Exploring psychological impact of hand-arm vibration syndrome (HAVS).

Background: Hand-arm vibration syndrome (HAVS) is an occupational disease associated with long-term exposure to power tools leading to hand-transmitted vibration exposure. Prior research has focussed on physical manifestations with little known about the psychological impacts of HAVS.

Aims: To examine if HAVS severity and/or functional impairment is associated with psychological outcomes.

Inhibition of Receptor-Interacting Protein Kinase 1 in Chronic Plaque Psoriasis: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study.

Introduction: Receptor-interacting protein kinase 1 (RIPK1), a key mediator of inflammation through necroptosis and proinflammatory cytokine production, may play a role in the pathogenesis of immune-mediated inflammatory diseases such as chronic plaque psoriasis. An experimental medicine study of RIPK1 inhibition with GSK2982772 immediate-release formulation at doses up to 60 mg three times daily in mild to moderate plaque psoriasis indicated that efficacy may be improved with higher trough concentrations of GSK2982772.

Methods: This multicenter, randomized, double-blind, placebo-controlled, repeat-dose study (NCT04316585) assessed the efficacy, safety, pharmacokinetics, and pharmacodynamics of 960 mg GSK2982772 (once-daily modified-release formulation) in patients with moderate to severe plaque psoriasis.

Study to Explore the Association of the Renin-Angiotensin System and Right Ventricular Function in Mechanically Ventilated Patients.

Background: Right ventricular () dysfunction is associated with pulmonary vasoconstriction in mechanically ventilated patients. Enhancing the activity of angiotensin-converting enzyme 2 (2), a key enzyme of the renin-angiotensin system (), using recombinant human 2 (2) could alleviate -mediated vasoconstriction and vascular remodeling.

Methods: This prospective observational study investigated the association between concentrations of peptides (Ang II or Ang(1-7)) and markers of function, as assessed by echocardiography (ratio of to left ventricular end-diastolic area, interventricular septal motion, and pulmonary arterial systolic pressure ()).

An open-label, dose-escalation study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single doses of GSK2586881 in participants with pulmonary arterial hypertension.

Preclinical and early clinical studies suggest that angiotensin-converting enzyme type 2 activity may be impaired in patients with pulmonary arterial hypertension (PAH); therefore, administration of exogenous angiotensin-converting enzyme type 2 (ACE2) may be beneficial. This Phase IIa, multi-center, open-label, exploratory, single-dose, dose-escalation study (NCT03177603) assessed the potential vasodilatory effects of single doses of GSK2586881 (a recombinant human ACE2) on acute cardiopulmonary hemodynamics in hemodynamically stable adults with documented PAH who were receiving background PAH therapy. Successive cohorts of participants were administered a single intravenous dose of GSK2586881 of 0.

Pruritus in the Pediatric Burn Population.

Postburn pruritus is a significant issue that can have a devastating impact on patient quality of life. Despite its known negative impact, few studies have focused on the pediatric population. Thus, the aim of this study was to determine the incidence of pruritus among pediatric burn patients as well as identify its predictive factors and commonly used treatments, including the novel use of laser therapy.

Effects of Recombinant Human Angiotensin-Converting Enzyme 2 on Response to Acute Hypoxia and Exercise: A Randomised, Placebo-Controlled Study.

Introduction: Angiotensin-converting enzyme 2 (ACE2) is a key enzyme of the renin-angiotensin system (RAS) that has been implicated in the pathogenesis of acute respiratory distress syndrome (ARDS). Enhancing ACE2 activity using GSK2586881, a recombinant form of human ACE2, could be beneficial in diseases such as ARDS but may blunt the hypoxic pulmonary vasoconstriction (HPV) response and potentially impact systemic and tissue oxygenation. This study aimed to evaluate the effect of GSK2586881 0.

Testing the joint health and safety committee assessment tool in the education sector.

Joint Health and Safety Committee (JHSC) effectiveness has been identified as an area of concern for Ontario's education sector. The JHSC Assessment Tool has been previously tested in hospitals with positive results. This study assessed the feasibility and usability of the JHSC Assessment Tool in the education sector.

Raising awareness of hand-arm vibration syndrome (HAVS) using posters.

Background: Hand-arm vibration syndrome (HAVS) is caused by prolonged occupational exposure to hand-transmitted vibration. Although HAVS is preventable, disease awareness and prevention knowledge are lacking in high-risk workplaces; this may contribute to under-diagnosis, delays in seeking care, and poor health outcomes. Posters may be used to increase awareness in the workplace.

Pharmacologic targeting of the ATX/LPA axis attenuates bleomycin-induced pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing lung disease with a dismal prognosis and a largely unknown etiology. Autotaxin (ATX) is a secreted lysophospholipase D, largely responsible for extracellular production of lysophosphatidic acid (LPA), a bioactive phospholipid. LPA has numerous effects in most cell types, signaling through at least 6 receptors (LPAR) exhibiting wide spread distribution and overlapping specificities.

Functional limitations in workers with hand-arm vibration syndrome (HAVS).

Background: Hand-arm vibration syndrome (HAVS) is a chronic occupational disease affecting workers exposed to hand-transmitted vibration. However, limited information exists on task-related disability experienced by workers with HAVS.

Aims: This study was conducted to characterize the impact of HAVS on task-related disability and daily life activities.

Registered Replication Report: Dijksterhuis and van Knippenberg (1998).

Dijksterhuis and van Knippenberg (1998) reported that participants primed with a category associated with intelligence ("professor") subsequently performed 13% better on a trivia test than participants primed with a category associated with a lack of intelligence ("soccer hooligans"). In two unpublished replications of this study designed to verify the appropriate testing procedures, Dijksterhuis, van Knippenberg, and Holland observed a smaller difference between conditions (2%-3%) as well as a gender difference: Men showed the effect (9.3% and 7.

Correction to "Discovery of Fevipiprant (NVP-QAW039), a Potent and Selective DP Receptor Antagonist for Treatment of Asthma".

[This corrects the article DOI: 10.1021/acsmedchemlett.7b00157.

Healthcare utilization and direct costs of non-infectious comorbidities in HIV-infected patients in the USA.

Objective: To estimate the incremental healthcare utilization and costs associated with common non-infectious comorbid conditions among commercially and Medicaid-insured HIV-infected patients in the US.

Methods: US administrative claims were used to select adult HIV patients with chronic kidney disease (CKD), cardiovascular disease (CVD) events, or fracture/osteoporosis, three common comorbidities that have been associated with HIV and HIV treatment, between 1 January 2004 and 30 June 2013. Propensity score matched controls with no CKD, no CVD events, and no fracture/osteoporosis were identified for comparison.

Discovery of Fevipiprant (NVP-QAW039), a Potent and Selective DP Receptor Antagonist for Treatment of Asthma.

Further optimization of an initial DP receptor antagonist clinical candidate NVP-QAV680 led to the discovery of a follow-up molecule 2-(2-methyl-1-(4-(methylsulfonyl)-2-(trifluoromethyl)benzyl)-1-pyrrolo[2,3-]pyridin-3-yl)acetic acid (compound , NVP-QAW039, fevipiprant), which exhibits improved potency on human eosinophils and Th2 cells, together with a longer receptor residence time, and is currently in clinical trials for severe asthma.

Examining the Usefulness of ISO 10819 Anti-Vibration Glove Certification.

Anti-vibration gloves are commonly worn to reduce hand-arm vibration exposure from work with hand-held vibrating tools when higher priority and more effective controls are unavailable. For gloves to be marketed as 'anti-vibration' they must meet the vibration transmissibility criteria described in the International Organization for Standardization (ISO) standard 10819 (2013). Several issues exist with respect to the methodology used for glove testing as well as the requirements for glove design and composition in ISO 10819 (2013).

Magma reservoir dynamics at Toba caldera, Indonesia, recorded by oxygen isotope zoning in quartz.

Quartz is a common phase in high-silica igneous rocks and is resistant to post-eruptive alteration, thus offering a reliable record of magmatic processes in silicic magma systems. Here we employ the 75 ka Toba super-eruption as a case study to show that quartz can resolve late-stage temporal changes in magmatic δO values. Overall, Toba quartz crystals exhibit comparatively high δO values, up to 10.

Transforming Growth Factor Beta Gene Signatures are Spatially Enriched in Keloid Tissue Biopsies and Ex vivo-Cultured Keloid Fibroblasts.

The keloid lesion is recognised as a spatially heterogeneous mass both in cellular and acellular composition and biological activity. Here, we have utilised a bioinformatic approach to determine whether this spatial heterogeneity is also evident at the molecular level and to identify key upstream regulators of signalling pathways enriched in the lesion in a spatially-restricted manner. Differentially expressed genes (20% change, p < 0.

Dynamics of salivary cortisol in chronic kidney disease patients at stages 1 through 4.

Context: End-stage renal disease has been associated with derangement of the HPA function. The dynamics of this axis in early stages of renal disease (CKD) has not been assessed.

Objectives: To evaluate in patients with CKD at stages 1-4 (KDOQI): the diurnal variation of salivary cortisol; the suppressibility of cortisol in saliva and serum after an overnight oral 1 mg dexamethasone suppression test (1 mg DST) with simultaneous measurement of circulating dexamethasone.

Development of Autotaxin Inhibitors: An Overview of the Patent and Primary Literature.

The autotaxin-lysophophatidic acid (ATX-LPA) signaling pathway is implicated in a variety of human disease states including angiogenesis, autoimmune diseases, cancer, fibrotic diseases, inflammation, neurodegeneration, and neuropathic pain, among others. As a result, ATX-LPA has become of significant interest within both the industrial and the academic communities. This review aims to provide a concise overview of the development of novel ATX inhibitors, including the disclosure of the first ATX clinical trial data.

Comparison of "Word" vs. "Picture" Version of the Free and Cued Selective Reminding Test (FCSRT) in Older Adults.

Background: This study examined the psychometric relationship between the Word and Picture versions of the Free and Cued Selective Reminding Test (FCSRT) and developed an equation for score conversion.

Methods: 187 participants were administered the FCSRT-Picture and FCSRT-Word on two visits using a randomized counterbalanced design.

Results: Participants had a mean age of 82.

Discovery of novel non-carboxylic acid 5-amino-4-cyanopyrazole derivatives as potent and highly selective LPA1R antagonists.

High throughput screening (HTS) of our chemical library identified 3-alkylamino-2-aryl-5H-imidazo[1,2,b]pyrazol-7-carbonitrile 1 as a potent antagonist of the LPA1 receptor (LPA1R). Further evaluation of this class of compounds indicated that LPA1R antagonist activity originated from the degradation of the parent molecule in DMSO during the assay conditions. Here, we describe the isolation and characterization of the degradation products and their LPA1R antagonist activity.

The construction and implementation of a novel postburn pruritus scale for infants and children aged five years or less: introducing the Toronto Pediatric Itch Scale.

The authors' objectives were to design, refine, validate and implement a behavior-anchored postburn pruritus scale for children aged 5 years or less. We engaged a range of professionals involved in the care of children with burns. We used Q-methodology in interprofessional team exercises to identify and stratify itch behaviors into categories of increasing severity, and then iteratively refined these into a draft scale.

Development of lysophosphatidic acid pathway modulators as therapies for fibrosis.

Lysophosphatidic acid (LPA) is a class of bioactive phospholipid that displays a wide range of cellular effects via LPA receptors, of which six have been identified (LPAR1-6). In serum and plasma, LPA production occurs mainly by the hydrolysis of lysophosphatidylcholine by the phospholipase D activity of autotaxin (ATX). The involvement of the LPA pathway in driving chronic wound-healing conditions, such as idiopathic pulmonary fibrosis, has suggested targets in this pathway could provide potential therapeutic approaches.