Medicine and Health Sciences Commons^™

Dual-Transmitter Systems Regulating Arousal, Attention, Learning And Memory, Sherie Ma, Balázs Hangya, Christopher S. Leonard, William Wisden, Andrew L. Gundlach

NYMC Faculty Publications

An array of neuromodulators, including monoamines and neuropeptides, regulate most behavioural and physiological traits. In the past decade, dramatic progress has been made in mapping neuromodulatory circuits, in analysing circuit dynamics, and interrogating circuit function using pharmacogenetic, optogenetic and imaging methods This review will focus on several distinct neural networks (acetylcholine/GABA/glutamate; histamine/GABA; orexin/glutamate; and relaxin-3/GABA) that originate from neural hubs that regulate wakefulness and related attentional and cognitive processes, and highlight approaches that have identified dual transmitter roles in these behavioural functions. Modulation of these different neural networks might be effective treatments of diseases related to arousal/sleep dysfunction and of …

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Library, clinicaltrials.gov, and PharmaPendium up to May 2017 identified 11 meta-analyses, multiple publications, and unpublished data from 29 randomized controlled trials (RCTs).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 …

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 …

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.

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 …

Complete Genome Sequence Of A Colistin-Resistant Escherichia Coli Strain Harboring Mcr-1 On An Inchi2 Plasmid In The United States, V Gilrane, S Lobo, Weihua Huang, J Zhuge, Changhong Yin, Donald Chen, K Alvarez, Alexandra Budhai, I Nadelman, Nevenka Dimitrova, John Fallon, Guiqing Wang

NYMC Faculty Publications

We report here the incidental detection and complete genome sequence of a urinary Escherichia coli strain harboring mcr-1 and resistant to colistin in a New York patient returning from Portugal in 2016. This strain, with sequence type 1485 (ST1485), was a non-extended-spectrum beta-lactamase (ESBL) and non-carbapenemase producer and carried the mcr-1 gene on an IncHI2 plasmid.

Drug-Induced Causes Of Secondary Hypertension, Wilbert S. Aronow

NYMC Faculty Publications

No abstract provided.

The Global Alliance For Infections In Surgery: Defining A Model For Antimicrobial Stewardship-Results From An International Cross-Sectional Survey, M Sartelli, F Labricciosa, P Barbadoro, L Pagani, L Ansaloni, Rifat Latifi, N Shafiq, K Koike, I Kozlovska, A Kumar, L Lagunes, Rifat Latifi, J Lee, N Shafiq

NYMC Faculty Publications

BACKGROUND: Antimicrobial Stewardship Programs (ASPs) have been promoted to optimize antimicrobial usage and patient outcomes, and to reduce the emergence of antimicrobial-resistant organisms. However, the best strategies for an ASP are not definitively established and are likely to vary based on local culture, policy, and routine clinical practice, and probably limited resources in middle-income countries. The aim of this study is to evaluate structures and resources of antimicrobial stewardship teams (ASTs) in surgical departments from different regions of the world. METHODS: A cross-sectional web-based survey was conducted in 2016 on 173 physicians who participated in the AGORA (Antimicrobials: A Global …

Towards A Personalized Cancer Gene Therapy: A Case Of Clear Cell Renal Cell Carcinoma, Dumitru Iacobas, Sanda Iacobas

NYMC Faculty Publications

No abstract provided.

Complete Versus Culprit Only Revascularization In St-Elevation Myocardial Infarction-A Perspective On Recent Trials And Recommendations, Gabriela Andries, Sahil Khera, Robert Timmermans, Wilbert Aronow

NYMC Faculty Publications

The presence of multivessel coronary artery disease (CAD) is strongly associated with higher 30-day mortality, reduced myocardial reperfusion success, reinfarction, and occurrence of major adverse cardiac events (MACE) at 1 year compared with single-vessel CAD. Despite higher morbidity and mortality in patients with ST-elevation myocardial infarction (STEMI) and coexistent multivessel CAD, major guidelines recommended against percutaneous coronary intervention (PCI) on non-culprit lesions at the time of primary PCI in patients with STEMI who are hemodynamically stable. The presence of multivessel CAD often poses a therapeutic dilemma for interventional cardiologists. A few larger scale randomized controlled trials (RCTs) and meta-analyses have …

The Transcriptional Regulation Of The Human Angiotensinogen Gene After High-Fat Diet Is Haplotype-Dependent: Novel Insights Into The Gene-Regulatory Networks And Implications For Human Hypertension, A Rana, S Jain, N Puri, M Kaw, N Sirianni, D Eren, Brahma Mopidevi, Anand Kumar

NYMC Faculty Publications

Single nucleotide polymorphisms (SNPs) in the human angiotensinogen (hAGT) gene may modulate its transcription and affect the regulation of blood pressure via activation of the renin-angiotensin aldosterone system (RAAS). In this regard, we have identified polymorphisms in the 2.5 Kb promoter of the hAGT gene that form two haplotype (Hap) blocks: -6A/G (-1670A/G, -1562C/T, -1561T/C) and -217A/G (-532T/C, -793A/G, -1074T/C & -1178G/A). hAGT gene with Hap -6A/-217A (Hap I) is associated with increased blood pressure whereas, Hap -6G/-217G (Hap II) is associated with normal blood pressure in human subjects. Since RAAS over activity contributes to hypertension in obesity, we have …

Evidence Of Strain Structure In Plasmodium Falciparum Var Gene Repertoires In Children From Gabon, West Africa, K Day, Y Artzy-Randrup, K Tiedje, V Rougeron, Donald S. Chen, T Rask, M Rorick, F Migot-Nabias, P Deloron, A Luty, M Pascual

NYMC Faculty Publications

Existing theory on competition for hosts between pathogen strains has proposed that immune selection can lead to the maintenance of strain structure consisting of discrete, weakly overlapping antigenic repertoires. This prediction of strain theory has conceptual overlap with fundamental ideas in ecology on niche partitioning and limiting similarity between coexisting species in an ecosystem, which oppose the hypothesis of neutral coexistence. For Plasmodium falciparum, strain theory has been specifically proposed in relation to the major surface antigen of the blood stage, known as PfEMP1 and encoded by the multicopy multigene family known as the var genes. Deep sampling of the …

A Comparative Study Of Three Different Types Of Stem Cells For Treatment Of Rat Spinal Cord Injury, Jiri Ruzicka, L Machova-Urdzikova, John Gillick, T Amemori, N Romanyuk, K Karova, K Zaviskova, J Dubisova, S Kubinova, Raj Murali, E Sykova, Meena Jhanwar-Uniyal, P Jendelova

NYMC Faculty Publications

Three different sources of human stem cells-bone marrow-derived mesenchymal stem cells (BM-MSCs), neural progenitors (NPs) derived from immortalized spinal fetal cell line (SPC-01), and induced pluripotent stem cells (iPSCs)-were compared in the treatment of a balloon-induced spinal cord compression lesion in rats. One week after lesioning, the rats received either BM-MSCs (intrathecally) or NPs (SPC-01 cells or iPSC-NPs, both intraspinally), or saline. The rats were assessed for their locomotor skills (BBB, flat beam test, and rotarod). Morphometric analyses of spared white and gray matter, axonal sprouting, and glial scar formation, as well as qPCR and Luminex assay, were conducted to …

Clinical Significance Of A False Positive Glucose Challenge Test In Patients With A High Body Mass Index, A Borja, M Moretti, Nisha Lakhi

NYMC Faculty Publications

OBJECTIVE: To determine if there is an increased maternal or neonatal morbidity in overweight and obese patients with a false positive glucose challenge test (GCT). METHODS: Patients with a body mass index (BMI) >/=25.0 at registration were included in this prospective 36-month study. The study cohort consisted of patients with a false positive (FP) GCT, with two comparison cohorts: those with a (1) screen negative (SN) GCT result and (2) true positive (TP) GCT result. Risks were reported as odd ratios with 95% confidence intervals, with a P/=4000 g in the FP cohort, but this fell short of reaching statistical …

Identification And Characterization Of Microrna Differentially Expressed In Macrophages Exposed To Porphyromonas Gingivalis Infection, Olivier Huck, J Al-Hashemi, L Poidevin, O Poch, J Davideau, H Tenenbaum, Salomon Amar

NYMC Faculty Publications

MicroRNAs (miRNAs) are short, noncoding RNAs involved in the regulation of several processes associated with inflammatory diseases and infection. Bacterial infection modulates miRNA expression to subvert any innate immune response. In this study we analyzed, using microarray analysis, the bacterial modulation of miRNAs in bone marrow-derived macrophages (BMMs) in which activity was induced by infection with Porphyromonas gingivalis The expression of several miRNAs was modulated 3 h postinfection (at a multiplicity of infection of 25). A bioinformatic analysis was performed to further identify pathways related to the innate immune host response under the influence of selected miRNAs. To assess the …

Microrna-494 And Atf3 The Targets Of Onconase(?), Zbigniew Darzynkiewicz

NYMC Faculty Publications

No abstract provided.

Intravenous Formulation Of Het0016 Decreased Human Glioblastoma Growth And Iimplicated Survival Benefit In Rat Xenograft Models, M Jain, N Gamage, M Alsulami, A Shankar, B Achyut, Austin Guo, A Arbab, A Arbab

NYMC Faculty Publications

Glioblastoma (GBM) is a hypervascular primary brain tumor with poor prognosis. HET0016 is a selective CYP450 inhibitor, which has been shown to inhibit angiogenesis and tumor growth. Therefore, to explore novel treatments, we have generated an improved intravenous (IV) formulation of HET0016 with HPssCD and tested in animal models of human and syngeneic GBM. Administration of a single IV dose resulted in 7-fold higher levels of HET0016 in plasma and 3.6-fold higher levels in tumor at 60 min than that in IP route. IV treatment with HPssCD-HET0016 decreased tumor growth, and altered vascular kinetics in early and late treatment groups …

Atypical Hemolytic Uremic Syndrome In First Trimester Pregnancy Successfully Treated With Eculizumab, Gabriela Andries, Michael Karass, Srikanth Yandrapalli, M Karass, Delong Liu, John Nelson, R Pawar, Savneek Chugh

NYMC Faculty Publications

BACKGROUND: Atypical hemolytic uremic syndrome is a rare disorder which is known to cause acute thrombotic microangiopathy during pregnancy with poor maternal and fetal outcomes. Atypical hemolytic uremic syndrome is caused mostly by dysregulation of alternative complement pathway secondary to genetic mutations. Most of the cases reported have been in the post-partum period. We report a rare case of a patient who presents with thrombotic microangiopathy in the first trimester of her eleventh pregnancy and was successfully treated with eculizumab. CASE PRESENTATION: A 30-year-old woman presented at 10 weeks of gestation with hypertension, hemolytic anemia, thrombocytopenia, and acute kidney injury, …

The Beta-1-Receptor Blocker Nebivolol Elicits Dilation Of Cerebral Arteries By Reducing Smooth Muscle [Ca2+]I, Peter Cseplo, Zoltan Vamos, Ivan Ivic, Orsolya Torok, Attila Toth, Akos Koller

NYMC Faculty Publications

RATIONALE: Nebivolol is known to have beta-1 blocker activity, but it was also suggested that it elicits relaxation of the peripheral arteries in part via release of nitric oxide (NO). However, the effect of nebivolol on the vasomotor tone of cerebral arteries is still unclear.

OBJECTIVE: To assess the effects of nebivolol on the diameter of isolated rat basilar arteries (BA) in control, in the presence of inhibitors of vasomotor signaling pathways of know action and hemolysed blood.

METHODS AND RESULTS: Vasomotor responses were measured by videomicroscopy and the intracellular Ca2+ by the Fura-2 AM ratiometric method. Under control conditions, …

Cyp2c44 Gene Disruption Exacerbated Pulmonary Hypertension And Heart Failure In Female But Not Male Mice, Sachindra R. Joshi, Anand Lakhkar, Vidhi Dhagia, Ariadne Zias, Vasiliki Soldatos, Kaori Oshima, Houli Jiang, Katherine Gotlinger, Jorge H Capdevila, Michal L. Schwartzman, Ivan F. Mcmurtry, Sachin A. Gupte

NYMC Faculty Publications

Epoxyeicosatrienoicacids (EETs), synthesized from arachidonic acid by epoxygenases of the CYP2C and CYP2J gene subfamilies, contribute to hypoxic pulmonary vasoconstriction (HPV) in mice. Despite their roles in HPV, it is controversial whether EETs mediate or ameliorate pulmonary hypertension (PH). A recent study showed that deficiency of Cyp2j did not protect male and female mice from hypoxia-induced PH. Since CYP2C44 is a functionally important epoxygenase, we hypothesized that knockout of the Cyp2c44 gene would protect both sexes of mice from hypoxia-induced PH. We tested this hypothesis in wild-type (WT) and Cyp2c44 knockout (Cyp2c44 (-/-)) mice exposed to normoxia (room air) and …

Sexually Dimorphic Adaptation Of Cardiac Function: Roles Of Epoxyeicosatrienoic Acid And Peroxisome Proliferator-Activated Receptors, Jun Qin, Yicong Le, Ghezal Froogh, Sharath Kandhi, Houli Jiang, Dong Sun, An Huang

NYMC Faculty Publications

Epoxyeicosatrienoic acids (EETs) are cardioprotective mediators metabolized by soluble epoxide hydrolase (sEH) to form corresponding diols (DHETs). As a sex-susceptible target, sEH is involved in the sexually dimorphic regulation of cardiovascular function. Thus, we hypothesized that the female sex favors EET-mediated potentiation of cardiac function via downregulation of sEH expression, followed by upregulation of peroxisome proliferator-activated receptors (PPARs). Hearts were isolated from male (M) and female (F) wild-type (WT) and sEH-KO mice, and perfused with constant flow at different preloads. Basal coronary flow required to maintain the perfusion pressure at 100 mmHg was significantly greater in females than males, and …

Spinal Cord Compression Secondary To Extramedullary Hematopoiesis: Case Report And Review Of The Literature, Arthur Wang, Nathan Carberry, Elena Solli, John Gillick, Humayun Islam, Virany Hillard

NYMC Faculty Publications

Extramedullary hematopoiesis (EMH) is a rare cause of spinal cord compression (SCC). EMH represents the growth of blood cells outside of the bone marrow and occurs in a variety of hematologic illnesses, including various types of anemia and myeloproliferative disorders. Although EMH usually occurs in the liver, spleen, and lymph nodes, it may also occur within the spinal canal. When this occurs, the mass effect can compress the spinal cord, potentially leading to the development of neurological deficits. We present a case of SCC secondary to EMH. This report illustrates the importance of considering EMH in the differential diagnosis of …