The surge of antimicrobial resistance threatens efficacy of current antibiotics, particularly against Pseudomonas aeruginosa, a highly resistant gram-negative pathogen. The asymmetric outer membrane (OM) of P. aeruginosa combined with its array of efflux pumps provide a barrier to xenobiotic accumulation, thus making antibiotic discovery challenging.
View Article and Find Full Text PDFCultivations of Chinese Hamster Ovary (CHO) cells in a perfusion setup were conducted in the presence of super physiological concentrations of L-Arginine to investigate the impact on transmission through the perfusion filter for production of a recombinant domain antibody. Our study revealed that the presence of L-Arginine within the range of 30-50 mM had a positive impact on transmission. However, the higher concentrations were found to have a negative correlation with cell viability, and an optimal concentration of approximately 40 mM was identified.
View Article and Find Full Text PDFThe surge of antimicrobial resistance threatens efficacy of current antibiotics, particularly against , a highly resistant gram-negative pathogen. The asymmetric outer membrane (OM) of combined with its array of efflux pumps provide a barrier to xenobiotic accumulation, thus making antibiotic discovery challenging. We adapted PROSPECT , a target-based, whole-cell screening strategy, to discover small molecule probes that kill mutants depleted for essential proteins localized at the OM.
View Article and Find Full Text PDFBackground: The emerging use of biomarkers in research and tailored care introduces a need for information about the association between biomarkers and basic demographics and lifestyle factors revealing expectable concentrations in healthy individuals while considering general demographic differences.
Methods: A selection of 47 biomarkers, including markers of inflammation and vascular stress, were measured in plasma samples from 9876 Danish Blood Donor Study participants. Using regression models, we examined the association between biomarkers and sex, age, Body Mass Index (BMI), and smoking.
Aim: Our goal was to describe a precision medicine program in a regional academic hospital, characterize features of included patients and present early data on clinical impact.
Materials And Methods: We prospectively included 163 eligible patients with late-stage cancer of any diagnosis from June 2020 to May 2022 in the Proseq Cancer trial. Molecular profiling of new or fresh frozen tumor biopsies was done by WES and RNAseq with parallel sequencing of non-tumoral DNA as individual reference.
Aims: To evaluate the experience with use of sotrovimab following severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in high-risk groups.
Methods: In a nationwide, population-based cohort study, we identified all individuals treated with sotrovimab (N = 2933) and stratified them by 4 high-risk groups: (A) malignant haematological disease, (B) solid organ transplantation, (C) anti-CD20 therapy ≤1 year and (D) other risks. Cox regression analysis was used to calculate hazard ratios for hospitalization, death and associated prognostic factors.
Aims/hypothesis: Normalisation of blood glucose in individuals with diabetes is recommended to reduce development of diabetic complications. However, risk of severe hypoglycaemia with intensive insulin therapy is a major obstacle that prevents many individuals with diabetes from obtaining the recommended reduction in HbA. Inhibition of glucagon receptor signalling and liver-preferential insulin action have been shown individually to have beneficial effects in preclinical models and individuals with diabetes (i.
View Article and Find Full Text PDFBackground And Objectives: Lateral occlusion prior to TLH has been suggested to reduce perioperative bleeding, operative time, and hospital stay. Furthermore, reducing the amount of bleeding and the length of the operation may affect parameters such as postoperative pain and the number of patients with postoperative vaginal vault hematoma.
Methods: This RCT was conducted at a single center at Odense University Hospital in Denmark.
Background: In livestock breeding, selection for some traits can be improved with direct selection for crossbred performance. However, genetic analyses with phenotypes from crossbred animals require methods for multibreed relationship matrices; especially when some animals are rotationally crossbred. Multiple methods for multibreed relationship matrices exist, but there is a lack of knowledge on how these methods compare for prediction of breeding values with phenotypes from rotationally crossbred animals.
View Article and Find Full Text PDFTransposon-insertion sequencing (Tn-Seq) allows for identification of bacterial genes and pathways essential for growth under a given condition. A transposon mutant is created by the stable and random integration of a transposable element into a genome of interest, followed by a period of outgrowth and selection for relative fitness on one or more growth media. By pooling hundreds of thousands of mutants, sequencing the transposon-genomic DNA junctions, and mapping sequencing reads to the genome, one can identify an abundance of reads in nonessential insertion regions and the absence of reads in essential regions and thus identify which genes are essential for a given growth condition.
View Article and Find Full Text PDFRuthenium polypyridyl complexes which can sensitise the photo-oxidation of nucleic acids and other biological molecules show potential for photo-therapeutic applications. In this article a combination of transient visible absorption (TrA) and time-resolved infra-red (TRIR) spectroscopy are used to compare the photo-oxidation of guanine by the enantiomers of [Ru(TAP)(dppz)] in both polymeric {poly(dG-dC), poly(dA-dT) and natural DNA} and small mixed-sequence duplex-forming oligodeoxynucleotides. The products of electron transfer are readily monitored by the appearance of a characteristic TRIR band centred at 1700 cm for the guanine radical cation and a band centered at 515 nm in the TrA for the reduced ruthenium complex.
View Article and Find Full Text PDFBackground: There are limited data on outcomes of moderate to severe coronavirus disease 2019 (COVID-19) among patients treated with remdesivir and dexamethasone in a real-world setting. We sought to compare the effectiveness of standard of care (SOC) alone versus SOC plus remdesivir and dexamethasone.
Methods: Two population-based nationwide cohorts of individuals hospitalized with COVID-19 during February through December 2020 were studied.
Purpose: The aim of this study was to describe the implementation and uptake of biosimilar trastuzumab in Denmark compared with other European countries.
Methods: European data for usage of trastuzumab was supplied by IQVIA™, using the MIDAS® dataset. A comparison was performed based on market share estimated in sales volume.
Background: In breeding programs, recording large-scale feed intake (FI) data routinely at the individual level is costly and difficult compared with other production traits. An alternative approach could be to record FI at the group level since animals such as pigs are normally housed in groups and fed by a shared feeder. However, to date there have been few investigations about the difference between group- and individual-level FI recorded in different environments.
View Article and Find Full Text PDFTransposon insertion sequencing is a useful tool to identify the genes that are essential for a bacterial species to grow and divide effectively. In this issue of , Fabian et al. present the first set of transposon insertion sequencing data highlighting the genes essential to the plant-commensal species strain Pf-5 and describe comparative analyses with other pseudomonads (B.
View Article and Find Full Text PDFBackground: Several studies have found that the growth rate of a pig is influenced by the genetics of the group members (indirect genetic effects). Accounting for these indirect genetic effects in a selection program may increase genetic progress for growth rate. However, indirect genetic effects are small and difficult to predict accurately.
View Article and Find Full Text PDFLongevity in commercial sows is often selected for through stayability traits measured in purebred animals. However, this may not be justifiable because longevity and stayability may be subject to both genotype by environment interaction (G × E) and genotype by genotype interaction (G × G). This study tested the hypothesis that stayability to service after first parity is more strongly genetically correlated with longevity in commercial herds when stayability is measured in commercial herds rather than multiplier herds.
View Article and Find Full Text PDFBackground Transdermal opioids are widely used among elderly adults with chronic pain. However, transdermal patches may be involved in a significant proportion of opioid-related patient safety incidents, as the application process includes several subprocesses, each associated with an individual risk of error. Objective The aim was to obtain specific knowledge on patient safety incidents related to transdermal opioid treatment within both the primary care sector and the hospital sector in Denmark.
View Article and Find Full Text PDFPurpose: A rapidly increasing use of biological drugs has led to substantial costs. Shift to biosimilars enables considerable reduction of these costs without jeopardizing the treatment of patients, but most countries have extensive possibilities of untapped cost-savings. The aim of this study was to describe the Danish quick and near-complete implementation of the two first TNF inhibitor biosimilars (infliximab and etanercept).
View Article and Find Full Text PDFAntimicrob Agents Chemother
September 2019
is a major bacterial pathogen associated with a rising prevalence of antibiotic resistance. We evaluated the resistance mechanisms of against POL7080, a species-specific, first-in-class antibiotic in clinical trials that targets the lipopolysaccharide transport protein LptD. We isolated a series of POL7080-resistant strains with mutations in the two-component sensor gene Transcriptomic and confocal microscopy studies support a resistance mechanism shared with colistin, involving lipopolysaccharide modifications that mitigate antibiotic cell surface binding.
View Article and Find Full Text PDFGenomics offered the promise of transforming antibiotic discovery by revealing many new essential genes as good targets, but the results fell short of the promise. While numerous factors contributed to the disappointing yield, one factor was that essential genes for a bacterial species were often defined based on a single or limited number of strains grown under a single or limited number of in vitro laboratory conditions. In fact, the essentiality of a gene can depend on both the genetic background and growth condition.
View Article and Find Full Text PDFBackground: Hysteroscopy is a technically challenging procedure. Specialty curricula of obstetrics and gynaecology appraise hysteroscopy for trainees but there is no present evidence-based training program that certifies the fundamental technical skills before performance on patients. The objectives of this study were to develop and gather validity evidence for a simulation-based test that can ensure basic competence in hysteroscopy.
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