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Abstract Introduction UVA-UVB increases skin matrix metalloproteinases and breaks down extracellular proteins and fibrillar type 1 collagen, leading to photodamage. Topical application of nicotinamide prevents UV-induced immunosuppression. Several studies have demonstrated the importance of protection against UV. This study aims to determine the biological effect of a high broad-spectrum UVB-UVA sunscreen containing nicotinamide and panthenol (SSNP) on photodamaged skin using linear confocal optical coherence tomography (LC-OCT), immunohistochemistry, and RNA profiling. Methods Two areas of severely photodamaged forearm skin (L01 and L02) and one less sun-damaged (naturally protected) area on the inner part of the forearm (L03) were identified in 14 subjects. These areas were imaged using LC-OCT and L01 and L03 were biopsied at baseline. After 4 weeks of treatment with SSNP, L02 was reimaged using LC-OCT, and biopsied. Histology, immunostaining with p21, p53, PCNA, and CPD, and RNA sequencing were performed in all samples. Results LC-OCT analysis showed that epidermis thickness and the number of keratinocytes is higher in the sun-exposed areas than in the non-exposed areas. Comparing before and after treatment, even though there is a trend towards normalization, the differences were not statistically significant. The expression of p21, PCNA, p53, and CPD increased in severely photodamaged skin compared to less-damaged skin. When comparing before and after treatment, only p21 showed a trend to decrease expression. RNA sequencing analysis identified 1552 significant genes correlating with the progression from non-visibly photodamaged skin to post-treatment and pre-treatment samples; in the analysis comparing pre- and post-treatment samples, 5429 genes were found to be significantly associated. A total of 1115 genes are common in these two analyses. Additionally, nine significant genes from the first analysis and eight from the second are related to collagen. Six of these collagen genes are common in the two analyses. MAPK and cGMP-PKG signalling pathways are upregulated in the progression to photodamage analysis. In the pre- and post-treatment analysis, 32 pathways are downregulated after treatment, the most statistically significant being the ErbB, Hippo, NOD-like receptor, TNF, and NF-kB signalling pathways. Conclusion This study demonstrates the role of SSNP in collagen generation, highlights the relevance of the cGMP-PKG and MAPK signalling pathways in photodamage, and shows the ability of SSNP to downregulate pathways activated by UV exposure. Additionally, it deepens our understanding of the effect of SSNP on immune-related pathways.

Abstract Southeast Greenland contributes significantly to global sea level rise, with mass loss having increased by about 600% over the past 30 years due to enhanced melt and dynamic instabilities of marine-terminating glaciers. Accurate modelling of glacier dynamics is crucial to minimise uncertainties in predictions of future sea level rise, necessitating detailed reconstructions of long-term glacial histories. One key complexity in these models that is not well understood or documented is ice flow piracy, where ice is redirected between catchment basins, significantly influencing regional glacier dynamics and mass balance. Here, we document and characterise the collapse of Midgaard Glacier in Southeast Greenland using a multi-data approach, providing a 90-year record of the area’s complex glacial history. Initiated over 80 years ago, this collapse triggered catchment-scale dynamic changes in several neighbouring glaciers, impacting local glacial stability throughout the 20th century and into the present. Our analysis reveals that catchment-scale ice flow piracy can cause substantial disturbances in mass balance evolution and catchment reconfigurations, independent of climatic conditions. These findings underscore the importance of understanding long-term changes in complex glacier systems to make accurate predictions of future glacial mass loss and associated sea-level rise.

Abstract Background There is a lack of up-to-date information on the prevalence and burden of headache in Norway. Here we describe the methods and validation of the diagnostic tool of the PopHEAD study, a study designed to determine the prevalence and burden of migraine, tension-type headache, and medication-overuse headache. Method PopHEAD is a Norwegian population-based cross-sectional study conducted in Vestfold and Telemark County in 2023. A random sample of 28,753 individuals aged 18 to 70 was invited to participate. The study used a digital version of the Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) questionnaire, translated into Norwegian using the Lifting The Burden translation protocol. A subsample of participants was contacted by telephone within four weeks for an interview with a headache neurologist blinded to the questionnaire responses. Headache disorders were diagnosed according to the criteria of the International Classification of Headache Disorders version 3. Validity was expressed by sensitivity, specificity and Cohen’s kappa (κ). Results In total, 8,265 (3,344 men and 4,921 women) responded. Most men (75.0%) and women (89.7%) reported having had a headache in the past year. Of 667 participants contacted for a telephone interview, 505 responded. The sensitivity and specificity of the questionnaire-based diagnoses were 97% and 72% for self-reported headache in the previous year (Cohen’s kappa κ = 0.72), 77% and 85% for migraine (κ = 0.61), 77% and 74% for tension-type headache (κ = 0.51), and 58% and 99% for medication-overuse headache (κ = 0.63), respectively. Conclusion The PopHEAD questionnaire is a valid tool for identifying individuals with lifetime headache, migraine, tension-type headache, and medication overuse headache.

Abstract Background Anorexia of aging (AA) is a condition in older adults that includes loss of appetite and reduced food intake. There is a lack of detailed analysis of the potential influence of educational initiatives in addressing AA. This study aimed to clarify the current state of knowledge and practice regarding AA and its relationship with the availability of continuing education opportunities among Japanese healthcare professionals involved in treating older patients. Methods The Japan Geriatrics Society and the Japanese Association on Sarcopenia and Frailty, in collaboration with the Society on Sarcopenia, Cachexia, and Wasting Disorders, conducted an online questionnaire survey on the knowledge and practices in AA detection and management. Questions were asked in the areas of demographics, screening, definition/diagnosis, treatment, referral, and awareness, with those who ‘participate’ in continuing education and professional development programmes in nutrition for their patients were classified as the ‘education group’ and those who ‘do not participate’ were classified as the ‘non‐education group’. The results for each question were compared. Results The analysis included 870 participants (physicians, 48%; registered dietitians, 16%; rehabilitation therapists, 14%; pharmacists, 12%; nurses, 6%; and other professionals, 5%). The education group (45%) was more likely than the non‐education group (55%) to use the Mini‐Nutritional Assessment Short Form (MNA‐SF) to screen for AA (49% vs. 27%) and less likely not to use a validated tool (33% vs. 47%). More participants used evidence‐based tools and materials for AA care (38% vs. 12%), and fewer used their clinical judgement (23% vs. 35%) or were unaware of the tools and materials (9% vs. 23%). The proportion using a team of professionals experienced in AA care were 47% and 24% of the education and non‐education groups, respectively. By profession, few physicians used specific validated tools and resources for AA screening and treatment. More than half of the dietitians used the MNA‐SF regardless of training opportunity availability. Regarding professional availability and team use, differences in educational opportunities were particularly large among physicians. Conclusions Participation in continuing education programmes on nutrition is associated with responsiveness to AA screening and treatment and the availability of a team of professionals, which may influence the quality of AA treatment. Nutrition education may support the confidence of healthcare professionals working with older adults in AA with complex clinical signs and encourage them to conduct evidence‐based practice.

Abstract Aims Interatrial shunts are under evaluation as a treatment for heart failure (HF); however, their in vivo flow performance has not been quantitatively studied. We aimed to investigate the fluid dynamics properties of the 0.51 cm orifice diameter Ventura shunt and assess its lumen integrity with serial transesophageal echocardiography (TEE). Methods and results Computational fluid dynamics (CFD) and bench flow tests were used to establish the flow‐pressure relationship of the shunt. Open‐label patients from the RELIEVE‐HF trial underwent TEE at shunt implant and at 6 and 12 month follow‐up. Shunt effective diameter (Deff) was derived from the vena contracta, and flow was determined by the continuity equation. CFD and bench studies independently validated that the shunt's discharge coefficient was 0.88 to 0.89. The device was successfully implanted in all 97 enrolled patients; mean age was 70 ± 11 years, 97% were NYHA class III, and 51% had LVEF ≤40%. Patency was confirmed in all instances, except for one stenotic shunt at 6 months. Deff remained unchanged from baseline at 12 months (0.47 ± 0.01 cm, P = 0.376), as did the trans‐shunt mean pressure gradient (5.1 ± 3.9 mmHg, P = 0.316) and flow (1137 ± 463 mL/min, P = 0.384). TEE measured flow versus pressure closely correlated (R2 ≥ 0.98) with a fluid dynamics model. At 12 months, the pulmonary/systemic flow Qp/Qs ratio was 1.22 ± 0.12. Conclusions When implanted in patients with advanced HF, this small interatrial shunt demonstrated predictable and durable patency and performance.

Abstract Background Numerous studies have examined associations between overweight and obesity and risk of low back pain (LBP), but the exact magnitude of these associations is not yet clear. The purpose of this work was to assess such sex-specific associations in a community-based setting in Norway, taking into account potential relationships with other risk factors. Methods A cohort study was conducted combining data from two waves of the Trøndelag Health Study, HUNT3 (2006–2008) and HUNT4 (2017–2019). Separate analyses were performed of risk of chronic LBP in HUNT4 among 14,775 individuals without chronic LBP in HUNT3, and of recurrence or persistence in HUNT4 among 5034 individuals with chronic LBP in HUNT3. Relative risks were estimated in generalised linear models for overweight and obesity compared to normal weight. Body size classification was based on values of BMI computed from measurements of height and weight. Chronic LBP was defined as LBP persisting at least 3 months during last year. Results After adjustment for age, smoking, physical activity in leisure time and work activity, analysis of risk among women produced relative risks 1.11 (95% CI 1.00–1.23) for overweight, 1.36 (95% CI 1.20–1.54) for obesity class I and 1.68 (95% CI 1.42–2.00) for obesity classes II-III. Relative risks among men were 1.10 (95% CI 0.94–1.28) for overweight, 1.36 (95% CI 1.13–1.63) for obesity class I and 1.02 (95% CI 0.70–1.50) for obesity classes II-III, the last estimate being based on relatively few individuals. Analyses of recurrence or persistence indicated similar relationships but with smaller magnitude of relative risks and no drop in risk among obesity classes II-III in men. The change in BMI from HUNT3 to HUNT4 hardly differed between individuals with and without chronic LBP in HUNT3. Conclusions Risk of chronic LBP increases with higher values of BMI in both sexes, although it is uncertain whether this applies to very obese men. Very obese women carry a particularly large risk. Probabilities of recurrence or persistence of chronic LBP among those already afflicted also increase with higher values of BMI. Adjustment for other factors does not influence relationships with overweight and obesity to any major extent.

Abstract Background Penicillin allergy delabelling (PAD), the process of evaluating penicillin allergy labels, is a key target in antibiotic stewardship, but uptake of the procedure outside clinical studies is limited. We aimed to explore factors that need to be addressed to sustainably implement a clinical pathway for PAD. Methods We conducted a qualitative study based on semi-structured interviews with focus groups consisting of a purposive sample of twenty-five nurses and physicians working in four different hospitals in Western Norway. Systematic text condensation was applied for analysis. Results Psychological safety was reported as crucial for clinicians to perform PAD. A narrative of uncertainty and anticipated negative outcomes were negatively associated with PAD performance. Education, guidelines, and colleague- and leadership support could together create psychological safety and empower health personnel to perform PAD. Key factors for sustainable implementation of PAD were facilitating the informant’s profound motivation for providing optimal health care and for reducing antimicrobial resistance. Informants were motivated by the prospect of a simplified PAD procedure. We identified three main needs for implementation of PAD: (1) creating psychological safety; (2) utilising clinicians’ inherent motivation and (3) optimal organisational structures. Conclusion A planned implementation of PAD must acknowledge clinicians’ need for psychological safety and aid reassurance through training, leadership, and guidelines. To implement PAD as an everyday practice it must be minimally disruptive and provide a contextually adaptive logistic chain. Also, the clinician’s motivation for providing the best possible healthcare should be utilised to aid implementation. The results of this study will aid sustainable implementation of PAD in Norway. Ethics The study was approved by the Western Norway Regional Committee for Medical Research Ethics (Study No:199210).

Abstract Acute kidney injury (AKI) prevalence in surgical patients is high, emphasizing the need for preventative measures. This study addresses the insufficient evidence on nephroprotective intraoperative fluid resuscitation and highlights the drawbacks of relying solely on serum creatinine/urine output to monitor kidney function. This study assessed the impact of intraoperative fluid management on AKI in female breast cancer patients undergoing autologous breast reconstruction, utilizing novel urinary biomarkers (TIMP-2 and IGFBP-7). In a monocentric prospective randomized controlled trial involving 40 patients, liberal (LFA) and restrictive (FRV) fluid management strategies were compared. TIMP-2 and IGFBP-7 biomarker levels were assessed using the NephroCheck (bioMerieux, France) test kit at preoperative, immediate postoperative, and 24-h postoperative stages. FRV showed significantly higher immediate postoperative biomarker levels, indicating renal tubular stress. FRV patients had 21% (4/19) experiencing AKI compared to 13% (2/15) in the LFA group according to KDIGO criteria (p = 0.385). Restrictive fluid resuscitation increases the risk of AKI in surgical patients significantly, emphasizing the necessity for individualized hemodynamic management. The findings underscore the importance of urinary biomarkers in early AKI detection.

Abstract Background The effect of empagliflozin, a sodium-glucose-co-transporter-2 inhibitor, on risk for myocardial infarction has not been fully characterized. Methods This study comprised prespecified and post-hoc analyses of the EMPA-REG OUTCOME trial in which 7020 people with type 2 diabetes (T2D) and cardiovascular disease [mostly atherosclerotic (ASCVD)] were randomized to empagliflozin or placebo and followed for a median 3.1 years. We assessed the effect of empagliflozin on total (first plus recurrent) events of centrally adjudicated fatal and non-fatal myocardial infarction (MI) using a negative binomial model with robust confidence intervals (CI) that preserves randomization and accounts for the within-patient correlation of multiple events. Post hoc, we analyzed types of MI: type 1 (related to plaque-rupture/thrombus), type 2 (myocardial supply–demand imbalance), type 3 (sudden-death related, i.e. fatal MI), type 4 (percutaneous coronary intervention-related), and type 5 (coronary artery bypass graft-related). MIs could be assigned to > 1 type. Results There were 421 total MIs (including recurrent); 299, 86, 26, 19, and 1 were classified as type 1, 2, 3, 4, and 5 events, respectively. Overall, empagliflozin reduced the risk of total MI events by 21% [rate ratio for empagliflozin vs. placebo, 0.79 (95% CI, 0.620–0.998), P = 0.0486], largely driven by its effect on type 1 [rate ratio, 0.79 (95% CI, 0.61–1.04)] and type 2 MIs [rate ratio, 0.67 (95% CI, 0.41–1.10)]. Conclusions In T2D patients with ASCVD, empagliflozin reduced the risk of MIs, with consistent effects across the two most common etiologies, i.e. type 1 and 2. Trail Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01131676.

BackgroundOlder veterans with anxiety disorders encounter multiple barriers to receiving mental health services, including transportation difficulties, physical limitations, and limited access to providers trained to work with older persons. To address both accessibility and the shortage of available providers, evidence-based treatments that can be delivered via guided self-management modalities are a potential solution. ObjectiveThis study aims to determine the feasibility and acceptability of a randomized controlled trial of 2 guided self-management interventions. This study compared the treatment effects of these 2 interventions (relaxation and health psychoeducation) on anxiety symptom severity and functioning in older veterans with anxiety disorders. Our exploratory aims examined factors related to home practices and treatment engagement and perceptions of the practices. MethodsParticipants were randomized to one of two video-delivered interventions: (1) Breathing, Relaxation, and Education for Anxiety Treatment in the Home Environment (BREATHE)—breathing and progressive relaxation or (2) Healthy Living for Reduced Anxiety—psychoeducation about lifestyle changes. Telephone coaching calls were conducted weekly. Measures of anxiety, depression, and functioning were obtained at baseline, week 4 (end of treatment), week 8, and week 12. Participants completed a semistructured interview at week 12. Analyses included descriptive statistics to summarize measures of intervention engagement; mixed-effects models to characterize symptom change, and qualitative analyses. ResultsOverall, 56 participants (n=48, 86% men; n=23, 41% from ethnic or racial minority groups; mean age 71.36, SD 6.19 y) were randomized. No difference in retention between study arms was found. The Healthy Living group (29/56, 52%) completed significantly more lessons (mean 3.68, SD 0.86) than the BREATHE group (27/56, 48%; mean 2.85, SD 1.43; t53=2.60; P=.01) but did not differ in completion of coaching calls. In the BREATHE group, greater baseline anxiety scores (r=–0.41; P=.03) and greater severity of medical comorbidity (r=–0.50; P=.009) were associated with fewer completed practices. There was no effect of intervention on change in total anxiety scores or functioning. For specific anxiety subtypes, Healthy Living produced a greater decline in somatic anxiety compared with BREATHE. Qualitative analyses found barriers to practicing, including difficulty setting time aside to practice, forgetting, or having other activities that interfered with BREATHE practices. Some participants described adapting their practice routine to fit their daily lives; some also used relaxation skills in everyday situations. ConclusionsThese findings suggest that a larger randomized controlled trial of guided self-management approaches to treating late-life anxiety is feasible; however, BREATHE was not effective in reducing anxiety compared with Healthy Living. Possible contributing factors may have been the reliance on a single technique. Progressive relaxation was reported to be enjoyable for most participants, but maintaining home practices was challenging. Those with milder anxiety severity and fewer health problems were better able to adhere to practices. Trial RegistrationClinicalTrials.gov NCT02400723; https://clinicaltrials.gov/study/NCT02400723

BackgroundThe identification of modifiable risk factors for intracranial glioma remains a significant challenge. While lifestyle factors and metabolic syndrome are well-established risk factors for various other cancers, their association with glioma risk remains unclear.ObjectivesThis study aims to conduct a comprehensive analysis of lifestyle factors and metabolic factors in relation to glioma risk.MethodsThe Cohort of Norway (CONOR) is a prospective, population-based health survey encompassing anthropometric measurements, blood tests and health questionnaires. CONOR data were linked to the National Cancer Registry to identify incident glioma cases. Follow-up time was calculated in person-years from the baseline examination until the date of glioma diagnosis, death, or the end of the follow-up period. Cox proportional hazards regression was used to calculate hazard ratios (HR).ResultsThe study cohort included 160,938 women and men. Over 2.8 million person-years of follow-up, 319 intracranial gliomas were diagnosed. Lifestyle factors such as physical activity, alcohol consumption, smoking, and marital status were not associated with glioma risk. There was no increased glioma risk among participants with diabetes mellitus or hypertension. Furthermore, metabolic syndrome in both women and men was not associated with an elevated risk of glioma. Blood lipids, including total cholesterol, triglycerides, and HDL, were not linked to glioma risk. However, increasing LDL levels were associated with a decreased risk of glioma in men (HR per category 0.84; 95% CI 0.74-0.96), but not in women.ConclusionThis is the first comprehensive prospective cohort study to evaluate potentially modifiable risk factors for glioma. Our findings do not support previously suggested associations between smoking, alcohol consumption, or metabolic syndrome and glioma risk.

Study region: Yarkon-Taninim groundwater basin, Israel. Study focus: A Paleocene-Eocene thermal episode caused an anomaly of barium and silica concentrations in the Eocene aquitard that were used as natural tracers for identifying and quantifying leakage into the Turonian – Upper Cenomanian aquifer through the Senonian-Paleocene (Mount-Scopus Group) strata. Increased concentrations of both Ba2+ and SiO2 in Turonian – Upper Cenomanian aquifer groundwater were supposed to be a sign of downward leakage from the Eocene aquitard. Within the Menashe syncline where these tracers pointed to the leakage, it was estimated by the balance method. Using this estimate, the area-averaged hydraulic conductivity of the intermedium layer was assessed from the Darcy’s law by using this layer thickness and a hydraulic gradient between the Avdat-Group aquitard and the Turonian – Upper Cenomanian aquifer. The calculation and integration of its results over the balance area by a grid with 1×1 km2 cells was performed by using the GIS-based ARGUS ONE software. Cl- and SO42- concentrations in the leakage have been estimated by using the mixing model considering the assessed leakage. PHREEQC software was used for solubility calculation of amorphous silica, quartz and barite at different temperatures, pH and salinities and for calculation of saturation indices of Ba-bearing minerals. New hydrological insights for the region: Previously the Senonian layers within synclines in the Yarkon-Taninim basin, which is the primary source of the groundwater supply in Israel, were supposed to be impermeable. This study has shown that the main leakage is concentrated in the Menashe syncline vicinity north of the Yarkon-Taninim basin. The two tracers first provided a possibility of the leakage assessment within the Menashe syncline: more than 2.3*106 – 11.4*106 m3 yr−1 (leakage rate of 5.4*10−5 – 2.6*10−4 m day−1 at the Eocene outcrops of the syncline). The average regional permeability of the Senonian aquiclude within the Menashe syncline was estimated in the range 7.7*10−5 – 3.8*10−4 m day−1, essentially higher as compared to the values for the Bet-Govrin syncline. The salinity of the slow leakage was assessed to be low; therefore, it will not damage the high-quality groundwater in the Turonian – Upper Cenomanian aquifer that is exploited for the potable water supply.

For the first time, the preparation of 3D biophotonic scaffolds is reported. Scaffolds are prepared using the porogen burn-off technique and are capable of converting NIR to green emission, used to release nitric oxide from S-Nitroso-N-Acetylpenicillamine. NIR to green conversion is obtained by mixing CaWO4 crystals (codoped with Yb3+ and Er3+) with bioactive borosilicate glass prior to the sintering process. The scaffold fabrication process has a detrimental impact on the upconversion properties of the crystals embedded in the porous scaffold due to the formation of internal/surface crystalline defects and surface chemical bonds in the crystals. Nonetheless, we demonstrate that the brightness of the green emission, under 980 nm pumping, is sufficient to release nitric oxide from the scaffold covered with S-Nitroso-N-Acetylpenicillamine. Addition of upconverter crystals, in the bioactive scaffold, has no impact on porosity, mechanical properties, reactivity in simulated body fluid nor cytocompatibility. The progressive dissolution of the scaffold, associated with the precipitation of a reactive layer (HA), has no noticeable influence on the green emission under 980 nm pumping, showing that the development of such biophotonic scaffolds opens the path to light actuated drug release in a spatial–temporal manner, in vivo. Degradation of the up-converter particles does not lead to differences in cells viability.

Background Inappropriate prescribing may have detrimental consequences for the patient and increase healthcare utilisation and costs. Academic detailing (AD) is an interactive outreach method to deliver non-commercial evidence-based medical information to healthcare professionals, aiming to improve patient care. Performing AD virtually has recently become more relevant, especially with the COVID-19 pandemic.Objectives The aim of this study was to explore general practitioners’ (GP’s) experiences and perceptions of virtually delivered AD.Methods We invited practicing GPs that had received virtual AD in Norway during autumn 2020. Semistructured individual interviews were audio and video recorded during February–May 2021. Interviews were transcribed and analysed applying thematic analysis according to Braun and Clarke.Results From interviews with nine GPs, we identified five themes concerning (1) informants’ satisfaction with virtual AD and their opinions about the detailers and their characteristics, (2) factors that are important for participation in AD, with the campaign topic being the most important, (3) a paradox between the informants’ desire for more time for discussion and the time constraint they are facing, (4) the many benefits of virtual AD compared with in-person AD and (5) the informants’ perceived learning outcomes are unaffected by mode of AD delivery.Conclusion Virtual AD worked very well in terms of scheduling the visit, using technology to facilitate the visit and achieving the same learning outcomes. Virtual AD should be offered to GPs as an alternative to the traditional in-person AD, especially in remote geographical areas or in circumstances when physical outreach is challenging.

Fotball er et globalt populærkulturelt fenomen. På grunn av det enorme engasjementet fotball skaper, følelsene som leves ut, deltakelsen i felles ritualer og dyrkelsen av lag og enkeltspillere, kan fotball sammenlignes med religion. Vi bruker Argentinas seier i fotball-VM i 2022 som utgangspunkt og viser gjennom empiriske eksempler hvordan den enorme interessen for fotball i Argentina og dyrkelsen av Maradona kan forstås som en form for folkereligion. Mot slutten av artikkelen diskuterer vi hvordan utforsking av fotball og religion kan brukes didaktisk i undervisningen om religion i skolen i Norge. Nøkkelord: fotball, fotball-VM, folkereligion, folkehelgener, cábala, Maradona