Increasing the Writing Capacity and Dissemination of Evaluation Findings Among US Public Health Practitioners Funded to Improve Cardiovascular Health.

Context: Contributing to the evidence base, by disseminating findings through written products such as journal articles, is a core competency for public health practitioners. Disseminating practice-based evidence that supports improving cardiovascular health is necessary for filling literature gaps, generating health policies and laws, and translating evidence-based strategies into practice. However, a gap exists in the dissemination of practice-based evidence in public health.

Potential exposure of adults and children to particles from resuspended nano-enabled consumer sprays.

The increasing application of nanotechnology has resulted in a growing number of nano-enabled consumer products, and they could be important contributors to indoor particulate matter, with potential adverse health effects. This study investigated the exposure of adults and children to the released and resuspended manufactured particles from seven nano-enabled consumer sprays. Sedimentation and resuspension of released particles were investigated in a newly constructed 2.

Exploration of the P1 residue in 3CL protease inhibitors leading to the discovery of a 2-tetrahydrofuran P1 replacement.

The virally encoded 3C-like protease (3CL) is a well-validated drug target for the inhibition of coronaviruses including Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Most inhibitors of 3CL are peptidomimetic, with a γ-lactam in place of Gln at the P1 position of the pseudopeptide chain. An effort was pursued to identify a viable alternative to the γ-lactam P1 mimetic which would improve physicochemical properties while retaining affinity for the target.

Impact of Electronic Medical Records Within the Maternity Environment: An Ethnographic Exploration of Midwifery Practice.

Integration of care through digitalisation of paper records is important for childbearing women who may see multiple clinicians both within the hospital and the community. It is important that in the implementation of an EMR, the established benefits of a paper and handheld records are transferred and not lost. Acceptance and positive use of digital records in maternity settings has occurred despite concerns regarding workload interrupting women centred care.

Identification, Synthesis, and Characterization of a Major Circulating Human Metabolite of TRPV4 Antagonist GSK2798745.

GSK2798745, an antagonist of the transient receptor potential vanilloid 4 (TRPV4) ion channel, was recently investigated in clinical trials for the treatment of cardiac and respiratory diseases. Human plasma and urine samples collected from healthy volunteers following oral administration were analyzed to identify circulating and excreted metabolites of the parent drug. One major circulating metabolite () was found in pooled human plasma samples, accounting for approximately half of the observed drug-related material.

Effect of a Workplace Weight-Loss Program for Overweight and Obese Healthcare Workers.

Purpose: Examining the effect of a workplace weight-loss program on weight loss, and physical, behavioral and mental well-being among overweight/obese healthcare workers.

Design: Quasi experimental design.

Setting: Single healthcare setting.

Synthesis of Unsaturated Silyl Heterocycles an Intramolecular Silyl-Heck Reaction.

We report the synthesis of unsaturated silacycles an intramolecular silyl-Heck reaction. Using palladium catalysis, silicon electrophiles tethered to alkenes cyclize to form 5- and 6-membered silicon heterocycles. The effects of alkene substitution and tether length on the efficiency and regioselectivity of the cyclizations are described.

Association of Home Food Availability with Prediabetes and Diabetes among Adults in the United States.

This study examined associations of home food availabilities with prediabetes and diabetes among 8929 adults (20-70 years) participating in 2007-2010 National Health and Nutrition Examination Surveys. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated by logistic regression. Relative to non-diabetic participants (individuals without diabetes or prediabetes), prediabetes participants were associated with lower availabilities of green vegetables (OR = 0.

Discovery of GSK3527497: A Candidate for the Inhibition of Transient Receptor Potential Vanilloid-4 (TRPV4).

GSK3527497, a preclinical candidate for the inhibition of TRPV4, was identified starting from the previously reported pyrrolidine sulfonamide TRPV4 inhibitors and . Optimization of projected human dose was accomplished by specifically focusing on in vivo pharmacokinetic parameters CL, Vdss, and MRT. We highlight the use of conformational changes as a novel approach to modulate Vdss and present results that suggest that molecular-shape-dependent binding to tissue components governs Vdss in addition to bulk physicochemical properties.

Mobile Phone Text Message Intervention on Diabetes Self-Care Activities, Cardiovascular Disease Risk Awareness, and Food Choices among Type 2 Diabetes Patients.

This study examines the effects of educational text messages on diabetes self-care activities, cardiovascular disease (CVD) risk awareness, and home food availabilities related to food choices among patients with type 2 diabetes. Quasi-experimental design was used with 40 patients (58.0 ± 10.

Design and Optimization of Sulfone Pyrrolidine Sulfonamide Antagonists of Transient Receptor Potential Vanilloid-4 with in Vivo Activity in a Pulmonary Edema Model.

Pulmonary edema is a common ailment of heart failure patients and has remained an unmet medical need due to dose-limiting side effects associated with current treatments. Preclinical studies in rodents have suggested that inhibition of transient receptor potential vanilloid-4 (TRPV4) cation channels may offer an alternative-and potentially superior-therapy. Efforts directed toward small-molecule antagonists of the TRPV4 receptor have led to the discovery of a novel sulfone pyrrolidine sulfonamide chemotype exemplified by lead compound 6.

Discovery of Pyrrolidine Sulfonamides as Selective and Orally Bioavailable Antagonists of Transient Receptor Potential Vanilloid-4 (TRPV4).

A novel series of pyrrolidine sulfonamide transient receptor potential vanilloid-4 (TRPV4) antagonists was developed by modification of a previously reported TRPV4 inhibitor (1). Several core-structure modifications were identified that improved TRPV4 activity by increasing structural rigidity and reducing the entropic energy penalty upon binding to the target protein. The new template was initially discovered as a minor regio-isomeric side product formed during routine structure-activity relationship (SAR) studies, and further optimization resulted in highly potent compounds with a novel pyrrolidine diol core.

Exposure to violence, neighborhood context, and health-related outcomes in low-income urban mothers.

Exposure to violence in youths has been associated with negative health outcomes, yet evidence of such in adults is limited. Additionally, it is unknown whether these negative associations persist over time and whether neighborhood characteristics affect such associations. Using longitudinal data from a sample of 2481 mostly low-income urban mothers, logistic regressions indicate that exposure to violence is associated with several poorer health outcomes after accounting for neighborhood and social factors.

Reducing biomass recalcitrance by heterologous expression of a bacterial peroxidase in tobacco (Nicotiana benthamiana).

Commercial scale production of biofuels from lignocellulosic feed stocks has been hampered by the resistance of plant cell walls to enzymatic conversion, primarily owing to lignin. This study investigated whether DypB, the lignin-degrading peroxidase from Rodococcus jostii, depolymerizes lignin and reduces recalcitrance in transgenic tobacco (Nicotiana benthamiana). The protein was targeted to the cytosol or the ER using ER-targeting and retention signal peptides.

A Bench-Stable, Single-Component Precatalyst for Silyl-Heck Reactions.

Studies of the silyl-Heck reaction aimed at identifying active palladium complexes have revealed a new species that is formed in situ. This complex has been identified as the palladium iodide dimer, [(JessePhos)PdI], which has been found to be a competent single-component precatalyst for the silyl-Heck reaction. This complex is easily prepared and is temperature, moisture, and air stable.

Simplified Preparation of Trialkylvinylsilanes via the Silyl-Heck Reaction Utilizing a Second Generation Catalyst.

Recently we reported a second-generation ligand, bis(3,5-di--butylphenyl)(-butyl)phosphine, for the preparation of allyl silanes using the silyl-Heck reaction. We now show that this new ligand also provides superior reactivity in the preparation of vinylsilanes from styrene derivatives. For the first time, this new ligand provides exceptionally high yields of trialkylvinylsilanes using a widely available palladium pre-catalyst, Pd(dba).

Rational design of a second generation catalyst for preparation of allylsilanes using the silyl-Heck reaction.

Using rational ligand design, we have developed of a second-generation ligand, bis(3,5-di-tert-butylphenyl)(tert-butyl)phosphine, for the preparation of allylsilanes using the palladium-catalyzed silyl-Heck reaction. This new ligand provides nearly complete suppression of starting material alkene isomerization that was observed with our first-generation catalyst, providing vastly improved yields of allylsilanes from simple alkene starting materials. The studies quantifying the electronic and steric properties of the new ligand are described.

The First Example of Nickel-Catalyzed Silyl-Heck Reactions: Direct Activation of Silyl Triflates Without Iodide Additives.

For the first time, nickel-catalyzed silyl-Heck reactions are reported. Using simple phosphine-supported nickel catalysts, direct activation of silyl triflates has been achieved. These results contrast earlier palladium-catalyzed systems, which require iodide additives to activate silyl-triflates.

The discovery of potent blockers of the canonical transient receptor channels, TRPC3 and TRPC6, based on an anilino-thiazole pharmacophore.

Lead optimization of piperidine amide HTS hits, based on an anilino-thiazole core, led to the identification of analogs which displayed low nanomolar blocking activity at the canonical transient receptor channels 3 and 6 (TRPC3 & 6) based on FLIPR (carbachol stimulated) and electrophysiology (OAG stimulated) assays. In addition, the anilino-thiazole amides displayed good selectivity over other TRP channels (TRPA1, TRPV1, and TRPV4), as well as against cardiac ion channels (CaV1.2, hERG, and NaV1.

Discovery of 1-(1,3,5-triazin-2-yl)piperidine-4-carboxamides as inhibitors of soluble epoxide hydrolase.

1-(1,3,5-Triazin-yl)piperidine-4-carboxamide inhibitors of soluble epoxide hydrolase were identified from high through-put screening using encoded library technology. The triazine heterocycle proved to be a critical functional group, essential for high potency and P450 selectivity. Phenyl group substitution was important for reducing clearance, and establishing good oral exposure.

Elucidation of Diels-Alder Reaction Network of 2,5-Dimethylfuran and Ethylene on HY Zeolite Catalyst.

The reaction of 2,5-dimethylfuran and ethylene to produce p-xylene represents a potentially important route for the conversion of biomass to high-value organic chemicals. Current preparation methods suffer from low selectivity and produce a number of byproducts. Using modern separation and analytical techniques, the structure of many of the byproducts produced in this reaction when HY zeolite is employed as a catalyst has been identified.

Preparation of allyl and vinyl silanes by the palladium-catalyzed silylation of terminal olefins: a silyl-Heck reaction.

A high-yielding protocol for the palladium-catalyzed silylation of terminal alkenes using silyl halides is reported. This method allows facile conversion of styrenes to -β-silyl styrenes using either TMSI or TMSCl/LiI. Terminal allyl silanes with good ratios are also readily accessed from α-olefins by this method.

Cassette dosing for pharmacokinetic screening in drug discovery: comparison of clearance, volume of distribution, half-life, mean residence time, and oral bioavailability obtained by cassette and discrete dosing in rats.

The purpose of this investigation was to compare selected pharmacokinetic (PK) parameters obtained by cassette and discrete dosing of compounds in rats. The concordance of PK properties obtained by the two dosing strategies was evaluated for 116 compounds representing various therapeutic programs and diverse chemical structures. The correspondence between cassette- and discrete-dosing-derived PK properties was examined semiquantitatively and qualitatively.

Sustained growth factor delivery promotes axonal regeneration in long gap peripheral nerve repair.

The aim of this study was to evaluate the long-term effect of localized growth factor delivery on sciatic nerve regeneration in a critical-size (> 1 cm) peripheral nerve defect. Previous work has demonstrated that bioactive proteins can be encapsulated within double-walled, poly(lactic-co-glycolic acid)/poly(lactide) microspheres and embedded within walls of biodegradable polymer nerve guides composed of poly(caprolactone). Within this study, nerve guides containing glial cell line-derived neurotrophic factor (GDNF) were used to bridge a 1.

Highly brominated antimicrobial metabolites from a marine Pseudoalteromonas sp.

Extracts of a marine Pseudoalteromonas sp. (CMMED 290) isolated from the surface of a nudibranch collected in Kaneohe Bay, Oahu, displayed significant antimicrobial activity against methicillin-resistant Staphylococcus aureus. Bioassay-guided fractionation of the lipophilic extract led to the isolation and structure elucidation of two new highly brominated compounds, 2,3,5,7-tetrabromobenzofuro[3,2-b]pyrrole (1) and 4,4',6-tribromo-2,2'-biphenol (2).