Precision targeting of the plasminogen activator inhibitor-1 mechanism increases efficacy of fibrinolytic therapy in empyema.

Plasminogen activator inhibitor-1 (PAI-1) is an endogenous irreversible inhibitor of tissue-type (tPA) and urokinase (uPA) plasminogen activators. PAI-1-targeted fibrinolytic therapy (PAI-1-TFT) is designed to decrease the therapeutic dose of tPA and uPA, attenuating the risk of bleeding and other complications. Docking site peptide (DSP) mimics the part of the PAI-1 reactive center loop that interacts with plasminogen activators, thereby affecting the PAI-1 mechanism.

Students with mild intellectual disability engaging in proportions word problems.

The researchers conducted a qualitative case study to describe the experiences of two seventh grade students with mild intellectual disability as they engaged in mathematics word problems involving proportions. The researchers analyzed student performance in large group settings and with individualized instruction to gain perspective on the students' tendencies with challenging mathematics content. During the teaching sessions in this study, one of the participants initially struggled with the proportions word problems, but demonstrated success after teachers connected new information in the tasks to students' long-term memory and utilized gestures and diagrams to facilitate the students' processing of information.

Glycogen Synthase Kinase-3β Inhibition with 9-ING-41 Attenuates the Progression of Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with a median survival of 3 years after diagnosis. Although the etiology of IPF is unknown, it is characterized by extensive alveolar epithelial cell apoptosis and proliferation of myofibroblasts in the lungs. While the origins of these myofibroblast appear to be diverse, fibroblast differentiation contributes to expansion of myofibroblasts and to disease progression.

Increased expression of plasminogen activator inhibitor-1 (PAI-1) is associated with depression and depressive phenotype in C57Bl/6J mice.

Plasminogen activator inhibitor 1 (PAI-1), which is elevated in numerous disease states, has been implicated as a stress-related protein involved in the pathogenesis of depression. We measured PAI-1 in the plasma of healthy and depressed individuals and assessed plasminogen activator (PA) expression and regulation by PAI-1 in cultured normal human astrocytes (NHA). Elevated plasma PAI-1 levels were found in depressed patients.

Lack of durable protection against cotton smoke-induced acute lung injury in sheep by nebulized single chain urokinase plasminogen activator or tissue plasminogen activator.

Background: Airway fibrin casts are clinically important complications of severe inhalational smoke-induced acute lung injury (ISIALI) for which reliable evidence-based therapy is lacking. Nebulized anticoagulants or a tissue plasminogen activator; tPA, has been advocated, but airway bleeding is a known and lethal potential complication. We posited that nebulized delivery of single chain urokinase plasminogen activator, scuPA, is well-tolerated and improves physiologic outcomes in ISIALI.

Inhibition of Glycogen Synthase Kinase 3β Blocks Mesomesenchymal Transition and Attenuates Streptococcus pneumonia-Mediated Pleural Injury in Mice.

Pleural loculation affects about 30,000 patients annually in the United States and in severe cases can resolve with restrictive lung disease and pleural fibrosis. Pleural mesothelial cells contribute to pleural rind formation by undergoing mesothelial mesenchymal transition (MesoMT), whereby they acquire a profibrotic phenotype characterized by increased expression of α-smooth muscle actin and collagen 1. Components of the fibrinolytic pathway (urokinase plasminogen activator and plasmin) are elaborated in pleural injury and strongly induce MesoMT in vitro.

Dose dependency of outcomes of intrapleural fibrinolytic therapy in new rabbit empyema models.

The incidence of empyema (EMP) is increasing worldwide; EMP generally occurs with pleural loculation and impaired drainage is often treated with intrapleural fibrinolytic therapy (IPFT) or surgery. A number of IPFT options are used clinically with empiric dosing and variable outcomes in adults. To evaluate mechanisms governing intrapleural fibrinolysis and disease outcomes, models of Pasteurella multocida and Streptococcus pneumoniae were generated in rabbits and the animals were treated with either human tissue (tPA) plasminogen activator or prourokinase (scuPA).

Organizing empyema induced in mice by Streptococcus pneumoniae: effects of plasminogen activator inhibitor-1 deficiency.

Background: Pleural infection affects about 65,000 patients annually in the US and UK. In this and other forms of pleural injury, mesothelial cells (PMCs) undergo a process called mesothelial (Meso) mesenchymal transition (MT), by which PMCs acquire a profibrogenic phenotype with increased expression of α-smooth muscle actin (α-SMA) and matrix proteins. MesoMT thereby contributes to pleural organization with fibrosis and lung restriction.

Assessment of Scientific Reasoning: the Effects of Task Context, Data, and Design on Student Reasoning in Control of Variables.

Scientific reasoning is an important component under the cognitive strand of the 21st century skills and is highly emphasized in the new science education standards. This study focuses on the assessment of student reasoning in control of variables (COV), which is a core sub-skill of scientific reasoning. The main research question is to investigate the extent to which the existence of experimental data in questions impacts student reasoning and performance.

The time course of resolution of adhesions during fibrinolytic therapy in tetracycline-induced pleural injury in rabbits.

The time required for the effective clearance of pleural adhesions/organization after intrapleural fibrinolytic therapy (IPFT) is unknown. Chest ultrasonography and computed tomography (CT) were used to assess the efficacy of IPFT in a rabbit model of tetracycline-induced pleural injury, treated with single-chain (sc) urokinase plasminogen activators (scuPAs) or tissue PAs (sctPA). IPFT with sctPA (0.

Mesomesenchymal transition of pleural mesothelial cells is PI3K and NF-κB dependent.

Pleural organization follows acute injury and is characterized by pleural fibrosis, which may involve the visceral and parietal pleural surfaces. This process affects patients with complicated parapneumonic pleural effusions, empyema, and other pleural diseases prone to pleural fibrosis and loculation. Pleural mesothelial cells (PMCs) undergo a process called mesothelial mesenchymal transition (MesoMT), by which PMCs acquire a profibrotic phenotype characterized by cellular enlargement and elongation, increased expression of α-smooth muscle actin (α-SMA), and matrix proteins including collagen-1.

Thrombin down-regulates tissue factor pathway inhibitor expression in a PI3K/nuclear factor-κB-dependent manner in human pleural mesothelial cells.

Tissue factor pathway inhibitor (TFPI) is the primary inhibitor of the extrinsic coagulation cascade, and its expression is reported to be relatively stable. Various pathophysiologic agents have been shown to influence TFPI activity by regulating its expression or by modifying the protein. It is not clear how TFPI activity is regulated in normal physiology or in injury.

Targeting of plasminogen activator inhibitor 1 improves fibrinolytic therapy for tetracycline-induced pleural injury in rabbits.

Endogenous active plasminogen activator inhibitor 1 (PAI-1) was targeted in vivo with monoclonal antibodies (mAbs) that redirect its reaction with proteinases to the substrate branch. mAbs were used as an adjunct to prourokinase (single-chain [sc] urokinase [uPA]) intrapleural fibrinolytic therapy (IPFT) of tetracycline-induced pleural injury in rabbits. Outcomes of scuPA IPFT (0.

Plasminogen activator inhibitor-1 deficiency augments visceral mesothelial organization, intrapleural coagulation, and lung restriction in mice with carbon black/bleomycin-induced pleural injury.

Local derangements of fibrin turnover and plasminogen activator inhibitor (PAI)-1 have been implicated in the pathogenesis of pleural injury. However, their role in the control of pleural organization has been unclear. We found that a C57Bl/6j mouse model of carbon black/bleomycin (CBB) injury demonstrates pleural organization resulting in pleural rind formation (14 d).

The perception and identification of facial emotions in individuals with autism spectrum disorders using the Let's Face It! Emotion Skills Battery.

Background: Although impaired social-emotional ability is a hallmark of autism spectrum disorder (ASD), the perceptual skills and mediating strategies contributing to the social deficits of autism are not well understood. A perceptual skill that is fundamental to effective social communication is the ability to accurately perceive and interpret facial emotions. To evaluate the expression processing of participants with ASD, we designed the Let's Face It! Emotion Skills Battery (LFI! Battery), a computer-based assessment composed of three subscales measuring verbal and perceptual skills implicated in the recognition of facial emotions.

Lipoprotein receptor-related protein 1 regulates collagen 1 expression, proteolysis, and migration in human pleural mesothelial cells.

The low-density lipoprotein receptor-related protein 1 (LRP-1) binds and can internalize a diverse group of ligands, including members of the fibrinolytic pathway, urokinase plasminogen activator (uPA), and its receptor, uPAR. In this study, we characterized the role of LRP-1 in uPAR processing, collagen synthesis, proteolysis, and migration in pleural mesothelial cells (PMCs). When PMCs were treated with the proinflammatory cytokines TNF-α and IL-1β, LRP-1 significantly decreased at the mRNA and protein levels (70 and 90%, respectively; P < 0.

Effects of risperidone and parent training on adaptive functioning in children with pervasive developmental disorders and serious behavioral problems.

Objective: Children with Pervasive Developmental Disorders (PDDs) have social interaction deficits, delayed communication, and repetitive behaviors as well as impairments in adaptive functioning. Many children actually show a decline in adaptive skills compared with age mates over time.

Method: This 24-week, three-site, controlled clinical trial randomized 124 children (4 through 13 years of age) with PDDs and serious behavioral problems to medication alone (MED; n = 49; risperidone 0.

Using computerized games to teach face recognition skills to children with autism spectrum disorder: the Let's Face It! program.

Background: An emerging body of evidence indicates that relative to typically developing children, children with autism are selectively impaired in their ability to recognize facial identity. A critical question is whether face recognition skills can be enhanced through a direct training intervention.

Methods: In a randomized clinical trial, children diagnosed with autism spectrum disorder were pre-screened with a battery of subtests (the Let's Face It! Skills battery) examining face and object processing abilities.

Promoting social skill development in children with pervasive developmental disorders: a feasibility and efficacy study.

A randomized controlled design was employed to evaluate a social skills intervention for children with pervasive developmental disorders. Aims included evaluating the acceptability of the program and gathering preliminary evidence on efficacy. Forty-four children, ages 8-11 years, were randomly assigned to treatment or wait list.

Medication and parent training in children with pervasive developmental disorders and serious behavior problems: results from a randomized clinical trial.

Objective: Many children with pervasive developmental disorders (PDDs) have serious, functionally impairing behavioral problems. We tested whether combined treatment (COMB) with risperidone and parent training (PT) in behavior management is superior to medication alone (MED) in improving severe behavioral problems in children with PDDs.

Method: This 24-week, three-site, randomized, parallel-groups clinical trial enrolled 124 children, aged 4 through 13 years, with PDDs, accompanied by frequent tantrums, self-injury, and aggression.

Group intervention to promote social skills in school-age children with pervasive developmental disorders: reconsidering efficacy.

A consistent result in the evaluation of group-delivered intervention to promote social reciprocity in children with PDDs is that outcome data are inconclusive. Lack of robust evidence of efficacy confounds understanding of these interventions and their value to the field. It is conceivable that the construct of impaired social reciprocity in PDD presents unique circumstances that require special consideration when evaluating the evidence base.

Cognitive effects of risperidone in children with autism and irritable behavior.

Objective: The objective of this research was to explore the effects of risperidone on cognitive processes in children with autism and irritable behavior.

Method: Thirty-eight children, ages 5-17 years with autism and severe behavioral disturbance, were randomly assigned to risperidone (0.5 to 3.

Educational placements and service use patterns of individuals with autism spectrum disorders.

This project was undertaken to identify child characteristics associated with educational placement and service use in high-functioning children with autism spectrum disorders. The sample of 101 (nine females) had a mean age of 12 +/- 3 years (mean IQ = 101.77 +/- 19.

Children's Yale-Brown Obsessive Compulsive Scale modified for pervasive developmental disorders.

Objective: To examine the psychometric properties of the Children's Yale-Brown Obsessive Compulsive Scales (CYBOCS) modified for pervasive developmental disorders (PDDs).

Method: Raters from five Research Units on Pediatric Psychopharmacology (RUPP) Autism Network were trained to reliability. The modified scale (CYBOCS-PDD), which contains only the five Compulsion severity items (range 0-20), was administered to 172 medication-free children (mean 8.