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BackgroundAlcohol use disorder (AUD) is a chronic, relapsing brain disorder that accounts for 5% of deaths annually, and there is an urgent need to develop new targets for therapeutic intervention. The glucagon-like peptide-1 (GLP-1) receptor agonist exenatide reduces alcohol consumption in rodents and nonhuman primates, but its efficacy in patients with AUD is unknown.MethodsIn a randomized, double-blinded, placebo-controlled clinical trial, treatment-seeking AUD patients were assigned to receive exenatide (2 mg subcutaneously) or placebo once weekly for 26 weeks, in addition to standard cognitive-behavioral therapy. The primary outcome was reduction in number of heavy drinking days. A subgroup also completed functional MRI (fMRI) and single-photon emission CT (SPECT) brain scans.ResultsA total of 127 patients were enrolled. Our data revealed that although exenatide did not significantly reduce the number of heavy drinking days compared with placebo, it significantly attenuated fMRI alcohol cue reactivity in the ventral striatum and septal area, which are crucial brain areas for drug reward and addiction. In addition, dopamine transporter availability was lower in the exenatide group compared with the placebo group. Exploratory analyses revealed that exenatide significantly reduced heavy drinking days and total alcohol intake in a subgroup of obese patients (BMI > 30 kg/m2). Adverse events were mainly gastrointestinal.ConclusionThis randomized controlled trial on the effects of a GLP-1 receptor agonist in AUD patients provides new important knowledge on the effects of GLP-1 receptor agonists as a novel treatment target in addiction.Trial registrationEudraCT: 2016-003343-11. ClinicalTrials.gov (NCT03232112).FundingNovavi Foundation; Research Foundation, Mental Health Services, Capital Region of Denmark; Research Foundation, Capital Region of Denmark; Ivan Nielsen Foundation; A.P. Moeller Foundation; Augustinus Foundation; Woerzner Foundation; Grosserer L.F. Foghts Foundation; Hartmann Foundation; Aase and Ejnar Danielsen Foundation; P.A. Messerschmidt and Wife Foundation; and Lundbeck Foundation.

Objectives This discussion paper aims to provide scientifically based recommendations on night shift schedules, including consecutive shifts, shift intervals and duration of shifts, which may reduce health and safety risks. Short-term physiological effects in terms of circadian disruption, inadequate sleep duration and quality, and fatigue were considered as possible links between night shift work and selected health and safety risks, namely, cancer, cardio-metabolic disease, injuries, and pregnancy-related outcomes. Method In early 2020, 15 experienced shift work researchers participated in a workshop where they identified relevant scientific literature within their main research area. Results Knowledge gaps and possible recommendations were discussed based on the current evidence. The consensus was that schedules which reduce circadian disruption may reduce cancer risk, particularly for breast cancer, and schedules that optimize sleep and reduce fatigue may reduce the occurrence of injuries. This is generally achieved with fewer consecutive night shifts, sufficient shift intervals, and shorter night shift duration. Conclusions Based on the limited, existing literature, we recommend that in order to reduce the risk of injuries and possibly breast cancer, night shift schedules have: (i) ≤3 consecutive night shifts; (ii) shift intervals of ≥11 hours; and (iii) ≤9 hours shift duration. In special cases - eg, oil rigs and other isolated workplaces with better possibilities to adapt to daytime sleep - additional or other recommendations may apply. Finally, to reduce risk of miscarriage, pregnant women should not work more than one night shift in a week.

A substantial untapped potential for risk reduction may be fulfilled by applying intensive lifestyle interventions targeting the co-existing risky lifestyle factors Smoking, Nutrition (both malnutrition and obesity), risky Alcohol intake, and Physical inactivity (SNAP) before surgery. This trial will compare the effect of combined and individually tailored prehabilitation with standard care on postoperative outcomes, health, and cost-effectiveness in short and long term in participants undergoing ventral hernia repair. An interview study will be nested within the randomised trial. The study is a multicenter, parallel-group, superiority randomised clinical trial. A total of 400 adult participants undergoing ventral hernia repair with ≥1 SNAP factor will be allocated to the individually tailored STRONG programme or standard care. The STRONG programme is initiated at least four weeks prior to surgery and consists of six sessions. It is delivered as one session a week, approximately, and includes patient education, motivational, and pharmaceutical supports. The primary outcome is postoperative complications requiring treatment within 30 days. Secondary outcomes address other surgical outcomes, changes in lifestyle, health, and cost-effectiveness. Follow-up takes place after 6 weeks (the end of intervention), at surgery, and 30 days, 90 days, and 6 months after surgery, respectively. Long-term data on health and costs will be obtained from nationwide registries after two years. Eligible trial participants will be invited to a semi-structured interview study at baseline. Their reflections on the STRONG programme and the choice of participating in the trial or not will be explored. Many patients have multiple SNAP factors adding to the risk of complications related to surgery. As these are modifiable, prehabilitation may be an area with great potential for risk reduction. Nevertheless, no well-acknowledged and evidence-based strategies exist in the preoperative period. The STRONG programme is tailored specifically to the individual patient's preidentified needs including up to all five common risky SNAP factors and may tap into the large unused potential for risk reduction. Overall, the study will add important new knowledge on the effect of individually tailored prehabilitation on complications and other important outcomes in elective surgery, and also clarify if this intervention will have long-lasting implications. www.clinicaltrials.gov (NCT06611462).

Blooms of pigmented algae darken the surface of glaciers and ice sheets, thereby enhancing solar energy absorption and amplifying ice and snow melt. The impacts of algal pigment and community composition on surface darkening are still poorly understood. Here, we characterise glacier ice and snow algal pigment signatures on snow and bare ice surfaces and study their role in photophysiology and energy absorption on three glaciers in Southeast Greenland. Purpurogallin and astaxanthin esters dominated the glacier ice and snow algal pigment pools (mass ratios to chlorophyll a of 32 and 56, respectively). Algal biomass and pigments impacted chromophoric dissolved organic matter concentrations. Despite the effective absorption of astaxanthin esters at wavelengths where incoming irradiance peaks, the cellular energy absorption of snow algae was 95% lower than anticipated from their pigmentation, due to pigment packaging. The energy absorption of glacier ice algae was consequently ~ 5 × higher. On bare ice, snow algae may have locally contributed up to 13% to total biological radiative forcing, despite contributing 44% to total biomass. Our results give new insights into the impact of algal community composition on bare ice energy absorption and biomass accumulation during snow melt.

Overweight and obesity are linked to mitochondrial alterations, impaired glucose tolerance and a high risk of type 2 diabetes. Time-restricted eating (TRE) may aid in facilitating weight loss to prevent diabetes. Here, we investigated if TRE in individuals with overweight and prediabetes or obesity affects mitochondrial bioenergetics of peripheral blood mononuclear cells (PBMCs) and platelets using the Seahorse extracellular flux technology. In a 3-month randomized controlled trial, PBMCs/platelets were analyzed from 52 participants before and after a TRE intervention with a 10-h eating window or habitual living. PBMC and platelet respiratory function was evaluated through sequential addition of substrates, uncouplers, and inhibitors in living cells. After 3 months, there were no statistically significant differences in mitochondrial respiration within or between the TRE and control groups. Association analyses between PBMC/platelet respiration and clinical parameters including body mass index and fat mass showed no significant effects. In conclusion, 3 months of 10-h TRE does not alter the mitochondrial bioenergetics of PBMCs and platelets in individuals with high risk of type 2 diabetes.

IntroductionAttention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder among children and adolescents. The disorder negatively influences their academic performance and social relations, and their quality of life (QoL) is lower than that of peers without ADHD. The majority of children and adolescents with ADHD are treated with medication that potentially has an insufficient effect or frequently occurring adverse events. Physical activity is thought to alter the physiology of ADHD by affecting the same catecholaminergic system in the brain which is targeted by medication.Methods and analysisThis protocol is written in accordance with the ‘Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols’ guideline. Randomised clinical trials with participating children and adolescents between the ages of 3 and 18 years with a primary diagnosis of ADHD or hyperkinetic disorder will be included in the systematic review. The main objective of the review is to examine the effect of physical activity on QoL, executive functions, symptoms and functional impairment in this population. Previous systematic reviews on the effect of physical activity in children and adolescents with ADHD have several methodological and conceptual limitations. These reviews, for example, included both randomised and non-randomised clinical trials or had restrictions regarding the frequency and intensity of the physical activity interventions they included. The present review will include the newest studies in the field and follow the main principles outlined in the ‘Cochrane Handbook for Systematic Reviews of Interventions’. Furthermore, it will be the first review in the field to include QoL as an outcome and to apply trial sequential analysis as part of the meta-analysis.Ethics and disseminationAs the systematic review is a secondary analysis of data from primary trials, approval from an ethics committee is not required. The results of the review will be published in a peer-reviewed scientific journal and presented at relevant conferences.Trial registration numberThis protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) on 16 August 2024 (CRD42024576670).

Abstract Context Increased triglyceride-rich remnants represent a causal risk factor for ischemic cardiovascular disease. Objective We tested the hypothesis that low high-density lipoprotein (HDL) cholesterol can be used to monitor long-term high triglycerides/remnant cholesterol, just as high hemoglobin A1c (HbA1c) can be used to monitor long-term high glucose levels. Design, Setting, Participants, and Interventions We studied cross-sectionally 108 731 individuals, dynamically 1313 individuals with lipid measurement at 10 repeated visits, short-term 305 individuals during a fat load, and long-term 10 479 individuals with 2 lipid measurements 10 years apart. Main Outcome Measures Levels of HDL cholesterol and triglycerides. Results Cross-sectionally, HDL cholesterol was inversely associated with triglycerides (R2 = 0.26) and remnant cholesterol (R2 = 0.26). Dynamically, major changes in triglyceride levels from measurement to measurement were mimicked by corresponding modest changes in HDL cholesterol. In the short-term after a fat load, median triglycerides increased 96% while HDL cholesterol decreased only 1%. Long-term, in individuals with measurements 10 years apart, those who initially had the highest triglycerides and corresponding lowest HDL cholesterol, still had highest triglycerides and lowest HDL cholesterol 10 years later. Prospectively, individuals with increased triglycerides/remnant cholesterol had increased risk of myocardial infarction; however, when the HDL cholesterol monitoring was removed, increased triglycerides/remnant cholesterol were largely no longer associated with increased risk of myocardial infarction. Conclusions Low HDL cholesterol is a stable marker of average high triglycerides/remnant cholesterol. This suggests that low HDL cholesterol can be used to monitor long-term average high triglycerides and remnant cholesterol, analogous to high HbA1c as a long-term monitor of average high glucose levels.

Background Cardiovascular autonomic neuropathy (CAN) is a life-threatening complication associated with diabetes but may also be present without diabetes. A glycaemic threshold for autonomic impairment is not yet established. The purpose of this study was to compare CAN status in people with and without diabetes and to investigate which factors contributed the most to the presence and severity of CAN. Methods We included 240 participants from three different cohorts: non-diabetic people ( n  = 40), people with overweight or obesity with or without prediabetes ( n  = 100), and people with type 2 diabetes ( n  = 100). All participants underwent cardiovascular autonomic reflex tests using the Vagus™ device, and clinical variables, including age, sex, body mass index, blood pressure, HbA1c, blood lipid profile, and cardiovascular risk score, were recorded. Results In total, 14% without and 42% with diabetes had CAN. HbA1c had the most significant influence on CAN scores, with a cutpoint of 45.5 mmol/l corresponding to established prediabetes (sensitivity: 0.66; specificity: 0.71). In people with HbA1c levels below the cutpoint, those with CAN had lower levels of high-density lipoprotein (HDL) (1.1 vs. 1.4 mmol/mol, p  = 0.003) and higher cardiovascular risk scores ( p  < 0.001) compared to people without CAN. No differences in any of the investigated clinical factors were seen between people with HbA1c levels above the cutpoint with or without CAN. Conclusions In individuals with HbA1c levels below 45.5 mmol/l, both HDL levels and cardiovascular risk score were associated with CAN status. Therefore, it may be beneficial to screen for CAN in individuals susceptible to prediabetes, who also exhibit low HDL levels and a high cardiovascular risk.

Gut-derived hormones have been suggested to play a role in bone homeostasis following food intake, although the associations are highly complex and not fully understood. In a randomized, two-day cross-over study on 14 healthy individuals, we performed postprandial time-course studies to examine the associations of the bone remodeling markers carboxyl-terminal collagen type I crosslinks (CTX) and procollagen type 1 N-terminal propeptide (P1NP) with the gut hormones glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP-1), and peptide YY (PYY) using two different meal types—a standardized mixed meal (498 kcal) or a granola bar (260 kcal). Plasma concentrations of total GIP, total GLP-1, total PYY, CTX, and P1NP were measured up to 240 min after meal intake, and the incremental area under the curve (iAUC) for each marker was calculated. The iAUC of CTX and P1NP were used to assess associations with the iAUC of GIP, GLP-1, and PYY in linear mixed effect models adjusted for meal type. CTX was positively associated with GIP and GLP-1, and it was inversely associated with PYY (all p < 0.001). No associations of P1NP with GIP or GLP-1 and PYY were found. In conclusion, the postprandial responses of the gut hormones GIP, GLP-1, and PYY are associated with the bone resorption marker CTX, supporting a link between gut hormones and bone homeostasis following food intake.

The aim of this article is to provide an overview of the work within the field of intercultural communication which specifically investigates interactions through verbal humor. By the term intercultural we mean encounters by speakers of different languages and we defi ne verbal humor as natural (i.e. not pre-planned or scripted) and expressed via spoken language in face–to–face interactions. We have specifically sought to include studies published within the last 20 years, which rely on naturalistic data (as opposed to experimental data). We found that studies within the areas of workplace interactions and second language learning were the most prominent. We reflect on the reviewed studies and the methods employed. Finally, we suggest avenues for further research.