasma lipidomic, metabolomic, and fecal 16 S microbiome) data-driven stratification and characterization to identify the metabolic at-risk profile within PWH. Through network analysis and similarity network fusion (SNF), we identified three groups of PWH (SNF-1–3): healthy (HC)-like (SNF-1), mild at-risk (SNF-3), and severe at-risk (SNF-2). The PWH in the SNF-2 (45%) had a severe at-risk metabolic profile with increased visceral adipose tissue, BMI, higher incidence of metabolic syndrome (MetS), and increased di- and triglycerides despite having higher CD4+ T-cell counts than the other two clusters. However, the HC-like and the severe at-risk group had a similar metabolic profile differing from HIV-negative controls (HNC), with dysregulation of amino acid metabolism. At the microbiome profile, the HC-like group had a lower α-diversity, a lower proportion of men having sex with men (MSM) and was enriched in Bacteroides. In contrast, in at-risk groups, there was an increase in Prevotella, with a high proportion of MSM, which could potentially lead to higher systemic inflammation and increased cardiometabolic risk profile. The multi-omics integrative analysis also revealed a complex microbial interplay of the microbiome-associated metabolites in PWH. Those severely at-risk clusters may benefit from personalized medicine and lifestyle intervention to improve their dysregulated metabolic traits, aiming to achieve healthier aging.

Introduction The prevalence of cardiovascular disease (CVD) is increasing. Furthermore, asymptomatic individuals may not receive timely preventive initiatives to minimise the risk of further CVD events. Paradoxically, 80% of CVD events are preventable by early detection, followed by prophylactic initiatives. Consequently, we introduced the population-based Viborg Screening Programme (VISP) for subclinical and manifest CVD, focusing on commonly occurring, mainly asymptomatic conditions, followed by prophylactic initiatives.The aim of the VISP was to evaluate the health benefits, harms and cost-effectiveness of the VISP from a healthcare sector perspective. Furthermore, we explored the participants’ perspectives.Methods and analysis From August 2014 and currently ongoing, approximately 1100 men and women from the Viborg municipality, Denmark, are annually invited to screening for abdominal aortic aneurysm, peripheral arterial disease, carotid plaque, hypertension, diabetes mellitus and cardiac arrhythmia on their 67th birthday. A population from the surrounding municipalities without access to the VISP acts as a control. The VISP invitees and the controls are followed on the individual level by nationwide registries. The primary outcome is all-cause mortality, while costs, hospitalisations and deaths from CVD are the secondary endpoints.Interim evaluations of effectiveness and cost-effectiveness are planned every 5 years using propensity score matching followed by a Cox proportional hazards regression analysis by the ‘intention-to-treat’ principle. Furthermore, censoring-adjusted incremental costs, life-years and quality-adjusted life-years are estimated. Finally, the participants’ perspectives are explored by semistructured face-to-face interviews, with participant selection representing participants with both negative and positive screening results.Ethics and dissemination The VISP is not an interventional trial. Therefore, approval from a regional scientific ethical committee is not needed. Data collection from national registries was approved by the Regional Data Protection Agency (record no. 1-16-02-232-15). We ensure patient and public involvement in evaluating the acceptability of VISP by adopting an interviewing approach in the study.Trial registration number NCT03395509.

IntroductionPeople living with HIV (PLWH) are at twice the risk of developing cardiovascular diseases and have more than four times higher odds of aortic aneurysm (AA) than the uninfected population. However, biomarkers of AA in PLWH are yet to be discovered. We aimed to investigate whether circulating biomarkers reflecting platelet activation, hemostasis and endothelial disruption, i.e. sCD40L, D-dimer, syndecan-1, and thrombomodulin, were associated with AA in PLWH.MethodsFive hundred seventy one PLWH from the Copenhagen Comorbidity in HIV Infection (COCOMO) study ≥40 years of age with an available contrast-enhanced CT scan as well as available biomarker analyses were included. The biomarkers were analyzed on thawed plasma. For each biomarker, we defined high level as a concentration in the upper quartile and low level as a concentration below the upper quartile. For D-dimer, the cut-off was defined as the lower limit of detection. Using unadjusted and adjusted logistic and linear regression models, we analyzed associations between AA and sCD40L, D-dimer, syndecan-1, and thrombomodulin, respectively in PLWH.ResultsPLWH had median (IQR) age 52 years (47-60), 88% were male, median (IQR) time since HIV diagnosis was 15 years (8-23), and 565 (99%) were currently on antiretroviral treatment. High level of sCD40L was associated with lower odds of AA in both unadjusted (odds ratio, OR, 0.23 (95% CI 0.07-0.77; P=0.017)) and adjusted models (adjusted OR, aOR, 0.23 (95% CI 0.07-0.78; P=0.019)). Detectable level of D-dimer was associated with higher odds of AA in both unadjusted (OR 2.76 (95% CI 1.34-5.67; P=0.006)) and adjusted models (aOR 2.22 (95% CI 1.02-4.85; P=0.045)).ConclusionsSCD40L was associated with lower odds of AA whereas D-dimer was independently associated with higher odds of AA in PLWH. This calls for further investigations into specific biomarkers to aid early diagnosis of AA in PLWH.

The transportation sector is gradually evolving to become independent of fossil fuels. Here, the authors report a metal-based monolithic solid oxide fuel cell with a power density of 5.6 kW/L suitable for transport applications.

In Denmark, a 10-year plan for psychiatry has been agreed on. The content of the plan was developed in collaboration between the Danish Health Authority and the Danish Authority for Social Services and Housing, and it involved many stakeholders. Recently, the government presented a planned investment that would increase the overall budget in Danish regions and municipalities by almost 20 percent over a 10-year period. Epidemiological research demonstrating shortened life expectancy and high levels of burden of disease for people with mental disorders contributed to emphasizing the need for improvement of psychiatric services. User organizations, trade unions, and scientific societies in the field of mental health were unified in a common organization, called the Psychiatry Alliance, and this alliance agreed on common action points and acted together to influence politicians. An assertive approach toward politicians and media was pivotal, and being a first mover and presenting tentative budgets was very influential.