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Baltimore Highlands, MD, United States

Miller L.E.,Miller Scientific Consulting Inc. | Razavi M.K.,Heart and Vascular Center | Lal B.K.,University of Maryland Baltimore County | Lal B.K.,Baltimore Veterans Affairs Medical Center
Journal of Vascular Surgery | Year: 2015

Objective: The effect of stent graft fixation type on renal function after endovascular aneurysm repair (EVAR) remains controversial. This systematic review and meta-analysis was conducted to determine whether suprarenal (SR) or infrarenal (IR) fixation influences the risk of renal complications after EVAR. Methods: We searched MEDLINE and EMBASE with no date or language restrictions for comparative studies evaluating EVAR with SR vs IR fixation on renal dysfunction, renal artery stenosis, renal artery occlusion, renal infarction, and new need for hemodialysis. For each outcome, we calculated the absolute risk difference (RD) with a random effects meta-analysis and performed assessments of heterogeneity and publication bias. Post hoc subgroup analyses explored the influence of individual moderator variables. Results: A total of 21 nonrandomized studies comparing SR vs IR fixation representing 4474 unique patients (SR, 1949; IR, 2525) were included. Baseline patient characteristics were similar between the SR and IR groups. Median patient follow-up was 12 months in each group. There were no statistically significant differences in the risk of any renal complication between SR and IR fixation groups. The absolute RD between the SR and IR fixation groups was <1%, with no evidence of heterogeneity or publication bias for renal dysfunction, renal artery stenosis, renal artery occlusion or new need for hemodialysis after EVAR. Renal infarction occurred in 6.4% of SR patients and in 2.5% of IR patients (P =.09), with evidence of heterogeneity (I2 = 85%) and publication bias (Egger P =.08). Subgroup analyses revealed that older studies (median treatment period before 2000) reported greater risks of renal infarction with SR fixation (RD, 6.2%; P =.01). However, more contemporary studies (median treatment period after 2000) demonstrated no difference between SR and IR fixation on renal infarction risk (RD, 0.2%; P =.75). Conclusions: There is no difference in the risk of postoperative renal complications when comparing stent grafts using SR vs IR fixation, particularly with newer-generation devices. Contemporary comparative studies with longer-term follow-up are warranted to further elucidate the influence of SR and IR fixation on renal complications. Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc.

Xiao L.,Baltimore Veterans Affairs Medical Center
Methods in molecular biology (Clifton, N.J.) | Year: 2011

In addition to regulating gene transcription, polyamines also potently modulate gene expression posttranscriptionally. Posttranscriptional gene regulation, which includes processes such as mRNA transport, turnover, and translation, involves specific mRNA sequences (cis-element) that interact with transacting factors such as RNA-binding proteins (RBPs) and microRNAs. U- or AU-rich elements (ARE) are the best characterized cis-acting sequences located in the 3'-untranslated regions of many labile mRNAs. Several RBPs, including AUF1, BRF1, TTP, and KSRP, promote ARE-mRNA decay through the recruitment of the ARE-bearing mRNA to sites of mRNA degradation, whereas RBPs such as HuR, HuB, HuC, and HuD stabilize target mRNAs and stimulate their translation. HuR is one of the best-studied RBPs and has emerged as a key regulator of posttranscriptional control of gene expression and its activity is tightly regulated by cellular polyamines. Ribonucleoprotein immunoprecipitation assays and biotin pull-down assays are two major methods used extensively in experiments investigating the roles and mechanisms of cellular polyamines in the posttranscriptional regulation and are described in detail in this chapter.

Blanchard J.J.,University of Maryland College Park | Collins L.M.,University of Maryland College Park | Aghevli M.,Baltimore Veterans Affairs Medical Center | Leung W.W.,University of Maryland College Park | Cohen A.S.,Louisiana State University
Schizophrenia Bulletin | Year: 2011

Social anhedonia has been employed in psychometric high-risk studies to identify putative schizotypes. To date, this research has focused almost exclusively on college samples. The current study sought to examine the validity of social anhedonia as an indicator of risk for schizophrenia-spectrum disorders within a community sample. Furthermore, we evaluated the role of other individual difference variables in accounting for variable clinical severity within the social anhedonia group including trait affectivity, social support, and family environment. Following the mailed questionnaire screening of 2434 eighteen-year olds, laboratory assessments were conducted with individuals identified as being high in social anhedonia (n = 86) and a comparison sample (n = 89). Compared with the control group, individuals in the social anhedonia group were found to have higher rates of mood disorders, elevated schizophrenia-spectrum personality disorder characteristics, greater negative symptom characteristics, and lower global functioning. Individuals within the social anhedonia group also reported greater trait negative affectivity, lower positive affectivity, less social support, and more family conflict. Low social support and problematic family environment were found to be related to elevations in spectrum personality disorder characteristics and poorer functioning within the social anhedonia group. These cross-sectional findings from a community sample provide further support for social anhedonia as a possible indicator of schizotypy. © The Author 2009.

Forrester L.W.,University of Maryland, Baltimore | Roy A.,University of Maryland, Baltimore | Krebs H.I.,University of Maryland, Baltimore | Krebs H.I.,Massachusetts Institute of Technology | And 2 more authors.
Neurorehabilitation and Neural Repair | Year: 2011

Background. Task-oriented therapies such as treadmill exercise can improve gait velocity after stroke, but slow velocities and abnormal gait patterns often persist, suggesting a need for additional strategies to improve walking. Objectives. To determine the effects of a 6-week visually guided, impedance controlled, ankle robotics intervention on paretic ankle motor control and gait function in chronic stroke. Methods. This was a single-arm pilot study with a convenience sample of 8 stroke survivors with chronic hemiparetic gait, trained and tested in a laboratory. Subjects trained in dorsiflexion-plantarflexion by playing video games with the robot during three 1-hour training sessions weekly, totaling 560 repetitions per session. Assessments included paretic ankle ranges of motion, strength, motor control, and overground gait function. Results. Improved paretic ankle motor control was seen as increased target success, along with faster and smoother movements. Walking velocity also increased significantly, whereas durations of paretic single support increased and double support decreased. Conclusions. Robotic feedback training improved paretic ankle motor control with improvements in floor walking. Increased walking speeds were comparable with reports from other task-oriented, locomotor training approaches used in stroke, suggesting that a focus on ankle motor control may provide a valuable adjunct to locomotor therapies. © The Author(s) 2011.

Zhang G.,Pancreatic Cancer Unit | He P.,Pancreatic Cancer Unit | Tan H.,Pancreatic Cancer Unit | Budhu A.,Pancreatic Cancer Unit | And 9 more authors.
Clinical Cancer Research | Year: 2013

Purpose: To identify metabolic pathways that are perturbed in pancreatic ductal adenocarcinoma (PDAC), we investigated gene-metabolite networks with integration of metabolomics and transcriptomics. Experimental Design: Weconducted global metabolite profiling analysis on two independent cohorts of resected PDAC cases to identify critical metabolites alteration that may contribute to the progression of pancreatic cancer. We then searched for gene surrogates that were significantly correlated with the key metabolites, by integrating metabolite and gene expression profiles. Results: Fifty-five metabolites were consistently altered in tumors as compared with adjacent nontumor tissues in a test cohort (N=33) and an independent validation cohort (N=31). Weighted network analysis revealed a unique set of free fatty acids (FFA) that were highly coregulated and decreased in PDAC. Pathway analysis of 157 differentially expressed gene surrogates revealed a significantly altered lipid metabolism network, including key lipolytic enzymes PNLIP, CLPS, PNLIPRP1, and PNLIPRP2. Gene expressions of these lipases were significantly decreased in pancreatic tumors as compared with nontumor tissues, leading to reduced FFAs. More importantly, a lower gene expression of PNLIP in tumors was associated with poorer survival in two independent cohorts. We further showed that two saturated FFAs, palmitate and stearate, significantly induced TRAIL expression, triggered apoptosis, and inhibited proliferation in pancreatic cancer cells. Conclusions: Our results suggest that impairment in a lipolytic pathway involving lipases, and a unique set of FFAs,may play an important role in the development and progression of pancreatic cancer and provide potential targets for therapeutic intervention. © 2013 American Association for Cancer Research.

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