The accuracy of ultra-sonographic findings in detection of abdominal tumor size in children (our experience in Children Medical Center)

Introduction: Since abdominal tumors are one of the common causes of childhood death, studying the clinico-pathologic features of them is important for early diagnosis. Our aim in this study was to determine these features in Iranian children and to evaluate the accuracy of ultrasonography in diagnosing abdominal masses in children.Materials and Methods: In this retrospective case series study, data about sex, age, primary chief complaint, physical examination, imaging report and pathology finding of 156 children with abdominal tumor, who were admitted to the Children Medical Center in the last 6 years were gathered.Results: Male to female ratio was 0.69. The most common type of tumor in this study was Willm’s (37.5%) and Neuroblastoma (35.7%). Mean age of children with Willm’s tumor and Neuroblastoma was 38.95 and 26.65 months respectively. Ultrasonography has a lower accuracy in patients with tenderness, children with Willm’s tumor, female patients and children under 5 years old.Conclusion: Our different findings regarding tumor type and distribution as opposed to previous studies may be due to genetic and geographic variations. In addition, this study shows that the accuracy of Ultrasonography in children with abdominal tumors depends on children’s sex, age, pain and the type of tumor

α8β1 integrin regulates nutrient absorption through an Mfge8-PTEN dependent mechanism.

Coordinated gastrointestinal smooth muscle contraction is critical for proper nutrient absorption and is altered in a number of medical disorders. In this work, we demonstrate a critical role for the RGD-binding integrin α8β1 in promoting nutrient absorption through regulation of gastrointestinal motility. Smooth muscle-specific deletion and antibody blockade of α8 in mice result in enhanced gastric antral smooth muscle contraction, more rapid gastric emptying, and more rapid transit of food through the small intestine leading to malabsorption of dietary fats and carbohydrates as well as protection from weight gain in a diet-induced model of obesity. Mechanistically, ligation of α8β1 by the milk protein Mfge8 reduces antral smooth muscle contractile force by preventing RhoA activation through a PTEN-dependent mechanism. Collectively, our results identify a role for α8β1 in regulating gastrointestinal motility and identify α8 as a potential target for disorders characterized by hypo- or hyper-motility

Solving the Iranian Nuclear Puzzle: An analysis of nationalism, unipolarity, and regional security

This paper analyzes the history of Iran's nuclear program, situating it within internal, regional, and global contexts. It ends with a series of recommendations for U.S. policy with respect to Iran's nuclear program and proliferation in the Middle East

IQGAP1-dependent scaffold suppresses RhoA and inhibits airway smooth muscle contraction.

The intracellular scaffold protein IQGAP1 supports protein complexes in conjunction with numerous binding partners involved in multiple cellular processes. Here, we determined that IQGAP1 modulates airway smooth muscle contractility. Compared with WT controls, at baseline as well as after immune sensitization and challenge, Iqgap1-/- mice had higher airway responsiveness. Tracheal rings from Iqgap1-/- mice generated greater agonist-induced contractile force, even after removal of the epithelium. RhoA, a regulator of airway smooth muscle contractility, was activated in airway smooth muscle lysates from Iqgap1-/- mice. Likewise, knockdown of IQGAP1 in primary human airway smooth muscle cells increased RhoA activity. Immunoprecipitation studies indicated that IQGAP1 binds to both RhoA and p190A-RhoGAP, a GTPase-activating protein that normally inhibits RhoA activation. Proximity ligation assays in primary airway human smooth muscle cells and mouse tracheal sections revealed colocalization of p190A-RhoGAP and RhoA; however, these proteins did not colocalize in IQGAP1 knockdown cells or in Iqgap1-/- trachea. Compared with healthy controls, human subjects with asthma had decreased IQGAP1 expression in airway biopsies. Together, these data demonstrate that IQGAP1 acts as a scaffold that colocalizes p190A-RhoGAP and RhoA, inactivating RhoA and suppressing airway smooth muscle contraction. Furthermore, our results suggest that IQGAP1 has the potential to modulate airway contraction severity in acute asthma

Targeting integrin α5β1 ameliorates severe airway hyperresponsiveness in experimental asthma

Treatment options are limited for severe asthma, and the need for additional therapies remains great. Previously, we demonstrated that integrin αvβ6-deficient mice are protected from airway hyperresponsiveness, due in part to increased expression of the murine ortholog of human chymase. Here, we determined that chymase protects against cytokine-enhanced bronchoconstriction by cleaving fibronectin to impair tension transmission in airway smooth muscle (ASM). Additionally, we identified a pathway that can be therapeutically targeted to mitigate the effects of airway hyperresponsiveness. Administration of chymase to human bronchial rings abrogated IL-13-enhanced contraction, and this effect was not due to alterations in calcium homeostasis or myosin light chain phosphorylation. Rather, chymase cleaved fibronectin, inhibited ASM adhesion, and attenuated focal adhesion phosphorylation. Disruption of integrin ligation with an RGD-containing peptide abrogated IL-13-enhanced contraction, with no further effect from chymase. We identified α5β1 as the primary fibronectin-binding integrin in ASM, and α5β1-specific blockade inhibited focal adhesion phosphorylation and IL-13-enhanced contraction, with no additional effect from chymase. Delivery of an α5β1 inhibitor into murine airways abrogated the exaggerated bronchoconstriction induced by allergen sensitization and challenge. Finally, α5β1 blockade enhanced the effect of the bronchodilator isoproterenol on airway relaxation. Our data identify the α5β1 integrin as a potential therapeutic target to mitigate the severity of airway contraction in asthma

Functional genomic screen identifies novel mediators of collagen uptake

Tissue fibrosis occurs when matrix production outpaces matrix degradation. Degradation of collagen, the main component of fibrotic tissue, is mediated through an extracellular proteolytic pathway and intracellular pathway of cellular uptake and lysosomal digestion. Recent studies demonstrate that disruption of the intracellular pathways can exacerbate fibrosis. These pathways are poorly characterized. Here we identify novel mediators of the intracellular pathway of collagen turnover through a genome-wide RNA interference screen in Drosophila S2 cells. Screening of 7505 Drosophila genes conserved among metazoans identified 22 genes that were required for efficient internalization of type I collagen. These included proteins involved in vesicle transport, the actin cytoskeleton, and signal transduction. We show further that the flotillin genes have a conserved and central role in collagen uptake in Drosophila and human cells. Short hairpin RNA-mediated silencing of flotillins in human monocyte and fibroblasts impaired collagen uptake by promoting lysosomal degradation of the endocytic collagen receptors uPARAP/Endo180 and mannose receptor. These data provide an initial characterization of intracellular pathways of collagen turnover and identify the flotillin genes as critical regulators of this process. A better understanding of these pathways may lead to novel therapies that reduce fibrosis by increasing collagen turnover

The Role of Daily Measurement of Lower Limb Circumference in Early Diagnosis of Deep Vein Thrombosis in the Presence of Other Risk Factors in Patients Admitted to Infectious Diseases Ward of Imam Reza Hospital, Mashhad, during 2012-2013

Introduction: Considering the high rate of mortality in patients with Deep Vein Thrombosis (DVT) and pulmonary embolism, the aim of this study was to evaluate the role of daily measurement of lower limb circumference in early diagnosis of DVT in patients admitted to Infectious Diseases Ward of Imam Reza Hospital, Mashhad, during 2012-2013. Materials and Methods: This cross-sectional study was conducted in Infectious Diseases Ward of Imam Reza Hospital of Mashhad, Iran. Patients were divided into two age- and gender-matched groups. In the first group, the difference between the two legs was greater than 1 cm and in the second group it was 3 cm or more. Circumference of the two legs was assessed on a daily basis at 10 cm above tibial tuberosity. Doppler sonography was performed to rule out DVT. Data were analyzed using SPSS, Version 16.   Results:A total of 204 patients were enrolled in this study, 18 of whom (8/8%) were diagnosed with DVT through Doppler sonography. In addition, 17 patients (11/3%) had fever as a comorbidity. Mean difference of the two legs was more than 3 cm in 16 DVT patients (14%), and two patients with mean difference of less than 3 cm had DVT. Conclusion: Daily measurement of lower limb circumference was an accurate and cost-effective technique for early diagnosis of DVT