Larvicidal, Ovicidal, and Repellent Activities of (Hochst. ex Benth.) Briq Essential Oil against .

Larvicidal, ovicidal, and repellent activities of the essential oil extracted by hydrodistillation from the leaves of the endemic Ethiopian plant (Hochst. ex Benth.) Briq were investigated against , the dominant malaria vector species in Ethiopia with the objective of searching for a plant-based malaria vector control strategy from medicinal plants.

Discovery of tetrazolo-pyridazine-based small molecules as inhibitors of MACC1-driven cancer metastasis.

Metastasis is directly linked to poor prognosis of cancer patients and warrants search for effective anti-metastatic drugs. MACC1 is a causal key molecule for metastasis. High MACC1 expression is prognostic for metastasis and poor survival.

CLK2 and CLK4 are regulators of DNA damage-induced NF-κB targeted by novel small molecule inhibitors.

Transcription factor NF-κB potently activates anti-apoptotic genes, and its inactivation significantly reduces tumor cell survival following genotoxic stresses. We identified two structurally distinct lead compounds that selectively inhibit NF-κB activation by DNA double-strand breaks, but not by other stimuli, such as TNFα. Our compounds do not directly inhibit previously identified regulators of this pathway, most critically including IκB kinase (IKK), but inhibit signal transmission in-between ATM, PARP1, and IKKγ.

Intraregional hospital outbreak of OXA-244-producing ST38 in Norway, 2020.

Infections with OXA-244-carbapenemase-producing with sequence type (ST)38 have recently increased in Europe. Due to its low-level activity against carbapenems, OXA-244 can be difficult to detect. Previous assessments have not revealed a clear source and route of transmission for OXA-244-producing , but there are indications of non-healthcare related sources and community spread.

Histologic chorioamnionitis in extremely preterm births, microbiological findings and infant outcome.

Background: Histologic chorioamnionitis (HCA) is most often caused by ascending bacterial infection originating from the cervicovaginal tract.

Objectives: To investigate whether HCA with a fetal inflammatory response (FIR) has a worse clinical outcome than HCA alone. Further, if FIR or a positive maternal microbiologic culture obtained prior to birth were related to adverse neonatal outcomes in a cohort of extremely preterm (EP) neonates.

sp. nov., a new species isolated from the hot water distribution systems of a hospital and a shopping center during routine sampling.

Two -like strains isolated from hot water distribution systems in 2012 have been characterized phenotypically, biochemically and genomically in terms of DNA relatedness. Both strains, HCPI-6 and EUR-108, exhibited biochemical phenotypic profiles typical of species. Cells were Gram-negative motile rods which grew on BCYEα agar but not on blood agar and displayed phenotypic characteristics typical of the family , including a requirement for l-cysteine and testing catalase positive.

[Methicillin-resistant Staphylococcus aureus in wound drainage in children].

Background: Skin and soft tissue infections are common in children. We wished to investigate the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in wound drainage from children in Norway.

Material And Method: We conducted an observational study based on data from the Norwegian Surveillance System for Antimicrobial Drug Resistance (NORM) for the period 2013-21.

Probing Factor Xa Protein-Ligand Interactions: Accurate Free Energy Calculations and Experimental Validations of Two Series of High-Affinity Ligands.

The accurate prediction of protein-ligand binding affinity belongs to one of the central goals in computer-based drug design. Molecular dynamics (MD)-based free energy calculations have become increasingly popular in this respect due to their accuracy and solid theoretical basis. Here, we present a combined study which encompasses experimental and computational studies on two series of factor Xa ligands, which enclose a broad chemical space including large modifications of the central scaffold.

Compound Interaction Screen on a Photoactivatable Cellulose Membrane (CISCM) Identifies Drug Targets.

Identifying the protein targets of drugs is an important but tedious process. Existing proteomic approaches enable unbiased target identification but lack the throughput needed to screen larger compound libraries. Here, we present a compound interaction screen on a photoactivatable cellulose membrane (CISCM) that enables target identification of several drugs in parallel.

Weizhouochrones: Gorgonian-Derived Symmetric Dimers and Their Structure Elucidation Using Anisotropic NMR Combined with DP4+ Probability and CASE-3D.

Natural product dimers have intriguing structural features and often have remarkable pharmacological activities. We report here two uncommon marine gorgonian-derived symmetric dimers, weizhouochrones A () and B (), with indenone-derived monomers, that were isolated from the coral collected from the South China Sea. These dimers are difficult targets for structure elucidation that solely relies upon conventional NMR data such as NOEs and -couplings.

Case Report: Whole-Genome Sequencing of Serially Collected From a Patient With Common Variable Immunodeficiency Reveals Within-Host Evolution of Resistance to Trimethoprim-Sulfamethoxazole and Azithromycin After Prolonged Treatment With These Antibiotics.

We report within-host evolution of antibiotic resistance to trimethoprim-sulfamethoxazole and azithromycin in a nontypeable strain from a patient with common variable immunodeficiency (CVID), who received repeated or prolonged treatment with these antibiotics for recurrent respiratory tract infections. Whole-genome sequencing of three longitudinally collected sputum isolates during the period April 2016 to January 2018 revealed persistence of a strain of sequence type 2386. Reduced susceptibility to trimethoprim-sulfamethoxazole in the first two isolates was associated with mutations in genes encoding dihydrofolate reductase ( and its promotor region, dihydropteroate synthase (), and thymidylate synthase (), while subsequent substitution of a single amino acid in dihydropteroate synthase (G225A) rendered high-level resistance in the third isolate from 2018.

Emergence and dissemination of antimicrobial resistance in Escherichia coli causing bloodstream infections in Norway in 2002-17: a nationwide, longitudinal, microbial population genomic study.

Background: The clonal diversity underpinning trends in multidrug resistant Escherichia coli causing bloodstream infections remains uncertain. We aimed to determine the contribution of individual clones to resistance over time, using large-scale genomics-based molecular epidemiology.

Methods: This was a longitudinal, E coli population, genomic, cohort study that sampled isolates from 22 512 E coli bloodstream infections included in the Norwegian surveillance programme on resistant microbes (NORM) from 2002 to 2017.

European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines for the treatment of infections caused by multidrug-resistant Gram-negative bacilli (endorsed by European society of intensive care medicine).

Scope: These ESCMID guidelines address the targeted antibiotic treatment of third-generation cephalosporin-resistant Enterobacterales (3GCephRE) and carbapenem-resistant Gram-negative bacteria, focusing on the effectiveness of individual antibiotics and on combination versus monotherapy.

Methods: An expert panel was convened by ESCMID. A systematic review was performed including randomized controlled trials and observational studies, examining different antibiotic treatment regimens for the targeted treatment of infections caused by the 3GCephRE, carbapenem-resistant Enterobacterales, carbapenem-resistant Pseudomonas aeruginosa and carbapenem-resistant Acinetobacter baumannii.

Effect of leukoreduction and temperature on risk of bacterial growth in CPDA-1 whole blood: A study of Escherichia coli.

Background: Collection of non-leukoreduced citrate-phosphate-dextrose-adenine (CPDA-1) whole blood is performed in walking blood banks. Blood collected under field conditions may have increased risk of bacterial contamination. This study was conducted to examine the effects of WBC reduction and storage temperature on growth of Escherichia coli (ATCC® 25922™) in CPDA-1 whole blood.

Antibiotic resistance in paediatric UTIs in Norway.

Background: Urinary tract infections are common in children. The purpose of this study was to describe national resistance data from urinary isolates from children with a view to informing antibiotic use.

Method: We conducted an observational study based on culture responses with resistance determination in urine from the Norwegian Surveillance System for Antimicrobial Drug Resistance (NORM).

Epidemiology and Antimicrobial Susceptibility of Invasive Bacterial Infections in Children-A Population-Based Study From Norway.

Objective: To describe epidemiology and antimicrobial susceptibility testing (AST) data of bacteria causing invasive infections in Norwegian children (0-18 years).

Methods: Population-based observational study using prospectively collected AST data from the Norwegian Surveillance System of Antimicrobial Resistance from 2013 to 2017. We included all clinically relevant bacterial isolates (blood and cerebrospinal fluid), and compared incidence of invasive infections and AST data in isolates from children and adults.

Designed nanomolar small-molecule inhibitors of Ena/VASP EVH1 interaction impair invasion and extravasation of breast cancer cells.

Battling metastasis through inhibition of cell motility is considered a promising approach to support cancer therapies. In this context, Ena/VASP-depending signaling pathways, in particular interactions with their EVH1 domains, are promising targets for pharmaceutical intervention. However, protein-protein interactions involving proline-rich segments are notoriously difficult to address by small molecules.

A Palladium-Catalyzed Domino Reaction To Access 3-Amino-2-indazoles from Hydrazines and 2-Halobenzonitriles.

The development of a novel selective synthesis of 3-amino-2-indazoles from readily available 2-halobenzonitriles is presented. The reaction proceeds through a domino reaction sequence, consisting of a regioselective palladium-catalyzed coupling of monosubstituted hydrazines with 2-halobenzonitriles, followed by an intramolecular hydroamination through a 5-exo-dig cyclization and subsequent isomerization to directly afford a wide variety of substituted 2-indazole analogues in good to excellent yields.

Horizontal Plasmid Transfer among Klebsiella pneumoniae Isolates Is the Key Factor for Dissemination of Extended-Spectrum β-Lactamases among Children in Tanzania.

Increased knowledge about the role of horizontal gene transfer is key to improve our understanding of the spread of antimicrobial resistance (AMR) in human populations. We therefore studied the dissemination of the extended-spectrum-β-lactamase (ESBL) gene in isolates obtained from stool samples from hospitalized children and healthy controls below 2 years of age in Dar es Salaam, Tanzania, from August 2010 to July 2011. We performed Illumina whole-genome sequencing (WGS) to characterize resistance genes, multilocus sequence type (MLST), plasmid incompatibility group (Inc), and plasmid MLST of 128 isolates of with recovered from both healthy and hospitalized children.

sp. nov., isolated from brain abscess and blood.

We herein describe the first novel species within the genus since it was established in 1972 by the reclassification of ' to . From a polymicrobial brain abscess, we encountered an isolate, PXX, that could not validly be named . The isolate grew on blood agar with small, translucent, pitting colonies after 3 days of anaerobic incubation.

Probing 2H-Indazoles as Templates for SGK1, Tie2, and SRC Kinase Inhibitors.

The broader and systematic application of a novel scaffold is often hampered by the unavailability of a short and reliable synthetic access. We investigated a new strategy for the design and synthesis of an array of N2-substituted aza-2H-indazole derivatives as potential kinase inhibitors. Guided by a rational ligand alignment approach to qualify the so-far underrepresented aza-2H-indazole scaffold, indazoles were connected at the N2 position with a phenyl spacer and an arylsulfonamide or amide linkage.

Susceptibility of Legionella pneumophila to antimicrobial agents and the presence of the efflux pump LpeAB.

Objectives: Legionella pneumophila strains resistant to antimicrobial agents are rare. We tested 10 antimicrobial agents against clinical and environmental strains and performed WGS to screen for the presence of resistance mechanisms.

Methods: A total of 122 clinical and environmental strains of L.