Inflammatory Response of Pulmonary Artery Smooth Muscle Cells Exposed to Oxidative and Biophysical Stress.

Pulmonary hypertension in the neonate requires treatment with oxygen and positive pressure ventilation, both known to induce lung injury. The direct response of pulmonary artery smooth muscle cells, the most abundant cells in the artery wall, to the stress of positive pressure and hyperoxia has not been previously studied. Pulmonary artery smooth muscle cells were cultured in temperature- and pressure-controlled air-tight chambers under conditions of positive pressure or hyperoxia for 24 h.

Extracorporeal membrane oxygenation in severe respiratory failure resulting from burns and smoke inhalation injury.

Extracorporeal membrane oxygenation (ECMO) is one of the most frequent forms of extracorporeal life support (ECLS) and can be used as rescue therapy in patients with severe respiratory failure resulting from burns and/or smoke inhalation injury. Experience and literature on this treatment option is still very limited, consequently results are varied. We report a retrospective analysis of our experience with veno-venous (VV) ECMO in burn patients.

The use of VV-ECMO in patients with drug dependencies.

The purpose of this study is to determine the effect of illicit drug and alcohol dependencies on mortality, length of stay, and complications in patients who have been supported with veno-venous extracorporeal membrane oxygenation (VV-ECMO) following respiratory failure not responsive to conventional methods of ventilation. 584 VV-ECMO referrals received at Wythenshawe Hospital were reviewed for evidence of drug dependency. 13 patients were identified as being drug-dependent and having undergone treatment with VV-ECMO.

Added value of electromyography in the diagnosis of myopathy: A consensus exercise.

Objective: Currently, neurologists may primarily rely on blood biomarkers, muscle biopsy, MRI, and genetics in the diagnostic work-up of suspected myopathy. Using expert consensus as diagnostic reference standard, this study addressed the added value of electrodiagnostic medicine (EDX) in diagnosis of myopathies.

Methods: One hundred ninety-four EDX evaluations of patients with a peer-review consensus diagnosis of myopathy were collected by seven European centres.

Human mass balance study of TAS-102 using (14)C analyzed by accelerator mass spectrometry.

Background: TAS-102 is an oral fluoropyrimidine prodrug composed of trifluridine (FTD) and tipiracil hydrochloride (TPI) in a 1:0.5 ratio. FTD is a thymidine analog, and it is degraded by thymidine phosphorylase (TP) to the inactive trifluoromethyluracil (FTY) metabolite.

Intra-abdominal hypertension complicating pancreatitis-induced acute respiratory distress syndrome in three patients on extracorporeal membrane oxygenation.

Background: Severe acute pancreatitis is associated with sever multiorgan failure from 15 to 50%, depending on the series. In some of these patients, conventional methods of ventilation and respiratory support will fail, demanding the use of extracorporeal membrane oxygenation (ECMO). Abdominal compartment syndrome is potentially harmful in this cohort of patients.

The role of transforming growth factor β signaling in fibroblast-like synoviocytes from patients with oligoarticular juvenile idiopathic arthritis: dysregulation of transforming growth factor β signaling, including overexpression of bone morphogenetic protein 4, may lead to a chondrocyte phenotype and may contribute to bony hypertrophy.

Objective: This study was designed to investigate the pathogenic contributions of fibroblast-like synoviocytes (FLS) to juvenile idiopathic arthritis (JIA) by identifying pathways with dysregulated gene expression in FLS from patients with oligoarticular JIA.

Methods: FLS were derived from synovial fluid obtained by arthrocentesis from patients with JIA undergoing intraarticular steroid injections and from orthopedic control patients. Gene expression profiles of the JIA and control FLS were obtained using the Affymetrix platform, with application of Ingenuity Pathway Analysis and Gene Set Enrichment Analysis software to define gene sets in dysregulated pathways and networks of potential pathologic relevance in this disease.

Jasechko et al. reply.

replying to A. M. J.

The ArrayGrid: a methodology for applying multiple samples to a single TEM specimen grid.

High throughput transmission electron microscopy (TEM) is limited by the time that it takes to prepare each specimen and insert it on the microscope. It is further impeded by the deteriorating vacuum of the microscope upon frequent specimen cycling. Nevertheless, in most cases only a small fraction of the specimen is examined and sufficient to provide hundreds of images.

Chronic carvedilol treatment partially reverses the right ventricular failure transcriptional profile in experimental pulmonary hypertension.

Right ventricular failure (RVF) is the most frequent cause of death in patients with pulmonary arterial hypertension (PAH); however, specific therapies targeted to treat RVF have not been developed. Chronic treatment with carvedilol has been shown to reduce established maladaptive right ventricle (RV) hypertrophy and to improve RV function in experimental PAH. However, the mechanisms by which carvedilol improves RVF are unknown.

Terrestrial water fluxes dominated by transpiration.

Renewable fresh water over continents has input from precipitation and losses to the atmosphere through evaporation and transpiration. Global-scale estimates of transpiration from climate models are poorly constrained owing to large uncertainties in stomatal conductance and the lack of catchment-scale measurements required for model calibration, resulting in a range of predictions spanning 20 to 65 per cent of total terrestrial evapotranspiration (14,000 to 41,000 km(3) per year) (refs 1, 2, 3, 4, 5). Here we use the distinct isotope effects of transpiration and evaporation to show that transpiration is by far the largest water flux from Earth's continents, representing 80 to 90 per cent of terrestrial evapotranspiration.

Sensory neuronopathy in patients harbouring recessive polymerase γ mutations.

Defects in the mitochondrial DNA replication enzyme, polymerase γ, are an important cause of mitochondrial disease with ∼25% of all adult diagnoses attributed to mutations in the POLG gene. Peripheral neuronopathy is often part of the clinical syndrome and can represent the most disabling feature. In spite of this, the molecular mechanisms underlying the neuronopathy remain to be elucidated and treatment strategies are limited.

Visual thinking in action: visualizations as used on whiteboards.

While it is still most common for information visualization researchers to develop new visualizations from a data- or taskdriven perspective, there is growing interest in understanding the types of visualizations people create by themselves for personal use. As part of this recent direction, we have studied a large collection of whiteboards in a research institution, where people make active use of combinations of words, diagrams and various types of visuals to help them further their thought processes. Our goal is to arrive at a better understanding of the nature of visuals that are created spontaneously during brainstorming, thinking, communicating, and general problem solving on whiteboards.

Molecular signature of a right heart failure program in chronic severe pulmonary hypertension.

Right heart failure is the cause of death of most patients with severe pulmonary arterial hypertensive (PAH) disorders, yet little is known about the cellular and molecular causes of right ventricular failure (RVF). We first showed a differential gene expression pattern between normal rat right and left ventricles, and postulated the existence of a molecular right heart failure program that distinguishes RVF from adaptive right ventricular hypertrophy (RVH), and that may differ in some respects from a left heart failure program. By means of microarrays and transcriptional sequencing strategies, we used two models of adaptive RVH to characterize a gene expression pattern reflective of growth and the maintenance of myocardial structure.

Impact of medical audit on electrodiagnostic medicine in polyneuropathy.

Objective: The aim of the study was to investigate whether experienced physicians' electrodiagnostic practice and criteria can be influenced by international collaboration involving peer review medical audit.

Methods: Data was obtained from the ESTEEM project, an ongoing collaboration since 1991 among European neurophysiologists concerned with quality improvement in electrodiagnostic medicine. Three sets of the physicians' polyneuropathy examinations performed with intervals of 2-4 years were analysed.

Curcumin-induced HDAC inhibition and attenuation of medulloblastoma growth in vitro and in vivo.

Background: Medulloblastoma is the most common brain tumor in children, and its prognosis is worse than for many other common pediatric cancers. Survivors undergoing treatment suffer from serious therapy-related side effects. Thus, it is imperative to identify safer, effective treatments for medulloblastoma.

Physiological and molecular characterization of genetic competence in Streptococcus sanguinis.

Streptococcus sanguinis is a major component of the oral flora and an important cause of infective endocarditis. Although S. sanguinis is naturally competent, genome sequencing has suggested significant differences in the S.

Extended megadroughts in the southwestern United States during Pleistocene interglacials.

The potential for increased drought frequency and severity linked to anthropogenic climate change in the semi-arid regions of the southwestern United States (US) is a serious concern. Multi-year droughts during the instrumental period and decadal-length droughts of the past two millennia were shorter and climatically different from the future permanent, 'dust-bowl-like' megadrought conditions, lasting decades to a century, that are predicted as a consequence of warming. So far, it has been unclear whether or not such megadroughts occurred in the southwestern US, and, if so, with what regularity and intensity.

Variation in the neurophysiological examination of amyotrophic lateral sclerosis in Europe.

Our objective was to analyse how patients with amyotrophic lateral sclerosis (ALS) are examined neurophysiologically at different European centres in order to identify possible areas with variation or disagreement in the neurophysiological examination of ALS. Ninety-three prospectively collected examinations from six out of seven neurophysiologists in the European ESTEEM project were analysed. All examinations were peer reviewed with an electromyographic consensus diagnosis of motor neuron disease and the diagnosis of ALS confirmed by clinical follow-up.

Gliclazide reduces MKC intestinal transport in healthy but not diabetic rats.

The aim is to investigate the influence of the antidiabetic drug gliclazide on the ileal permeation of the semisynthetic bile acid, MKC, in tissues from healthy and diabetic rats. Sixteen Wistar rats (350 +/- 50 g) were randomly allocated into four groups (4 rats per group, 8 chambers per rat, i.e.

Predicting duration of beneficial effect of joint injection among children with chronic arthritis by measuring biomarkers concentration in synovial fluid at the time of injection.

Objectives: Intra-articular corticosteroids injection (IAC) is a mainstay for the treatment of children with chronic arthritis; nonetheless its efficacy showed variability among published studies and it is still not possible to predict the outcome in a single patient. Our objective was to study the profile of biomarkers in the synovial fluid (SF) obtained at the time of injection and establish if such profile predicts duration of effect.

Methods: SF obtained from patients who underwent knee arthrocentesis and injection was procured and stored for cytokine analysis.

Prolonged synovitis in pediatric Lyme arthritis cannot be predicted by clinical or laboratory parameters.

Ten percent of Lyme arthritis (LA) patients have continued synovitis despite antimicrobial therapy. The current study was designed to (1) investigate predictors of prolonged disease and (2) further define natural history of pediatric LA. Medical records of 94 children fulfilling Centers for Disease Control criteria for Lyme disease were reviewed, classified into groups according to duration of synovitis, and SPSS statistical software was used for analysis.

Function of mitochondrial Stat3 in cellular respiration.

Cytokines such as interleukin-6 induce tyrosine and serine phosphorylation of Stat3 that results in activation of Stat3-responsive genes. We provide evidence that Stat3 is present in the mitochondria of cultured cells and primary tissues, including the liver and heart. In Stat3(-/-) cells, the activities of complexes I and II of the electron transport chain (ETC) were significantly decreased.

Expression profile of interferon stimulated genes in central nervous system of mice infected with dengue virus Type-1.

Dengue virus (DENV) infection can cause a self-limiting disease (dengue fever) or a more severe clinical presentation known as dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS). Furthermore, data from recent dengue epidemics in Brazil indicate that the neurological manifestations are becoming more prevalent. However, the neuropathogenesis of dengue are not well understood.