Comparison of initial dental treatment decisions between in-person and asynchronous teledentistry examinations for people with special health care needs.

Background: People with special health care needs in long-term care settings have difficulty accessing a traditional dental office. The goal of the authors was to assess initial treatment decision concordance between dentists conducting traditional in-person examinations using mobile equipment and additional dentists conducting examinations using asynchronous teledentistry technology.

Methods: Six dentists from Access Dental Care, a North Carolina mobile dentistry nonprofit, saw new patients on-site at 12 participating facilities or asynchronously off-site with electronic dental records, radiographs, and intraoral images, all captured by an on-site dental hygienist.

Incidence of breakthrough fungal infections on isavuconazole prophylaxis compared to posaconazole and voriconazole.

Background: Invasive fungal infections (IFIs) are a common infectious complication during the treatment of acute myeloid leukemia (AML), high-risk myelodysplastic syndrome (MDS) or post hematopoietic cell transplantation (HCT). For these patients, the National Comprehensive Cancer Network recommends posaconazole or voriconazole for IFI prophylaxis. In clinical practice, however, there has been increased use of isavuconazole due to favorable pharmacokinetic and pharmacodynamic parameters despite limited data for this indication.

Improving Compliance with a Rounding Checklist through Low- and High-technology Interventions: A Quality Improvement Initiative.

Introduction: Checklists aid in ensuring consistency and completeness in medical care delivery. However, using an improvement and safety checklist during rounds was variable in our neonatology intensive care unit (NICU), and completion was not tracked sustainably. This quality improvement (QI) initiative's primary aim was to increase compliance with checklist completion from 31% to >75% within 1 year.

Development and characterization of a CNS-penetrant benzhydryl hydroxamic acid class IIa histone deacetylase inhibitor.

We have identified a potent, cell permeable and CNS penetrant class IIa histone deacetylase (HDAC) inhibitor 22, with >500-fold selectivity over class I HDACs (1,2,3) and ∼150-fold selectivity over HDAC8 and the class IIb HDAC6 isoform. Dose escalation pharmacokinetic analysis demonstrated that upon oral administration, compound 22 can reach exposure levels in mouse plasma, muscle and brain in excess of cellular class IIa HDAC IC levels for ∼8 h. Given the interest in aberrant class IIa HDAC function for a number of neurodegenerative, neuromuscular, cardiac and oncology indications, compound 22 (also known as CHDI-390576) provides a selective and potent compound to query the role of class IIa HDAC biology, and the impact of class IIa catalytic site occupancy in vitro and in vivo.

The Impact of Policies to Reduce Fat Consumption: A Systematic Review of the Evidence.

The consumption of industrially produced fatty acids (TFAs) has been associated with an increased risk of heart disease. In recognition of this, countries, states, and cities worldwide have implemented TFA policies aimed at reducing their availability in the food supply. This article aims to provide an update of the evidence of the effectiveness of policies aimed at reducing TFAs in the food supply.

Are dietary inequalities among Australian adults changing? a nationally representative analysis of dietary change according to socioeconomic position between 1995 and 2011-13.

Background: Increasing inequalities in rates of obesity and chronic disease may be partly fuelled by increasing dietary inequalities, however very few nationally representative analyses of socioeconomic trends in dietary inequalities exist. The release of the 2011-13 Australian National Nutrition and Physical Activity Survey data allows investigation of change in dietary intake according to socioeconomic position (SEP) in Australia using a large, nationally representative sample, compared to the previous national survey in 1995. This study examined change in dietary intakes of energy, macronutrients, fiber, fruits and vegetables among Australian adults between 1995 and 2011-13, according to SEP.

Enhancing Care Transitions for Older People through Interprofessional Simulation: A Mixed Method Evaluation.

Introduction: The educational needs of the health and social care workforce for delivering effective integrated care are important. This paper reports on the development, pilot and evaluation of an interprofessional simulation course, which aimed to support integrated care models for care transitions for older people from hospital to home.

Theory And Methods: The course development was informed by a literature review and a scoping exercise with the health and social care workforce.

Contribution of Trans-Fatty Acid Intake to Coronary Heart Disease Burden in Australia: A Modelling Study.

Trans-fatty acids (TFAs) intake has been consistently associated with a higher risk of coronary heart disease (CHD) mortality. We provided an updated assessment of TFA intake in Australian adults in 2010 and conducted modeling to estimate CHD mortality attributable to TFA intake. Data of the 2011-2012 National Nutrition and Physical Activity Survey was used to assess TFA intake.

High variation in manufacturer-declared serving size of packaged discretionary foods in Australia.

Despite the potential of declared serving size to encourage appropriate portion size consumption, most countries including Australia have not developed clear reference guidelines for serving size. The present study evaluated variability in manufacturer-declared serving size of discretionary food and beverage products in Australia, and how declared serving size compared with the 2013 Australian Dietary Guideline (ADG) standard serve (600 kJ). Serving sizes were obtained from the Nutrition Information Panel for 4466 packaged, discretionary products in 2013 at four large supermarkets in Sydney, Australia, and categorised into fifteen categories in line with the 2013 ADG.

Selective inhibitors of trypanosomal uridylyl transferase RET1 establish druggability of RNA post-transcriptional modifications.

Non-coding RNAs are crucial regulators for a vast array of cellular processes and have been implicated in human disease. These biological processes represent a hitherto untapped resource in our fight against disease. In this work we identify small molecule inhibitors of a non-coding RNA uridylylation pathway.

Typical food portion sizes consumed by Australian adults: results from the 2011-12 Australian National Nutrition and Physical Activity Survey.

Considerable evidence has associated increasing portion sizes with elevated obesity prevalence. This study examines typical portion sizes of commonly consumed core and discretionary foods in Australian adults, and compares these data with the Australian Dietary Guidelines standard serves. Typical portion sizes are defined as the median amount of foods consumed per eating occasion.

Indications for Omega-3 Long Chain Polyunsaturated Fatty Acid in the Prevention and Treatment of Cardiovascular Disease.

Background: The National Heart Foundation of Australia (NHFA) 2008 review on omega-3 long-chain polyunsaturated fatty acids (LCPUFA) made recommendations with respect to supplementation for primary and secondary prevention of cardiovascular disease. Since then, new findings have been published regarding the relationship between omega-3 polyunsaturated fatty acids, including supplementation, and cardiovascular health.

Methods: A literature search was undertaken in PubMed and Medline, for literature published between January 1, 2007 and August 31, 2013.

The safety of urban cycle tracks: a review of the literature.

Cycling has to be a safe activity, and perceived as such, if bicycle trips by all populations are to increase and the public health benefits are to be realized. A key characteristic of developed countries with a high cycling mode share is their provision of cycle tracks--separated bikeways along city streets--on major routes. This literature review therefore sought to examine studies of cycle tracks from different countries in order elucidate the safety of these facilities relative to cycling in the street and to point to areas where further research is needed.

Simulation training for improving the quality of care for older people: an independent evaluation of an innovative programme for inter-professional education.

Introduction: This paper describes the evaluation of a 2-day simulation training programme for staff designed to improve teamwork and inpatient care and compassion in an older persons' unit.

Objective: The programme was designed to improve inpatient care for older people by using mixed modality simulation exercises to enhance teamwork and empathetic and compassionate care.

Methods: Healthcare professionals took part in: (a) a 1-day human patient simulation course with six scenarios and (b) a 1-day ward-based simulation course involving five 1-h exercises with integrated debriefing.

Preclinical evaluation of local JAK1 and JAK2 inhibition in cutaneous inflammation.

JAKs are required for signaling initiated by several cytokines (e.g., IL-4, IL-12, IL-23, thymic stromal lymphopoietin (TSLP), and IFNγ) implicated in the pathogenesis of inflammatory skin diseases such as psoriasis and atopic dermatitis (AD).

Identification and characterization of INCB9471, an allosteric noncompetitive small-molecule antagonist of C-C chemokine receptor 5 with potent inhibitory activity against monocyte migration and HIV-1 infection.

C-C chemokine receptor 5 (CCR5) is a clinically proven target for inhibition of HIV-1 infection and a potential target for various inflammatory diseases. In this article, we describe 5-[(4-{(3S)-4-[(1R,2R)-2-ethoxy-5-(trifluoromethyl)-2,3-dihydro-1H-inden-1-yl]-3-methylpiperazin-1-yl}-4-methylpiperidin-1-yl)carbonyl]-4,6-dimethylpyrimidine dihydrochloride (INCB9471), a potent and specific inhibitor of human CCR5 that has been proven to be safe and efficacious in viral load reduction in phase I and II human clinical trails. INCB9471 was identified using a primary human monocyte-based radioligand competition binding assay.

Selective inhibition of JAK1 and JAK2 is efficacious in rodent models of arthritis: preclinical characterization of INCB028050.

Inhibiting signal transduction induced by inflammatory cytokines offers a new approach for the treatment of autoimmune diseases such as rheumatoid arthritis. Kinase inhibitors have shown promising oral disease-modifying antirheumatic drug potential with efficacy similar to anti-TNF biologics. Direct and indirect inhibition of the JAKs, with small molecule inhibitors like CP-690,550 and INCB018424 or neutralizing Abs, such as the anti-IL6 receptor Ab tocilizumab, have demonstrated rapid and sustained improvement in clinical measures of disease, consistent with their respective preclinical experiments.

Selective inhibition of IDO1 effectively regulates mediators of antitumor immunity.

Indoleamine 2,3-dioxygenase-1 (IDO1; IDO) mediates oxidative cleavage of tryptophan, an amino acid essential for cell proliferation and survival. IDO1 inhibition is proposed to have therapeutic potential in immunodeficiency-associated abnormalities, including cancer. Here, we describe INCB024360, a novel IDO1 inhibitor, and investigate its roles in regulating various immune cells and therapeutic potential as an anticancer agent.

INCB16562, a JAK1/2 selective inhibitor, is efficacious against multiple myeloma cells and reverses the protective effects of cytokine and stromal cell support.

Cytokines in the bone marrow of multiple myeloma patients activate Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathways in tumor cells and promote tumor growth, survival, and drug resistance. INCB16562 was developed as a novel, selective, and orally bioavailable small-molecule inhibitor of JAK1 and JAK2 markedly selective over JAK3. The specific cellular activity of the inhibitor was demonstrated by its potent and dose-dependent inhibition of cytokine-dependent JAK/STAT signaling and cell proliferation in the absence of effects on Bcr-Abl-expressing cells.

Protein engineering strategies for sustained glucagon-like peptide-1 receptor-dependent control of glucose homeostasis.

Objective: We have developed a novel platform for display and delivery of bioactive peptides that links the biological properties of the peptide to the pharmacokinetic properties of an antibody. Peptides engineered in the MIMETIBODY platform have improved biochemical and biophysical properties that are quite distinct from those of Fc-fusion proteins. CNTO736 is a glucagon-like peptide 1 (GLP-1) receptor agonist engineered in our MIMETIBODY platform.

A new scaleable freeze-thaw technology for bulk protein solutions.

A new method of freeze-thaw is described using experimental data obtained from freezing of purified rhGH (recombinant human growth hormone). The method is based on freezing protein solutions in rectangular rather than cylindrical containers. It is hypothesized that the change in container geometry allows for linear scale-up of the freeze-thaw operation based on equivalency of temperature-time profile.

Biophysical signatures of noncovalent aggregates formed by a glucagonlike peptide-1 analog: a prototypical example of biopharmaceutical aggregation.

LY307161 is a 31 amino acid analog of glucagonlike peptide-1(7-37)OH susceptible to physical instability associated with pharmaceutical processing. Orthogonal biophysical studies were conducted to explore the origins of this physical instability and to distinguish pharmaceutically desirable states of this aggregating peptide from undesirable ones. Equilibrium sedimentation analysis established that LY307161 exists as a monomer at pH 3, and reversibly self-associates in the pH range 7.

Discovery and pharmacological characterization of a novel rodent-active CCR2 antagonist, INCB3344.

This report describes the characterization of INCB3344, a novel, potent and selective small molecule antagonist of the mouse CCR2 receptor. The lack of rodent cross-reactivity inherent in the small molecule CCR2 antagonists discovered to date has precluded pharmacological studies of antagonists of this receptor and its therapeutic relevance. In vitro, INCB3344 inhibits the binding of CCL2 to mouse monocytes with nanomolar potency (IC(50) = 10 nM) and displays dose-dependent inhibition of CCL2-mediated functional responses such as ERK phosphorylation and chemotaxis with similar potency.

Distribution of total and methyl mercury in sediments along Steamboat Creek (Nevada, USA).

In the late 1800s, mills in the Washoe Lake area, Nevada, used elemental mercury to remove gold and silver from the ores of the Comstock deposit. Since that time, mercury contaminated waste has been distributed from Washoe Lake, down Steamboat Creek, and to the Truckee River. The creek has high mercury concentrations in both water and sediments, and continues to be a constant source of mercury to the Truckee River.

Inhibition of mixed lineage kinase 3 attenuates MPP+-induced neurotoxicity in SH-SY5Y cells.

The neuropathology of Parkinson's Disease has been modeled in experimental animals following MPTP treatment and in dopaminergic cells in culture treated with the MPTP neurotoxic metabolite, MPP(+). MPTP through MPP(+) activates the stress-activated c-Jun N-terminal kinase (JNK) pathway in mice and SH-SY5Y neuroblastoma cells. Recently, it was demonstrated that CEP-1347/KT7515 attenuated MPTP-induced nigrostriatal dopaminergic neuron degeneration in mice, as well as MPTP-induced JNK phosphorylation.