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Rajendiran S.,University of North Texas Health Science Center | Parwani A.V.,UPMC Shadyside Hospital | Hare R.J.,Plaza Medical Center | Dasgupta S.,University of North Texas Health Science Center | And 4 more authors.
Molecular Cancer | Year: 2014

Background: MicroRNAs (miRNAs) are crucial molecules that regulate gene expression and hence pathways that are key to prostate cancer progression. These non-coding RNAs are highly deregulated in prostate cancer thus facilitating progression of the disease. Among the many genes that have gained importance in this disease, Migration and invasion enhancer 1 (MIEN1), a novel gene located next to HER2/neu in the 17q12 amplicon of the human chromosome, has been shown to enhance prostate cancer cell migration and invasion, two key processes in cancer progression. MIEN1 is differentially expressed between normal and cancer cells and tissues. Understanding the regulation of MIEN1 by microRNA may enable development of better targeting strategies. Methods: The miRNAs that could target MIEN1 were predicted by in silico algorithms and microarray analysis. The validation for miRNA expression was performed by qPCR and northern blotting in cells and by in situ hybridization in tissues. MIEN1 and levels of other molecules upon miRNA regulation was determined by Western blotting, qPCR, and immunofluorescence. The functional effects of miRNA on cells were determined by wound healing cell migration, Boyden chamber cell invasion, clonal and colony formation assays. For knockdown or overexpression of the miRNA or overexpression of MIEN1 3'UTR, cells were transfected with the oligomiRs and plasmids, respectively. Results: A novel miRNA, hsa-miR-940 (miR-940), identified and validated to be highly expressed in immortalized normal cells compared to cancer cells, is a regulator of MIEN1. Analysis of human prostate tumors and their matched normal tissues confirmed that miR-940 is highly expressed in the normal tissues compared to its low to negligible expression in the tumors. While MIEN1 is a direct target of miR-1, miR-940 alters MIEN1 RNA, in a quantity as well as cell dependent context, along with altering its downstream effectors. The miR-940 inhibited migratory and invasive potential of cells, attenuated their anchorage-independent growth ability, and increased E-cadherin expression, implicating its role in mesenchymal-to-epithelial transition (MET). Conclusions: These results, for the first time, implicate miR-940, a regulator of MIEN1, as a promising novel diagnostic and prognostic tool for prostate cancer. © Rajendiran et al.; licensee BioMed Central Ltd. Source


Busis N.,UPMC Shadyside Hospital | Busis N.,Neurodiagnostic Laboratory | Busis N.,Pittsburgh Neurology Center
Neurologic Clinics | Year: 2010

Smartphones make mobile computing at point of care practical. Smartphones can think, sync, and link. Built-in and user-installed applications facilitate communications between neurologists and their medical colleagues and patients and augment data acquisition and processing in the core medical information domains of patient data, clinical decision support, and practice management. Mobile telemedicine is becoming practical in certain scenarios. Smartphones can improve neurologic diagnosis and treatment, teaching, and research. Patients can benefit from smartphone technology. In addition to enhanced communication, patient education, and social networking, these devices can promote healthy lifestyles, preventive medicine, and compliance and even serve as monitoring and prosthetic devices. © 2010 Elsevier Inc. All rights reserved. Source


Rajendiran S.,University of North Texas Health Science Center | Parwani A.V.,UPMC Shadyside Hospital | Hare R.J.,Plaza Medical Center | Dasgupta S.,University of North Texas Health Science Center | And 2 more authors.
Molecular Cancer | Year: 2015

Background: MicroRNAs (miRNAs) are crucial molecules that regulate gene expression and hence pathways that are key to prostate cancer progression. These non-coding RNAs are highly deregulated in prostate cancer thus facilitating progression of the disease. Among the many genes that have gained importance in this disease, Migration and invasion enhancer 1 (MIEN1), a novel gene located next to HER2/neu in the 17q12 amplicon of the human chromosome, has been shown to enhance prostate cancer cell migration and invasion, two key processes in cancer progression. MIEN1 is differentially expressed between normal and cancer cells and tissues. Understanding the regulation of MIEN1 by microRNA may enable development of better targeting strategies. Methods: The miRNAs that could target MIEN1 were predicted by in silico algorithms and microarray analysis. The validation for miRNA expression was performed by qPCR and northern blotting in cells and by in situ hybridization in tissues. MIEN1 and levels of other molecules upon miRNA regulation was determined by Western blotting, qPCR, and immunofluorescence. The functional effects of miRNA on cells were determined by wound healing cell migration, Boyden chamber cell invasion, clonal and colony formation assays. For knockdown or overexpression of the miRNA or overexpression of MIEN1 3'UTR, cells were transfected with the oligomiRs and plasmids, respectively. Results: A novel miRNA, hsa-miR-940 (miR-940), identified and validated to be highly expressed in immortalized normal cells compared to cancer cells, is a regulator of MIEN1. Analysis of human prostate tumors and their matched normal tissues confirmed that miR-940 is highly expressed in the normal tissues compared to its low to negligible expression in the tumors. While MIEN1 is a direct target of miR-940, miR-940 alters MIEN1 RNA, in a quantity as well as cell dependent context, along with altering its downstream effectors. The miR-940 inhibited migratory and invasive potential of cells, attenuated their anchorage-independent growth ability, and increased E-cadherin expression, implicating its role in mesenchymal-to-epithelial transition (MET). Conclusions: These results, for the first time, implicate miR-940, a regulator of MIEN1, as a promising novel diagnostic and prognostic tool for prostate cancer. © 2014 Rajendiran et al.; licensee BioMed Central Ltd. Source


Mitchell A.M.,University of Pittsburgh | Davies M.A.,University of Pittsburgh | Cassesse C.,Childrens Community Pediatrics | Curran R.,UPMC Shadyside Hospital
Journal for Nurse Practitioners | Year: 2014

Depression in children, adolescents, and young adults can jeopardize health status, well-being, and development. Almost a decade ago, risks and benefits of antidepressant use in this group prompted the Food and Drug Administration (FDA) to ask manufacturers toinclude black box warnings on antidepressant prescriptions. This article reviews initial FDA decisions related to black box warnings for antidepressants in youth, reviews effects of the warnings, and considers clinical implications of prescribing antidepressants for treatment of youth depression. Health care providers must consider the risks and benefits of initiating antidepressant medication treatment, closely monitoring adherence, patient outcomes, and suicidal ideation. © 2014 Elsevier Inc. Source


Badheka A.O.,Detroid Medical Center | Chothani A.,MedStar Washington Hospital Center | Mehta K.,UPMC Shadyside Hospital | Patel N.J.,Staten Island University Hospital | And 19 more authors.
Circulation: Arrhythmia and Electrophysiology | Year: 2015

Background - Safety data on percutaneous left atrial appendage closure arises from centers with considerable expertise in the procedure or from clinical trial, which might not be reproducible in clinical practice. We sought to estimate the frequency and predictors of adverse outcomes and costs of percutaneous left atrial appendage closure procedure in the US. Methods and Results - The data were obtained from the Nationwide Inpatient Sample from the years 2006 to 2010. The Nationwide Inpatient Sample is the largest all-payer inpatient data set in the US. Complications were calculated using patient safety indicators and International Classification of Diseases-Ninth Revision, Clinical Modification codes. Annual hospital volume was calculated using unique hospital identifiers. Weights provided by the Nationwide Inpatient Sample were used to generate national estimates. A total of 268 (weighted=1288) procedures were analyzed. The overall composite rate of mortality or any adverse event was 24.3% (65), with 3.4% patients required open cardiac surgery after procedure. Average length of stay was 4.61±1.05 days and cost of care was 26 024±34 651. Annual hospital procedural volume was significantly associated with reduced complications and mortality (every unit increase: odds ratio, 0.89; 95% confidence interval, 0.85-0.94; P<0.001), decrease in length of stay (every unit increase: hazard ratio, 0.95; 95% confidence interval, 0.92-0.98; P<0.001) and cost of care (every unit increase: hazard ratio, 0.96; 95% confidence interval, 0.93-0.98; P<0.001). Conclusions - Our study demonstrates that the frequency of inhospital adverse outcomes associated with percutaneous left atrial appendage closure is higher in the real-world population than in clinical trials. We also demonstrate that higher annual hospital volume is associated with safer procedures, with lower length of stay and cost. © 2014 American Heart Association, Inc. Source

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