Medicine and Health Sciences Commons^™

Mathematical Modeling And Simulations Of The Pathophysiology Of Type-2 Diabetes Mellitus, Frank K. Nani, Mingxian Jin

Math and Computer Science Faculty Working Papers

The pathophysiology of Type 2 Diabetes Mellitus (T2DM) is modelled using a coupled system of non-linear deterministic differential equations. An attempt is made to construct to a clinically plausible mathematical model that incorporates the homeostasis associated with endocrinological regulation of glucose and glycogen levels in the human body, by the hormones, insulin and glucagon. The model variables include the concentrations of glucose in the venous blood plasma, the concentration of glycogen in the liver/tissues, the concentration of the hormone glucagon, and the concentration of insulin in the venous blood plasma. The physiological interactions between the model parameters are depicted by …

Carcinogenic Parasite Secretes Growth Factor That Accelerates Wound Healing And Potentially Promotes Neoplasia., Michael J. Smout, Javier Sotillo, Thewarach Laha, Atiroch Papatpremsiri, Gabriel Rinaldi, Rafael N. Pimenta, Paul J. Brindley, +11 More

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Infection with the human liver fluke Opisthorchis viverrini induces cancer of the bile ducts, cholangiocarcinoma (CCA). Injury from feeding activities of this parasite within the human biliary tree causes extensive lesions, wounds that undergo protracted cycles of healing, and re-injury over years of chronic infection. We show that O. viverrini secreted proteins accelerated wound resolution in human cholangiocytes, an outcome that was compromised following silencing of expression of the fluke-derived gene encoding the granulin-like growth factor, Ov-GRN-1. Recombinant Ov-GRN-1 induced angiogenesis and accelerated mouse wound healing. Ov-GRN-1 was internalized by human cholangiocytes and induced gene and protein expression changes associated …

Functional Linear Models Extensions Uncover Pleiotropic Effects Of Chronic Pain Phenotypes, Dmitri V. Zaykin, L. Qing, G. D. Slade, R. Dubner, R. B. Fillingim, J. D. Greenspan, R. Ohrbach, W. Maixner, L. B. Diatchenko, Olga A. Vsevolozhskaya

Biostatistics Presentations

Growing scientific evidence suggests that intricate interactions of genetic risk factors with environmental exposures play a major role in the development of chronic pain conditions. In studies of relative contribution of an individual’s genetic composition to the perception of pain, the general characteristics of pain sensitivity are typically measured by a wide range of different, yet possibly etiologically related pain phenotypes. Testing each of these pain-perception traits individually is subject to problems of multiple testing and low statistical power. Furthermore, pain-related traits may share common etiology and comprise binary, categorical, and quantitative measurements. In the current study, we propose a …

Methods Of Reducing Pain During Bone Marrow Biopsy: A Narrative Review, Mohammad Faizan Zahid

Medical College Documents

Bone marrow examination plays a crucial role in the diagnosis and management of various hematological and systemic diseases. Even though the procedure has been carried out for decades, it remains an extremely painful and uncomfortable experience for a majority of patients. This paper reviews the different strategies used to provide analgesia and summarizes the advantages and drawbacks of one strategy over the other. A literature review was carried out addressing the different approaches to providing pain relief during bone marrow aspiration and biopsy. Several different methods, procedure modifications and protocols are employed at various centers but pain control and analgesia …

Effects Of Adipocyte Aryl Hydrocarbon Receptor Deficiency On Pcb-Induced Disruption Of Glucose Homeostasis In Lean And Obese Mice, Nicki A. Baker, Robin Shoemaker, Victoria English, Nika Larian, Manjula Sunkara, Andrew J. Morris, Mary Walker, Frederique Yiannikouris, Lisa A. Cassis

Saha Cardiovascular Research Center Faculty Publications

BACKGROUND: Coplanar polychlorinated biphenyls (PCBs) promote adipocyte inflammation and impair glucose homeostasis in lean mice. The diabetes-promoting effects of lipophilic PCBs have been observed only during weight loss in obese mice. The molecular mechanisms linking PCB exposures to impaired glucose metabolism are unclear.

OBJECTIVES: In this study we tested the hypothesis that coplanar PCBs act at adipocyte aryl hydrocarbon receptors (AhRs) to promote adipose inflammation and impair glucose homeostasis in lean mice and in obese mice during weight loss.

METHODS AND RESULTS: PCB-77 administration impaired glucose and insulin tolerance in LF (low fat diet)-fed control (AhR^fl/fl) mice …

Parasite Manipulation Of The Invariant Chain And The Peptide Editor H2-Dm Affects Major Histocompatibility Complex Class Ii Antigen Presentation During Toxoplasma Gondii Infection, Louis-Philippe Leroux, Manami Nishi, Sandy El-Hage, Barbara A. Fox, David I Bzik, Florence Dzierszinsk

Dartmouth Scholarship

Toxoplasma gondii is an obligate intracellular protozoan parasite. This apicomplexan is the causative agent of toxoplasmosis, a leading cause of central nervous system disease in AIDS. It has long been known that T. gondii interferes with major histocompatibility complex class II (MHC-II) antigen presentation to attenuate CD4(+) T cell responses and establish persisting infections. Transcriptional downregulation of MHC-II genes by T. gondii was previously established, but the precise mechanisms inhibiting MHC-II function are currently unknown. Here, we show that, in addition to transcriptional regulation of MHC-II, the parasite modulates the expression of key components of the MHC-II antigen presentation pathway, …

Tracing The Human Healthcare Roots Of Antibiotic Resistance In India: Causes, Challenges, And Promising Solutions, Kelsey Matteson

Independent Study Project (ISP) Collection

The rapid development of biological defense mechanisms by bacteria, or antibiotic resistance, is a dangerously progressing public health concern worldwide. The spread of antibiotic resistant pathogens are not only a threat to the security of healthcare facilities and the stability of modern medicine across the globe, but this phenomenon also creates a particular burden on countries with a high prevalence of infectious disease such as India. This study attempts to explore India’s unique human healthcare causes of the emergence and spread of antibiotic resistance, comprehend the obstacles that have created roadblocks to change, and outline possible solutions to overcome these …

The Relationship Of Spasticity And Impairments In Force Regulation And Neuromuscular Fatigue Post Stroke, Reivian Berrios Barillas

Dissertations (1934 -)

Hyperreflexia that causes muscle spasticity may contribute to limitations in force regulation and walking ability post stroke. Additionally, neuromuscular fatigue may reduce force regulation, which is important because fatigue can assist to strengthen muscles that control walking. Hyperreflexia may be caused by cortical disinhibition that allows Ia afferents to amplify excitatory synaptic inputs to motoneuron pools. Cortical disinhibition is presumably caused by stroke-related motor cortex damage. Although, other excitatory synaptic sources to motoneurons contribute to motor control, hyperreflexia may be one contributor that affects stroke survivors. However, hyperreflexia is reported infrequently to effect force regulation post stroke. The goal was …

Autophosphorylation Of The Smk1 Mapk Is Spatially And Temporally Regulated By Ssp2 During Meiotic Development In Yeast., Chong Wai Tio, Gregory Omerza, Sham Sunder, Edward Winter

Department of Biochemistry and Molecular Biology Faculty Papers

Smk1 is a meiosis-specific MAPK that controls spore wall morphogenesis in Saccharomyces cerevisiae. Although Smk1 is activated by phosphorylation of the threonine (T) and tyrosine (Y) in its activation loop, it is not phosphorylated by a dual-specificity MAPK kinase. Instead, the T is phosphorylated by the cyclin-dependent kinase (CDK)-activating kinase, Cak1. The Y is autophosphorylated in an intramolecular reaction that requires a meiosis-specific protein named Ssp2. The meiosis-specific CDK-like kinase, Ime2, was previously shown to positively regulate Smk1. Here we show that Ime2 activity is required to induce the translation of SSP2 mRNA at anaphase II. Ssp2 protein is then …

A Neurobiological Pathway That Mediates Stress-Induced Drug Use, Oliver Vranjkovic

Dissertations (1934 -)

Cocaine addiction represents a tremendous health and financial burden on our society and the high rate of relapse to cocaine use in abstinent addicts represents a major barrier to effective therapy. Thus, understanding the factors that contribute to relapse and the underlying neurobiological processes is important for guiding the development of treatment for addiction. Stressful life events often trigger drug use in recovering addicts. The contribution of stress to drug use is problematic due to the unpredictable and often uncontrollable nature of stress. A growing literature indicates that norepinephrine and corticotropin releasing factor (CRF) in the brain play key roles …

“Respect The Way I Need To Communicate With You”: Healthcare Experiences Of Adults On The Autism Spectrum, Christina Nicolaidis, Dora Raymaker, Katherine E. Mcdonald, Amelia E.V. Baggs, Sebastian Dern, Steven K. Kapp, Michael Weiner, Cody Boisclair, Elesia Ashkenazy

School of Social Work Faculty Publications and Presentations

Our objective was to obtain an in-depth understanding of autistic adults’ experiences with healthcare and their recommendations for improving care. Our academic-community partnership used a community based participatory research (CBPR) approach to conduct semi-structured, open-ended interviews with 39 autistic adults and 16 people who had experience supporting autistic adults in healthcare settings. Participants identified patient-level, autism-related factors that impact healthcare interactions, including verbal communication skills, sensory sensitivities, challenges with body awareness, slow processing speed, atypical non-verbal communication, and challenges with organization. However, the success of healthcare interactions largely depended on the interplay between patient- and provider-level factors, as well as …

Tct- 597 Two-Year Ischemic And Bleeding Outcomes After Coronary Intervention Of Calcified Vs. Non-Calcified Lesion Treated With Drug-Eluting Stents: The Adapt Des Study, Philippe Généreux Md, Guillaume Marquis Gravel, Bernhard Witzenbichler Md, Giora Weisz Md, Thomas D. Stuckey Md, Michael J. Rinaldi Md, Franz-Josef Neumann Md, D Christopher Metzger Md, Timothy D. Henry Md, David A. Cox Md, Peter L. Duffy Md, Ernest L. Mazzaferri Md, Girish B. Ramteke, Claire Litherland Ms, Ajay J. Kirtane Md, Roxana Mehran Md, Gregg W. Stone Md

Department of Medicine

No abstract provided.

Tct-64 Incidence, Predictors, And Impact Of Post-Discharge Bleeding Compared To Myocardial Infarction After Percutaneous Coronary Intervention, Philippe Généreux Md, Gennaro Giustino Md, Bernhard Witzenbichler Md, Giora Weisz Md, Thomas D. Stuckey Md, Michael J. Rinaldi Md, Franz-Josef Neumann Md, D Christopher Metzger Md, Timothy D. Henry Md, David A. Cox Md, Peter L. Duffy Md, Ernest L. Mazzaferri Md, Mayank Yadav, Ajay J. Kirtane Md, Claire Litherland Ms, Roxana Mehran Md, Gregg W. Stone Md

Department of Medicine

No abstract provided.

Human Polyclonal Antibodies Produced Through Dna Vaccination Of Transchromosomal Cattle Provide Mice With Post-Exposure Protection Against Lethal Zaire And Sudan Ebolaviruses., Callie E Bounds, Steven A Kwilas, Ana I Kuehne, Jennifer M Brannan, Russell R Bakken, John M Dye, Jay W Hooper, Lesley C Dupuy, Barry Ellefsen, Drew Hannaman, Hua Wu, Jin-An Jiao, Eddie J Sullivan, Connie S Schmaljohn, Matthias J. Schnell

Department of Medicine Faculty Papers

DNA vaccination of transchromosomal bovines (TcBs) with DNA vaccines expressing the codon-optimized (co) glycoprotein (GP) genes of Ebola virus (EBOV) and Sudan virus (SUDV) produce fully human polyclonal antibodies (pAbs) that recognize both viruses and demonstrate robust neutralizing activity. Each TcB was vaccinated by intramuscular electroporation (IM-EP) a total of four times and at each administration received 10 mg of the EBOV-GPco DNA vaccine and 10 mg of the SUDV-GPco DNA vaccine at two sites on the left and right sides, respectively. After two vaccinations, robust antibody responses (titers > 1000) were detected by ELISA against whole irradiated EBOV or SUDV …

The Dna Structure And Sequence Preferences Of Wrn Underlie Its Function In Telomeric Recombination Events, Deanna N. Edwards, Amrita Machwe, Li Chen, Vilhelm A. Bohr, David K. Orren

Toxicology and Cancer Biology Faculty Publications

Telomeric abnormalities caused by loss of function of the RecQ helicase WRN are linked to the multiple premature ageing phenotypes that characterize Werner syndrome. Here we examine WRN's role in telomeric maintenance, by comparing its action on a variety of DNA structures without or with telomeric sequences. Our results show that WRN clearly prefers to act on strand invasion intermediates in a manner that favours strand invasion and exchange. Moreover, WRN unwinding of these recombination structures is further enhanced when the invading strand contains at least three G-rich single-stranded telomeric repeats. These selectivities are most pronounced at NaCl concentrations within …

Distributed Task Related Bold Signal During Auditory Sub-Second Timing, Yuriy Bronshteyn

Kaleidoscope

The brain's input/output functions depend heavily on temporal processing. We sought to identify regions of the brain active in task performance during temporal discrimination of a sub-second auditory interval. We presented ten subjects with 40 paired tones and asked them to judge whether these comparison intervals were longer or shorter than a 100 ms standard. We then localized correlations between the Blood Oxygenation Level Dependent signal and task performance across subjects using event-related functional magnetic resonance imaging. We saw no task-related frontal cortex activation and significant activation of traditional auditory areas. Auditory regions included the bilateral superior and middle temporal …

Week Of September 28, 2015, New York Medical College

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The Controversy Of Vaccinations, Nicholas G. Aboreden

The Kabod

Recently vaccination has become a controversial topic. There is a growing number of people who believe that vaccines carry great health risks to patients and therefore refuse to be vaccinated or to vaccinate their children. This ill-informed view of immunizations is beginning to cause serious problems in the United States as growing numbers of disease cases are being seen. A closer look into the science of vaccines and the benefits they have brought, clearly show that not only do vaccines carry very little risk to patients, but they are responsible for the eradication and reduction of multiple debilitating diseases.

Lipin1 Regulates Skeletal Muscle Differentiation Through Extracellular Signal-Regulated Kinase (Erk) Activation And Cyclin D Complex-Regulated Cell Cycle Withdrawal, Weihua Jiang, Jing Zhu, Xun Zhuang, Xiping Zhang, Tao Luo, Karyn Esser, Hongmei Ren

Saha Cardiovascular Research Center Faculty Publications

Lipin1, an intracellular protein, plays critical roles in controlling lipid synthesis and energy metabolism through its enzymatic activity and nuclear transcriptional functions. Several mouse models of skeletal muscle wasting are associated with lipin1 mutation or altered expression. Recent human studies have suggested that children with homozygous null mutations in the LPIN1 gene suffer from rhabdomyolysis. However, the underlying pathophysiologic mechanism is still poorly understood. In the present study we examined whether lipin1 contributes to regulating muscle regeneration. We characterized the time course of skeletal muscle regeneration in lipin1-deficient fld mice after injury. We found that fld mice exhibited smaller regenerated …

Microlymphoma, A Rare Clinicopathologic Entity During The Evolution Of An Aggressive Lymphoma: A Case Report, Andrew Heisel Ms4, Arsha Sreedhar Md, Nicholas Lamparella Do, Ranjit R. Nair Md, Shereen M. Gheith Md, Phd

Department of Medicine

No abstract provided.

Initial Validation Of A Novel Method Of Presurgical Language Localization Through Functional Connectivity (Fcmri), Stephanie M. Noble, Dustin Scheinost, Susan Y. Bookheimer, Patricia Walshaw, R Todd Constable, Christopher F. Benjamin

Yale Day of Data

OBJECTIVE: Neurosurgery is potentially curative in chronic epilepsy but can only be offered to patients if the surgical risk to language is known. Clinical functional magnetic resonance imaging (fMRI) is an ideal, noninvasive method for localizing language cortex yet remains to be validated for this purpose. We have recently presented a novel method for localizing language cortex. Here we present a preliminary evaluation of this method’s validity. We hypothesized language regions identified using this novel method would demonstrate stronger functional connectivity than randomly generated set of proximal networks. METHOD: fMRI data were collected from sixteen temporal lobe patients …

An Overview Of Leber’S Hereditary Optic Neuropathy, Matthew R. Dalton

The Kabod

Typically affecting males ranging from 20 to 24 years of age, Leber’s Hereditary Optic Neuropathy (LHON) is a disorder that is characterized by an acute loss of central vision. Although a heritable disease, LHON does not follow the patterns of classical Mendelian genetics. In fact, one of the most striking characteristics of LHON is that the disease is virtually always inherited maternally. Unlike most genetic disorders that result from a mutation in genomic DNA, LHON is caused by a mutation in the genetic information of mitochondria (mtDNA). Currently there is no treatment for LHON. Despite this, pharmaceutical interventions and contemporary …

Isoflurane Inhibits Synaptic Vesicle Exocytosis Through Reduced Ca2+ Influx, Not Ca2+-Exocytosis Coupling, Joel Baumgart, Zhen-Yu Zhou, Masato Hara, Daniel Cook, Michael Hoppa

Dartmouth Scholarship

Identifying presynaptic mechanisms of general anesthetics is critical to understanding their effects on synaptic transmission. We show that the volatile anesthetic isoflurane inhibits synaptic vesicle (SV) exocytosis at nerve terminals in dissociated rat hippocampal neurons through inhibition of presynaptic Ca2+ influx without significantly altering the Ca2+ sensitivity of SV exocytosis. A clinically relevant concentration of isoflurane (0.7 mM) inhibited changes in [Ca2+]i driven by single action potentials (APs) by 25 ± 3%, which in turn led to 62 ± 3% inhibition of single AP-triggered exocytosis at 4 mM extracellular Ca2+ ([Ca2+]e). Lowering external Ca2+ to match the isoflurane-induced reduction in …

Mir-497 Decreases Cisplatin Resistance In Ovarian Cancer Cells By Targeting Mtor/P70s6k1., Shaohua Xu, Guang-Bo Fu, Zhen Tao, Jun Ouyang, Fanfei Kong, Bing-Hua Jiang, Xiaoping Wan, Ke Chen

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The mechanism of cisplatin resistance in ovarian cancer is not clearly understood. In the present investigation, we found that the expression levels of miR-497 were reduced in chemotherapy-resistant ovarian cancer cells and tumor tissues due to hypermethylation of miR-497 promoter. Low miR-497 expression levels were associated with chemo-resistant phonotype of ovarian cancer. By analyzing the expression levels of miR-497, mTOR and p70S6K1 in a clinical gene-expression array dataset, we found that mTOR and p70S6K1, two proteins correlated to chemotherapy-resistance in multiple types of human cancers, were inversely correlated with miR-497 levels in ovarian cancer tissues. By using an orthotopic ovarian …

Statins Increase Plasminogen Activator Inhibitor Type 1 Gene Transcription Through A Pregnane X Receptor Regulated Element., Frederick M Stanley, Kathryn M Linder, Timothy J Cardozo

Department of Medical Genetics Faculty Papers

Plasminogen activator inhibitor type 1 (PAI-1) is a multifunctional protein that has important roles in inflammation and wound healing. Its aberrant regulation may contribute to many disease processes such as heart disease. The PAI-1 promoter is responsive to multiple inputs including cytokines, growth factors, steroids and oxidative stress. The statin drugs, atorvastatin, mevastatin and rosuvastatin, increased basal and stimulated expression of the PAI-1 promoter 3-fold. A statin-responsive, nuclear hormone response element was previously identified in the PAI-1 promoter, but it was incompletely characterized. We characterized this direct repeat (DR) of AGGTCA with a 3-nucleotide spacer at -269/-255 using deletion and …

Eisosomes Provide Membrane Reservoirs For Rapid Expansion Of The Yeast Plasma Membrane, Ruth Kabeche, Louisa Howard, James B. Moseley

Dartmouth Scholarship

Cell surface area rapidly increases during mechanical and hypoosmotic stresses. Such expansion of the plasma membrane requires 'membrane reservoirs' that provide surface area and buffer membrane tension, but the sources of this membrane remain poorly understood. In principle, the flattening of invaginations and buds within the plasma membrane could provide this additional surface area, as recently shown for caveolae in animal cells. Here, we used microfluidics to study the rapid expansion of the yeast plasma membrane in protoplasts, which lack the rigid cell wall. To survive hypoosmotic stress, yeast cell protoplasts required eisosomes, protein-based structures that generate long invaginations at …

Compatibility Of Vancomycin And Oxacillin During Simulated Y-Site Delivery, Chad A. Knoderer, Hilary M. Teibel, Kristen R. Nichols

Scholarship and Professional Work – COPHS

Background: Vancomycin and oxacillin may be used together as empiric coverage in patients with proven or suspected Staphylococcus aureus infections. Though vancomycin hydrochloride 20 mg/mL and oxacillin sodium 160 mg/mL are reported to be compatible via Y-site delivery, Y-site compatibility of commonly used concentrations, vancomycin 10 mg/mL and oxacillin 20 mg/mL, has not yet been reported. Objective: To determine the Y-site compatibility of vancomycin 10 mg/mL and oxacillin 20 mg/mL. Methods: One vancomycin hydrochloride 1 g vial was reconstituted with 10 mL sterile water for injection (SWFI) and diluted with 90 mL 5% dextrose in water (D5W) …

Conservation Of Inner Nuclear Membrane Targeting Sequences In Mammalian Pom121 And Yeast Heh2 Membrane Proteins., Annemarie Kralt, Noorjahan B Jagalur, Vincent Van Den Boom, Ravi K Lokareddy, Anton Steen, Gino Cingolani, Maarten Fornerod, Liesbeth M Veenhoff

Department of Biochemistry and Molecular Biology Faculty Papers

Endoplasmic reticulum-synthesized membrane proteins traffic through the nuclear pore complex (NPC) en route to the inner nuclear membrane (INM). Although many membrane proteins pass the NPC by simple diffusion, two yeast proteins, ScSrc1/ScHeh1 and ScHeh2, are actively imported. In these proteins, a nuclear localization signal (NLS) and an intrinsically disordered linker encode the sorting signal for recruiting the transport factors for FG-Nup and RanGTP-dependent transport through the NPC. Here we address whether a similar import mechanism applies in metazoans. We show that the (putative) NLSs of metazoan HsSun2, MmLem2, HsLBR, and HsLap2β are not sufficient to drive nuclear accumulation of …

Week Of September 14, 2015, New York Medical College

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• Dean Miller Hosts School of Medicine Retreat
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High Throughput Sequencing Identifies Micrornas Mediating Α-Synuclein Toxicity By Targeting Neuroactive-Ligand Receptor Interaction Pathway In Early Stage Of Drosophila Parkinson's Disease Model., Yan Kong, Xijun Liang, Lin Liu, Dongdong Zhang, Chao Wan, Zhenji Gan, Liudi Yuan, Bing-Hua Jiang

Department of Medicine Faculty Papers

Parkinson's disease (PD) is a prevalent neurodegenerative disorder with pathological features including death of dopaminergic neurons in the substantia nigra and intraneuronal accumulations of Lewy bodies. As the main component of Lewy bodies, α-synuclein is implicated in PD pathogenesis by aggregation into insoluble filaments. However, the detailed mechanisms underlying α-synuclein induced neurotoxicity in PD are still elusive. MicroRNAs are ~20nt small RNA molecules that fine-tune gene expression at posttranscriptional level. A plethora of miRNAs have been found to be dysregulated in the brain and blood cells of PD patients. Nevertheless, the detailed mechanisms and their in vivo functions in PD …