Oral switch antibiotic therapy in uncomplicated bloodstream infection.

Background: The role of oral switch antibiotic therapy in uncomplicated bloodstream infection (BSI) remains unclear. This retrospective cohort study examines the effectiveness of oral switch compared with standard intravenous antibiotic therapy in uncomplicated BSI.

Methods: Adults with first episodes of uncomplicated monomicrobial BSI were admitted to 10 Prisma Health hospitals in South Carolina from January 2021 to June 2023 were included.

Macrophage Colony Stimulating Factor (M-CSF) and Interleukin-34 (IL-34) Expression in Canine Osteosarcoma in the Context of the Tumour Immune Microenvironment.

Canine osteosarcoma (OSA) is a malignancy that has been shown to modulate the host immune system. Macrophage colony-stimulating factor (M-CSF; CSF1) and interleukin-34 (IL-34; IL34) are both ligands of colony stimulating factor 1 receptor (CSF-1R), and may play a role in the pathogenesis of a variety of human cancers, including OSA. This study aimed to, (1) assess M-CSF and IL-34 expression in canine OSA cell lines and tissue samples, and (2) determine any correlations between M-CSF and IL-34 expression and immune cell infiltrates within canine OSA tissues.

Synthesis and glycosidase inhibition of 3,4,5-trihydroxypiperidines using a one-pot amination-cyclisation cascade reaction.

Trihydroxypiperidines are a therapeutically valuable class of iminosugar. We applied a one-pot amination-cyclisation cascade reaction to synthesise 3,4,5-trihydroxypiperidine stereoisomers in three steps from commercially available pentoses and in excellent overall yields. Using our methodology, the yields of the syntheses of meso-1, meso-2 and 3L are the highest reported to date.

Carbohydrate-active enzyme (CAZyme) discovery and engineering (Ultra)high-throughput screening.

Carbohydrate-active enzymes (CAZymes) constitute a diverse set of enzymes that catalyze the assembly, degradation, and modification of carbohydrates. These enzymes have been fashioned into potent, selective catalysts by millennia of evolution, and yet are also highly adaptable and readily evolved in the laboratory. To identify and engineer CAZymes for different purposes, (ultra)high-throughput screening campaigns have been frequently utilized with great success.

An alternative broad-specificity pathway for glycan breakdown in bacteria.

The vast majority of glycosidases characterized to date follow one of the variations of the 'Koshland' mechanisms to hydrolyse glycosidic bonds through substitution reactions. Here we describe a large-scale screen of a human gut microbiome metagenomic library using an assay that selectively identifies non-Koshland glycosidase activities. Using this, we identify a cluster of enzymes with extremely broad substrate specificities and thoroughly characterize these, mechanistically and structurally.

Novel paradigm enables accurate monthly gestational screening to prevent congenital toxoplasmosis and more.

Background: Congenital toxoplasmosis is a treatable, preventable disease, but untreated causes death, prematurity, loss of sight, cognition and motor function, and substantial costs worldwide.

Objectives: We asked whether high performance of an Immunochromatographic-test (ICT) could enable accurate, rapid diagnosis/treatment, establishing new, improved care-paradigms at point-of-care and clinical laboratory.

Methods: Data were obtained in 12 studies/analyses addressing: 1-feasibility/efficacy; 2-false-positives; 3-acceptability; 4-pink/black-line/all studies; 5-time/cost; 6-Quick-Information/Limit-of-detection; 7, 8-acute;-chronic; 9-epidemiology; 10-ADBio; 11,12-Commentary/Cases/Chronology.

Vocal convergence and social proximity shape the calls of the most basal Passeriformes, New Zealand Wrens.

Despite extensive research on avian vocal learning, we still lack a general understanding of how and when this ability evolved in birds. As the closest living relatives of the earliest Passeriformes, the New Zealand wrens (Acanthisitti) hold a key phylogenetic position for furthering our understanding of the evolution of vocal learning because they share a common ancestor with two vocal learners: oscines and parrots. However, the vocal learning abilities of New Zealand wrens remain unexplored.

Characterization of the dissemination of canine cancer misinformation on YouTube.

YouTube is the third most popular app in the world and continues to grow each year while it reaches over 2 billion users a month. A variety of veterinary topics are addressed on YouTube but to date there have been no studies analysing misinformation of various canine cancer topics on YouTube or social media. This study described the characteristics of 99 unique videos and used the validated DISCERN quality criteria for consumer health information and the Patient Education Materials Assessment Tool (PEMAT) to characterize their usefulness.

Advances in the understanding and exploitation of carbohydrate-active enzymes.

Carbohydrate-active enzymes (CAZymes) are responsible for the biosynthesis, modification and degradation of all glycans in Nature. Advances in genomic and metagenomic methodologies, in conjunction with lower cost gene synthesis, have provided access to a steady stream of new CAZymes with both well-established and novel mechanisms. At the same time, increasing access to cryo-EM has resulted in exciting new structures, particularly of transmembrane glycosyltransferases of various sorts.

Enzymatic conversion of human blood group A kidneys to universal blood group O.

ABO blood group compatibility restrictions present the first barrier to donor-recipient matching in kidney transplantation. Here, we present the use of two enzymes, FpGalNAc deacetylase and FpGalactosaminidase, from the bacterium Flavonifractor plautii to enzymatically convert blood group A antigens from the renal vasculature of human kidneys to 'universal' O-type. Using normothermic machine perfusion (NMP) and hypothermic machine perfusion (HMP) strategies, we demonstrate blood group A antigen loss of approximately 80% in as little as 2 h NMP and HMP.

An autonomous wheelchair with health monitoring system based on Internet of Thing.

Assistive powered wheelchairs will bring patients and elderly the ability of remain mobile without the direct intervention from caregivers. Vital signs from users can be collected and analyzed remotely to allow better disease prevention and proactive management of health and chronic conditions. This research proposes an autonomous wheelchair prototype system integrated with biophysical sensors based on Internet of Thing (IoT).

Treatment of retroperitoneal sarcoma results in improved outcomes.

Objective: To report the clinical characteristics, treatments, and outcomes in a cohort of dogs with histologically confirmed retroperitoneal sarcoma (RPS) and to identify potential variables of prognostic significance.

Animals: 46 client-owned dogs from 10 clinics with histopathologic diagnosis of a sarcoma originating from the retroperitoneal space.

Methods: Medical records were retrospectively reviewed to obtain information regarding clinical characteristics, treatments, and outcomes.

Bilateral intracochlear schwannomas: histopathological confirmation and outcomes following tumour removal and cochlear implantation with lateral wall electrodes.

Intracochlear schwannomas (ICS) are very rare benign tumours of the inner ear. We present histopathological proof of the extremely rare bilateral occurrence of intracochlear schwannomas with negative blood genetic testing for neurofibromatosis type 2 (NF2). Bilateral schwannomas are typically associated with the condition NF2 and this case is presumed to have either mosaicism for NF2 or sporadic development of bilateral tumours.

A quinolin-8-ol sub-millimolar inhibitor of UGGT, the ER glycoprotein folding quality control checkpoint.

Misfolded glycoprotein recognition and endoplasmic reticulum (ER) retention are mediated by the ER glycoprotein folding quality control (ERQC) checkpoint enzyme, UDP-glucose glycoprotein glucosyltransferase (UGGT). UGGT modulation is a promising strategy for broad-spectrum antivirals, rescue-of-secretion therapy in rare disease caused by responsive mutations in glycoprotein genes, and many cancers, but to date no selective UGGT inhibitors are known. The small molecule 5-[(morpholin-4-yl)methyl]quinolin-8-ol (5M-8OH-Q) binds a UGGT "WY" conserved surface motif conserved across UGGTs but not present in other GT24 family glycosyltransferases.

Intravenous versus Partial Oral Antibiotic Therapy in the Treatment of Uncomplicated Bloodstream Infection Due to Species.

This retrospective cohort study examines effectiveness of partial oral antibiotic regimens in uncomplicated bloodstream infections (BSIs) due to species compared to standard intravenous therapy. Adult patients with uncomplicated streptococcal BSIs from April 2016 to June 2020 in seven hospitals in South Carolina, USA, were evaluated. Multivariate Cox proportional hazards regression was used to examine the time to treatment failure within 90 days of a BSI after adjustment for the propensity to receive partial oral therapy.

Branched montbretin A mimics allow derivatisation and potent amylase inhibition.

Mimics of the complex flavonol glycoside montbretin A in which a flavonol moiety is coupled to a caffeic acid partially peptidic linkers have proved to be potent inhibitors of human pancreatic alpha-amylase with potential as therapeutics for control of blood glucose levels. After exploring optimal linker length, a synthetic route to a version with a branched linker was devised based on the structure of the enzyme/inhibitor complex. The resultant branched inhibitors were shown to retain nanomolar potency even when decorated with polymers as a means of modifying solubility.

Ligand-Directed Chemistry on Glycoside Hydrolases - A Proof of Concept Study.

Selective covalent labelling of enzymes using small molecule probes has advanced the scopes of protein profiling. The covalent bond formation to a specific target is the key step of activity-based protein profiling (ABPP), a method which has become an indispensable tool for measuring enzyme activity in complex matrices. With respect to carbohydrate processing enzymes, strategies for ABPP so far involve labelling the active site of the enzyme, which results in permanent loss of activity.

Characterization of a new family of 6-sulfo-N-acetylglucosaminidases.

Sulfation is widespread in nature and plays an important role in modulating biological function. Among the strategies developed by microbes to access sulfated oligosaccharides as a nutrient source is the production of 6-sulfoGlcNAcases to selectively release 6-sulfoGlcNAc from target oligosaccharides. Thus far, all 6-sulfoGlcNAcases identified have belonged to the large GH20 family of β-hexosaminidases.

A high-throughput screening platform for enzymes active on mucin-type O-glycoproteins.

Mucin-type O-glycosylation is a post-translational modification present at the interface between cells where it has important roles in cellular communication. However, deciphering the function of O-glycoproteins and O-glycans can be challenging, especially as few enzymes are available for their assembly or selective degradation. Here, to address this deficiency, we developed a genetically encoded screening methodology for the discovery and engineering of the diverse classes of enzymes that act on O-glycoproteins.

Structural basis for Lewis antigen synthesis by the α1,3-fucosyltransferase FUT9.

Mammalian cell surface and secreted glycoproteins exhibit remarkable glycan structural diversity that contributes to numerous physiological and pathogenic interactions. Terminal glycan structures include Lewis antigens synthesized by a collection of α1,3/4-fucosyltransferases (CAZy GT10 family). At present, the only available crystallographic structure of a GT10 member is that of the Helicobacter pylori α1,3-fucosyltransferase, but mammalian GT10 fucosyltransferases are distinct in sequence and substrate specificity compared with the bacterial enzyme.

Novel paradigm enables accurate monthly gestational screening to prevent congenital toxoplasmosis and more.

Background: Congenital toxoplasmosis is a treatable, preventable disease, but untreated causes death, prematurity, loss of sight, cognition and motor function, and substantial costs worldwide.

Methods/findings: In our ongoing USA feasibility/efficacy clinical trial, data collated with other ongoing and earlier published results proved high performance of an Immunochromatographic-test(ICT) that enables accurate, rapid diagnosis/treatment, establishing new paradigms for care. Overall results from patient blood and/or serum samples tested with ICT compared with gold-standard-predicate-test results found ICT performance for 4606 sera/1876 blood, 99.

Effect of stimulator of interferon genes (STING) signaling on radiation-induced chemokine expression in human osteosarcoma cells.

Cancer cell-intrinsic mechanisms affecting radiation immunomodulation could be exploited to optimize systemic effects of localized radiation. Radiation-induced DNA damage is sensed by cyclic GMP-AMP synthase (cGAS), which ultimately activates stimulator of interferon (IFN) genes (STING). Resultant expression of soluble mediators such as CCL5 and CXCL10 can facilitate recruitment of dendritic cells and immune effector cells into the tumor.