High Prevalence of New Clinically Significant Findings in Patients With Embolic Stroke of Unknown Source Evaluated by Cardiac Magnetic Resonance Imaging.

Background: Embolic stroke of unknown source (ESUS) accounts for 1 in 6 ischemic strokes. Current guidelines do not recommend routine cardiac magnetic resonance (CMR) imaging in ESUS, and beyond the identification of cardioembolic sources, there are no data assessing new clinical findings from CMR in ESUS. This study aimed to assess the prevalence of new cardiac and noncardiac findings and to determine their impact on clinical care in patients with ESUS.

Dural arteriovenous fistula causing reversible cognitive impairment.

A previously independent 82-year-old woman presented with 5 months of worsening confusion, mobility and cognitive decline, with deficits in orientation, language and executive function. A cerebral dural arteriovenous fistula was identified and successfully embolised, after which her cognitive ability and independence dramatically improved. Although rare, a dural arteriovenous fistula may mimic a rapidly progressive dementia, but its early recognition and treatment can completely reverse the dementia.

ProHeart® 12, a moxidectin extended-release injectable formulation for prevention of heartworm (Dirofilaria immitis) disease in dogs in the USA for 12 months.

Background: The efficacy of an extended-release injectable moxidectin (0.5 mg/kg) suspension (ProHeart® 12) (PH 12) in preventing the development of Dirofilaria immitis in dogs for 12 months was investigated in laboratory and field studies in the USA.

Methods: In each of two laboratory studies, 20 dogs ≥ 12 months of age were randomly allocated to receive a subcutaneous injection of saline or PH 12 on Day 0 and were then inoculated with 50 D.

Nanoparticles for Bioapplications: Study of the Cytotoxicity of Water Dispersible CdSe(S) and CdSe(S)/ZnO Quantum Dots.

Semiconductor nanocrystals or quantum dots (QDs) have unique optical and physical properties that make them potential imaging tools in biological and medical applications. However, concerns over the aqueous dispersivity, toxicity to cells, and stability in biological environments may limit the use of QDs in such applications. Here, we report an investigation into the cytotoxicity of aqueously dispersed CdSe(S) and CdSe(S)/ZnO core/shell QDs in the presence of human colorectal carcinoma cells (HCT-116) and a human skin fibroblast cell line (WS1).

A blinded, randomized, placebo-controlled, dose determination trial of lokivetmab (ZTS-00103289), a caninized, anti-canine IL-31 monoclonal antibody in client owned dogs with atopic dermatitis.

Background: Pruritus is the hallmark clinical sign of atopic dermatitis (AD) in dogs. Lokivetmab, a caninized anti-canine IL-31 monoclonal antibody, reduced pruritus and associated inflammatory skin lesions in a proof-of-concept study in dogs with AD.

Hypothesis/objectives: The objective was to describe lokivetmab dose response in a randomized, double blind, placebo-controlled trial.

Hydrothermal synthesis of highly luminescent blue-emitting ZnSe(S) quantum dots exhibiting low toxicity.

Highly luminescent quantum dots (QDs) that emit in the visible spectrum are of interest to a number of imaging technologies, not least that of biological samples. One issue that hinders the application of luminescent markers in biology is the potential toxicity of the fluorophore. Here we show that hydrothermally synthesized ZnSe(S) QDs have low cytotoxicity to both human colorectal carcinoma cells (HCT-116) and human skin fibroblast cells (WS1).

The Pseudomonas aeruginosa AmrZ C-terminal domain mediates tetramerization and is required for its activator and repressor functions.

Pseudomonas aeruginosa is an important bacterial opportunistic pathogen, presenting a significant threat towards individuals with underlying diseases such as cystic fibrosis. The transcription factor AmrZ regulates expression of multiple P. aeruginosa virulence factors.

Effectively delivering a unique hsp90 inhibitor using star polymers.

We report the synthesis of a novel heat shock protein 90 (hsp90) inhibitor conjugated to a star polymer. Using reversible addition-fragmentation chain-transfer (RAFT) polymerization, we prepared star polymers comprised of PEG attached to a predesigned functional core. The stars were cross-linked using disulfide linkers, and a tagged version of our hsp90 inhibitor was conjugated to the polymer core to generate nanoparticles (14 nM).

Mechanistic studies of sanguinamide B derivatives: a unique inhibitor of eukaryotic ribosomes.

Described are mechanistic studies of two Sanguinamide B (San B) derivatives. These compounds were identified as eukaryotic ribosomal inhibitors. Two biotinylated San B derivatives were synthesized and used to capture protein targets in a pull-down assay.

Psammaplysin F: a unique inhibitor of bacterial chromosomal partitioning.

Described is the antibiotic activity of a marine natural product. Psammaplysin F (1) inhibited the growth of four Gram-positive strains by >80% at 50μM, and the amine at position C-20 is responsible for the observed antibacterial activity. When tested against two strains of methicillin resistant Staphylococcus aureus (MRSA), the minimum inhibitory concentrations (MICs) for psammaplysin F (40-80μM) were similar to the structurally-related alkaloid psammaplysin H (2).

A potential rhodium cancer therapy: studies of a cytotoxic organorhodium(I) complex that binds DNA.

Described is a novel organorhodium(I) complex that is cytotoxic to the colon cancer cell line HCT116 and alters cell migration, DNA replication, and DNA condensation. Most importantly, the mechanism observed is not seen for the parent organorhodium dimer complex [{RhCl(COD)}2], RhCl3, or the free ligand/proligands (COD and 1-(n)butyl-3-methylimidazolium chloride). Thus, the activity of this organorhodium complex is attributable to its unique structure.

A structure-activity relationship study on multi-heterocyclic molecules: two linked thiazoles are required for cytotoxic activity.

We report the synthesis, cytotoxicity, and phenotypic analysis of oxazole and thiazole containing fragments. Evaluating the optimal size and heterocycle for growth inhibition and apoptosis showed that activity required at least two thiazoles sequentially connected. This is the first detailed comparison of biological activity between multi-heterocyclic containing fragments.

Simultaneous bone marrow and composite tissue transplantation in rats treated with nonmyeloablative conditioning promotes tolerance.

Background: Approaches to safely induce tolerance in vascularized composite allotransplantation (VCA) with chimerism through bone marrow transplantation (BMT) are currently being pursued. However, VCA was historically performed sequentially after donor chimerism was established. Delayed VCA is not clinically applicable due to the time constraints associated with procurement from deceased donors.

Halting metastasis through CXCR4 inhibition.

Metastasis occurs when cancer cells leave the primary tumor site and migrate to distant parts of the body. The CXCR4-SDF-1 pathway facilitates this migration, and its expression has become the hallmark of several metastatic cancers. Targeted approaches are currently being developed to inhibit this pathway, and several candidates are now in clinical trials.

Synthesis, structure-activity analysis, and biological evaluation of sanguinamide B analogues.

We report the first synthesis of sanguinamide B analogues. Substituting N-methylated (N-Me) amino acids, glycine (Gly), and L- or D-phenylalanine (Phe) into the backbone of sanguinamide B showed that only l- and d-Phe residues controlled the macrocycle conformation. The N-methylated and glycine analogues all had multiple conformations, whereas the L- and D-Phe derivatives only had a single conformation.

An Hsp90 modulator that exhibits a unique mechanistic profile.

Described is the synthesis of two biotinylated derivatives of a cytotoxic macrocycle. Pull-down assays indicate that this macrocycle targets the N-middle domain of Hsp90. Untagged compound can effectively compete away tagged compound-Hsp90 protein complexes, confirming the binding specificity of the macrocycle for Hsp90.

Total synthesis of trans,trans-Sanguinamide B and conformational isomers.

The first total synthesis of Sanguinamide B is reported, prepared via an efficient synthetic strategy. The natural product, trans,trans-Sanguinamide B (1), was generated in a thermodynamic ratio with trans,cis-Sanguinamide B (2) and cis,cis-Sanguinamide B (3). Complete conversion of the cis,cis-Sanguinamide B conformer (3) to the natural product (1) and the trans,cis- conformer (2) was achieved by heating to 170 °C.

Clinical efficacy and safety of dexmedetomidine used as a preanesthetic prior to general anesthesia in cats.

Objective: To evaluate the clinical efficacy of dexmedetomidine as a preanesthetic medication administered prior to anesthetic induction with ketamine or propofol and with or without isoflurane for maintenance of anesthesia.

Design: Randomized, blinded, controlled clinical trial.

Animals: 184 client-owned cats.

Efficacy of sublingual administration of detomidine gel for sedation of horses undergoing veterinary and husbandry procedures under field conditions.

Objective: To determine whether sublingual detomidine gel administration to horses would be effective in providing an appropriate degree of sedation and restraint to facilitate completion of veterinary and husbandry procedures under field conditions.

Design: Multicenter, prospective, randomized, blinded, placebo-controlled clinical study.

Animals: 270 client-owned horses known to require sedation or strong restraint to enable veterinary and husbandry procedures to be performed.

AmrZ beta-sheet residues are essential for DNA binding and transcriptional control of Pseudomonas aeruginosa virulence genes.

AmrZ is a putative ribbon-helix-helix (RHH) transcriptional regulator. RHH proteins utilize residues within the β-sheet for DNA binding, while the α-helices promote oligomerization. AmrZ is of interest due to its dual roles as a transcriptional activator and as a repressor, regulating genes encoding virulence factors associated with both chronic and acute Pseudomonas aeruginosa infection.

Evaluation of two antimicrobial therapies in the treatment of Leptospira borgpetersenii serovar hardjo infection in experimentally infected cattle.

This study demonstrated the ability of the antimicrobials tulathromycin (Draxxin) and ceftiofur crystalline free acid sterile suspension (Excede) to clear the spirochete Leptospira borgpetersenii serovar hardjo type hardjo-bovis (L. hardjo-bovis) from experimentally infected cattle. Treatment with tulathromycin resulted in clearance of L.

Can pulse oximetry or a bedside swallowing assessment be used to detect aspiration after stroke?

Background And Purpose: Desaturation during swallowing may help to identify aspiration in stroke patients. This study investigated pulse oximetry, bedside swallowing assessment (BSA), and videofluoroscopy as tests for detecting aspiration after stroke.

Methods: Swallowing was assessed in 189 stroke patients (mean+/-SD age, 70.

Silent aspiration: what do we know?

Although clinically evident aspiration is common in subjects with dysphagia, a significant proportion may aspirate silently, i.e., without any outward signs of swallowing difficulty.

The Pseudomonas aeruginosa ribbon-helix-helix DNA-binding protein AlgZ (AmrZ) controls twitching motility and biogenesis of type IV pili.

Pseudomonas aeruginosa is an opportunistic pathogen that is commonly found in water and soil. In order to colonize surfaces with low water content, P. aeruginosa utilizes a flagellum-independent form of locomotion called twitching motility, which is dependent upon the extension and retraction of type IV pili.

Is the gag reflex useful in the management of swallowing problems in acute stroke?

The goal of this study was to compare the diagnostic value of an absent gag reflex in acute stroke patients with the bedside swallowing assessment (BSA) and assess its relationship to outcomes. Two hundred forty-two acute stroke patients had their gag reflex tested and a BSA performed. Numbers needing nasogastric or gastrostomy tube insertion were noted, also their discharge destination, discharge Barthel Index, and mortality.