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Abstract Background Engagement in Non-Suicidal Self-Injury (NSSI) is high among adolescents with borderline personality disorder (BPD), but the trajectory of NSSI in the transition period from adolescence to adulthood is unclear, and studies that look at predictors of persistence are highly needed. Methods This study followed 111 adolescents aged 14–17 with BPD over a five-year period to observe the prevalence and predictors of NSSI. Information on NSSI was based on both self-report and clinician-administered interviews. Results At the outset, 92.8% reported a history of NSSI, with an average of nearly five different types of NSSI. Despite this high initial prevalence, the rates of NSSI within the past two weeks decreased over time from 48% at baseline to 26% after one year, and further to 10% after two years. After five years, 37% reported engaging in NSSI within the past six months. Notably, all but one participant who reported NSSI after five years had engaged in NSSI already at baseline. The study identified that higher adolescent-rated but lower parent-rated BPD severity was associated with engagement in NSSI at baseline. Furthermore, ongoing NSSI after five years was predicted by lower parent-rated BPD severity and externalizing behaviors. Conclusions NSSI is frequent in the early course of BPD, and persists in more than one-third after five years. Our findings highlight that baseline engagement in NSSI is a risk factor for persistence of NSSI in the transition period into early adulthood. Furthermore, the findings underscore the significance of integrating both adolescent and parent perspectives on BPD pathology in the assessment and management of NSSI.

Abstract Community-acquired pneumonia (CAP) in chronic obstructive pulmonary disease (COPD) often result in sudden and persistent reduction in health-related quality of life (HRQoL), which may be alleviated with palliative care. Among individuals with COPD, we aimed to investigate potential associations between HRQoL at admission with CAP and the risk of re-hospitalization and mortality and potential associations between specific HRQoL domains and CAP treatment outcomes. HRQoL was assessed at admission and the participants were grouped into tertiles based on the HRQoL utility index and specific domains. The results revealed that participants in the middle and highest tertiles of HRQoL had a lower 90-day re-hospitalization risk compared to those in the lowest tertile, whereas no differences in re-hospitalization risk were observed 30 and 180 days after discharge. Almost one in four had severe pain or discomfort at admission and the domain pain or discomfort emerged as a predictor of re-hospitalization. In addition, participants in the middle and highest tertiles had lower risk of 180-day mortality compared to those in the lowest, while no differences were observed in 30-day or 90-day mortality risk. An increased focus on in-hospital palliative care could alleviate the pain and discomfort reported by many participants with potential to reduce re-hospitalization rates.

Abstract Background Diabetes affects 10.5% of adults globally, with type 2 diabetes accounting for 90–95% of cases. Achieving optimal glycemic control is crucial yet challenging, particularly with insulin therapy, where 30–50% of patients fail to meet treatment targets. Telemedicine can improve diabetes management but generates vast amounts of data, burdening healthcare professionals. Integrating clinical decision support tools into telemonitoring systems may enhance care efficiency and glycemic control. Methods The trial is a multicenter 3-month, three-arm, open-label, randomized controlled trial. The trial aims to enroll 51 participants with type 2 diabetes on insulin therapy. Participants will be divided with a 3:1:1 ratio into telemonitoring with decision support, telemonitoring without decision support, and usual care groups. The study employs connected insulin pens, continuous glucose monitors (CGMs), and activity trackers to enable telemonitoring. Outcomes measured include CGM time in range, HbA1c, hypo- and hyperglycemia incidents, total daily insulin dose, body weight, treatment satisfaction, and adherence. Discussion Telemonitoring with decision support has the potential to revolutionize diabetes management by offering personalized treatment suggestions, thereby reducing the burden on healthcare professionals, and improving patient outcomes. This study will provide valuable insights into the effectiveness of such an approach in achieving glycemic control in people with type 2 diabetes on insulin therapy. By evaluating both clinical outcomes and patient and healthcare professionals’ satisfaction, the study aims to contribute to the development of efficient, scalable telehealth solutions for diabetes care. Trial registration ClinicalTrials.gov NCT06185296. Registered on December 14, 2023.

Abstract Fungal infections pose a great threat to public health and there are only four main types of antifungal drugs, which are often limited with toxicity, drug-drug interactions and antibiotic resistance. Streptomyces is an important source of antibiotics, represented by the clinical drug amphotericin B. Here we report the discovery of alligamycin A (1) as an antifungal compound from the rapamycin-producer Streptomyces iranensis through genome-mining, genetics and natural product chemistry approaches. Alligamycin A harbors a unique chemical scaffold with 13 chiral centers, featuring a β-lactone moiety, a [6,6]-spiroketal ring, and an unreported 7-oxo-octylmalonyl-CoA extender unit incorporated by a potential crotonyl-CoA carboxylase/reductase. It is biosynthesized by a type I polyketide synthase which is confirmed through CRISPR-based gene editing. Alligamycin A displayed potent antifungal effects against numerous clinically relevant filamentous fungi, including resistant Aspergillus and Talaromyces species. β-Lactone ring is essential for the antifungal activity since alligamycin B (2) with disruption in the ring abolished the antifungal effect. Proteomics analysis revealed alligamycin A potentially disrupts the integrity of fungal cell walls and induces the expression of stress-response proteins in Aspergillus niger. Discovery of the potent antifungal candidate alligamycin A expands the limited antifungal chemical space.

Abstract Background To examine whether weekday-to-weekend sleep duration (WWD) difference and specific WWD patterns are associated with mental and somatic health and academic performance in a student population. Methods This study utilized cross-sectional data from the SHoT-2018 survey which includes responses from 50,054 full-time university/college students in Norway. Participants completed online questionnaires and reported sleep duration separately for weekdays and weekends. Medium sleep duration was defined as 7 to 9 h, short sleep duration as 9 h. Regression analyses were used to examine whether the degree and patterns of WWD was associated with health-related outcomes and academic performance. Results The mean age of the sample was 23.2 years and comprised of 68.8% women. Most students (81.7%) slept longer on weekends compared to weekdays and 30.0% of the students reported a mean sleep duration shorter than 7 h. WWD difference was positively associated with higher odds of overweight/obesity, dissatisfaction with life, psychological distress, somatic burden and failed study exam. Concerning WWD patterns, the odds of students reporting unfavorably on the outcomes were particularly high for those who slept short on both weekdays and weekends, while those who slept short on weekdays seemed to benefit from sleeping longer (“catching up”) on weekends. Conclusions Overall, WWD was associated with adverse health outcomes for students. Short sleep duration both on weekday and weekend was associated with the most detrimental outcomes in terms of health and academic performance, while sleeping in on weekends may alleviate some of the detriments.

Frederik Østergaard Klit,1,2 Jakob Dal,1– 3 Stine Linding Andersen,1,4 Amar Nikontovic,3 Peter Vestergaard,2,3 Jesper Scott Karmisholt1,2 1Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; 2Department of Endocrinology, Aalborg University Hospital, Aalborg, Denmark; 3Steno Diabetes Center North Denmark, Aalborg, Denmark; 4Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, DenmarkCorrespondence: Frederik Østergaard Klit, Email f.klit@rn.dkPurpose: Graves’ disease (GD) is one of the most common causes of thyrotoxicosis. It has been proposed to identify incident GD by using the GD-specific code, E05.0, of the 10th revision of the International Classification of Disease (ICD-10) in the Danish National Patient Register (DNPR). We aimed to report the incidence of GD and to investigate the validity and completeness of E05.0 registration using Aalborg University Hospital (AaUH) as a single centre-sample.Patients and Methods: The study included registry data from 2020 to 2022. The study population (n=2,893) comprised all people (15– 99 years) in the catchment area of AaUH (n=244,872) with either positive anti-thyroid stimulating hormone receptor antibodies (TRAb), or registered with a thyroid disease related ICD-10 code E03.0-E07.9, O99.2 or O90.5 at the Department of Endocrinology, AaUH. To identify incident cases, all subjects occurring for the first time in 2020 were excluded (n=2,339). The incident subjects were categorized into a general practice (n=63) or hospital care group (n=491) and underwent GD verification by biochemical tests and thyroid imaging. Validity was evaluated by positive (PPV) and negative (NPV) predictive values and completeness of E05.0 registration was estimated to the total number of verified GD subjects in hospital care only and in overall (groups combined).Results: One hundred thirty-one incident GD subjects were identified corresponding to an incidence of 26.8 per 100,000/year. E05.0 had a PPV of 90% [95% CI: 81;96] and a NPV of 90% [95% CI: 85;93] to identify incident cases of GD. Completeness was estimated to be 73% [95% CI: 63;82] in hospital care and 50– 60% [95% CI: 41;68] in overall.Conclusion: We report on a similar incidence of GD as previous studies in Denmark. Despite a high PPV, incident cases of GD could not adequately be identified by E05.0 in DNPR due to low completeness. Researchers should rely on biochemical test results to identify incident GD.Keywords: E05.0, epidemiology, hyperthyroid disease, validation, ICD, DNPR

Summary: Background & aims: Accurate fat mass (FM) and muscle mass (MM) assessment is an informative marker of an individual's health. However, the optimal method for assessing body composition in transgender men remains to be determined. Here, we aim to compare body composition estimates in transgender men by bioimpedance analysis (BIA) using the reference settings for “males” and “females” and by dual x-ray absorptiometry (DXA) scans. Methods: We conducted a cross-sectional pilot study investigating the body composition of 10 transgender men undergoing hormonal therapy using BIA and DXA scans. Results: BIA yielded significantly different estimates of body composition depending on the use of either “female” or “male” settings (P

ABSTRACT: Milk production and overall dairy farm economics depend on rearing dairy heifers. This study investigated the presence of a genotype by environment interaction in Holstein (HOL), Nordic Red dairy cattle (RDC), and their F1 crossbreeds (HOL × RDC) when provided different feed rations. The aim of our study was to assess how different energy concentrations in feed rations affect growth, BCS, feed intake, and feed efficiency in the 3 groups during the prepubertal period. The 3 breed groups were randomly allocated to receive either a standard or a low-energy feed ration. Holstein heifers exhibited reduced growth and a lower BCS when they were fed the low-energy feed ration. In contrast, the RDC heifers demonstrated similar growth rates with the different feed rations and maintained similar BCS irrespective of feed energy concentration. The HOL × RDC crossbred heifers performed as an intermediate between the HOL and RDC groups. Significant differences were observed in DMI and energy intake in the HOL and HOL × RDC groups depending on feed ration treatment. The RDC heifers had similar feed intake irrespective of treatment. There were no significant differences in the feed conversion ratio among breeds and feed treatments. These results indicate the presence of a genotype by environment interaction in prepubertal HOL and RDC heifers in response to differences in feed ration treatment. Due to the influence of prepubertal growth on future milk production, reproduction, and health status, it is important to be aware of breed-specific requirements during the prepubertal period, particularly in mixed breed and crossbred groups, to optimize growth rates and production potential.

Background Antibiotic prescription rates can be affected by pandemic measures such as lockdowns, social distancing, and remote consultations in general practice. Therefore, such emergency states may negatively affect antimicrobial stewardship, specifically in out-of-hours (OOH) primary care. As contact patterns changed in the COVID-19 pandemic, it would be relevant to explore the impact on antimicrobial stewardship.Aim To study the impact of the pandemic on antibiotic prescription rates in OOH primary care, overall and per age group.Methods This cross-sectional register-based study used routine data from OOH primary care in the Central Denmark Region. We included all patient contacts in two equivalent time periods: pre-pandemic and pandemic period. The main outcome measure was defined as the number of antibiotic prescriptions per contact (antibiotic prescription rate).Results The overall antibiotic prescription rate decreased during the first year of the pandemic compared to the pre-pandemic period (RR = 0.97, 95%CI: 0.96–0.98). Likewise, the rate decreased for clinic consultations (RR = 0.63, 95%CI: 0.62–0.64). However, an increase was seen for telephone consultations (RR = 1.73, 95%CI: 1.70–1.76). The decline in clinic consultations was largest for consultations involving children aged 0–10 years (RR = 0.53, 95%CI: 0.51–0.56).Conclusion Antibiotic prescription rates in Danish OOH primary care decreased during the first year of the COVID-19 pandemic, especially for young children. Prescription rates decreased in clinic consultations, whereas the rates increased in telephone consultations. Further research should explore if antibiotic prescription rates have returned to pre-pandemic levels, and if the introduction of video consultations has affected antibiotic prescription patterns in OOH primary care.

Abstract Infectious mononucleosis (IM) is suspected to be associated with inflammatory bowel disease (IBD) development. Using a Danish nationwide cohort of people developing severe IM and their age-, sex-, and socioeconomic (SES) index-matched counterparts, we investigated the subsequent risk of IBD, Crohn’s disease (CD), or ulcerative colitis (UC) development from 1977 to 2021. Among 39,684 severe IM patients we find a sex-, age-, and SES index-adjusted HR for IBD of 1.35 (95% CI: 1.22–1.49). This significantly increased risk was seen for both CD (HR: 1.56; 95% CI: 1.34–1.83) and to a lesser extent UC (HR: 1.23; 95% CI: 1.08–1.40) and remains following negative control matching with a cohort diagnosed with Chlamydia trachomatis infection (HR: 1.39; 95% CI: 1.01–1.91). Those with severe IM at 0–9 years had a particularly increased risk for CD (HR: 1.77; 95% CI: 1.26–2.49). Here we show an increased risk for IBD diagnosis following IM hospitalisation, indicating an association between severe EBV disease and later IBD development. Further exploration of the potential factors contributing to IBD susceptibility following EBV disease is warranted.

Frederik PB Kristensen,1 Sia K Nicolaisen,1 Jens S Nielsen,2,3 Diana H Christensen,1,4 Kurt Højlund,2,3 Henning Beck-Nielsen,2 Jørgen Rungby,5 Søren G Friborg,6 Ivan Brandslund,7,8 Jens S Christiansen4 ,† Peter Vestergaard,9,10 Niels Jessen,11– 13 Michael H Olsen,14,15 Mette K Andersen,16 Torben Hansen,16 Charlotte Brøns,5 Allan Vaag,5,17 Reimar W Thomsen,1 Henrik T Sørensen1 1Department of Clinical Epidemiology, Aarhus University and Aarhus University Hospital, Aarhus, Denmark; 2Steno Diabetes Center Odense, Odense University Hospital, Odense, Denmark; 3Department of Clinical Research, University of Southern Denmark, Odense, Denmark; 4Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark; 5Steno Diabetes Center Copenhagen, Herlev, Denmark; 6Department of Endocrinology, Odense University Hospital, Odense, Denmark; 7Department of Biochemistry, Lillebaelt Hospital, Vejle, Denmark; 8Regional Health Research, University of Southern Denmark, Odense, Denmark; 9Department of Clinical Medicine and Endocrinology, Aalborg University Hospital, Aalborg, Denmark; 10Steno Diabetes Center North Denmark, Aalborg, Denmark; 11Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark; 12Department of Clinical Pharmacology, Aarhus University Hospital, Aarhus, Denmark; 13Department of Biomedicine, Aarhus University, Aarhus, Denmark; 14Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark; 15Department of Internal Medicine and Steno Diabetes Center Zealand, Holbæk Hospital, Holbæk, Denmark; 16Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, København, Denmark; 17Lund University Diabetes Centre, Lund University, Malmö, Sweden†Dr Jens S Christiansen passed away on 16 December 2015Correspondence: Frederik PB Kristensen, Department of Clinical Epidemiology, Aarhus University, Olof Palmes Alle 43-45, Aarhus N, 8200, Denmark, Tel +45 87 16 82 37, Email fpk@clin.au.dkPurpose: This paper provides an overview of the Danish Centre for Strategic Research in Type 2 Diabetes (DD2) cohort and biobank, including baseline characteristics of participants enrolled up to 2023, and post-enrollment rates of cardiovascular disease outcomes and mortality.Methods: Since 2010, the DD2 project has enrolled individuals with type 2 diabetes mellitus (T2DM) recently diagnosed by general practitioners and by hospital-based clinicians across Denmark. Data from questionnaires, clinical examinations, and biological samples are collected at enrollment. Additional baseline and longitudinal follow-up data are accessed via linkage to health registries.Results: Between 2010 and 2023, the DD2 project enrolled 11,369 participants (41.3% women, median age 61.4 years). Median T2DM duration at enrollment was 1.3 years, and median BMI was 31.6 kg/m2 for women and 30.5 kg/m2 for men. 18.3% were smokers, 5.7% consumed more than 14/21 units of alcohol weekly (women/men), and 17.9% reported leisure-time physical inactivity. Original midwife records dating back > 80 years revealed that 20.2% of cohort participants had birth weights < 3000 g. Based on complete hospital contact history 10 years before enrollment, 20.7% of cohort participants had macrovascular complications, 17.0% had microvascular complications, and 21.7% had kidney disease based on eGFR or urine albumin-creatinine measurements. At enrollment, statins were used by 68.2%, antihypertensive drugs by 69.9%, and glucose-lowering drugs by 86.5% of individuals. Median HbA1c was 48 mmol/mol and median LDL cholesterol 2.2 mmol/L. Genome-wide genotyping and biomarker data have been analyzed for over 9000 individuals. During the current follow-up time from the enrollment date (median 7.9 years), incident cardiovascular disease rate has been 13.8 per 1000 person-years and the mortality rate has been 17.6 per 1000 person-years.Conclusion: The DD2 cohort, with its detailed information and long-term follow up, can improve our understanding of the progression and prevention of complications among individuals with newly diagnosed T2DM.Keywords: cohort profile, type 2 diabetes mellitus, patient characteristics, Denmark