Medical Specialties Commons^™

Pomalidomide Reverses Gamma-Globin Silencing Through The Transcriptional Reprogramming Of Adult Hematopoietic Progenitors, B. M. Dulmovits, A. O. Appiah-Kubi, J. Papoin, M. He, Y. Al-Abed, S. Didier, M. Gould, S. Husain-Krautter, S. A. Singh, A. Vlachos, S. L. Allen, J. M. Lipton, J. M. Liu, L. Blanc, +7 Additional Authors

Journal Articles

Current therapeutic strategies for sickle cell anemia are aimed at reactivating fetal hemoglobin. Pomalidomide, a third-generation immunomodulatory drug, was proposed to induce fetal hemoglobin production by an unknown mechanism. Here, we report that pomalidomide induced a fetal-like erythroid differentiation program, leading to a reversion of gamma-globin silencing in adult human erythroblasts. Pomalidomide acted early by transiently delaying erythropoiesis at the BFU-E/CFU-E transition, but without affecting terminal differentiation. Further, the transcription networks involved in gamma-globin repression were selectively and differentially affected by pomalidomide including BCL11A, SOX6, IKZF1, KLF1, and LSD1. IKAROS (IKZF1), a known target of pomalidomide, was degraded by the …

High-Density Lipoprotein (Hdl) Counter-Regulates Serum Amyloid A (Saa)-Induced Spla(2)-Iie And Spla(2)-V Expression In Macrophages, S. Zhu, Y. Wang, W. Chen, W. Li, A. Wang, J. Li, H. Yang, K. J. Tracey, J. D'Angelo, H. Wang, +2 Additional Authors

Journal Articles

No abstract provided.

Skin Conductance At Baseline And Post-Heel Lance Reflects Sympathetic Activation In Neonatal Opiate Withdrawal, C. N. Oji-Mmuo, E. J. Michael, J. Mclatchy, M. M. Lewis, J. E. Becker, K. K. Doheny

Journal Articles

AIM: Skin conductance (SC) provides an objective measure of autonomic system regulation through sympathetic-mediated filling of sweat glands. This study aimed to test the utility of SC to detect sympathetic activation in neonatal abstinence syndrome (NAS). METHODS: 14 term (mean, SE: 38.8 + 0.35 weeks gestational age) neonates with chronic prenatal opiate exposure were enrolled. SC (peaks/sec and mean of peaks) were measured at baseline, during heel lance/squeeze (HLS) and recovery from HLS at 24-48 (mean 38) hours of life prior to treatment for NAS. Blinded coders with established reliability assessed neonates using the Modified Finnegan Neonatal Scoring System (MFNSS). …

Baseline Striatal Functional Connectivity As A Predictor Of Response To Antipsychotic Drug Treatment, D. Sarpal, M. Argyelan, D. G. Robinson, P. R. Szeszko, K. H. Karlsgodt, M. John, N. Weissman, J. A. Gallego, J. M. Kane, T. Lencz, A. K. Malhotra

Journal Articles

OBJECTIVE: Clinical response to antipsychotic drug treatment is highly variable, yet prognostic biomarkers are lacking. The authors recently demonstrated that successful antipsychotic drug treatment alters resting-state functional connectivity of the striatum. The goal of the present study was to test whether intrinsic striatal connectivity patterns provide prognostic information and can serve as a potential biomarker of treatment response to antipsychotic drugs. METHOD: The authors used resting-state functional MRI (fMRI) to develop a prognostic index in a discovery cohort of 41 first-episode schizophrenia patients, then tested this index in an independent cohort of 40 newly hospitalized chronic patients with acute psychosis. …

Type Vi Choledochal Cyst—An Unusual Presentation Of Jaundice, L. Nambiar, E. Siskind, A. W. Shen, C. Fan, G. Grimaldi, C. Choy, J. Madariaga, J. Nicastro, E. P. Molmenti, G. Coppa, +1 Additional Author

Journal Articles

No abstract provided.

Development Of A Novel Renal Activity Index Of Lupus Nephritis In Children & Young Adults, H. I. Brunner, M. Bennett, K. Abulaban, M. Klein-Gitelman, K. O'Neil, L. Tucker, S. Ardoin, K. Rouster-Stevens, B. A. Eberhard, P. Devarajan, +8 Additional Authors

Journal Articles

BACKGROUND: Noninvasive estimation of the degree of inflammation seen on kidney biopsy with lupus nephritis (LN) remains difficult. The objective of this study was to develop a Renal Activity Index for Lupus (RAIL) that, based solely on laboratory measures, accurately reflects histological LN activity. METHODS: We assayed traditional LN laboratory tests and 16 urine biomarkers (UBMs) in children (n=47) at the time of kidney biopsy. Histological LN activity was measured by the NIH Activity Index (NIH-AI) and the Tubulointerstitial Activity Index (TIAI). High LN-activity status (vs. moderate/low) was defined as NIH-AI scores > 10 (vs.5 (vs.92% accuracy and LN-activityTIAI status with …

Increased Hepcidin In Transferrin-Treated Thalassemic Mice Correlates With Increased Liver Bmp2 Expression And Decreased Hepatocyte Erk Activation, H. Chen, T. Choesang, H. Li, S. Sun, P. Pham, W. Bao, M. Feola, M. Westerman, L. Blanc, Y. Z. Ginzburg, +4 Additional Authors

Journal Articles

Iron overload results in significant morbidity and mortality in beta-thalassemic patients. Insufficient hepcidin is implicated in parenchymal iron overload in beta-thalassemia and approaches to increase hepcidin have therapeutic potential. We have previously shown that exogenous apo-transferrin markedly ameliorates ineffective erythropoiesis and increases hepcidin expression in Hbb(th1/th1) (thalassemic) mice. We utilize in vivo and in vitro systems to investigate effects of exogenous apo-transferrin on Smad and ERK1/2 signaling, pathways that participate in hepcidin regulation. Our results demonstrate that apo-transferrin increases hepcidin expression in vivo despite decreased circulating and parenchymal iron concentrations and unchanged liver Bmp6 mRNA expression in thalassemic mice. Hepatocytes …

Elevate Wellness: Unlocking The Potential Of Creative Problem Solving To Improve Wellness In Residency Programs., B. Pathak, E. Parry, L. Block, S. V. Desai

Journal Articles

No abstract provided.

A Contemporary Dose Selection Algorithm For Stereotactic Radiosurgery In The Treatment Of Brain Metastases - An Initial Report., R. J. Colaco, J. B. Yu, J. S. Bond, R. S. Bindra, J. N. Contessa, J. P. S. Knisely, V. L. Chiang

Journal Articles

Indications and treatment goals for SRS have changed since the publication of RTOG 90-05. We present initial retrospective outcomes from a new dose selection algorithm in use at our institution felt to be more contemporary with doses being used in the radiosurgery community today and report our local control and toxicity outcomes. This dose selection algorithm will be subject to a forthcoming prospective phase 2 trial.To evaluate safety and efficacy of an institutional dose selection algorithm in the treatment of brain metastases (BM) with single fraction radio-surgery (SRS).The medical records of 65 patients with ≤10 BM treated with GK at …

Defining The Value Framework For Prostate Brachytherapy Using Patient-Centered Outcome Metrics And Time-Driven Activity-Based Costing, N. G. Thaker, T. J. Pugh, U. Mahmood, S. Choi, T. E. Spinks, N. E. Martin, T. T. Sio, B. W. Cox, L. Potters, S. J. Frank, +8 Additional Authors

Journal Articles

No abstract provided.

Effect Of The Normalized Prescription Isodose Line On The Magnitude Of Monte Carlo Vs. Pencil Beam Target Dose Differences For Lung Stereotactic Body Radiotherapy, D. Zheng, Q. Zhang, X. Liang, X. Zhu, V. Verma, S. Wang, S. Zhou

Journal Articles

© This work is licensed under a Creative Commons Attribution 3.0 Unported License. In lung stereotactic body radiotherapy (SBRT) cases, the pencil beam (PB) dose calculation algorithm is known to overestimate target dose as compared to the more accurate Monte Carlo (MC) algorithm. We investigated whether changing the normalized prescription isodose line affected the magnitude of MC vs. PB target dose differences. Forty-eight patient plans and twenty virtual-tumor phantom plans were studied. For patient plans, four alternative plans prescribed to 60%, 70%, 80%, and 90% isodose lines were each created for 12 patients who previously received lung SBRT treatments. Using …

Outcomes In Patients With Vestibular Schwannoma After Subtotal Resection And Adjuvant Radiosurgery, H. Radwan, M. Bruce Eisenberg, J. P. S. Knisely, M. M. Ghaly, M. Schulder

Journal Articles

No abstract provided.

Target Dose Conversion Modeling From Pencil Beam (Pb) To Monte Carlo (Mc) For Lung Sbrt, D. Zheng, X. Zhu, Q. Zhang, X. Liang, W. Zhen, C. Lin, V. Verma, S. Wang, A. Wahl, C. Zhang, +2 Additional Authors

Journal Articles

© 2016 The Author(s). Background: A challenge preventing routine clinical implementation of Monte Carlo (MC)-based lung SBRT is the difficulty of reinterpreting historical outcome data calculated with inaccurate dose algorithms, because the target dose was found to decrease to varying degrees when recalculated with MC. The large variability was previously found to be affected by factors such as tumour size, location, and lung density, usually through sub-group comparisons. We hereby conducted a pilot study to systematically and quantitatively analyze these patient factors and explore accurate target dose conversion models, so that large-scale historical outcome data can be correlated with more …

Quality Measurement In Wonderland: The Curious Case Of A Dialysis Readmissions Measure, S. Fishbane, J. B. Wish

Journal Articles

The standardized readmission ratio is a new quality measure for dialysis facilities that will affect public reporting and payment beginning in 2017. Like all quality measures affecting public reporting and payment, the standardized readmission ratio was vetted by a process that included a technical expert panel convened by the US Centers for Medicare and Medicaid Services, and, then, the National Quality Forum. Unlike previous measures, standardized readmission ratio followed a tortuous path that exposed problems in the development and endorsement process. Although it is acknowledged that processes in the dialysis facility can be improved to decrease readmissions, multiple objections to …

Predicting Treatment Related Imaging Changes (Trics) After Radiosurgery For Brain Metastases Using Treatment Dose And Conformality Metrics., B. F. Taylor, J. P. Knisely, J. M. Qian, J. B. Yu, V. L. Chiang

Journal Articles

Purpose: Treatment-related imaging changes (TRICs) after stereotactic radiosurgery (SRS) involves the benign transient enlargement of radiographic lesions after treatment. Identifying the radiation dose volumes and conformality metrics associated with TRICs for different post-treatment periods would be helpful and improve clinical decision making.

Methods: 367 metastases in 113 patients were treated using Gamma Knife SRS between 1/1/2007-12/31/2009. Each metastasis was measured at each imaging follow-up to detect TRICs (defined as ≥ 20% increase in volume). Fluctuations in small volume lesions (less than 108 mm

Results: From 0-6 months, all measures correlated with the incidence of TRICs (p

Conclusions: All metrics except …

Estradiol-Mediated Spine Changes In The Dorsal Hippocampus And Medial Prefrontal Cortex Of Ovariectomized Female Mice Depend On Erk And Mtor Activation In The Dorsal Hippocampus, J. J. Tuscher, V. Luine, M. Frankfurt, K. M. Frick

Journal Articles

No abstract provided.

Simeprevir Plus Sofosbuvir (12 And 8 Weeks) In Hepatitis C Virus Genotype 1-Infected Patients Without Cirrhosis: Optimist-1, A Phase 3, Randomized Study, P. Kwo, N. Gitlin, R. Nahass, D. Bernstein, K. Etzkorn, S. Rojter, E. Schiff, M. Davis, P. Ruane, J. Witek, +8 Additional Authors

Journal Articles

No abstract provided.

Efficacy Of Direct-Acting Antiviral Combination For Patients With Hepatitis C Virus Genotype 1 Infection And Severe Renal Impairment Or End-Stage Renal Disease, P. J. Pockros, K. R. Reddy, P. S. Mantry, E. Cohen, M. Bennett, M. S. Sulkowski, D. E. Bernstein, D. E. Cohen, N. S. Shulman, E. Lawitz, +4 Additional Authors

Journal Articles

© 2016 AGA Institute. Background & Aims Although hepatitis C virus (HCV) infection is common in patients with end-stage renal disease, highly efficacious, well-tolerated, direct-acting antiviral regimens have not been extensively studied in this population. We investigated the safety and efficacy of ombitasvir co-formulated with paritaprevir and ritonavir, administered with dasabuvir (with or without ribavirin) in a prospective study of patients with stage 4 or 5 chronic kidney disease (CKD). Methods We performed a single-arm, multicenter study of treatment-naïve adults with HCV genotype 1 infection, without cirrhosis and with CKD stage 4 (estimated glomerular filtration rate, 15-30 mL/min/1.73 m2) or …

Cytoplasmic, Full Length And Novel Cleaved Variant, Tblr1 Reduces Apoptosis In Prostate Cancer Under Androgen Deprivation, G. Daniels, X. Zhang, X. Zhong, L. Santiago, L. H. Wang, X. Wu, J. Y. Zhang, F. Liang, X. Li, P. Lee, +6 Additional Authors

Journal Articles

No abstract provided.

Differential Protein Expression In Small Intestinal Neuroendocrine Tumors And Liver Metastases, M. K. Kim, F. Ye, D. Wang, M. Cui, S. C. Ward, R. R. Warner, S. Roayaie, M. Schwartz, D. Zhang, S. Itzkowitz, +1 Additional Author

Journal Articles

OBJECTIVE: Small intestinal neuroendocrine tumors (SI-NETs) are often detected after they have become metastatic. Using a novel protein array, we identified pathways important in SI-NET metastasis development in surgically resected patients. METHODS: Paired primary tumors and liver metastases from 25 patients undergoing surgical resection for metastatic SI-NETs were harvested. Extracted proteins were separated by sodium dodecyl sulfate gel and multiplex immunoblots were performed with 136 antibodies. Significant Analysis of Microarray was used to select for differentially expressed proteins. A tissue microarray was constructed from 27 archived specimens and stained by immunohistochemistry. RESULTS: Comparing primary SI-NETs with matched normal small-bowel mucosa, …

Acalabrutinib (Acp-196) In Relapsed Chronic Lymphocytic Leukemia, J. C. Byrd, B. Harrington, S. O'Brien, J. A. Jones, A. Schuh, S. Devereux, J. Chaves, W. G. Wierda, J. C. Barrientos, R. R. Furman, +20 Additional Authors

Journal Articles

Background Irreversible inhibition of Bruton's tyrosine kinase (BTK) by ibrutinib represents an important therapeutic advance for the treatment of chronic lymphocytic leukemia (CLL). However, ibrutinib also irreversibly inhibits alternative kinase targets, which potentially compromises its therapeutic index. Acalabrutinib (ACP-196) is a more selective, irreversible BTK inhibitor that is specifically designed to improve on the safety and efficacy of first-generation BTK inhibitors. Methods In this uncontrolled, phase 1-2, multicenter study, we administered oral acalabrutinib to 61 patients who had relapsed CLL to assess the safety, efficacy, pharmacokinetics, and pharmacodynamics of acalabrutinib. Patients were treated with acalabrutinib at a dose of 100 …

First Trimester Fetal Heart Rate As A Predictor Of Newborn Sex, L. A. Bracero, D. J. Seybold, S. Witsberger, L. Rincon, A. Modak, L. V. Baxi

Journal Articles

OBJECTIVE: To predict the sex of newborns using first trimester fetal heart rate (FHR). METHODS: This was a retrospective review of medical records and ultrasounds performed between 8 and 13 weeks of gestation. Continuous variables were compared using Student's t-tests while categorical variables were compared using Chi-square test. RESULTS: We found no significant differences between 332 (50.7%) female and 323 (49.3%) male FHRs during the first trimester. The mean FHR for female fetuses was 167.0 +/- 9.1 bpm and for male fetuses 167.3 +/- 10.1 bpm (p = 0.62). There was no significant difference in crown rump length between female …

Effect Of Single Embryo Transfer On The Risk Of Preterm Birth Associated With In Vitro Fertilization, A. J. Fechner, K. R. Brown, N. Onwubalili, S. K. Jindal, G. Weiss, L. T. Goldsmith, P. G. Mcgovern

Journal Articles

To determine whether elective single embryo transfer (eSET) reduces the risk of preterm delivery associated with in vitro fertilization (IVF). This is an observational study of 3125 eSET cycles performed from 2008 to 2009 and reported to the Society for Assisted Reproductive Technology (SART) database. Preterm delivery rates were compared to the overall preterm delivery rate among all patients undergoing IVF over the same time period. The 3125 eSET cycles resulted in 1507 live births (live birth rate 48.2 %) Among these deliveries were 27 twins (1.8 %) and one set of triplets (0.07 %). The overall preterm delivery rate …

A Critical Role For The Host Mediator Macrophage Migration Inhibitory Factor In The Pathogenesis Of Malarial Anemia, M. A. Mcdevitt, J. Xie, S. Ganapathy-Kanniappan, J. Griffith, A. Liu, C. Mcdonald, P. Thuma, V. R. Gordeuk, C. N. Metz, R. Mitchell, J. Keefer, J. David, L. Leng, R. Bucala

Journal Articles

No abstract provided.

Metabolic Resting-State Brain Networks In Health And Disease, P. G. Spetsieris, J. H. Ko, C. C. Tang, A. Nazem, W. Sako, S. Peng, Y. Ma, V. Dhawan, D. Eidelberg

Journal Articles

The delineation of resting state networks (RSNs) in the human brain relies on the analysis of temporal fluctuations in functional MRI signal, representing a small fraction of total neuronal activity. Here, we used metabolic PET, which maps nonfluctuating signals related to total activity, to identify and validate reproducible RSN topographies in healthy and disease populations. In healthy subjects, the dominant (first component) metabolic RSN was topographically similar to the default mode network (DMN). In contrast, in Parkinson's disease (PD), this RSN was subordinated to an independent disease-related pattern. Network functionality was assessed by quantifying metabolic RSN expression in cerebral blood …

Implications Of Epigenetic Variability Within A Cell Population For "Cell Type" Classification, I. Tabansky, J. N.H. Stern, D. W. Pfaff

Journal Articles

Here, we propose a new approach to defining nerve "cell types" in reaction to recent advances in single cell analysis. Among cells previously thought to be equivalent, considerable differences in global gene expression and biased tendencies among differing developmental fates have been demonstrated within multiple lineages. The model of classifying cells into distinct types thus has to be revised to account for this intrinsic variability. A "cell type" could be a group of cells that possess similar, but not necessarily identical properties, variable within a spectrum of epigenetic adjustments that permit its developmental path toward a specific function to be …

Parkinson's Disease-Related Spatial Covariance Pattern Identified With Resting-State Functional Mri, T. Wu, Y. Ma, Z. Zheng, S. Peng, X. Wu, D. Eidelberg, P. Chan

Journal Articles

In this study, we sought to identify a disease-related spatial covariance pattern of spontaneous neural activity in Parkinson's disease using resting-state functional magnetic resonance imaging (MRI). Time-series data were acquired in 58 patients with early to moderate stage Parkinson's disease and 54 healthy controls, and analyzed by Scaled Subprofile Model Principal Component Analysis toolbox. A split-sample analysis was also performed in a derivation sample of 28 patients and 28 control subjects and validated in a prospective testing sample of 30 patients and 26 control subjects. The topographic pattern of neural activity in Parkinson's disease was characterized by decreased activity in …

First-In-Human, Phase 1, Randomized, Dose-Escalation Trial With Recombinant Anti-Il-20 Monoclonal Antibody In Patients With Psoriasis, A. B. Gottlieb, J. G. Krueger, M. Sandberg Lundblad, M. Gothberg, B. E. Skolnick

Journal Articles

BACKGROUND: The current trial was a first-in-human clinical trial evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of the recombinant monoclonal anti-interleukin-20 (IL-20) antibody, NNC0109-0012, which targets the inflammatory cytokine IL-20. METHODS: In total, 48 patients aged 18 to 75 years with moderate to severe stable chronic plaque psoriasis with affected body surface area >/=15% and physician global assessment score >/=3 were enrolled in this randomized, double-blind, multicenter, placebo-controlled, phase 1 dose-escalation trial. Patients were randomized within each single dose cohort (0.01, 0.05, 0.2, 0.6, 1.5, or 3.0 mg/kg) or multiple dose cohort (0.05, 0.2, 0.5, 1.0, or 2.0 …

New Best1 Mutations In Autosomal Recessive Bestrophinopathy, A. T. Fung, S. Yzer, N. Goldberg, H. Wang, M. Nissen, A. Giovannini, J. E. Merriam, E. N. Bukanova, L. A. Yannuzzi, R. Allikmets, +2 Additional Authors

Journal Articles

PURPOSE: To report the ocular phenotype in patients with autosomal recessive bestrophinopathy and carriers, and to describe novel BEST1 mutations. METHODS: Patients with clinically suspected and subsequently genetically proven autosomal recessive bestrophinopathy underwent full ophthalmic examination and investigation with fundus autofluorescence imaging, spectral domain optical coherence tomography, electroretinography, and electrooculography. Mutation analysis of the BEST1 gene was performed through direct Sanger sequencing. RESULTS: Five affected patients from four families were identified. Mean age was 16 years (range, 6-42 years). All affected patients presented with reduced visual acuity and bilateral, hyperautofluorescent subretinal yellowish deposits within the posterior pole. Spectral domain optical …

Lifitegrast Ophthalmic Solution 5.0% Versus Placebo For Treatment Of Dry Eye Disease: Results Of The Randomized Phase Iii Opus-2 Study, J. Tauber, P. Karpecki, R. Latkany, J. Luchs, J. Martel, K. Sall, A. Raychaudhuri, V. Smith, C. P. Semba

Journal Articles

PURPOSE: Lifitegrast is an integrin antagonist that decreases T-cell-mediated inflammation associated with dry eye disease (DED). We report the results of OPUS-2, a phase III study evaluating the efficacy and safety of lifitegrast compared with placebo for the treatment of DED. DESIGN: A 12-week, multicenter, randomized, prospective, double-masked, placebo-controlled clinical trial. PARTICIPANTS: Adults aged >/=18 years with use of artificial tears within 30 days, inferior corneal staining score >/=0.5 (0-4 scale), Schirmer tear test (without anesthesia) >/=1 and/=40 (0-100 visual analogue scale [VAS]). METHODS: Subjects were randomized 1:1 after 14-day placebo run-in to lifitegrast ophthalmic solution 5.0% or placebo twice …