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Background: At the regional transfusion service in the Region of Southern Denmark, serological investigations are primarily carried out using column agglutination techniques. This case study examines an unusual instance of reagent interference in pretransfusion testing using column agglutination at the Hospital of Southern Denmark, Aabenraa., Case Presentation: A 72-year-old male patient presented for pretransfusion testing prior to hernia surgery. He typed as O RhD negative without discrepancies, but the antibody screen showed weakly positive reactions. Routine investigations showed discrepancies, leading to further investigations., Methods: Various serological tests were performed using in-house and commercial red test cells suspended in different suspension media and with different column agglutination cards and cassettes. Further investigations included washing of test cells, testing alternative saline solutions, varying incubation temperatures, testing without antihuman-globulin, and applying proteolytic enzymes., Results: Reactivity was present with red cells suspended in ID-CellStab (BioRad) but not in Red Cell Diluent (Quidel-Ortho). Reactivity was abolished by using trypsin-treated cells, indicating either the presence of an antibody reacting with-or unspecific agglutination depending on-a trypsin-sensitive protein, in both cases enhanced by ID-CellStab., Conclusion: This case highlights the importance of recognising reagent-dependent reactivity in serological testing. Adjustments to the suspension media resolved the incompatibility. Immunohematology laboratories should consider potential reagent interference when unexpected agglutination occurs., (© 2024 The Author(s). Transfusion Medicine published by John Wiley & Sons Ltd on behalf of British Blood Transfusion Society.)

Background and Aims: Epidemiological studies have shown that subnormal levels of vitamin D (25[OH]D) are associated with a more aggravated clinical course of ulcerative colitis [UC]. Despite an increased focus on the therapeutic importance of vitamin D and vitamin D receptor [VDR] signalling, the mechanisms underlying the effects of the vitamin D-VDR axis on UC remain elusive. Therefore, we aimed to investigate whether exposure to active vitamin D (1,25[OH]2D3/VDR) signalling in human organoids could influence the maintenance of the colonic epithelium., Methods: Intestinal VDR expression was studied by immunohistochemistry, RNA expression arrays, and single-cell RNA sequencing of colonic biopsy specimens obtained from patients with UC and healthy individuals. To characterise the functional and transcriptional effects of 1,25[OH]2D3, we used patient-derived colonic organoids. The dependency of VDR was assessed by knocking out the receptor with CRISPR/Cas9., Results: Our results suggest that 1,25[OH]2D3/VDR stimulation supports differentiation of the colonic epithelium and that impaired 1,25[OH]2D3/VDR signalling thereby may compromise the structure of the intestinal epithelial barrier, leading to flares of UC. Furthermore, a transcriptional response to VDR activity was observed primarily in fully differentiated cells at the top of the colonic crypt, and this response was reduced during flares of UC., Conclusions: We identified an important role of vitamin D signalling in supporting differentiated cell states in the human colonic epithelium, and thereby maintenance of the intestinal barrier integrity. This makes the vitamin D-VDR signalling axis an interesting target for therapeutic efforts to achieve and maintain remission in patients with UC., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Background: Inequity in healthcare utilisation refers to differences between groups that remain after adjustment for need for health care. To our knowledge, no previous studies have aimed to assess social inequity in chiropractic utilisation in a general population. Therefore, the objective of this study was to evaluate social inequity in chiropractic utilisation in the general Danish population adjusted for health status as a proxy of need for chiropractic care., Methods: A population-based repeated cross-sectional study design was used based on the Danish National Health Survey in 2010 and 2017. Overall, we included 288,099 individuals aged 30 years or older in 2010 or 2017. For each individual, information on chiropractic utilisation, socioeconomic status, and health status as a proxy of need for chiropractic care was retrieved from nationwide registers using the unique personal identification number. Measures of health status included demographics, poor self-rated physical health, activity limitations, musculoskeletal pain, number of musculoskeletal conditions, and number of chronic diseases. We investigated social inequity in chiropractic utilisation (yes, no) using logistic regression adjusted for health status, stratified by sex and year. Three characteristics of socioeconomic status (educational level, employment status and income) were investigated. To further quantify the degree of social inequity in chiropractic utilisation, we estimated the concentration index of inequity for each of the three characteristics of socioeconomic status., Results: We found significantly higher odds of chiropractic utilisation among individuals with short or medium/long education compared with individuals with elementary education, and among employed individuals compared with individuals who were unemployed, receiving disability pension or retired. Furthermore, the odds of chiropractic utilisation increased with higher income. The concentration index indicated social inequity in chiropractic utilisation in favour of individuals with higher socioeconomic status, with income and employment status contributing more to inequity than educational level., Conclusion: The study demonstrated social inequity in chiropractic utilisation in Denmark beyond differences in health status as a proxy of need for chiropractic care in the general population. The results suggest that new strategies are required if equal treatment for equal need is the goal., (© 2024. The Author(s).)

Jellyfish as a potential sustainable food material has recently gained increasing interest. However, with their soft gel-like texture and easy spoilage, it remains challenging to achieve desirable edible structures from jellyfish. The culinary preparation of jellyfish is a complex process and extends beyond conventional cooking methods. In this study, we investigate the transformation of jellyfish into crispy-like structures by manipulating their microstructural and mechanical properties through a solvent-based preparation. The study focuses on the use of "poor solvents", namely ethanol and acetone, and employs rheology measurements and quantitative microscopy techniques to analyze the effects of these solvents on the mechanical properties and microstructure of jellyfish. Our findings reveal that both ethanol and acetone lead to a significant increase in jellyfish hardness and deswelling. Notably, a micro-scale network is formed within the jellyfish matrix, and this network is then mechanically reinforced before a crispy-like texture can be obtained. Our study points to solvent polarity as also being a crucial factor for creating these effects and determines an upper polarity limit in the range of 12.2-12.9 MPa 1/2 for added solvents, corresponding to approximately 60% of added ethanol or 70% of added acetone. Our study highlights that solvent-based preparation serves as a "reverse cooking" technique, where mechanical modification rather than traditional softening mechanisms are employed to stabilize and strengthen the microstructures and fibers of jellyfish. By elucidating the underlying mechanisms of solvent-induced stabilization, our findings may facilitate the development of innovative and sustainable culinary practices, paving the way for broader applications of jellyfish and other soft edible materials in the gastronomic landscape.

During intestinal organogenesis, equipotent epithelial progenitors mature into phenotypically distinct stem cells that are responsible for lifelong maintenance of the tissue. While the morphological changes associated with the transition are well characterized, the molecular mechanisms underpinning the maturation process are not fully understood. Here, we leverage intestinal organoid cultures to profile transcriptional, chromatin accessibility, DNA methylation, and three-dimensional (3D) chromatin conformation landscapes in fetal and adult epithelial cells. We observed prominent differences in gene expression and enhancer activity, which are accompanied by local changes in 3D organization, DNA accessibility, and methylation between the two cellular states. Using integrative analyses, we identified sustained Yes-Associated Protein (YAP) transcriptional activity as a major gatekeeper of the immature fetal state. We found the YAP-associated transcriptional network to be regulated at various levels of chromatin organization and likely to be coordinated by changes in extracellular matrix composition. Together, our work highlights the value of unbiased profiling of regulatory landscapes for the identification of key mechanisms underlying tissue maturation.

DNA methyltransferase (DNMT) inhibitors are used for treatment of certain hematological malignancies and exert anti-cancer activity through diverse mechanisms, including reexpression of tumor suppressor genes and anti-viral responses triggered by expression of endogenous retroviruses. Despite advances in the pharmacokinetic properties of DNMT inhibitors, the efficacy of these drugs in solid cancers remains low. Here, we show in cell lines and clinical and experimental tumors across multiple cancer types that DNMT inhibition induces the expression of interleukin-1 (IL-1), a cytokine with proinflammatory and protumorigenic properties. Specifically, this tumor-intrinsic IL-1 expression modulates the chemokine landscape of tumors and leads to the recruitment of monocytic myeloid-derived suppressor cells to the tumor microenvironment, processes that can be blocked by IL-1 antagonists. Molecular analysis demonstrates complex patterns of IL-1 and interferon activation and crosstalk in response to DNMT inhibition, which depend on the integrity of IRF- and NF-κB-mediated antiviral pathways and may determine the outcome of DNMT-inhibitor treatment. Together, our results show that DNMT inhibitors may negatively affect the microenvironment of a large subset of tumors and suggest that co-treatment with IL-1 antagonists may be a favorable combination for these patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Aims: Floorball training induces positive effects on health among untrained older adults. However, the effect of long-term participation (>2 years) in floorball training among elderly males has not been investigated. The aim of the present study was to examine the effect of 5 years of floorball training on risk factors for lifestyle diseases, fitness, physical function, and social capital of elderly males and compare to a control group that continued their usual lifestyle., Methods: Twenty-nine recreationally active elderly men aged 75.1 ± 3.3 (mean ± SD; range: 69-81) years with a height, body mass, and body mass index of 1.78 ± 0.06 m, 79.8 ± 10.9 kg, and 25.8 ± 4.1 kg/m 2 , respectively, volunteered to take part in follow-up investigations about 5 years after participating in a study on the effect of 12 weeks of floorball or petanque training. At the end of the parental study 15 subjects chose to participate in floorball training (floorball group [FG]) whereas 14 subjects (control group [CG]), resumed their usual lifestyle. FG participated in small-sided floorball training 1 h ~1.75 times/week for 5 years in a local sports club., Results: From baseline to 5 years, FG had reduced fat percentage, android, and visceral fat, increased total and leg bone mineral density, leg extension maximal voluntary contraction, maximal walk distance in 6 min and 30 s sit-to-stand repetitions, decreased time for 5 sit-to-stand repetitions and Timed Up and Go ( p  < 0.05). These changes were all different from less favorable changes in CG ( p  < 0.05). In FG there was a decline in maximum oxygen uptake which was smaller than the decline in CG ( p  < 0.05). In addition, FG had developed social capital through the 5 years strengthening their social connectedness and group cohesion., Conclusion: In conclusion, both from a sociological and physiological perspective, small-sided floorball training can be considered a health-promoting activity for older men., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

Organs are anatomically compartmentalised to cater for specialised functions. In the small intestine (SI), regionalisation enables sequential processing of food and nutrient absorption. While several studies indicate the critical importance of non-epithelial cells during development and homeostasis, the extent to which these cells contribute to regionalisation during morphogenesis remains unexplored. Here, we identify a mesenchymal-epithelial crosstalk that shapes the developing SI during late morphogenesis. We find that subepithelial mesenchymal cells are characterised by gradients of factors supporting Wnt signalling and stimulate epithelial growth in vitro. Such a gradient impacts epithelial gene expression and regional villus formation along the anterior-posterior axis of the SI. Notably, we further provide evidence that Wnt signalling directly regulates epithelial expression of Sonic Hedgehog (SHH), which, in turn, acts on mesenchymal cells to drive villi formation. Taken together our results uncover a mechanistic link between Wnt and Hedgehog signalling across different cellular compartments that is central for anterior-posterior regionalisation and correct formation of the SI., (© 2022. The Author(s).)

There is an emerging global need for new and more effective antibiotics against multi-resistant bacteria. This situation has led to massive industrial investigations on novel bacterial topoisomerase inhibitors (NBTIs) that target the vital bacterial enzymes DNA gyrase and topoisomerase IV. However, several of the NBTI compound classes have been associated with inhibition of the hERG potassium channel, an undesired cause of cardiac arrhythmia, which challenges medicinal chemistry efforts through lengthy synthetic routes. We herein present a solid-phase strategy that rapidly facilitates the chemical synthesis of a promising new class of NBTIs. A proof-of-concept library was synthesized with the ability to modulate both hERG affinity and antibacterial activity through scaffold substitutions., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The COVID-19 pandemic and its associated national lockdowns have been linked to deteriorations in mental health worldwide. A number of studies analysed changes in mental health indicators during the pandemic; however, these studies generally had a small number of timepoints, and focused on the initial months of the pandemic. Furthermore, most studies followed-up the same individuals, resulting in significant loss to follow-up and biased estimates of mental health and its change. Here we report on time trends in key mental health indicators amongst Danish adults over the course of the pandemic (March 2020 - July 2021) focusing on subgroups defined by gender, age, and self-reported previously diagnosed chronic and/or mental illness., Methods: We used time-series data collected by Epinion (N=8,261) with 43 timepoints between 20 March 2020 and 22 July 2021. Using a repeated cross-sectional study design, independent sets of individuals were asked to respond to the Copenhagen Corona-Related Mental Health questionnaire at each timepoint, and data was weighted to population proportions. The six mental health indicators examined were loneliness, anxiety, social isolation, quality of life, COVID-19-related worries, and the mental health scale. Gender, age, and the presence of previously diagnosed mental and/or chronic illness were used to stratify the population into subgroups for comparisons., Results: Poorer mental health were observed during the strictest phases of the lockdowns, whereas better outcomes occurred during reopening phases. Women, young individuals (<34 yrs), and those with a mental- and/or chronic illness demonstrated poorer mean time-series than others. Those with a pre-existing mental illness further had a less reactive mental health time-series. The greatest differences between women/men and younger/older age groups were observed during the second lockdown., Conclusions: People with mental illness have reported disadvantageous but stable levels of mental health indicators during the pandemic thus far, and they seem to be less affected by the factors that result in fluctuating time-series in other subgroups., (© 2022. The Author(s).)