Does semaglutide reduce alcohol intake in Danish patients with alcohol use disorder and comorbid obesity? Trial protocol of a randomised, double-blinded, placebo-controlled clinical trial (the SEMALCO trial).

Introduction: Alcohol use disorder (AUD) is a massive burden for the individual, relatives and society. Despite this, the treatment gap is wide compared with other mental health disorders. Treatment options are sparse, with only three Food and Drug Administration (FDA)-approved pharmacotherapies.

A multi-valent polymyxin-based fluorescent probe for the detection of Gram-negative infections.

A multi-branched fluorogenic probe for the rapid and specific detection of Gram-negative bacteria is reported. Three Gram-negative-targeting azido-modified polymyxins were clicked onto a trivalent scaffold functionalised with the environmental green-emitting fluorophore 7-nitrobenz-2-oxa-1,3-diazole. The probe allowed wash-free detection of target bacteria with increased sensitivity and lower limits of detection compared to monovalent probes.

Development and testing of a generic patient decision aid for end-of-life care.

Objectives: The objective of this study was to develop and test a patient decision aid for end-of-life care to be used when some or all life-sustaining treatments have been withheld or withdrawn.

Methods: A multi-professional, multi-sectorial group together with patients and relatives used a systematic process to develop and test the patient decision aid, including alpha and beta testing.

Results: Healthcare professionals, patients and relatives were involved in the development and testing.

E-consultation as existential media: Exploring doctor-patient 'digital thrownness' in Danish general practice.

In this article we use an existential media framework to explore the asynchronous, written and digital form of GP-patient communication that takes place through e-consultations in a Danish general practice context. This approach acknowledges e-consultation as more than a tool for information delivery and frames GP and patient not as skilful media users but as dependent co-existers: Both thrown into and trying to navigate the digital healthcare ecology. Through a thematic analysis of 38 semi-structured qualitative interviews with patients and GPs we carve out three themes unpacking the existential dimensions of e-consultation: 1.

Tweezer Dyads for H-Bond Assisted Cooperativity in Tandem Uncaging Systems.

"Tandem" uncaging systems, in which a photolabile protecting group (PPG) is sensitized by an energy-harvesting antenna, may increase the photosensitivity of PPGs by several orders of magnitude for two-photon (2P) photorelease. Yet, they remain poorly accessible because of arduous multi-step synthesis. In this work, we design efficient tandem uncaging systems by (i) using a convenient assembly of the building blocks relying on click chemistry, (ii) introducing H-bonding induced proximity thus facilitating (iii) photoinduced electron transfer (PeT) as a cooperative mechanism.

Benchmarking NGS-Based HLA Typing Algorithms.

Knowledge of the expected accuracy of HLA typing algorithms is important when choosing between algorithms and when evaluating the HLA typing predictions of an algorithm. This chapter guides the reader through an example benchmarking study that evaluates the performances of four NGS-based HLA typing algorithms as well as outlining factors to consider, when designing and running such a benchmarking study. The code related to this benchmarking workflow can be found at https://github.

Effect of the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide on alcohol consumption in alcohol-preferring male vervet monkeys.

Rationale: Glucagon-like peptide-1 (GLP-1) receptor agonists reduce alcohol consumption in rodents and non-human primates. Semaglutide is a new long-acting GLP-1 receptor agonist, widely used in the clinic against type 2 diabetes and obesity. It is also reported to reduce alcohol intake in rodents.

The LIVER CARE trial - screening for liver disease in individuals attending treatment for alcohol use disorder: a randomized controlled feasibility trial.

Background: Alcohol-related liver disease is a preventable disease with high mortality. If individuals with alcohol-related liver disease were to be diagnosed earlier by screening and they reduced their alcohol consumption, lives lost to alcohol-related liver disease might be saved. A liver stiffness measurement (FibroScan©) is a key tool to screen for alcohol-related liver disease in asymptomatic individuals.

My time, your time, our time. Older patients' and GPs' time sensibilities around email consultations.

In this study, we discuss how email consultations in general practice operate as a temporal technology, transforming working conditions and power relations between general practitioners (GPs) and patients. We draw on empirical material from Denmark in the form of a set of semi-structured interviews with 53 patients and 15 GPs, including two focus group discussions with 17 GPs. Our theoretical point of departure stems primarily from media theorist Sarah Sharma's (2014) concept of power-chronography, which describes how power is embedded in temporal relations and everyday life and secondarily from sociologist, Judy Wajcman's (2015) concept of multiple temporal landscapes.

A dual action coumarin-camptothecin polymer for light responsive drug release and photodynamic therapy.

A light-responsive polymer allowing the controlled release of camptothecin and the generation of reactive oxygen species (ROS) is reported. The polymer was prepared by controlled copolymerisation of water-soluble ,-dimethyl acrylamide with a bromocoumarin methacrylate monomer. The lipophilic chemotherapy agent camptothecin was caged onto the coumarin unit a photo-cleavable carbonate ester enabling light-triggered cargo release.

Riboflavin-Vancomycin Conjugate Enables Simultaneous Antibiotic Photo-Release and Photodynamic Killing against Resistant Gram-Positive Pathogens.

Decades of antibiotic misuse have led to alarming levels of antimicrobial resistance, and the development of alternative diagnostic and therapeutic strategies to delineate and treat infections is a global priority. In particular, the nosocomial, multidrug-resistant "ESKAPE" pathogens such as Gram-positive methicillin-resistant (MRSA) and vancomycin-resistant (VRE) urgently require alternative treatments. Here, we developed light-activated molecules based on the conjugation of the FDA-approved photosensitizer riboflavin to the Gram-positive specific ligand vancomycin to enable targeted antimicrobial photodynamic therapy.

Fluorophore-Tagged Poly-Lysine RAFT Agents: Controlled Synthesis of Trackable Cell-Penetrating Peptide-Polymers.

The conjugation of a fluorophore and a variety of cell-penetrating peptides onto a RAFT agent allowed for the synthesis of polymers of defined sizes with quantifiable cell-uptake. Each peptide-RAFT agent was used to polymerize acrylamide, acrylate, and styrene monomers to form high or low molecular weight polymers (here 50 or 7.5 kDa) with the peptide having no influence on the RAFT agent's control.

Module walking using an SH3-like cell-wall-binding domain leads to a new GH184 family of muramidases.

Muramidases (also known as lysozymes) hydrolyse the peptidoglycan component of the bacterial cell wall and are found in many glycoside hydrolase (GH) families. Similar to other glycoside hydrolases, muramidases sometimes have noncatalytic domains that facilitate their interaction with the substrate. Here, the identification, characterization and X-ray structure of a novel fungal GH24 muramidase from Trichophaea saccata is first described, in which an SH3-like cell-wall-binding domain (CWBD) was identified by structure comparison in addition to its catalytic domain.

DNA immunization with predicted T-cell epitopes protects against lethal SARS-CoV-2 infection in K18-hACE2 mice.

The global SARS-CoV-2 pandemic caused significant social and economic disruption worldwide, despite highly effective vaccines being developed at an unprecedented speed. Because the first licensed vaccines target only single B-cell antigens, antigenic drift could lead to loss of efficacy against emerging SARS-CoV-2 variants. Improving B-cell vaccines by including multiple T-cell epitopes could solve this problem.

Solid-Phase Synthesis of -Tetrazines.

An efficient synthesis of -tetrazines by solid-phase methods is described. This synthesis route was compatible with different solid-phase resins and linkers and did not require metal catalysts or high temperatures. Monosubstituted tetrazines were routinely synthesized using thiol-promoted chemistry, using dichloromethane as a carbon source, while disubstituted unsymmetrical aryl or alkyl tetrazines were synthesized using readily available nitriles.

Does the time to diagnosis and treatment influence outcome in adults with pleural infections.

Objective: To investigate the effect of early diagnosis and intervention in adult patients with complicated parapneumonic pleural effusion or pleural empyema and the impact on outcomes.

Methods: A systematic review based on a literature search of the PubMed database was performed.

Results: Eleven eligible studies were included; nine observational studies and two randomised controlled trials totalling a study population of 10,717 patients.

Benchmarking freely available HLA typing algorithms across varying genes, coverages and typing resolutions.

Identifying the specific human leukocyte antigen (HLA) allele combination of an individual is crucial in organ donation, risk assessment of autoimmune and infectious diseases and cancer immunotherapy. However, due to the high genetic polymorphism in this region, HLA typing requires specialized methods. We investigated the performance of five next-generation sequencing (NGS) based HLA typing tools with a non-restricted license namely HLA*LA, Optitype, HISAT-genotype, Kourami and STC-Seq.

Exenatide once weekly for alcohol use disorder investigated in a randomized, placebo-controlled clinical trial.

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.

Introducing quality clusters in general practice - a qualitative study of the experiences of cluster coordinators.

Background: In 2018, the concept of clusters was introduced as a new model for data-driven quality improvement in general practice in Denmark. However, there is little research on the development and implementation of general practice clusters. The study explores how the cluster coordinators responsible for leading the clusters forward enacted and experienced their role during the early years of the clusters with attention to the challenges and enablers perceived in the process.

Two-Photon Absorption: An Open Door to the NIR-II Biological Window?

The way in which photons travel through biological tissues and subsequently become scattered or absorbed is a key limitation for traditional optical medical imaging techniques using visible light. In contrast, near-infrared wavelengths, in particular those above 1000 nm, penetrate deeper in tissues and undergo less scattering and cause less photo-damage, which describes the so-called "second biological transparency window". Unfortunately, current dyes and imaging probes have severely limited absorption profiles at such long wavelengths, and molecular engineering of novel NIR-II dyes can be a tedious and unpredictable process, which limits access to this optical window and impedes further developments.

The role of glucagon-like peptide 1 (GLP-1) in addictive disorders.

Drug, alcohol and tobacco use disorders are a global burden affecting millions of people. Despite decades of research, treatment options are sparse or missing, and relapse rates are high. Glucagon-like peptide 1 (GLP-1) is released in the small intestine, promotes blood glucose homeostasis, slows gastric emptying and reduces appetite.