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Role Of Epigenome And Microbiome In Endocannabinoid-Mediated Regulation Of Inflammation During Diet-Induced Obesity, Kathryn Miranda

Theses and Dissertations

Obesity is an inflammatory disease involving accumulation of adipose tissue, gut microbiota dysbiosis, and over-activation of the endocannabinoid system (ECS). Mechanisms involved in ECS regulation of obesity-induced inflammation are not well understood. Presented here are three chapters involving microRNA (miR) regulation of inflammatory adipose tissue macrophages (ATM) during high-fat diet (HFD)-induced obesity and cannabinoid receptor-mediated regulation of gut microbiota dysbiosis.

ATMs are innate immune cells that drive chronic low-grade inflammation during obesity. Polarization between pro-(M1) and anti-(M2-like) inflammatory phenotypes influence insulin sensitivity and energy expenditure; however, the mechanisms involved are unclear. In study one, we characterized miRs involved in ATM …

Effect Of Tcdd, An Environmental Contaminant, On Activation Of Ahr Leading To Induction Of Myeloid Derived Suppressor Cells (Mdscs) And The Ability Of Resveratrol, A Botanical, To Neutralize This Effect, Wurood Hantoosh Neamah

Theses and Dissertations

Aryl hydrocarbon receptor (AhR), is a ligand-activated transcription factor that integrates environmental, dietary, microbial and metabolic cues to control various cellular processes, such as the cell cycle, epithelial barrier function, cell migration and immune function. AhR was discovered as the receptor that binds with high affinity to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and leads to numerous of toxicological outcomes. In the current study, we discovered a critical role played by AhR, following activation by TCDD, in modulating a variety of immunological functions through regulation of epigenetic and microbial pathways. Our data demonstrated that AhR activation triggers MDSC mobilization from bone marrow to peritoneal …

Behavioral Responses To Gold Nanoparticle Exposure And H2o2-Induced Oxidative Stress In Caenorhabditis Elegans, Rachel Pride, Ashley Wagner

DePaul Discoveries

Gold nanoparticles (AuNPs) have been utilized in many biomedical disciplines, most notably cancer therapy and drug delivery. Recent research suggests that with specific peptide manipulation, AuNPs can deliver drugs across the blood-brain barrier (BBB), allowing for treatment of neurodegeneration and other neurological afflictions. Neurodegeneration has been shown to be caused by oxidative stress. The present experiment aimed to assess the effects of AuNPs on C. elegans behavior that had undergone H₂O₂-induced oxidative stress. It was predicted that worms exposed to both H₂O₂ and AuNPs would have higher survival, mechanosensation, and thrashing rates than …

Week Of June 24, 2019, New York Medical College

InTouch

• NYMC Announces New Clinical Leadership in the School of Medicine
• Conference Addresses How the Microbiome Impacts Health and Wellness
• Robert B. Nadelman, M.D., Research Fellowship Pays Tribute to Esteemed Professor

Nrxn1 Deletion And Exposure To Methylmercury Increase Astrocyte Differentiation By Different Notch-Dependent Transcriptional Mechanisms, Marilena Raciti, Salma Jahan, Stefan Spulber, Giulia Gaudenzi, Zahra Khalajzeyqami, Mirko Conti, Britt-Marie Anderlid, Anna Falk, Ola Hermans, Sandra Ceccatelli

Centre for Regenerative Medicine & Stem Cell Research

Controversial evidence points to a possible involvement of methylmercury (MeHg) in the etiopathogenesis of autism spectrum disorders (ASD). In the present study, we used human neuroepithelial stem cells from healthy donors and from an autistic patient bearing a bi-allelic deletion in the gene encoding for NRXN1 to evaluate whether MeHg would induce cellular changes comparable to those seen in cells derived from the ASD patient. In healthy cells, a subcytotoxic concentration of MeHg enhanced astroglial differentiation similarly to what observed in the diseased cells (N1), as shown by the number of GFAP positive cells and immunofluorescence signal intensity. In both …

Structural Basis For The Homotypic Fusion Of Chlamydial Inclusions By The Snare-Like Protein Inca., Gino Cingolani, Michael Mccauley, Anna Lobley, Alexander J Bryer, Jordan Wesolowski, Deanna L Greco, Ravi K Lokareddy, Erik Ronzone, Juan R Perilla, Fabienne Paumet

Department of Biochemistry and Molecular Biology Faculty Papers

Many intracellular bacteria, including Chlamydia, establish a parasitic membrane-bound organelle inside the host cell that is essential for the bacteria's survival. Chlamydia trachomatis forms inclusions that are decorated with poorly characterized membrane proteins known as Incs. The prototypical Inc, called IncA, enhances Chlamydia pathogenicity by promoting the homotypic fusion of inclusions and shares structural and functional similarity to eukaryotic SNAREs. Here, we present the atomic structure of the cytoplasmic domain of IncA, which reveals a non-canonical four-helix bundle. Structure-based mutagenesis, molecular dynamics simulation, and functional cellular assays identify an intramolecular clamp that is essential for IncA-mediated homotypic membrane fusion during …

The Trend Of Osteoporosis And Osteoporotic Fragility Fractures In Inpatients: Results From A National Database., Rashmi Dhital, Theresa Lynn, Niranjan Tachamo, Dilli Ram Poudel

Reading Hospital Internal Medicine Residency

Osteoporosis is associated with an increased risk of pathologic fractures; however, most patients do not receive diagnosis and adequate treatment. The aim of our study was to compare the yearly trends of osteoporosis and osteoporotic fragility fractures in the USA (US) inpatients. We used National (Nationwide) Inpatient Sample database to identify adults ≥18 years with diagnoses of osteoporosis and pathologic fractures and excluded pathologic fractures due to other etiologies. We then studied the annual trends, in terms of annual percentage change (APC), of osteoporosis and osteoporotic fractures. Among overall hospitalizations, osteoporosis was noted to have an increasing trend from 2000 …

Chronic Nucleoside Reverse Transcriptase Inhibitors Disrupt Mitochondrial Homeostasis And Promote Premature Endothelial Senescence, Yi-Fan Chen

LSU Doctoral Dissertations

Combination antiretroviral therapy (cART) has been hugely successful in reducing the mortality associated with human immunodeficiency virus (HIV) infection, resulting in a growing population of people living with HIV (PLWH). Since PLWH now have a longer life expectancy, chronic comorbidities have become the focus of the clinical management of HIV. For example, cardiovascular complications are now one of the most prevalent causes of death in PLWH. Nucleoside reverse transcriptase inhibitors (NRTIs) are the backbone of cART, and two NRTIs are typically used in combination with one drug from another drug class, such as a non-NRTI, a protease inhibitor or an …

A Rapid Viability And Drug‑Susceptibility Assay Utilizing Mycobacteriophage As An Indicator Of Drug Susceptibilities Of Anti‑Tb Drugs Against Mycobacterium Smegmatis Mc2 155, Gillian Catherine Crowley, Jim O'Mahony, Aidan Coffey, Riona G. Sayers, Paul D. Cotter

Department of Biological Sciences Publications

Background: A rapid in-house TM4 mycobacteriophage-based assay, to identify multidrug resistance against various anti-tuberculosis drugs, using the fast-growing Mycobacterium smegmatis mc² 155 in a microtiter plate format was evaluated, based on phage viability assays. Methods: A variety of parameters were optimized before the study including the minimum incubation time for the drugs, phage and M. smegmatis mc² 155 to be in contact. An increase in phage numbers over 2 h was indicative that M. smegmatis mc² 155 is resistant to the drugs under investigation, however when phage numbers remained static, M. smegmatis mc² 155 found to …

Week Of June 11, 2019, New York Medical College

InTouch

• BioInc@NYMC Is Expanding
• Evening Honors Volunteer Preceptors

Failure Of Oxysterols Such As Lanosterol To Restore Lens Clarity From Cataracts, Damian M. Daszynski, Puttur Santhoshkumar, Ashutosh S. Phadte, K. Krishna Sharma, Haizhen A. Zhong, Marjorie F. Lou, Peter F. Kador

School of Veterinary and Biomedical Sciences: Faculty Publications

The paradigm that cataracts are irreversible and that vision from cataracts can only be restored through surgery has recently been challenged by reports that oxysterols such as lanosterol and 25-hydroxycholesterol can restore vision by binding to αB-crystallin chaperone protein to dissolve or disaggregate lenticular opacities. To confirm this premise, in vitro rat lens studies along with human lens protein solubilization studies were conducted. Cataracts were induced in viable rat lenses cultured for 48 hours in TC-199 bicarbonate media through physical trauma, 10 mM ouabain as Na+/K+ ATPase ion transport inhibitor, or 1 mM of an experimental compound that induces water …

Roles Of Gm-Csf In The Pathogenesis Of Autoimmune Diseases: An Update., Noushin Lotfi, Rodolfo Thome, Nahid Rezaei, Guang-Xian Zhang, Abbas Rezaei, A. M. Rostami, Nafiseh Esmaeil

Department of Neurology Faculty Papers

Granulocyte-macrophage colony-stimulating factor (GM-CSF) was first described as a growth factor that induces the differentiation and proliferation of myeloid progenitors in the bone marrow. GM-CSF also has an important cytokine effect in chronic inflammatory diseases by stimulating the activation and migration of myeloid cells to inflammation sites, promoting survival of target cells and stimulating the renewal of effector granulocytes and macrophages. Because of these pro-cellular effects, an imbalance in GM-CSF production/signaling may lead to harmful inflammatory conditions. In this context, GM-CSF has a pathogenic role in autoimmune diseases that are dependent on cellular immune responses such as multiple sclerosis (MS) …

Week Of June 3, 2019, New York Medical College

InTouch

• The Café Grand Opening Draws a Crowd
• Department of Cell Biology and Anatomy Hosts Annual Research Forum
• College Hosts 9th Annual Paul K. Woolf, M.D., Pediatric Trainee Research Day
• NYMC Observes World Hypertension Day

Panretinal Photocoagulation Versus Intravitreal Injection Of Bevacizumab As A Preoperative Adjuvant Before Vitrectomy In The Management Of Proliferative Diabetic Retinopathy, Mohammed S. Ahmed

Journal of Medicine in Scientific Research

Background Proliferative diabetic retinopathy (PDR) characterized by neovascularization of the optic disk, retina, and/or iris may be an aberrant attempt to alleviate hypoxia in eyes with severe capillary closure or other retinal ischemia. The new vessels grow perpendicular to the plane of the retina into the scaffolding provided by the vitreous cortex, typically from venules at the junction of the perfused and nonperfused retina. Objective This work aims to study the effect of panretinal photocoagulation (PRP) versus intravitreal injection of bevacizumab (Avastin) before vitrectomy in the management of PDR. Patients and methods Our clinical study was conducted on 60 eyes …

Application Of Bone Cement For Ossicular Chain Defects, Adly Tantawy, Ahmed Amin, Essam Fathey, Mohammed Mobasher, Wael Alzamil

Journal of Medicine in Scientific Research

Objective To evaluate the postoperative results and usefulness of bone cement application in repairing ossicular chain defects, to discuss surgical technique, and to compare preoperative and postoperative ABG. Study design This was a prospective case series study. Patients and methods This study was carried out in the ORL-HNS Department, Zagazig University Hospital and Hearing and Speech Institute, from March 2014 to March 2017, on 20 patients with ossicular chain defect. Rebridging of ossicular discontinuity was done by glass monomer bone cement in all patients. Results In this study, successful hearing restoration could be achieved in 95% of the patients represented, …

The Generation Of Novel Metal-Folate- Phenanthroline Complexes And Phenanthroline-Folate Conjugates With Potential As Chemotherapeutic Agents, Aisling Crowley

Doctoral

The folate receptor (FR) was identified in 1986 and has been established as a ‘molecular Trojan Horse’ target for the uptake of folate-conjugated organic molecules into cells. The FR is overexpressed in many malignancies, including those of the ovary, uterus, breast, cervix, and prostate, yet it is reportedly under-expressed in normal healthy cells. This difference in expression and the high affinity/specificity of folate towards the folate receptor presents a promising drug delivery system. The aim of this research was to utilise folic acid as a targeting moiety and generate simple metal folate and novel folate-phenanthroline complexes with cytotoxic properties. A …

Optimizing Clinical And Cost Outcomes For Patients On Enteral Nutrition Support For Treatment Of Exocrine Pancreatic Insufficiency: Proceedings From An Expert Advisory Board Meeting, Joseph I. Boullata, Janice L. Clarke, Archie Stone, Alexis Skoufalos, David B. Nash

College of Population Health Faculty Papers

No abstract provided.

High-Performance Learning Systems Using Low-Precision Nanoscale Devices, Nandakumar Sasidharan Rajalekshmi

Dissertations

Brain-inspired computation promises a paradigm shift in information processing, both in terms of its parallel processing architecture and the ability to learn to tackle problems deemed unsolvable by traditional algorithmic approaches. The computational capability of the human brain is believed to stem from an interconnected network of 100 billion compute nodes (neurons) that interact with each other through approximately 10¹⁵ adjustable memory junctions (synapses). The conductance of synapses is modifiable allowing the network to learn and perform various cognitive functions. Artificial neural networks inspired by this architecture have demonstrated even super-human performance in many complex tasks.

Computational systems based …

Neuroscience Journal Club Neu 460, Joanna Burkhardt

Library Impact Statements

No abstract provided.

Female Family Members Lack Understanding Of Indeterminate Negative Brca1/2 Test Results Shared By Probands, Deborah Himes, Deborah K. Gibbons, Wendy C. Birmingham, Renea L. Beckstrand, Amanda Gammon, Anita Y. Kinney, Margaret F. Clayton

Faculty Publications

Genetic test results have important implications for close family members. Indeterminate negative results are the most common outcome of BRCA1/2 mutation testing. Little is known about family members’ understanding of indeterminate negative BRCA1/2 test results. The purpose of this mixed-methods study was to investigate how daughters and sisters received and understood genetic test results as shared by their mothers or sisters. Participants included 81 women aged 40-74 with mothers or sisters previously diagnosed with breast cancer and who received indeterminate negative BRCA1/2 test results. Participants had never been diagnosed with breast cancer nor received their own genetic testing or counseling. …

Week Of May 28, 2019, New York Medical College

InTouch

• New York Medical College Celebrates 160th Commencement
• Looking Back: The History of New York Medical College

Leptin Produced By Obesity-Altered Adipose Stem Cells Promotes Metastasis But Not Tumorigenesis Of Triple-Negative Breast Cancer In Orthotopic Xenograft And Patient-Derived Xenograft Models, Rachel A. Sabol, Annie C. Bowles, Alex Côté, Rachel Wise, Benjamen O'Donnell, Margarite D. Matossian, Fokhrul M. Hossain, Hope E. Burks, Luis Del Valle, Lucio Miele, Bridgette M. Collins-Burow, Matthew E. Burow, Bruce A. Bunnell

School of Medicine Faculty Publications

BACKGROUND: Breast cancer is the second leading cause of cancer deaths in the USA. Triple-negative breast cancer (TNBC) is a clinically aggressive subtype of breast cancer with high rates of metastasis, tumor recurrence, and resistance to therapeutics. Obesity, defined by a high body mass index (BMI), is an established risk factor for breast cancer. Women with a high BMI have increased incidence and mortality of breast cancer; however, the mechanisms(s) by which obesity promotes tumor progression are not well understood. METHODS: In this study, obesity-altered adipose stem cells (obASCs) were used to evaluate obesity-mediated effects of TNBC. Both in vitro …

Week Of May 20, 2019, New York Medical College

InTouch

• Employees Celebrated for Years of Service
• Convocation of Thanks Offers Closure to Students and Families of Donors
• Looking Back: The History of New York Medical College
• NYMC Celebrates Jewish American Heritage Month
• Grand Opening is Set for the Café

Secreted Tumor-Associated Cytochrome As A Blood-Based Biomarker For Cancer, Rolf Joseph Craven

Pharmacology and Nutritional Sciences Faculty Patents

Disclosed herein are methods for detecting Pgrmc 1 in bodily fluids, e.g., blood, plasma and serum, wherein detection of Pgrmcl is a biomarker for the presence of cancer, e.g., lung cancer or head or neck cancer. Pgrmc 1 levels in bodily fluids may be used to predict patient prognosis, e.g., survival and response to therapy.

Hit And Run Versus Long-Term Activation Of Parp-1 By Its Different Domains Fine-Tunes Nuclear Processes., Colin Thomas, Md, Yingbiao Ji, Chao Wu, Haily Datz, Cody Boyle, Brett Macleod, Shri Patel, Michelle Ampofo, Michelle Currie, Jonathan Harbin, Kate Pechenkina, Niraj Lodhi, Sarah J. Johnson, Alexei V. Tulin

Department of Medicine Faculty Papers

Poly(ADP-ribose) polymerase 1 (PARP-1) is a multidomain multifunctional nuclear enzyme involved in the regulation of the chromatin structure and transcription. PARP-1 consists of three functional domains: the N-terminal DNA-binding domain (DBD) containing three zinc fingers, the automodification domain (A), and the C-terminal domain, which includes the protein interacting WGR domain (W) and the catalytic (Cat) subdomain responsible for the poly(ADP ribosyl)ating reaction. The mechanisms coordinating the functions of these domains and determining the positioning of PARP-1 in chromatin remain unknown. Using multiple deletional isoforms of PARP-1, lacking one or another of its three domains, as well as consisting of only …

Week Of May 13, 2019, New York Medical College

InTouch

• Department of Family and Community Medicine Hosts Seventh Annual Research Day
• NYMC Students Published in Academic Journals

Week Of May 6, 2019, New York Medical College

InTouch

• NYMC Observes Yom Hashoah, Holocaust Remembrance Day

Development Of A Sonically Powered Biodegradable Nanogenerator For Bone Regeneration, Avi Patel

Honors Scholar Theses

Background: Reconstruction of bone fractures and defects remains a big challenge in orthopedic surgery. While regenerative engineering has advanced the field greatly using a combination of biomaterial scaffolds and stem cells, one matter of difficulty is inducing osteogenesis in these cells. Recent works have shown electricity’s ability to promote osteogenesis in stem cell lines when seeded in bone scaffolds; however, typical electrical stimulators are either (a) externally housed and require overcomplex percutaneous wires be connected to the implanted scaffold or (b) implanted non-degradable devices which contain toxic batteries and require invasive removal surgeries.

Objective: Here, we establish a biodegradable, piezoelectric …

Understanding Awareness And Completion Of Advanced Care Directives: An Exploratory Study, Katherine Anna Chiu, Katherine Grace Topf

Senior Honors Projects, 2010-2019

Background: Advance Care Directives (ACDs) are forms that are beneficial for expressing end-of-life wishes during Advance Care Planning (ACP); however, few studies have focused on awareness and completion among college-aged populations. Completion of ACDs are more common among populations forced to think about potential of death, such as the elderly and chronically ill.

Methodology: This research is comprised of two parts in order to explore the availability of resources on four-year public institutions’ official websites (institutional level), and college-aged students’ beliefs and values. The institutional level took inventory of information available on the official websites of four-year public institutions (n=1,642). …

Notch Inhibitors And The Bet Inhibitor Jq-1 Decrease The Growth Of Primary Tumor Cells Derived From A Novel Mouse Model Of C11orf95-Rela Induced Brain Tumor, Ericka Randazzo, Jesse Dunnack, Justin Fang, Joseph Loturco Phd

University Scholar Projects

Brain tumors are the most common childhood solid malignancy, and because of remarkable advances in treating many cancers outside of the brain, they have become the leading cause of cancer mortality in children. Ependymomas are a class of brain tumors which can be further subdivided into three groups based upon their location and genetic features. Of the three classes, supratentorial ependymomas are the only subgroup known to be marked by an oncogenic driver gene, which consists of a fusion mutation between the C11orf95 and RELA genes. C11orf95-RELA positive tumors are the most aggressive and lethal of …