Effect of the phosphodiesterase 4 inhibitor apremilast on cardiometabolic outcomes in psoriatic disease-results of the Immune Metabolic Associations in Psoriatic Arthritis study.

Objectives: Studies have suggested phosphodiesterase 4 (PDE4) inhibition may be associated with weight loss and other cardiometabolic benefits. We evaluated the effect of the PDE4 inhibitor apremilast on body weight and composition, glucose homeostasis, lipid profiles and vascular function in psoriatic disease and whether weight change correlated with therapeutic response.

Methods: We conducted a prospective, open-label study (Immune Metabolic Associations in Psoriatic Arthritis) of adults receiving apremilast 30 mg as part of routine care for PsA and/or psoriasis.

Use of the Controlled Adverse Environment (CAE) in Clinical Research: A Review.

The many internal and external factors that contribute to the pathophysiology of dry eye disease (DED) create a difficult milieu for its study and complicate its clinical diagnosis and treatment. The controlled adverse environment (CAE) model has been developed to minimize the variability that arises from exogenous factors and to exacerbate the signs and symptoms of DED by stressing the ocular surface in a safe, standardized, controlled, and reproducible manner. By integrating sensitive, specific, and clinically relevant endpoints, the CAE has proven to be a unique and adaptable model for both identifying study-specific patient populations with modifiable signs and symptoms, and for tailoring the evaluation of interventions in clinical research studies.

Dynamic Sensitivity of Corneal TRPM8 Receptors to Menthol Instillation in Dry Eye Versus Normal Subjects.

Purpose: To assess the sensitivity of corneal cold receptors to a known transient receptor potential melastatin 8 (TRPM8) agonist, menthol, in dry eye and normals, and to determine whether factors such as disease duration or age affect responses.

Methods: Dry eye disease (DED) (N = 33) and normal (N = 15) subjects were randomly assigned to receive Rohto Hydra (0.01% menthol) or Systane Ultra treatments (OU) in a prospective, double-blind, crossover study.

Thymosin Beta 4: A Potential Novel Therapy for Neurotrophic Keratopathy, Dry Eye, and Ocular Surface Diseases.

Chronic ocular surface diseases such as dry eye, blepharitis, and neurotrophic keratopathies represent a significant and a growing therapeutic challenge. The basis of this expanding prevalence is multifactorial and may due to issues such as an aging population, an increasing use of video display terminals, and increases in frequency of refractive surgeries. The growing incidence of diseases such as diabetes may also be a contributing factor.

Establishing quality assurance criteria for serial dilution operations on liquid-handling equipment.

Since the advent of high-throughput screening (HTS) in the early 1990s, parallel multichannel liquid handlers have become a mainstay in every drug discovery setting. Although several peer-reviewed publications have discussed methods and criteria for stamping multiwell copies, there is very little information about establishing a standard operating procedure (SOP) for standard (microliter-level) serial dilutions of compounds used in dose-response experiments. The authors discuss the 4 main criteria any serial dilution process must pass (accuracy, precision, fold dilution, and outliers) and the process for establishing thresholds for all of these values in a compound management or biological screening laboratory.

Field experiments to assess approaches for spray drift incident investigation.

Background: Spray trials were conducted to determine the variation in primary spray drift deposition between trials under very similar conditions, in order to assess the feasibility of developing a computational tool to aid post-event investigations of pesticide spray incidents. Pesticide deposition was examined by analysis of filter paper and vegetation samples.

Results: Considerable variation in the drift profile was found.

P63 expression in conjunctival proliferative diseases: pterygium and laryngo-onycho-cutaneous (LOC) syndrome.

Purpose: Compare expression of p63 in pterygium and laryngo-onycho-cutaneous (LOC) syndrome with normal conjunctiva.

Methods: P63 immunohistochemical detection was carried out in normal, pterygium, and LOC conjunctival tissue. In vitro, growth of normal conjunctival biopsy specimens, pterygium, and LOC in growth tissue was compared.

Exercise distributed across day and night does not alter circadian period in humans.

In rodents, increased activity due to running-wheel access is associated with a change in observed circadian period. In humans, exposure to exercise has failed to demonstrate similar effects on period. Methodological issues with prior studies such as light exposure during exercise, length of study, and method of measuring period confounded those evaluations of the effect of exercise on period in humans.

Early repair of hemitruncus: excellent early and late outcomes.

Objective: Anomalous origin of 1 of the branch pulmonary arteries from the aorta with 2 normal semilunar valves (hemitruncus) is a rare entity. There have been several small case series reported. We report here our single-institution surgical experience with hemitruncus from 1982 to 2006.

Aortic atresia or severe left ventricular outflow tract obstruction with ventricular septal defect: results of primary biventricular repair in neonates.

Background: Aortic atresia or severe aortic stenosis and left ventricular outflow tract obstruction is a frequent component of complex congenital heart disease. Aortic atresia or severe aortic stenosis and left ventricular outflow tract obstruction with two adequate ventricles is sometimes treated by Norwood palliation followed by late biventricular repair. We reviewed our experience with primary biventricular repair in this group of neonates.

Regional low-flow perfusion versus circulatory arrest in neonates: one-year neurodevelopmental outcome.

Background: Regional low-flow perfusion of the brain is a bypass technique commonly used during stage 1 reconstruction in neonates with hypoplastic left heart syndrome and related variants. The neurodevelopmental outcome of these children is unknown.

Methods: Twenty-nine infants (22 boys, 7 girls) with hypoplastic left heart syndrome or variant requiring single ventricle palliation and aortic arch reconstruction were studied between 1999 and 2004.

Characteristics of pesticide pyrotechnic smoke devices.

Pesticide smoke generating products are widely used by amateurs and professionals but there is little published information available about their burn and deposition characteristics to enable the risks associated with using these devices to be assessed. This paper investigates their burn characteristics, deposition patterns, pesticide air concentrations and potential exposure to operators. Thirteen firings were carried out in different spaces with different ventilation conditions.

Identifying contemporary and historic sources of soil polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans in an industrial urban setting.

A study of soil polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/F) concentrations was undertaken in the vicinity of a municipal solid waste incinerator (MSWI) in Newcastle upon Tyne as a result of concerns raised by local residents about potential contamination from fugitive and stack emissions. The study area was divided into four sectors (north-east (NE), south-east (SE), north-west (NW) and south-west (SW)) around the MSWI, and sampling sites were located up to a distance of 2.25 km.

Characterisation of derivatised monomeric and prepolymeric isocyanates by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry and structural elucidation by tandem mass spectrometry.

Isocyanates are an important class of compounds in occupational hygiene monitoring due mainly to their behaviour as respiratory sensitisers. Here, we demonstrate the application of matrix-assisted laser desorption/ionisation mass spectrometry (MALDI-MS) and MALDI tandem mass spectrometry (MS-MS) to the analysis of derivatised isocyanate monomers and prepolymers. The aim of the work has been to gauge the selectivity obtainable from the direct analysis of isocyanate mixtures without prior separation.

Metal contamination of urban soils in the vicinity of a municipal waste incinerator: one source among many.

Concern from local residents about possible contamination with metals and PCDD/F (dioxins and furans) from fugitive and stack emissions from the Byker municipal solid waste incinerator in Newcastle upon Tyne led the City Council to initiate a study of the concentration of these pollutants in soils. We report here the results for the metals and arsenic. Soils were sampled at distances up to 2.

A novel hemoglobin-based blood substitute protects against myocardial reperfusion injury.

HBOC-201 (Biopure; Cambridge, MA) is a glutaraldehyde-polymerized bovine hemoglobin (Hb) solution that is stroma free, has lower viscosity than blood, and promotes O(2) unloading. We investigated the effects of HBOC-201 in a canine model of myocardial ischemia-reperfusion injury. Dogs were anesthetized and subjected to 90 min of regional myocardial ischemia and 270 min of reperfusion.

Pesticide residues on the external surfaces of field crop sprayers: occupational exposure.

There is a general perception, amongst farmers and researchers, that post-application residues on the external surfaces of sprayers are negligible compared with residues remaining on the internal surfaces, although there have been few attempts to verify this assumption. The aim of this study was to investigate, using cotton glove sampling, operator exposure resulting from three typical operations: entering and working in the cab, general handling of the sprayer and maintenance practices. Samples were analysed for azoxystrobin, carbendazim, chlorothalonil, cyanazine, cypermethrin, epoxiconazole, flusilazole, isoproturon, kresoxim-methyl, metazachlor, pendimethalin, pirimicarb and tebuconazole.

Operator exposure when applying amenity herbicides by all-terrain vehicles and controlled droplet applicators.

A total of 33 surveys of amenity herbicides took place during 1998-1999. These surveys concentrated on two application methods: all-terrain vehicles (ATVs) and controlled droplet applicators (CDAs). The purpose of these surveys was to measure surface deposition and potential inhalation exposure of the operators to the spray fluid used.

Pesticide residues on the external surfaces of field-crop sprayers: environmental impact.

There is increased awareness of the need to clean the external surfaces of sprayers, but the extent to which the washings may impact on the environment is not known. Quantification of the levels of external residues on sprayers could give an indication of the potential environmental impact of sprayer cleaning. The presence of azoxystrobin, carbendazim, chlorothalonil, cyanazine, cypermethrin, epoxiconazole, flusilazole, isoproturon, kresoxim-methyl, metazachlor, pendimethalin, pirimicarb and tebuconazole on thirteen sprayers, sampled on two occasions was investigated.

Relationships between soil heavy metal concentration and mycorrhizal colonisation in Thymus polytrichus in northern England.

A study was conducted to establish whether the wild thyme [ Thymus polytrichus A. Kerner ex Borbás ssp. britannicus (Ronn.

Effects of mycorrhizal colonisation on Thymus polytrichus from heavy-metal-contaminated sites in northern England.

A study was performed to establish whether colonisation with arbuscular mycorrhizal (AM) fungi is beneficial to wild thyme [ Thymus polytrichus A. Kerner ex Borbás ssp. britannicus (Ronn.

Floppy aortic graft reconstruction for germ cell tumor invasion of the infrarenal aorta.

Significant aortic invasion by metastatic nonseminomatous germ cell tumors can present difficult problems intraoperatively in attempted curative retroperitoneal lymph node dissection. Aortic replacement with Dacron graft has been a successful method of dealing with this predicament. We describe a new approach of intraoperative floppy aortic graft reconstruction in a young patient with testicular germ cell cancer in whom a 14 cm pseudoaneurysm involving the infrarenal aorta developed after four courses of preoperative chemotherapy.

Determination of dithiocarbamate pesticides in occupational hygiene sampling devices using the isooctane method and comparison with an automatic thermal desorption (ATD) method.

Two new methods for the determination of dithiocarbamate pesticides in occupational hygiene sampling devices are described. Dithiocarbamate spiked occupational hygiene sampling devices, consisting of glass fibre (GF/A) filters, cotton pads, cotton gloves and disposable overalls, were reduced under acidic conditions and the CS2 evolved as a decomposition product was extracted into isooctane. The isooctane was then analysed using gas chromatography with mass spectrometry, for CS2, which provided a quantitative result for dithiocarbamates.

Photic resetting of the human circadian pacemaker in the absence of conscious vision.

Ocular light exposure patterns are the primary stimuli for entraining the human circadian system to the local 24-h day. Many totally blind persons cannot use these stimuli and, therefore, have circadian rhythms that are not entrained. However, a few otherwise totally blind persons retain the ability to suppress plasma melatonin concentrations after ocular light exposure, probably using a neural pathway that includes the site of the human circadian pacemaker, suggesting that light information is reaching this site.

Direct vascular and cardioprotective effects of rosuvastatin, a new HMG-CoA reductase inhibitor.

Objective: We examined the possible effects of a novel 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, rosuvastatin, on endothelial nitric oxide (NO) production and myocardial ischemia-reperfusion injury.

Background: Recent studies suggest that HMG-CoA reductase inhibitors promote vascular endothelial function through enhanced endothelial NO production. However, it is unclear whether all statins share this beneficial side effect or whether this effect is limited to the "natural" statins.