Medicine and Health Sciences Commons^™

Gene Master Regulators Of Papillary And Anaplastic Thyroid Cancers, Dumitru Iacobas, Neha Tuli, Sanda Iacobas, John Rasamny, Augustine Moscatello, Jan Geliebter, Raj Tiwari

NYMC Faculty Publications

We hypothesize that distinct cell phenotypes are governed by different sets of gene master regulators (GMRs) whose strongly protected (by the homeostatic mechanisms) abundance modulates most cell processes by coordinating the expression of numerous genes from the corresponding functional pathways. Gene Commanding Height (GCH), a composite measure of gene expression control and coordination, is introduced to establish the gene hierarchy in each phenotype. If the hypothesis is true, than one can selectively destroy cancer nodules from a heterogeneous tissue by altering the expression of genes whose GCHs are high in cancer but low in normal cell phenotype. Here, we test …

Visual Outcomes, Efficacy, And Surgical Complications Associated With Intracameral Phenylephrine 1.0%/Ketorolac 0.3% Administered During Cataract Surgery, Eric Rosenberg, Alanna S. Nattis, David Alevi, Rachel L. Chu, Joseph Bacotti, Ronald J. Lopinto, Gerald D'Aversa, Eric Donnenfeld

NYMC Residents/Fellows Publications

Aim: The purpose of this study was to compare visual outcomes, surgical time, and perioperative surgical complications after intracameral use of either phenylephrine/ketorolac (P/K) or epinephrine (Epi) during cataract surgery.
Methods: This was a single-center, retrospective case review of patients undergoing cataract surgery from August to November 2015. Of the 641 eyes of 389 patients who underwent cataract surgery, 260 eyes were administered phenylephrine 1.0%/ketorolac 0.3% and 381 eyes received Epi in the irrigation solution intraoperatively. All patients received a topical nonsteroidal anti-inflammatory drug regimen (bromfenac 0.07%, nepafenac 0.3%, or ketorolac 0.5%) for 3 days before surgery and topical tropicamide …

Nocardiosis Incognito: Primary Cutaneous Nocardiosis With Extension To Myositis And Pleural Infection, Nhan Nguyen, Jacquelyn Sink, Adam Carter, Falguni Asrani

NYMC Residents/Fellows Publications

Primary cutaneous nocardiosis has a diverse variety of clinical presentations; thus, a high degree of clinical suspicion is essential in making the diagnosis and avoiding inappropriate treatment or surgery. We present the case of a patient with mycetoma on the back with contiguous extension to the cervicothoracolumbar musculature and pleura caused by Nocardia brasiliensis acquired by sleeping on the ground.

Setbp1 Mutations As A Biomarker For Myelodysplasia /Myeloproliferative Neoplasm Overlap Syndrome, Katherine Linder, C Iragavarapu, Delong Liu

NYMC Faculty Publications

Myelodysplasia (MDS) /myeloproliferative neoplasm (MPN) overlap syndrome has been described since the 2001 WHO classification as disorders that have both proliferative and dysplastic changes simultaneously. Specific disorders include chronic myelomonocytic leukemia (CMML), juvenile myelomonocytic leukemia (JMML), BCR-ABL negative atypical chronic myeloid leukemia (aCML) and unclassifiable MDS/MPN (MPN/MDS-U). Recurrent gene mutations in these conditions have been described. Among them, SETBP1 mutations have been identified in up to 32% of aCML, 24% of JMML, 18% of CMML and 10% of MDS/MPN-U patients. The mutation hotspot lies in the amino acid residues 858-871 in the SETBP1 protein. SETBP1 mutations in MDS/MPN overlap syndrome …

Recent Development In Clinical Applications Of Pd-1 And Pd-L1 Antibodies For Cancer Immunotherapy, B Liu, Y Song, Delong Liu

NYMC Faculty Publications

Antibodies against programmed death (PD) pathway are revolutionizing cancer immunotherapy. Currently five antibodies against PD-1/PD-L1 have been approved. The clinical use of these antibodies is rapidly expanding. Incorporation of PD antibodies into chemotherapy regimens is in active clinical investigations. The combination of pembrolizumab with carboplatin and pemetrexed has been approved for the first line therapy of metastatic non-squamous non-small cell lung cancer. Combination of PD-1/PD-L1 antibodies with small molecule inhibitors such as tyrosine kinase inhibitors and IDO inhibitors are in active clinical trials. This review summarized recent development in clinical trials of PD-1 and PD-L1 antibodies for cancer immunotherapy.

Masked Hypertension, Wilbert S. Aronow

NYMC Faculty Publications

No abstract provided.

Harmonizing Lipidomics: Nist Interlaboratory Comparison Exercise For Lipidomics Using Srm 1950-Metabolites In Frozen Human Plasma, J Bowden, C Ulmer, C Jones, J Koelmel, L Abdullah, Houli Jiang, Michal Schwartzman, Amaury Cazenave-Gassiot, Antonio Checa, Michelle Cinel, Romain Colas, Serge Cremers, Edward Dennis, James Evans, Alexander Fauland, Jun Han, Houli Jiang, Michal Schwartzman

NYMC Faculty Publications

As the lipidomics field continues to advance, self-evaluation within the community is critical. Here, we performed an interlaboratory comparison exercise for lipidomics using Standard Reference Material (SRM) 1950-Metabolites in Frozen Human Plasma, a commercially available reference material. The interlaboratory study comprised 31 diverse laboratories, with each laboratory using a different lipidomics workflow. A total of 1,527 unique lipids were measured across all laboratories and consensus location estimates and associated uncertainties were determined for 339 of these lipids measured at the sum composition level by five or more participating laboratories. These evaluated lipids detected in SRM 1950 serve as community-wide benchmarks …

Temporal Trends And Outcomes Of Acute Myocardial Infarction In Patients With Cancer, N Pothineni, N Shah, Yogita Rochlani, M Saad, S Kovelamudi, K Marmagkiolis, S Bhatti, M Cilingiroglu, Wilbert Aronow, A Hakeem

NYMC Faculty Publications

Background: Data on outcomes of ST-elevation myocardial infarction (STEMI) in patients with cancer are scarce. We investigated the nationwide trends in admissions for STEMI, utilization of percutaneous coronary intervention (PCI), and in-hospital outcomes in patients with the three most common cancer diagnoses (lung, breast, and colon) compared to patients without cancer. Methods: We conducted an administrative database study using the Nationwide Inpatient Sample (NIS). All in-patient hospitalizations for STEMI from 2001 to 2011 were identified. Patients with concomitant diagnosis of lung, breast or colon cancer were identified using appropriate International classification of diagnosis (ICD 9-CM) codes. Primary outcome was utilization …

Effects Of Asenapine On Agitation And Hostility In Adults With Acute Manic Or Mixed Episodes Associated With Bipolar I Disorder, Leslie L. Citrome, R Landbloom, C Chang, W Earley

NYMC Faculty Publications

BACKGROUND:

Bipolar disorder is associated with an increased risk of aggression. However, effective management of hostility and/or agitation symptoms may prevent patients from becoming violent. This analysis investigated the efficacy of the antipsychotic asenapine on hostility and agitation in patients with bipolar I disorder.

METHODS:

Data were pooled from three randomized, double-blind, placebo-controlled, Phase III trials of asenapine in adults with manic or mixed episodes of bipolar I disorder (NCT00159744, NCT00159796, and NCT00764478). Post hoc analyses assessed the changes from baseline to day 21 on the Young Mania Rating Scale (YMRS) and the Positive and Negative …

B-Type Natriuretic Peptide: A Predictor For Mortality, Intensive Care Unit Length Of Stay, And Hospital Length Of Stay In Patients With Resolving Sepsis, H Singh, D Ramai, H Patel, M Iskandir, S Sachdev, R Rai, J Patolia, Getaw Hassen

NYMC Faculty Publications

Background: B-type natriuretic peptide (BNP) is a hormone secreted by cardiomyocytes in response to myocardial ischemia, increased ventricular wall tension, and overload. BNP is utilized as a diagnostic and prognostic marker in congested heart failure (CHF). Its prognostic value in sepsis is unknown. The aim of this study is to determine if BNP correlates with increased in-hospital mortality for septic patients. Methods: This was a retrospective study of 505 patients admitted for sepsis or severe sepsis or septic shock during the period of January 2013 and August 2014. Patients that received > 3 L of intravenous fluids on presentation were included. …

The Neuroprotective Effect Of Human Cd34 Positive Stem Cells On The Survival Of Injured Retinal Ganglion Cells, Amro Ali, J Tiapo, Thaddeus Wandel, Sansar Sharma

NYMC Faculty Publications

No abstract provided.

Modulation Of Immunological Pathways In Autistic And Neurotypical Lymphoblastoid Cell Lines By The Enteric Microbiome Metabolite Propionic Acid, R Frye, Bistra Nankova, S Bhattacharyya, S Rose, S Bennuri, D Macfabe

NYMC Faculty Publications

Propionic acid (PPA) is a ubiquitous short-chain fatty acid which is a fermentation product of the enteric microbiome and present or added to many foods. While PPA has beneficial effects, it is also associated with human disorders, including autism spectrum disorders (ASDs). We previously demonstrated that PPA modulates mitochondrial dysfunction differentially in subsets of lymphoblastoid cell lines (LCLs) derived from patients with ASD. Specifically, PPA significantly increases mitochondrial function in LCLs that have mitochondrial dysfunction at baseline [individuals with autistic disorder with atypical mitochondrial function (AD-A) LCLs] as compared to ASD LCLs with normal mitochondrial function [individuals with autistic disorder …

Comparative Effectiveness And Safety Of Empagliflozin On Cardiovascular Mortality And Morbidity In Adults With Type 2 Diabetes, Wilbert S. Aronow, Tatyana Shamliyan

NYMC Faculty Publications

Background: Based on a single placebo-controlled randomized clinical trial, empagliflozin is licensed to reduce cardiovascular death in diabetes and comorbid cardiovascular disease. Methods: We examined the comparative effectiveness of empagliflozin on mortality and cardiovascular morbidity in type 2 diabetes. We conducted random-effects direct frequentist meta-analyses of aggregate data and appraised the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Our search in PubMed, EMBASE, the Cochrane Library, clinicaltrials.gov, and PharmaPendium up to May 2017 identified 11 meta-analyses, multiple publications, and unpublished data from 29 randomized controlled trials (RCTs). Results: Empagliflozin reduces all-cause mortality [relative …

Hypertension Associated With Atrial Fibrillation, Wilbert S. Aronow

NYMC Faculty Publications

No abstract provided.

Forty Five Percent Of The Israeli Population Were Infected With The Influenza B Victoria Virus During The Winter Season 2015-16, Sivan Sharabi, Ravit Bassal, Nehemya Friedman, Yaron Drori, Hadar Alter, Aharona Glatman-Freedman, Musa Hindiyeh, Daniel Cohen, Ella Mendelson, Tamy Shohat, Michal Mandelboim

NYMC Faculty Publications

While infection with influenza A viruses has been extensively investigated, infections with influenza B viruses which are commonly categorized into the highly homologous Victoria and Yamagata lineages, are less studied, despite their considerable virulence. Here we used RT-PCR assays, hemagglutination inhibition assays and antibody titers to determine the levels of influenza B infection. We report of high influenza B Victoria virus prevalence in the 2015-16 winter season in Israel, affecting approximately half of the Israeli population. We further show that the Victoria B virus infected individuals of all ages and that it was present in the country throughout the entire …

Ixekizumab Efficacy And Safety With And Without Concomitant Conventional Disease-Modifying Antirheumatic Drugs (Cdmards) In Biologic Dmard (Bdmard)-Naive Patients With Active Psoriatic Arthritis (Psa): Results From Spirit-P1, Laura Coates, M Kishimoto, Alice Gottlieb, C Shuler, C Lin, C Lee, P Mease

NYMC Faculty Publications

Objective: To evaluate the efficacy and safety of ixekizumab alone or with concomitant conventional disease-modifying antirheumatic drugs (cDMARDs) versus placebo in patients with active psoriatic arthritis (PsA) as part of a SPIRIT-P1 subgroup analysis (NCT01695239). Methods: Patients were stratified by cDMARD use (concomitant cDMARDs use (including methotrexate) or none (past or naive use)) and randomly assigned to treatment groups (ixekizumab 80 mg every 4 weeks (IXEQ4W) or every 2 weeks (IXEQ2W) or placebo). Efficacy was evaluated versus placebo at week 24 by the American College of Rheumatology criteria (ACR20/50/70), modified total Sharp score and Health Assessment Questionnaire-Disability Index (HAQ-DI). Safety …

High-Dose Sitagliptin For Systemic Inhibition Of Dipeptidylpeptidase-4 To Enhance Engraftment Of Single Cord Umbilical Cord Blood Transplantation, S Farag, R Nelson, Mitchell Cairo, H O'Leary, S Zhang, C Huntley, D Delgado, J Schwartz, M Zaid, R Abonour, M Robertson, H Broxmeyer

NYMC Faculty Publications

Delayed engraftment remains a limitation of umbilical cord blood (UCB) transplantation. We previously showed that inhibition of dipeptidylpeptidase (DPP)-4 using sitagliptin 600 mg daily was safe with encouraging results on engraftment, but inhibition was not sustained. We evaluated the efficacy and feasibility of higher doses of sitagliptin to enhance engraftment of UCB in patients with hematological cancers. Fifteen patients, median age 41 (range, 18-59) years, received single UCB grafts matched at 4 (n=11) or 5 (n=4) of 6 HLA loci with median nucleated cell dose of 3.5 (range, 2.57-4.57) x10(7)/kg. Sitagliptin 600 mg every 12 hours was administered days -1 …

Substitution Of Formal And Informal Home Care Service Use And Nursing Home Service Use: Health Outcomes, Decision-Making Preferences, And Implications For A Public Health Policy, Chia-Ching Chen, T Yamada, T Nakashima, I Chiu

NYMC Faculty Publications

Objectives: The purposes of this study are: (1) to empirically identify decision-making preferences of long-term health-care use, especially informal and formal home care (FHC) service use; (2) to evaluate outcomes vs. costs based on substitutability of informal and FHC service use; and (3) to investigate health outcome disparity based on substitutability. Methodology and data: The methods of ordinary least squares, a logit model, and a bivariate probit model are used by controlling for socioeconomic, demographic, and physical/mental health factors to investigate outcomes and costs based substitutability of informal and formal health-care use. The data come from the 2013 Japanese Study …

Comparative Trial Between Neonatal Intensive Care Incubator, Neonatal Laminar Flow And Radiant Warmer, J Perez, F Perez, Sergio Golombek, Augusto Sola

NYMC Faculty Publications

No abstract provided.

Incremental Contributions Of Fbaa And Other Impetigo-Associated Surface Proteins To Fitness And Virulence Of A Classical Group A Streptococcal Skin Strain, C Rouchon, A Ly, J Noto, F Luo, S Lizano, Debra Bessen

NYMC Faculty Publications

Group A streptococci (GAS) are highly prevalent human pathogens whose primary ecological niche is the superficial epithelial layers of the throat and/or skin. Many GAS strains having a strong tendency to cause pharyngitis are distinct from strains that tend to cause impetigo; thus, genetic differences between them may confer host tissue-specific virulence. In this study, the FbaA surface protein gene is found to be present in most skin specialist strains, but largely absent from a genetically-related subset of pharyngitis isolates. Using an DeltafbaA mutant constructed in the impetigo strain Alab49, loss of FbaA resulted in a slight but significant decrease …

The Evolutionary Origin Of Digit Patterning, T Stewart, Ramray Bhat, Stuart Newman

NYMC Faculty Publications

The evolution of tetrapod limbs from paired fins has long been of interest to both evolutionary and developmental biologists. Several recent investigative tracks have converged to restructure hypotheses in this area. First, there is now general agreement that the limb skeleton is patterned by one or more Turing-type reaction-diffusion, or reaction-diffusion-adhesion, mechanism that involves the dynamical breaking of spatial symmetry. Second, experimental studies in finned vertebrates, such as catshark and zebrafish, have disclosed unexpected correspondence between the development of digits and the development of both the endoskeleton and the dermal skeleton of fins. Finally, detailed mathematical models in conjunction with …

Sex-Specific Association Between Asthma And Hypertension In Nationally Representative Young Korean Adults, Hong-Seok Lee, Y Park, K Han, Gerald Pekler, S Lee, S Yoo, S Kim

NYMC Faculty Publications

It has been reported that people with asthma have an increased risk of hypertension. However, little is known about the specific relationship between asthma and hypertension in young adults. Among subjects who participated in the Korea National Health and Nutrition Examination Survey conducted in 2008-2013, a total of 10,138 young adults (4,226 men and 5,912 women) aged 19-39 years were analyzed. Multiple logistic regression analysis was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). The prevalence of ever asthma was 11.1% in men and 8.4% in women. The mean diastolic blood pressure (DBP) was lower in …

Blood Meal Acquisition Enhances Arbovirus Replication In Mosquitoes Through Activation Of The Gabaergic System, Y Zhu, R Zhang, B Zhang, T Zhao, Penghua Wang, G Liang, G Cheng

NYMC Faculty Publications

Mosquitoes are hematophagous insects that carry-on and transmit many human viruses. However, little information is available regarding the common mechanisms underlying the infection of mosquitoes by these viruses. In this study, we reveal that the hematophagous nature of mosquitoes contributes to arboviral infection after a blood meal, which suppresses antiviral innate immunity by activating the GABAergic pathway. dsRNA-mediated interruption of the GABA signaling and blockage of the GABAA receptor by the specific inhibitors both significantly impaired arbovirus replication. Consistently, inoculation of GABA enhanced arboviral infection, indicating that GABA signaling facilitates the arboviral infection of mosquitoes. The ingestion of blood by …

D-Shaped Left Ventricle, Anatomic, And Physiologic Implications, E Cativo Calderon, Tuoyo Mene-Afejuku, R Valvani, D Cativo, D Tripathi, H Reyes, Savi Mushiyev

NYMC Faculty Publications

Right ventricular loading/pressure influences left ventricular function because the two ventricles pump in series and because they are anatomically arranged in parallel, sharing the common ventricular septum. Flattening of the interventricular septum detected during echocardiographic examination is called D-shaped left ventricle. We present a case of an elderly male of African descent, who presented with increased shortness of breath. Transthoracic echocardiogram showed flattening and left sided deviation of interventricular septum causing a decreased size in left ventricle, secondary to volume/pressure overload in the right ventricle. While patient received hemodialysis therapy and intravascular volume was removed, patient blood pressure was noted …

Mighty Rapalink-1 Vanquishes Undruggable Mutant Mtor In Glioblastoma, Meena Jhanwar-Uniyal

NYMC Faculty Publications

No abstract provided.

Nuclear Gene 33/Mig6 Regulates The Dna Damage Response Through An Atm-Dependent Mechanism, C Li, S Park, X Zhang, Leonard Eisenberg, Hong Zhao, Zbigniew Darzynkiewicz, Dazhong Xu

NYMC Faculty Publications

Gene 33 (Mig6, ERRFI1) is an adaptor protein with multiple cellular functions. We recently linked Gene 33 to the DNA damage response (DDR) induced by hexavalent chromium [Cr(VI)], but the molecular mechanism remains unknown. Here we show that ectopic expression of Gene 33 triggers DDR in an ATM serine/threonine kinase-dependent fashion and through pathways dependent or not dependent on ABL proto-oncogene 1 non-receptor tyrosine kinase (c-Abl). We observe clear presence of Gene 33 in the nucleus and chromatin fractions of the cell. We also found that the nuclear localization of Gene 33 is regulated by its 14-3-3 binding motif (14-3-3BD) …

Sodium Dynamics In Pyramidal Neuron Dendritic Spines: Synaptically Evoked Entry Predominantly Through Ampa Receptors And Removal By Diffusion, K Miyazaki, William N. Ross

NYMC Faculty Publications

Dendritic spines are key elements underlying synaptic integration and cellular plasticity, but many features of these important structures are not known or are controversial. We examined these properties with newly developed simultaneous sodium and calcium imaging that had single spine resolution in pyramidal neurons in rat hippocampal slices from either sex. Indicators for both ions were loaded through the somatic patch pipette, which also recorded electrical responses. Fluorescence changes were detected with a high speed, low noise CCD camera. Following subthreshold electrical stimulation postsynaptic sodium entry is almost entirely through AMPA receptors with little contribution from entry through NMDA receptors …

Sophoraflavenone G Restricts Dengue And Zika Virus Infection Via Rna Polymerase Interference, A Sze, D Olagnier, S Hadj, X Han, X Tian, H Xu, Long Yang, Q Shi, Penghua Wang, M Wainberg, J Wu, R Lin

NYMC Faculty Publications

Flaviviruses including Zika, Dengue and Hepatitis C virus cause debilitating diseases in humans, and the former are emerging as global health concerns with no antiviral treatments. We investigated Sophora Flavecens, used in Chinese medicine, as a source for antiviral compounds. We isolated Sophoraflavenone G and found that it inhibited Hepatitis C replication, but not Sendai or Vesicular Stomatitis Virus. Pre- and post-infection treatments demonstrated anti-flaviviral activity against Dengue and Zika virus, via viral RNA polymerase inhibition. These data suggest that Sophoraflavenone G represents a promising candidate regarding anti-Flaviviridae research.

Peptidyl-Prolyl Isomerase 1 Regulates Ca(2+) Handling By Modulating Sarco(Endo)Plasmic Reticulum Calcium Atpase And Na(2+)/Ca(2+) Exchanger 1 Protein Levels And Function, V Sacchi, B Wang, D Kubli, A Martinez, J Jin, R Alvarez, N Hariharan, C Glembotski, T Uchida, J Malter, Y Yang, P Gross, C Zhang, S Houser, Marcello Rota, M Sussman

NYMC Faculty Publications

BACKGROUND: Aberrant Ca(2+) handling is a prominent feature of heart failure. Elucidation of the molecular mechanisms responsible for aberrant Ca(2+) handling is essential for the development of strategies to blunt pathological changes in calcium dynamics. The peptidyl-prolyl cis-trans isomerase peptidyl-prolyl isomerase 1 (Pin1) is a critical mediator of myocardial hypertrophy development and cardiac progenitor cell cycle. However, the influence of Pin1 on calcium cycling regulation has not been explored. On the basis of these findings, the aim of this study is to define Pin1 as a novel modulator of Ca(2+) handling, with implications for improving myocardial contractility and potential for …

Hmgb1 Redox During Sepsis, Wasan Abdulmahdi, Devika Patel, May Rabadi, Tala Azar, Edson Jules, Mark Lipphardt, Rameen Hashemiyoon, Brian B. Ratliff

NYMC Faculty Publications

During sepsis, the alarmin HMGB1 is released from tissues and promotes systemic inflammation that results in multi-organ damage, with the kidney particularly susceptible to injury. The severity of inflammation and pro-damage signaling mediated by HMGB1 appears to be dependent on the alarmin's redox state. Therefore, we examined HMGB1 redox in kidney cells during sepsis. Using intravital microscopy, CellROX labeling of kidneys in live mice indicated increased ROS generation in the kidney perivascular endothelium and tubules during lipopolysaccharide (LPS)-induced sepsis. Subsequent CellROX and MitoSOX labeling of LPS-stressed endothelial and kidney proximal tubule cells demonstrated increased ROS generation in these cells as …