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It is not well investigated whether exposure to specific drug classes is associated with COVID-19. We investigated the risk of SARS-CoV-2 infection and severe COVID-19 among healthcare workers according to prescription drug use. We conducted an observational study among Danish healthcare workers. SARS-CoV-2 positivity was defined as a positive PCR/ELISA test throughout 2020 and severe COVID-19 as any above 48-hour hospitalization within 14 days after infection. Patient characteristics came from online surveys while data on SARS-CoV-2, drugs and hospitalizations came from Danish Health Registers. Infected individuals were matched with uninfected controls based on age, sex, and chronic diseases. Drug exposure was defined as any prescription redemption in the past six and one month(s) before infection for each drug class. Models assessing the risk of infection (conditional logistic regression) and severe COVID-19 (logistic regressions) versus drug usage were adjusted for BMI, smoking, alcohol, education, region, and patient contact when possible. We matched 5,710 SARS-CoV-2-infected cases with 57,021 controls. The odds of infection were reduced by calcium channel blocker (adjusted odds ratio (aOR) 0.81, 95% Confidence Interval (CI): 0.66-1.00) and vasoprotective drug (aOR 0.77, CI: 0.62-0.95) usage during the six months before infection compared to no usage. Exposure to antibacterials in the past month increased the odds of infection (aOR 1.27, CI: 1.09-1.48). Among infected participants, the odds of severe COVID-19 were higher with usage of almost any investigated drug, especially, diuretics (crude odds radio (OR) 4.82, CI:2.15-10.83), obstructive airway disease drugs (OR 4.49, CI: 2.49-8.08), and antibacterials (OR 2.74 CI:1.62-4.61). In conclusion, antibacterials were associated with more SARS-CoV-2 infections and calcium channel blockers with less. Once infected, users of prescription drugs had higher odds of developing severe COVID-19. These findings suggest a need for studies to clarify interactions between specific drug groups, behaviour, known risk factors, and disease susceptibility/severity.

Abstract Glycans play an important role in biology with multiple cellular functions ranging from cell signaling, mobility and growth to protein folding and localization. The N-glycosylation state within a tissue has been found to vary greatly between healthy and diseased patients and has proven to have an important clinical diagnostic value. Matrix assisted laser-desorption ionization (MALDI) mass spectrometry imaging (MSI) allows for untargeted analysis of biomolecules, including N-glycans, on a tissue section and provides a spatial context of the analyte. Until now, N-glycans have been predominantly analyzed using MALDI MSI on formalin-fixed paraffin embedded (FFPE) tissue sections, however this greatly reduces the clinical applicability, as the FFPE embedding process alters the biological environment of the tissue. Here we developed a protocol that allows for MALDI MSI of N-glycans from fresh frozen tissue that matches the current standard of FFPE analysis. By optimizing several steps in the sample preparation, we see orders of magnitude increase in signal intensity. Furthermore, this method limits delocalization of released N-glycans, thus improving the effective spatial resolution of the label-free molecular images. This protocol provides a novel perspective towards clinical application of MALDI MSI and capitalizes on the diagnostic value of N-glycan analysis.

Summary: SARS-CoV-2 Omicron quickly spread globally, also in regions with high vaccination coverage, emphasizing the importance of exploring the immunological requirements for protection against Omicron breakthrough infection.The test-negative matched case-control study (N = 964) characterized Omicron breakthrough infections in triple-vaccinated individuals from the ENFORCE cohort. Within 60 days before a PCR test spike-specific IgG levels were significantly lower in cases compared to controls (GMR [95% CI] for BA.2: 0.83 [0.73–0.95], p = 0.006). Multivariable logistic regression showed significant associations between high antibody levels and lower odds of infection (aOR [95% CI] for BA.2 spike-specific IgG: 0.65 [0.48–0.88], p = 0.006 and BA.2 ACE2-blocking antibodies: 0.46 [0.30–0.69], p = 0.0002). A sex-stratified analysis showed more pronounced associations for females than males.High levels of vaccine-induced antibodies provide partial protection against Omicron breakthrough infections. This is important knowledge to further characterize a threshold for protection against new variants and to estimate the necessity and timing of booster vaccination.

Herein, we describe the design and synthesis of 16 neo‐glycolipids that are potential permeation enhancers for oral drug delivery of peptide therapeutics. These amphiphilic neo‐glycolipids are composed of fatty acids and various carbohydrates (d‐glucose, lactose, cellobiose, maltose) via an oxime linker. The ability of the synthesized neo‐glycolipids to enhance permeation of fluorescein‐labelled dextran (4 kDa) or 3H‐mannitol across intestinal epithelium was investigated in vitro using monolayers of human epithelial Caco‐2 cells. Their effects were compared with (pre‐)clinically known enhancers as reference compounds; sodium salts of octanoic, decanoic, and dodecanoic acid, and sodium salcaprozate (SNAC). Most neo‐glycolipids increased the permeation of the model compounds, proving that neo‐glycolipids, which possess vastly different properties from the reference compounds, e. g. in terms of clogD and polar surface area, are effective permeation enhancers. The neo‐glycolipid based on decanoic acid and glucose was more potent than related compounds based on disaccharides. Significant differences in solubility and cellular compatibility were found for neo‐glyolipids based on different carbohydrates. Finally, neo‐glycolipids were evaluated as permeation enhancers for the peptide hormone PYY3‐36. Glucose‐ and maltose‐derived neo‐glycolipids based on decanoic and dodecanoic acid showed promising enhancements in PYY3‐36 permeation in vitro while maintaining good cellular compatibility, relevant for oral delivery of obesity treatments. [ABSTRACT FROM AUTHOR]

Aims: The combination of cagrilintide and semaglutide (CagriSema) is being developed for the treatment of obesity and type 2 diabetes. The objective of this thorough QT study was to confirm that cagrilintide does not result in a clinically relevant prolongation in cardiac repolarization compared with placebo. Materials and Methods: This was a double‐blind study (NCT05804162) in which healthy participants were randomized to cagrilintide, administered as a once‐weekly subcutaneous injection dose escalated to 4.5 mg, or a placebo. The primary end point was the time‐matched change from baseline in Fridericia heart rate–corrected QT interval (QTcF) at 12‐, 24‐, 48‐ and 72 h after the last cagrilintide 4.5‐mg dose. To conclude that cagrilintide does not induce a clinically relevant prolongation, the upper limit of the two‐sided 90% confidence interval (CI) for the treatment difference at each of the four time points must fall below 10 ms. To establish QT assay sensitivity, participants in the placebo arms received a single 400‐mg oral moxifloxacin dose as a positive control and moxifloxacin placebo in a nested cross‐over fashion. Results: A total of 105 participants received cagrilintide (n = 53) or placebo (n = 52). No clinically relevant QTcF prolongation occurred after the last cagrilintide 4.5‐mg dose; the upper limits of the two‐sided 90% CIs of the placebo‐adjusted QTcF changes from baseline were below 10 ms at all time points. QT assay sensitivity was demonstrated with moxifloxacin as a positive control. Conclusions: Cagrilintide did not result in clinically relevant QTcF prolongation, indicating no increased risk of ventricular tachyarrhythmias. [ABSTRACT FROM AUTHOR]

It is not well investigated whether exposure to specific drug classes is associated with COVID-19. We investigated the risk of SARS-CoV-2 infection and severe COVID-19 among healthcare workers according to prescription drug use. We conducted an observational study among Danish healthcare workers. SARS-CoV-2 positivity was defined as a positive PCR/ELISA test throughout 2020 and severe COVID-19 as any above 48-hour hospitalization within 14 days after infection. Patient characteristics came from online surveys while data on SARS-CoV-2, drugs and hospitalizations came from Danish Health Registers. Infected individuals were matched with uninfected controls based on age, sex, and chronic diseases. Drug exposure was defined as any prescription redemption in the past six and one month(s) before infection for each drug class. Models assessing the risk of infection (conditional logistic regression) and severe COVID-19 (logistic regressions) versus drug usage were adjusted for BMI, smoking, alcohol, education, region, and patient contact when possible. We matched 5,710 SARS-CoV-2-infected cases with 57,021 controls. The odds of infection were reduced by calcium channel blocker (adjusted odds ratio (aOR) 0.81, 95% Confidence Interval (CI): 0.66–1.00) and vasoprotective drug (aOR 0.77, CI: 0.62–0.95) usage during the six months before infection compared to no usage. Exposure to antibacterials in the past month increased the odds of infection (aOR 1.27, CI: 1.09–1.48). Among infected participants, the odds of severe COVID-19 were higher with usage of almost any investigated drug, especially, diuretics (crude odds radio (OR) 4.82, CI:2.15–10.83), obstructive airway disease drugs (OR 4.49, CI: 2.49–8.08), and antibacterials (OR 2.74 CI:1.62–4.61). In conclusion, antibacterials were associated with more SARS-CoV-2 infections and calcium channel blockers with less. Once infected, users of prescription drugs had higher odds of developing severe COVID-19. These findings suggest a need for studies to clarify interactions between specific drug groups, behaviour, known risk factors, and disease susceptibility/severity. [ABSTRACT FROM AUTHOR]

The SARS-CoV-2 pandemic has, as of July 2022, infected more than 550 million people and caused over 6 million deaths across the world. COVID-19 vaccines were quickly developed to protect against severe disease, hospitalization and death. In the present study, we performed a direct comparative analysis of four COVID-19 vaccines: BNT162b2 (Pfizer/BioNTech), mRNA-1273 (Moderna), ChAdOx1 (Oxford/AstraZeneca) and Ad26.COV2.S (Johnson & Johnson/Janssen), following primary and booster vaccination. We focused on the vaccine-induced antibody-mediated immune response against multiple SARS-CoV-2 variants: wildtype, B.1.1.7 (Alpha), B.1.351 (Beta), B.1.617.2 (Delta) and B.1.1.529 (Omicron). The analysis included the quantification of total IgG levels against SARS-CoV-2 Spike, as well as the quantification of antibody neutralization titers. Furthermore, the study assessed the high-throughput ACE2 competition assay as a surrogate for the traditional pseudovirus neutralization assay. The results demonstrated marked differences in antibody-mediated immune responses. The lowest Spike-specific IgG levels and antibody neutralization titers were induced by one dose of the Ad26.COV2.S vaccine, intermediate levels by two doses of the BNT162b2 vaccine, and the highest levels by two doses of the mRNA-1273 vaccine or heterologous vaccination of one dose of the ChAdOx1 vaccine and a subsequent mRNA vaccine. The study also demonstrated that accumulation of SARS-CoV-2 Spike protein mutations was accompanied by a marked decline in antibody neutralization capacity, especially for B.1.1.529. Administration of a booster dose was shown to significantly increase Spike-specific IgG levels and antibody neutralization titers, erasing the differences between the vaccine-induced antibody-mediated immune response between the four vaccines. The findings of this study highlight the importance of booster vaccines and the potential inclusion of future heterologous vaccination strategies for broad protection against current and emerging SARS-CoV-2 variants.

Abstract Aims To explore Registered Nurses' experiences and perceptions with National Early Warning Score and Individual Early Warning Score to identify patient deterioration. Design A qualitative exploratory design. Methods Six focus groups were conducted at six Danish hospitals from February to June 2019. Registered Nurses from both medical, surgical and emergency departments participated. The focus groups were analysed using content analysis. Results One theme and four categories were identified. Theme: Meaningful in identifying patient deterioration but causing frustration due to lack of flexibility. Categories: (a) Inter‐professional collaboration strengthened through the use of Early Warning Score systems, (b) Enhanced professional development and communication among nurses when using Early Warning Score systems, (c) Detecting patient deterioration by integrating nurses' clinical gaze with Early Warning Score systems and (d) Modification and fear of making mistakes when using Early Warning Score systems.

We developed a synthesis strategy involving a diazo transfer reaction and subsequent click reaction to conjugate a murine cathelicidin-related antimicrobial peptide (CRAMP18–35) to chitosan and hydroxypropyl chitosan (HPC), confirmed the structure, and investigated the antimicrobial activity. Chitosan azide and HPC-azide were prepared with a low degree of azidation by reacting the parent chitosan and HPC with imidazole sulfonyl azide hydrochloride. CRAMP18–35 carrying an N-terminal pentynoyl group was successfully grafted onto chitosan and HPC via copper-catalyzed azide–alkyne cycloaddition (CuAAC) reaction. The chitosan–peptide conjugates were characterized by IR spectroscopy and proton NMR to confirm the conversion of the azide to 1,2,3-triazole and to determine the degree of substitution (DS). The DS of the chitosan and HPC CRAMP18–35 conjugates was 0.20 and 0.13, respectively. The antibacterial activity of chitosan–peptide conjugates was evaluated for activity against two species of Gram-positive bacteria, Staphylococcus aureus (S. aureus) and Enterococcus faecalis (E. faecalis), and two species of Gram-negative bacteria, Escherichia coli (E. coli) and Pseudomonas aeruginosa (P. aeruginosa). The antimicrobial peptide conjugates were selectively active against the Gram-negative bacteria and lacking activity against Gram-positive bacteria. [ABSTRACT FROM AUTHOR]

The wolf (Canis lupus) is arguably the most successful species at recolonizing its now human‐dominated former ranges in Europe and North America. Over the centuries while the wolf was absent, humans have transformed ecosystems to a large extent. In this paper, we highlight key aspects of these human‐modified ecosystems that include changes to (meso)carnivore communities, wolves themselves (genetics, behaviour), woody plant communities and the playing field for predator–prey interactions (landscape structure).We argue that the recognition of the novelty of human‐modified ecosystems logically leads to novel pathways of how wolves can influence ecosystem functioning. Thus far, the ecological impacts of wolves in human‐dominated systems have largely been predicted based on the documented effects they have on prey species or lower trophic levels in well‐preserved systems with low human impact. However, wolves in human‐modified ecosystems will engage in an array of novel interactions and potential novel trophic cascades that do not occur in more natural ecosystems with lower human impact.This should encourage us to re‐assess the questions we ask about wolf impacts in novel systems. A promising direction for future studies is exploring what novel interactions establish and under what conditions wolves can exert their ecosystem impacts (context dependence) in the human‐modified ecosystems wolves are recolonizing.Policy implications. Understanding these novel interactions and the context dependence of ecosystem impacts could guide us to act to improve conditions to enable wolves to exert their ecosystem impacts again. These novel interactions may be the true ecological and societal value of having wolves returning to human‐modified landscapes. [ABSTRACT FROM AUTHOR]

His-tagged proteins can undergo N-terminal acylation as an undesired side-reaction. Here, the authors utilize this to develop a method for highly selective acylation and further modification of peptides and proteins using an optimized His sequence and 4-methoxyphenyl esters as acyl donors.