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Treatment preferences and self-stigma in depression:Development and validation of the brief ATDT-SF
No full textBACKGROUND: Patients' beliefs about depression and different antidepressant treatment options may influence help-seeking behaviour, treatment adherence, and ultimately clinical outcomes. The Attitudes Toward Depression and its Treatment (ATDT) questionnaire was developed to assess these attitudes and beliefs; however, subsequent research revealed limitations in its psychometric properties. We sought to develop and validate a shortened version (ATDT-SF) with improved reliability.METHODS: We used data from 321 patients with first-episode depression initiating treatment enrolled in the BrainDrugs-Depression cohort (age 18-65, 71 % female). We randomly divided the sample into development (n = 209) and validation (n = 112) subsets. Exploratory factor analysis identified a parsimonious factor structure, which was confirmed using confirmatory factor analysis. We assessed associations between the ATDT-SF factors and clinical variables, and compared attitudes across Danish, Canadian, and Australian samples.RESULTS: A 13-item, four-factor model demonstrated an acceptable fit and resulted in the factors: negative attitudes toward antidepressants, help-seeking from medical professionals, self-stigma, and preference for psychotherapy. Age was positively associated with negative attitudes toward antidepressants (p = 0.004), while depression severity showed a significant positive association with experienced stigma (p = 0.004). Patients reported significantly stronger help-seeking from medical professionals and higher self-stigma compared to those from Canadian and Australian samples, while negative attitudes toward antidepressants were similar across countries.CONCLUSIONS: The ATDT-SF provides a reliable measure of attitudes toward depression and its treatment and self-stigma, which may be important contextual factors in treatment planning and depression management.</p
The Danish Nationwide osteoporosis cohort trials environment (NOCTE) - a DXA dataset for the 1900-1960 birth cohort
No full textBackground: Osteoporosis is a common, underdiagnosed condition causing increased risk of fracture. While dual-energy X-ray absorptiometry (DXA) is the diagnostic standard, this may not be successfully targeted to individuals at the highest risk. This study presents an extensive nationwide dataset characterizing DXA-scanning practices in Denmark.Methodology: In this study, we identified all Danish residents from the birth cohort 1900-1960, with a first DXA scan between 2010-2022 to form the Nationwide Osteoporosis Cohort Trials Environment (NOCTE) dataset. These individuals were matched 1:5 to a non-scanned reference population by birth year, sex, and region of residence. Individual data were linked to national registers for comprehensive sociodemographic and clinical information.Results: The final cohort included 263,651 individuals who underwent DXA scanning. At their first scan, 33% of women and 17% of men had osteoporosis. Compared to the matched reference, the scanned cohort had similar socioeconomic profiles but substantially different clinical profiles. Scanned individuals had a much higher prevalence of prior major osteoporotic fractures, prior systemic glucocorticoid exposure, and overall comorbidity burden.Conclusion: Referral for DXA in Denmark is driven by clinical risk rather than socioeconomic status, reflecting an equitable resource allocation. However, a significant diagnostic gap persists, as many high-risk individuals with prior fractures did not receive a DXA. The NOCTE cohort is a new, powerful resource for developing strategies to help close this gap.BACKGROUND: Osteoporosis is a common, underdiagnosed condition causing increased risk of fracture. While dual-energy X-ray absorptiometry (DXA) is the diagnostic standard, this may not be successfully targeted to individuals at the highest risk. This study presents an extensive nationwide dataset characterizing DXA-scanning practices in Denmark.METHODOLOGY: In this study, we identified all Danish residents from the birth cohort 1900-1960, with a first DXA scan between 2010-2022 to form the Nationwide Osteoporosis Cohort Trials Environment (NOCTE) dataset. These individuals were matched 1:5 to a non-scanned reference population by birth year, sex, and region of residence. Individual data were linked to national registers for comprehensive sociodemographic and clinical information.RESULTS: The final cohort included 263,651 individuals who underwent DXA scanning. At their first scan, 33% of women and 17% of men had osteoporosis. Compared to the matched reference, the scanned cohort had similar socioeconomic profiles but substantially different clinical profiles. Scanned individuals had a much higher prevalence of prior major osteoporotic fractures, prior systemic glucocorticoid exposure, and overall comorbidity burden.CONCLUSION: Referral for DXA in Denmark is driven by clinical risk rather than socioeconomic status, reflecting an equitable resource allocation. However, a significant diagnostic gap persists, as many high-risk individuals with prior fractures did not receive a DXA. The NOCTE cohort is a new, powerful resource for developing strategies to help close this gap.</p
Endoscopic treatment methods of suprasellar arachnoid cysts in children:A systematic review and meta-analysis
No full textEndoscopic procedures, especially ventriculocystostomy (VC) and ventriculocystocisternostomy (VCC), are preferred treatments for suprasellar arachnoid cysts (SACs). Yet, results from current studies on their effects are varied. This study offers a comprehensive systematic review on surgical and clinical outcomes after VC and VCC and the risk of reoperation is compared by a meta-analysis. We conducted a literature search following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to identify surgical articles evaluating endoscopic treatment modalities for SAC using PubMed/Medline and Embase. The primary outcome was the risk of reoperation with a subgroup analysis among infants < 1 years of age. Postoperative complications were described to the extend they were reported in the literature. The risk of bias was assessed using the Newcastle-Ottawa scoring system. The meta-analysis was performed using RevMan 5.0 to compare the reoperation rates for VC and VCC as a risk ratio from a Forest plot with 95% confidence intervals in a fixed-effects model. Publication bias was assessed visually using a funnel plot. Nineteen observational studies were eligible for inclusion, comprising 94 patients who underwent VCC and 427 patients who underwent VC. Patients who underwent VCC had a significantly lower risk of reoperation of 0.33 (95% CI 0.17–0.65; p < 0.002). However, the risk of postoperative complications was considerable for both VCC (16.7%) and VC (12.7%), yet not significantly different (p = 0.915). Within the subgroup of infants age < 1 year, the risk of reoperation was significantly higher (29.4%) compared to older children (5.7%) (95% CI 1.96–42.07; p < 0.002). The results support VCC as an effective and long-lasting treatment for symptomatic SACs with significantly lower reoperation rates, compared to VC.Endoscopic procedures, especially ventriculocystostomy (VC) and ventriculocystocisternostomy (VCC), are preferred treatments for suprasellar arachnoid cysts (SACs). Yet, results from current studies on their effects are varied. This study offers a comprehensive systematic review on surgical and clinical outcomes after VC and VCC and the risk of reoperation is compared by a meta-analysis. We conducted a literature search following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to identify surgical articles evaluating endoscopic treatment modalities for SAC using PubMed/Medline and Embase. The primary outcome was the risk of reoperation with a subgroup analysis among infants < 1 years of age. Postoperative complications were described to the extend they were reported in the literature. The risk of bias was assessed using the Newcastle-Ottawa scoring system. The meta-analysis was performed using RevMan 5.0 to compare the reoperation rates for VC and VCC as a risk ratio from a Forest plot with 95% confidence intervals in a fixed-effects model. Publication bias was assessed visually using a funnel plot. Nineteen observational studies were eligible for inclusion, comprising 94 patients who underwent VCC and 427 patients who underwent VC. Patients who underwent VCC had a significantly lower risk of reoperation of 0.33 (95% CI 0.17-0.65; p < 0.002). However, the risk of postoperative complications was considerable for both VCC (16.7%) and VC (12.7%), yet not significantly different (p = 0.915). Within the subgroup of infants age < 1 year, the risk of reoperation was significantly higher (29.4%) compared to older children (5.7%) (95% CI 1.96-42.07; p < 0.002). The results support VCC as an effective and long-lasting treatment for symptomatic SACs with significantly lower reoperation rates, compared to VC.</p
Who are we talking about when we talk about flexitarians?
No full textFlexitarians are becoming increasingly popular to study in social scientific consumer research and flexitarianism is often seen as a potential solution to the sustainability challenges related to high levels of meat consumption in rich countries. The paper examines popular, historical and scientific understandings of the term, and identifies and discusses three central challenges with how the term flexitarian has been applied in empirical research. First, there is no commonly agreed definition of who counts as a flexitarian. This makes it hard to ascertain shares of flexitarians across populations and makes it close to impossible to assess the accuracy of existing estimations. Second, there is a tendency to operationalize the term in ways that lead to large internal variations. This often leads to the inclusion of frequent meat eaters in the category, which risks leading to overly optimistic accounts of both the prevalence and the transformative potential of flexitarianism. Third, there is a lack of scientific discussion about the issues pertaining to the term ‘flexitarian’, which means that it is still unclear whether ‘flexitarians’ can usefully be viewed as a coherent consumer group. The paper contributes with a systematic discussion of the limitations and challenges associated with the term flexitarian(ism) and its use in empirical research. It concludes by discussing the potential implications for future research
Quercetin nanoemulsion ameliorates tremor and neuroinflammatory dysregulation:behavioral and molecular insights in a mouse model of essential tremor
No full textBACKGROUND: Essential tremor (ET) is a common movement disorder characterized by persistent limb tremors. Currently, no effective treatment for ET exists. Natural plant-derived compounds, like the flavonoid, quercetin may provide therapeutic benefits, particularly when delivered in nanoemulsion formulations that enhance bioavailability and efficacy. This study evaluated the neuroprotective potential of quercetin nanoemulsion (Que-NE) in a harmaline-induced mouse model of ET.METHODS: Thirty-two male Swiss mice were randomly divided into four groups (n = 8 each): Control, Harmaline (10 mg/kg, i.p., on days 3, 5, and 7), Que-NE (20 mg/kg, i.p., for 7 days), and Harmaline + Que-NE. Harmaline was used to reliably induce tremor via olivocerebellar hyperexcitability. Behavioral performance was assessed using the open field, elevated plus maze, tail suspension, wire grip, rotarod, and passive avoidance tests. Expression of NF-κB, TNF-α, IL-1β, IL-6, NMDA receptor, and Lingo-1 was determined by RT-PCR.RESULTS: Que-NE significantly reduced harmaline-induced tremor severity (p < 0.0001), decreased immobility time in the tail suspension test (p = 0.0003), and improved open field anxiety-like behaviors compared with harmaline alone (P = 0.0012). Que-NE downregulated pro-inflammatory mediators (P < 0.0001) and reduced Lingo-1 gene expression (P < 0.0001). However, Que-NE showed limited efficacy in severe motor coordination tasks (rotarod, wire grip) and passive avoidance memory.CONCLUSIONS: Que-NE exerts measurable anti-inflammatory, anxiolytic, and antidepressant-like effects in the harmaline model of ET. The impact of Que-NE on improving motor deficits, reducing inflammatory markers, and suppressing inhibitors of synaptic plasticity highlights the potential of Que-NE as a disease-modifying strategy. However, dose-response, protein-level, and long-term studies are needed to evaluate the therapeutic potential of Que-NE for ET management.</p
The AI Ideal:AIdealism and the Governance of AI
No full textThe AI Ideal: Aidealism and the Governance of AI offers an actionable vision for ensuring AI strengthens democracy, ethics, and human dignity. Instead of allowing AI to concentrate power in the hands of a few, the book argues for a new global framework—one where AI serves justice, enlightenment, and human betterment. Rooted in European Enlightenment ideals, Scandinavian social models and liberalism, and Swiss direct democracy, Aidealism rejects extreme ideologies and champions pragmatic, ethical, and forward-thinking solutions. From free education and healthcare to AI-driven economic justice and climate responsibility, this book explores how AI can help build a sustainable, free, and prosperous world.Instead of a warning of the catastrophe of AI, Dr. Lidströmer offers an actionable vision for ensuring AI strengthens democracy, ethics, and human dignity. The book explicitly gives a manifesto for practical action, including a plan for how to harness and use AI for the common good so that it benefits everyone, not just the few. It elaborates on the daily conundrums of the human species; our nature, origins, goodness and cruelty, memes, hierarchies, political structures, and how to build a fairer, more just, peaceful, and benevolent society. As the risks are real and the threats are mounting, sections cover how AI could empower autocrats, disrupt economies, and undermine human agency while also highlighting how AI could also be our greatest tool for wisdom, fairness, and progress—if governed with foresight and courage
Electrospun two-layer mucoadhesive patch for co-delivery of immunostimulatory Lactococcus lactis GEM particles and 33-mer gliadin peptide to the oral mucosa
No full textImmunotherapy is conventionally managed via subcutaneous injections, yet recently sublingual immunotherapy (SLIT) has been established as an effective and safer route. However, short retention times at the mucosa, in addition to insufficient presentation to antigen-presenting cells can lead to inefficient performance of SLIT. To overcome these challenges, we aimed to co-deliver 33-mer gliadin peptide, the primary trigger of celiac disease, with immunostimulatory Lactococcus lactis Gram-positive enhancer matrix (GEM) particles in a mucoadhesive patch. Accordingly, 33-mer gliadin peptide was co-loaded with GEMs in a two-layer mucoadhesive patch prepared by electrospinning. The delivery system consisted of i) a mucoadhesive layer based on chitosan/polyethylene oxide (PEO) nanofibers to ensure adherence to the mucosa and ii) an active layer of PEO nanofibers for fast co-release of 33-mer gliadin peptide and GEMs. Both layers displayed smooth nanofibers with the GEMs appearing as ‘beads on a string’. Upon wetting, 33-mer gliadin peptide and GEMs were released within minutes in vitro , with no changes in structure or morphology. The two-layer patch showed optimal mechanical properties, maintaining flexibility and shape during handling. Prolonged residence time at the oral mucosa is crucial for SLIT efficacy by enhancing antigen presentation. Strong adhesion of the two-layer patch was demonstrated by measuring adhesion to ex vivo porcine oral mucosa. Furthermore, biocompatibility was demonstrated by exposure to human oral epithelial cell monolayers in vitro . In conclusion, the two-layer patch displayed appropriate properties to serve as a dosage form for SLIT, capable of co-presentation of immunostimulatory actives and enhancing retention at the mucosal surface.</p
Elucidating the roles of TM7SF3 and LHFPL6 in the putative H +/OC antiporter function in the human brain capillary endothelial cell line, hCMEC/D3.
No full textINTRODUCTION: The putative proton/organic cation (H +/OC) antiporter has been shown to mediate transport of CNS drug compounds like oxycodone and pyrilamine across the blood-brain barrier (BBB). This transporter has a broad substrate profile and is able to transport substrates against their concentration gradient, making it an interesting target for brain drug delivery. However, the molecular identity of this transporter remains unknown. Recent studies have indicated that the two proteins TM7SF3 and LHFPL6 might be components of this transporter. The present study aimed to investigate the roles of TM7SF3 and LHFPL6 in the H +/OC antiporter function to advance understanding of its molecular identity and potential in CNS drug delivery. METHODS: CRISPR-Cas9 gene-editing was used to generate three hCMEC/D3 knockout (KO) cell lines: TM7SF3 KO (TM-KO), LHFPL6 KO (LH-KO), and a double KO of TM7SF3 and LHFPL6 (TMLH-KO). The uptake of pyrilamine analogue (EDMPG) and [ 3H]-pyrilamine was assessed in wild type (WT) and KO lines. Quantitative Realtime Polymerase Chain Reaction (qRT-PCR) confirmed successful gene knockouts. Passive diffusion properties and the expression and functionality of known BBB transporters, including LAT1 (SLC7A5), GLUT1 (SLC2A1), and MCT1 (SLC16A1), were also examined. RESULTS: The EDMPG uptake was significantly reduced in TM-, LH-, and TMLH-KO cells, suggesting that TM7SF3 and LHFPL6 contribute to the H +/OC antiporter function. However, [ 3H]-pyrilamine uptake remained unchanged across all KOs, indicating a TM7SF3- and LHFPL6-independent transport mechanism. This was further supported by the persistent inhibition of [ 3H]-pyrilamine uptake in the presence of known H +/OC antiporter substrates. While passive diffusion and GLUT1- and MCT1-mediated transport were unaffected, LAT1-mediated uptake of [ 3H]L-leucine and gabapentin was significantly reduced in LH- and TMLH-KO cells, correlating with decreased LAT1 mRNA expression in these cells. CONCLUSIONS: This study suggests that the H+/OC antiporter operates via two distinct mechanisms: a high-capacity, TM7SF3- and LHFPL6-independent pathway and a low-capacity, TM7SF3- and LHFPL6-dependent pathway. These findings underscore the complexity of the H +/OC antiporter molecular composition and highlight the need for further research to fully elucidate its identity. </p
Investigating stimuli-responsive liposomes for cutaneous applications: a guide to stimuli recognition and characterization
No full textIn recent years, stimuli-responsive liposomes have been proposed as advanced nanocarriers for cutaneous drug delivery. These liposomes are designed to release their cargo in response to specific triggers. A critical challenge in their development is the robust characterization of this responsive behavior to validate their performance. This review provides a methodological guide for comprehensively characterizing stimuli-responsive liposomes. The proposed guide systematically discusses experimental and computational characterization techniques based on the evidence they provide regarding structural transformation, functional outcomes and molecular mechanisms, and focuses on recent studies in cutaneous applications published within the last decade. A multifaceted characterization approach is essential as no single technique is sufficient. Structural techniques such as small angle X-ray scattering (SAXS) and cryo-transmission electron microscopy (cryo-TEM) provide direct evidence of stimuli-induced physical changes, that need to be correlated with functional data obtained using analytical techniques such as high-performance liquid chromatography (HPLC) to quantitatively determine drug release. Complementary computational simulations can elucidate molecular-level mechanisms, supporting rational formulation design. A comprehensive characterization framework is therefore essential for effective design and clinical application of stimuli-responsive liposomal formulations, facilitating the development of safer and more efficient cutaneous therapies
Gut Microbiota in IBD:The Beneficial and Adverse Effects of Diet and Medication
No full textBackground: Inflammatory bowel disease (IBD) is a global disease with a considerable increase in prevalence and the impact on the health and well-being of patients suffering from this condition is vast. Diet has been suspected of being a contributor to IBD severity as well as intake of antibiotics. Methods: A literary search was conducted on the most recent studies on the subject of IBD, diet, and medical treatment to identify high-quality research findings within this area of research. Research published within the last decade was prioritized. Studies in English language were included in the search, and the knowledge gained was synthesized in the review. Results: Dietary patterns, specifically intake of Westernized diets, were associated with increased inflammation and increased disease severity in patients suffering from IBD, specifically patients suffering from Crohn’s disease (CD). A co-administration of pre- and probiotics was found to contribute to disease remission in ulcerative colitis patients, however, to a lesser extent in patients with CD. A bidirectional effect on the intestinal microbiome was seen as a result of intake of the medicines used for the treatment of IBD patients, which affects both bioavailability of the drug and efficacy of the treatment. The baseline composition of the intestinal microbiome in IBD patients dictates their response to the different treatments. Conclusions: Diet and medical treatment both have a large impact on the architecture of the intestinal Microbiome in IBD patients and are, as such, both essential to understand to enable individualized and optimized treatment