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Mighty Rapalink-1 Vanquishes Undruggable Mutant Mtor In Glioblastoma, Meena Jhanwar-Uniyal Oct 2017

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

NYMC Faculty Publications

No abstract provided.


The Path Report Volume 1 Issue 2, Pathology Department, New York Medical College Oct 2017

The Path Report Volume 1 Issue 2, Pathology Department, New York Medical College

The Path Report

No abstract provided.


Nucleotide-Dependent Preferential Localization Of Ras In Model Membranes With Lipid Raft Nanodomains, Anna Shishina Oct 2017

Nucleotide-Dependent Preferential Localization Of Ras In Model Membranes With Lipid Raft Nanodomains, Anna Shishina

Dissertations (1934 -)

Membrane proteins constitute a third of all proteins in the cell and more than 50% of drug targets. However, the analysis of membrane proteins has many challenges owing to their partially hydrophobic surfaces, flexibility and lack of stability. One example of an essential membrane protein is Ras superfamily. Ras is a small monomeric GTPase involved in regulation of cell growth, proliferation and differentiation. Therefore, Ras and its effectors are among the most important targets for cancer therapy. A detailed knowledge of the processes occurring during signal propagation via Ras might help to elucidate the mechanisms of the involved signal cascades. …


Inhibition Of Apoptosis Signal-Regulating Kinase 1 Alters The Wound Epidermis And Enhances Auricular Cartilage Regeneration., Qian-Shi Zhang, Deepa S. Kurpad, My G. Mahoney, Marla J. Steinbeck, Theresa A. Freeman Oct 2017

Inhibition Of Apoptosis Signal-Regulating Kinase 1 Alters The Wound Epidermis And Enhances Auricular Cartilage Regeneration., Qian-Shi Zhang, Deepa S. Kurpad, My G. Mahoney, Marla J. Steinbeck, Theresa A. Freeman

Department of Orthopaedic Surgery Faculty Papers

Why regeneration does not occur in mammals remains elusive. In lower vertebrates, epimorphic regeneration of the limb is directed by the wound epidermis, which controls blastema formation to promote regrowth of the appendage. Herein, we report that knockout (KO) or inhibition of Apoptosis Signal-regulated Kinase-1 (ASK1), also known as mitogen-activated protein kinase kinase kinase 5 (MAP3K5), after full thickness ear punch in mice prolongs keratinocyte activation within the wound epidermis and promotes regeneration of auricular cartilage. Histological analysis showed the ASK1 KO ears displayed enhanced protein markers associated with blastema formation, hole closure and regeneration of auricular cartilage. At seven …


Phase 1b Trial Of Proteasome Inhibitor Carfilzomib With Irinotecan In Lung Cancer And Other Irinotecan-Sensitive Malignancies That Have Progressed On Prior Therapy (Onyx Ist Reference Number: Car-Ist-553), Susanne M. Arnold, Kari Chansky, Markos Leggas, Michael A. Thompson, John L. Villano, John Hamm, Rachel E. Sanborn, Glen J. Weiss, Gurkamal Chatta, Maria Q. Baggstrom Oct 2017

Phase 1b Trial Of Proteasome Inhibitor Carfilzomib With Irinotecan In Lung Cancer And Other Irinotecan-Sensitive Malignancies That Have Progressed On Prior Therapy (Onyx Ist Reference Number: Car-Ist-553), Susanne M. Arnold, Kari Chansky, Markos Leggas, Michael A. Thompson, John L. Villano, John Hamm, Rachel E. Sanborn, Glen J. Weiss, Gurkamal Chatta, Maria Q. Baggstrom

Markey Cancer Center Faculty Publications

Introduction Proteasome inhibition is an established therapy for many malignancies. Carfilzomib, a novel proteasome inhibitor, was combined with irinotecan to provide a synergistic approach in relapsed, irinotecan-sensitive cancers. Materials and Methods Patients with relapsed irinotecan-sensitive cancers received carfilzomib (Day 1, 2, 8, 9, 15, and 16) at three dose levels (20/27 mg/m2, 20/36 mg/m2 and 20/45 mg/m2/day) in combination with irinotecan (Days 1, 8 and 15) at 125 mg/m2/day. Key eligibility criteria included measurable disease, a Zubrod PS of 0 or 1, and acceptable organ function. Patients with stable asymptomatic brain metastases were eligible. Dose escalation utilized a standard 3 …


Developmental Lead And/Or Prenatal Stress Exposures Followed By Different Types Of Behavioral Experience Result In The Divergence Of Brain Epigenetic Profiles In A Sex, Brain Region, And Time-Dependent Manner: Implications For Neurotoxicology., Deborah A. Cory-Slechta, Marissa Sobolewski, Garima Varma, Jay S. Schneider Oct 2017

Developmental Lead And/Or Prenatal Stress Exposures Followed By Different Types Of Behavioral Experience Result In The Divergence Of Brain Epigenetic Profiles In A Sex, Brain Region, And Time-Dependent Manner: Implications For Neurotoxicology., Deborah A. Cory-Slechta, Marissa Sobolewski, Garima Varma, Jay S. Schneider

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Over a lifetime, early developmental exposures to neurocognitive risk factors, such as lead (Pb) exposures and prenatal stress (PS), will be followed by multiple varied behavioral experiences. Pb, PS and behavioral experience can each influence brain epigenetic profiles. Our recent studies show a greater level of complexity, however, as all three factors interact within each sex to generate differential adult variation in global post-translational histone modifications (PTHMs), which may result in fundamentally different consequences for life-long learning and behavioral function. We have reported that PTHM profiles differ by sex, brain region and time point of measurement following developmental exposures to …


An Algorithmic Approach To Operative Management Of Complex Pediatric Dog Bites: 3-Year Review Of A Level I Regional Referral Pediatric Trauma Hospital, Kaveh Alizadeh, A Shayesteh, M Xu Oct 2017

An Algorithmic Approach To Operative Management Of Complex Pediatric Dog Bites: 3-Year Review Of A Level I Regional Referral Pediatric Trauma Hospital, Kaveh Alizadeh, A Shayesteh, M Xu

NYMC Faculty Publications

Background: Incidence of dog bites continues to rise among the pediatric population and serves as a public health threat for the well-being of children. Plastic surgeons are at the forefront of initial management and eventual outcome of these devastating injuries. This study set out to determine the nature of dog bite injuries treated over a 3-year period at a large level 1 pediatric trauma center. Methods: A retrospective review of emergency room records of all pediatric patients (age, 0-18 years old) who sustained dog bites between January 2012 and December 2014 were gathered. All details about age of patient, location …


Development And Validation Of A Hybrid Virtual/Physical Nuss Procedure Surgical Trainer, Mohammad F. Obeid Oct 2017

Development And Validation Of A Hybrid Virtual/Physical Nuss Procedure Surgical Trainer, Mohammad F. Obeid

Computational Modeling & Simulation Engineering Theses & Dissertations

With continuous advancements and adoption of minimally invasive surgery, proficiency with nontrivial surgical skills involved is becoming a greater concern. Consequently, the use of surgical simulation has been increasingly embraced by many for training and skill transfer purposes. Some systems utilize haptic feedback within a high-fidelity anatomically-correct virtual environment whereas others use manikins, synthetic components, or box trainers to mimic primary components of a corresponding procedure.

Surgical simulation development for some minimally invasive procedures is still, however, suboptimal or otherwise embryonic. This is true for the Nuss procedure, which is a minimally invasive surgery for correcting pectus excavatum (PE) – …


The Psychology Of Neurofeedback: Clinical Intervention Even If Applied Placebo, Robert T. Thibault, Amir Raz Oct 2017

The Psychology Of Neurofeedback: Clinical Intervention Even If Applied Placebo, Robert T. Thibault, Amir Raz

Psychology Faculty Articles and Research

Advocates of neurofeedback make bold claims concerning brain regulation, treatment of disorders, and mental health. Decades of research and thousands of peer-reviewed publications support neurofeedback using electroencephalography (EEG-nf); yet, few experiments isolate the act of receiving feedback from a specific brain signal as a necessary precursor to obtain the purported benefits. Moreover, while psychosocial parameters including participant motivation and expectation, rather than neurobiological substrates, seem to fuel clinical improvement across a wide range of disorders, for-profit clinics continue to sprout across North America and Europe. Here, we highlight the tenuous evidence supporting EEG-nf and sketch out the weaknesses of this …


Angptl4 Promotes The Progression Of Cutaneous Melanoma To Brain Metastasis., Sivan Izraely, Shlomit Ben-Menachem, Orit Sagi-Assif, Tsipi Meshel, Diego M Marzese, Shuichi Ohe, Inna Zubrilov, Metsada Pasmanik-Chor, Dave S B Hoon, Isaac P Witz Sep 2017

Angptl4 Promotes The Progression Of Cutaneous Melanoma To Brain Metastasis., Sivan Izraely, Shlomit Ben-Menachem, Orit Sagi-Assif, Tsipi Meshel, Diego M Marzese, Shuichi Ohe, Inna Zubrilov, Metsada Pasmanik-Chor, Dave S B Hoon, Isaac P Witz

Articles, Abstracts, and Reports

In an ongoing effort to identify molecular determinants regulating melanoma brain metastasis, we previously identified Angiopoietin-like 4 (ANGPTL4) as a component of the molecular signature of such metastases. The aim of this study was to determine the functional significance of ANGPTL4 in the shaping of melanoma malignancy phenotype, especially in the establishment of brain metastasis. We confirmed that ANGPTL4 expression is significantly higher in cells metastasizing to the brain than in cells from the cutaneous (local) tumor from the same melanoma in a nude mouse xenograft model, and also in paired clinical specimens of melanoma metastases than in primary melanomas …


Concussion As A Multi-Scale Complex System: An Interdisciplinary Synthesis Of Current Knowledge, Erin S. Kenzie, Elle L. Parks, Erin D. Bigler, Miranda M. Lim, James C. Chesnutt, Wayne Wakeland Sep 2017

Concussion As A Multi-Scale Complex System: An Interdisciplinary Synthesis Of Current Knowledge, Erin S. Kenzie, Elle L. Parks, Erin D. Bigler, Miranda M. Lim, James C. Chesnutt, Wayne Wakeland

Complex Systems Faculty Publications and Presentations

Traumatic brain injury (TBI) has been called “the most complicated disease of the most complex organ of the body” and is an increasingly high-profile public health issue. Many patients report long-term impairments following even “mild” injuries, but reliable criteria for diagnosis and prognosis are lacking. Every clinical trial for TBI treatment to date has failed to demonstrate reliable and safe improvement in outcomes, and the existing body of literature is insufficient to support the creation of a new classification system. Concussion, or mild TBI, is a highly heterogeneous phenomenon, and numerous factors interact dynamically to influence an individual’s recovery trajectory. …


Effects Of Once-Weekly Exenatide On Cardiovascular Outcomes In Type 2 Diabetes, Rury R Holman, M Angelyn Bethel, Robert J Mentz, Vivian P Thompson, Yuliya Lokhnygina, John B Buse, Juliana C Chan, Jasmine Choi, Stephanie M Gustavson, Nayyar Iqbal, Aldo P Maggioni, Steven P Marso, Peter Öhman, Neha J Pagidipati, Neil Poulter, Ambady Ramachandran, Bernard Zinman, Adrian F Hernandez Sep 2017

Effects Of Once-Weekly Exenatide On Cardiovascular Outcomes In Type 2 Diabetes, Rury R Holman, M Angelyn Bethel, Robert J Mentz, Vivian P Thompson, Yuliya Lokhnygina, John B Buse, Juliana C Chan, Jasmine Choi, Stephanie M Gustavson, Nayyar Iqbal, Aldo P Maggioni, Steven P Marso, Peter Öhman, Neha J Pagidipati, Neil Poulter, Ambady Ramachandran, Bernard Zinman, Adrian F Hernandez

Faculty, Staff and Student Publications

BACKGROUND: The cardiovascular effects of adding once-weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown.

METHODS: We randomly assigned patients with type 2 diabetes, with or without previous cardiovascular disease, to receive subcutaneous injections of extended-release exenatide at a dose of 2 mg or matching placebo once weekly. The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The coprimary hypotheses were that exenatide, administered once weekly, would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy.

RESULTS: …


Patient Centered Family Planning Care, Lauren Thaxton Sep 2017

Patient Centered Family Planning Care, Lauren Thaxton

Biomedical Sciences ETDs

The Institute of Medicine defines six important domains of health care quality: safety, efficacy, timeliness, efficiency, equitable delivery and patient-centeredness. Quality family planning care aims to provide individuals with the tools needed to engage in healthy and satisfying sex lives while planning and spacing pregnancies to achieve desired family size. The field of family planning strongly relies on the domain of patient-centeredness as individual values and preferences guide clinical care. Yet large gaps in knowledge exist in understanding how to improve patients’ clinical experience. This hybrid thesis posits avenues for improving the quality and patient-centeredness of clinical care.

Quality care …


Rabies Screen Reveals Gpe Control Of Cocaine-Triggered Plasticity., Kevin T. Beier, Christina K. Kim, Paul Hoerbelt, Lin Wai Hung, Boris D. Heifets, Katherine E. Deloach, Timothy J. Mosca, Sophie Neuner, Karl Deisseroth, Liqun Luo, Robert C. Malenka Sep 2017

Rabies Screen Reveals Gpe Control Of Cocaine-Triggered Plasticity., Kevin T. Beier, Christina K. Kim, Paul Hoerbelt, Lin Wai Hung, Boris D. Heifets, Katherine E. Deloach, Timothy J. Mosca, Sophie Neuner, Karl Deisseroth, Liqun Luo, Robert C. Malenka

Department of Neuroscience Faculty Papers

Identification of neural circuit changes that contribute to behavioural plasticity has routinely been conducted on candidate circuits that were preselected on the basis of previous results. Here we present an unbiased method for identifying experience-triggered circuit-level changes in neuronal ensembles in mice. Using rabies virus monosynaptic tracing, we mapped cocaine-induced global changes in inputs onto neurons in the ventral tegmental area. Cocaine increased rabies-labelled inputs from the globus pallidus externus (GPe), a basal ganglia nucleus not previously known to participate in behavioural plasticity triggered by drugs of abuse. We demonstrated that cocaine increased GPe neuron activity, which accounted for the …


Efficacy And Safety Comparison Between Suberoylanilide Hydroxamic Acid And Mitomycin C In Reducing The Risk Of Corneal Haze After Prk Treatment In Vivo, Govindaraj Anumanthan, Ajay Sharma, Michael R. Waggoner, Chuck W. Hamm, Suneel Gupta, Nathan P. Hesemann, Rajiv R. Mohan Sep 2017

Efficacy And Safety Comparison Between Suberoylanilide Hydroxamic Acid And Mitomycin C In Reducing The Risk Of Corneal Haze After Prk Treatment In Vivo, Govindaraj Anumanthan, Ajay Sharma, Michael R. Waggoner, Chuck W. Hamm, Suneel Gupta, Nathan P. Hesemann, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

PURPOSE:

This study compared the efficacy and safety of suberoylanilide hydroxamic acid (SAHA) and mitomycin C (MMC) up to 4 months in the prevention of corneal haze induced by photorefractive keratectomy (PRK) in rabbits in vivo.

METHODS:

Corneal haze in rabbits was produced with −9.00 diopter PRK. A single application of SAHA (25 μM) or MMC (0.02%) was applied topically immediately after PRK. Effects of the two drugs were analyzed by slit-lamp microscope, specular microscope, TUNEL assay, and immunofluorescence.

RESULTS:

Single topical adjunct use of SAHA (25 μM) or MMC (0.02%) after PRK attenuated more than 95% corneal …


Different Effects Of Maternal Low-Isoflavone Soy Protein And Genistein Consumption On Hepatic Lipid Metabolism Of 21-Day-Old Male Rat Offspring., Anna Han, Sae Bom Won, Young Hye Kwon Sep 2017

Different Effects Of Maternal Low-Isoflavone Soy Protein And Genistein Consumption On Hepatic Lipid Metabolism Of 21-Day-Old Male Rat Offspring., Anna Han, Sae Bom Won, Young Hye Kwon

Department of Cancer Biology Faculty Papers

Amino acid composition and isoflavone are alleged contributors to the beneficial effects of soy protein isolate (SPI) on lipid metabolism. Therefore, we investigated the contributing component(s) of SPI in a maternal diet to the regulation of lipid metabolism in offspring. We also determined serum parameters in dams to investigate specific maternal cues that might be responsible for this regulation. Female rats were fed either a casein (CAS), a low-isoflavone SPI, or a casein plus genistein (GEN, 250 mg/kg) diet for two weeks before mating, as well as during pregnancy and lactation. Male offspring (CAS, SPI and GEN groups) were studied …


Chronic Hypobaric Hypoxia Modulates Primary Cilia Differently In Adult And Fetal Ovine Kidneys, Kiumars Shamloo, Juan Chen, Jasmine Sardar, Rinzhin T. Sherpa, Rajasekharreddy Pala, Kimberly F. Atkinson, William J. Pearce, Lubo Zhang, Surya M. Nauli Sep 2017

Chronic Hypobaric Hypoxia Modulates Primary Cilia Differently In Adult And Fetal Ovine Kidneys, Kiumars Shamloo, Juan Chen, Jasmine Sardar, Rinzhin T. Sherpa, Rajasekharreddy Pala, Kimberly F. Atkinson, William J. Pearce, Lubo Zhang, Surya M. Nauli

Pharmacy Faculty Articles and Research

Hypoxic environments at high altitude have significant effects on kidney injury. Following injury, renal primary cilia display length alterations. Primary cilia are mechanosensory organelles that regulate tubular architecture. The effect of hypoxia on cilia length is still controversial in cultured cells, and no corresponding in vivo study exists. Using fetal and adult sheep, we here study the effect of chronic hypobaric hypoxia on the renal injury, intracellular calcium signaling and the relationship between cilia length and cilia function. Our results show that although long-term hypoxia induces renal fibrosis in both fetal and adult kidneys, fetal kidneys are more susceptible to …


Use Of Dark Chocolate For Diabetic Patients: A Review Of The Literature And Current Evidence, Syed Raza Shah, Richard Alweis, Najla Issa Najim, Amin Muhammad Dharani, Muhammad Ahmed Jangda, Maira Shahid, Ahmed Nabeel Kazi, Syed Arbab Shah Sep 2017

Use Of Dark Chocolate For Diabetic Patients: A Review Of The Literature And Current Evidence, Syed Raza Shah, Richard Alweis, Najla Issa Najim, Amin Muhammad Dharani, Muhammad Ahmed Jangda, Maira Shahid, Ahmed Nabeel Kazi, Syed Arbab Shah

Internal Medicine Faculty Publications

Dietary changes are a major lifestyle factor that can influence the progression of chronic diseases such as diabetes. Recently, flavanols, a subgroup of plant-derived phytochemicals called flavonoids, have gained increasing attention, due to studies showing an inverse correlation between dietary intake of flavanols and incidence of diabetes. Flavanoids in the cocoa plant may ameliorate insulin resistance by improving endothelial function, altering glucose metabolism, and reducing oxidative stress. Oxidative stress has been proposed as the main culprit for insulin resistance. The well-established effects of cocoa on endothelial function also points to a possible effect on insulin sensitivity. The relationship between insulin …


The Heat-Stable Enterotoxin Receptor, Guanylyl Cyclase C, As A Pharmacological Target In Colorectal Cancer Immunotherapy: A Bench-To-Bedside Current Report., Trevor R. Baybutt, Allison A. Aka, Adam E. Snook Sep 2017

The Heat-Stable Enterotoxin Receptor, Guanylyl Cyclase C, As A Pharmacological Target In Colorectal Cancer Immunotherapy: A Bench-To-Bedside Current Report., Trevor R. Baybutt, Allison A. Aka, Adam E. Snook

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Cancer immunotherapy is becoming a routine treatment modality in the oncology clinic, in spite of the fact that it is a relatively nascent field. The challenge in developing effective immunotherapeutics is the identification of target molecules that promote anti-tumor efficacy across the patient population while sparing healthy tissue from damaging autoimmunity. The intestinally restricted receptor guanylyl cyclase C (GUCY2C) is a target that has been investigated for the treatment of colorectal cancer and numerous animal, and clinical studies have demonstrated both efficacy and safety. Here, we describe the current state of GUCY2C-directed cancer immunotherapy and the future directions of this …


Posttranscriptional Regulation Of Parg Mrna By Hur Facilitates Dna Repair And Resistance To Parp Inhibitors, Saswati N. Chand, Mahsa Zarei, M. J. Schiewer, Akshay R. Sanan, Carmella Romeo, Shruti Lal, Joseph A. Cozzitorto, Avinoam Nevler, Laura Scolaro, Eric R. Londin, Wei Jiang, Nicole Meisner-Kober, Michael J. Pishvaian, Karen E. Knudsen, Charles Yeo, John M Pascal, Jordan M. Winter, Jonathan R. Brody Sep 2017

Posttranscriptional Regulation Of Parg Mrna By Hur Facilitates Dna Repair And Resistance To Parp Inhibitors, Saswati N. Chand, Mahsa Zarei, M. J. Schiewer, Akshay R. Sanan, Carmella Romeo, Shruti Lal, Joseph A. Cozzitorto, Avinoam Nevler, Laura Scolaro, Eric R. Londin, Wei Jiang, Nicole Meisner-Kober, Michael J. Pishvaian, Karen E. Knudsen, Charles Yeo, John M Pascal, Jordan M. Winter, Jonathan R. Brody

Department of Surgery Faculty Papers

The majority of pancreatic ductal adenocarcinomas (PDAC) rely on the mRNA stability factor HuR (ELAV-L1) to drive cancer growth and progression. Here, we show that CRISPR-Cas9–mediated silencing of the HuR locus increases the relative sensitivity of PDAC cells to PARP inhibitors (PARPi). PDAC cells treated with PARPi stimulated translocation of HuR from the nucleus to the cytoplasm, specifically promoting stabilization of a new target, poly (ADP-ribose) glycohydrolase (PARG) mRNA, by binding a unique sequence embedded in its 30 untranslated region. HuR-dependent upregulation of PARG expression facilitated DNA repair via hydrolysis of polyADP-ribose on related repair proteins. Accordingly, strategies to …


Impact Of Vitamin A And Carotenoids On The Risk Of Tuberculosis Progression, Omowunmi Aibana, Molly F Franke, Chuan-Chin Huang, Jerome T Galea, Roger Calderon, Zibiao Zhang, Mercedes C Becerra, Emily R Smith, Alayne G Ronnenberg, Carmen Contreras, Rosa Yataco, Leonid Lecca, Megan B Murray Sep 2017

Impact Of Vitamin A And Carotenoids On The Risk Of Tuberculosis Progression, Omowunmi Aibana, Molly F Franke, Chuan-Chin Huang, Jerome T Galea, Roger Calderon, Zibiao Zhang, Mercedes C Becerra, Emily R Smith, Alayne G Ronnenberg, Carmen Contreras, Rosa Yataco, Leonid Lecca, Megan B Murray

Faculty, Staff and Student Publications

BACKGROUND: Low and deficient levels of vitamin A are common in low- and middle-income countries where tuberculosis burden is high. We assessed the impact of baseline levels of vitamin A and carotenoids on tuberculosis disease risk.

METHODS: We conducted a case-control study nested within a longitudinal cohort of household contacts (HHCs) of pulmonary tuberculosis case patients in Lima, Peru. We defined case patients as human immunodeficiency virus (HIV)-negative HHCs with blood samples in whom tuberculosis disease developed ≥15 days after enrollment of the index patient. For each case patient, we randomly selected 4 controls from among contacts in whom tuberculosis …


Degree Of Twisting And Duration Of Symptoms Are Prognostic Factors Of Testis Salvage During Episodes Of Testicular Torsion, Adam S. Howe, Vinaya Vasudevan, Michael Kongnyuy, Kevin Rychik, Lisa A. Thomas, Maria Matuskova, Steven C. Friedman, Jordan S. Gitlin, Edward F. Reda, Lane S. Palmer Sep 2017

Degree Of Twisting And Duration Of Symptoms Are Prognostic Factors Of Testis Salvage During Episodes Of Testicular Torsion, Adam S. Howe, Vinaya Vasudevan, Michael Kongnyuy, Kevin Rychik, Lisa A. Thomas, Maria Matuskova, Steven C. Friedman, Jordan S. Gitlin, Edward F. Reda, Lane S. Palmer

Publications and Research

Background: Testicular torsion is surgical emergency. Prompt diagnosis and treatment of testicular torsion is essential for testicular viability. At surgical exploration, the spermatic cord is seen twisted a variable number of times around its longitudinal axis. There is scant data regarding the degree of twisting and its association with testis outcomes. The purpose of our study is to explore how the degree of torsion factors into testicular outcome using follow-up data.

Methods: We retrospectively reviewed the records of adolescent males who presented with testicular torsion to our institution, looking at duration of pain symptoms, degree of torsion documented in the …


St-Producing E. Coli Oppose Carcinogen-Induced Colorectal Tumorigenesis In Mice., Peng Li, Jieru E. Lin, Adam E. Snook, Scott A. Waldman Sep 2017

St-Producing E. Coli Oppose Carcinogen-Induced Colorectal Tumorigenesis In Mice., Peng Li, Jieru E. Lin, Adam E. Snook, Scott A. Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

There is a geographic inequality in the incidence of colorectal cancer, lowest in developing countries, and greatest in developed countries. This disparity suggests an environmental contribution to cancer resistance in endemic populations. Enterotoxigenic bacteria associated with diarrheal disease are prevalent in developing countries, including enterotoxigenic E. coli (ETEC) producing heat-stable enterotoxins (STs). STs are peptides that are structurally homologous to paracrine hormones that regulate the intestinal guanylyl cyclase C (GUCY2C) receptor. Beyond secretion, GUCY2C is a tumor suppressor universally silenced by loss of expression of its paracrine hormone during carcinogenesis. Thus, the geographic imbalance in colorectal cancer, in part, may …


A Global Staphylococcus Aureus Proteome Resource Applied To The In Vivo Characterization Of Host-Pathogen Interactions., Stephan Michalik, Maren Depke, Annette Murr, Manuela Gesell Salazar, Ulrike Kusebauch, Zhi Sun, Tanja C Meyer, Kristin Surmann, Henrike Pförtner, Petra Hildebrandt, Stefan Weiss, Laura Marcela Palma Medina, Melanie Gutjahr, Elke Hammer, Dörte Becher, Thomas Pribyl, Sven Hammerschmidt, Eric W Deutsch, Samuel L Bader, Michael Hecker, Robert L Moritz, Ulrike Mäder, Uwe Völker, Frank Schmidt Sep 2017

A Global Staphylococcus Aureus Proteome Resource Applied To The In Vivo Characterization Of Host-Pathogen Interactions., Stephan Michalik, Maren Depke, Annette Murr, Manuela Gesell Salazar, Ulrike Kusebauch, Zhi Sun, Tanja C Meyer, Kristin Surmann, Henrike Pförtner, Petra Hildebrandt, Stefan Weiss, Laura Marcela Palma Medina, Melanie Gutjahr, Elke Hammer, Dörte Becher, Thomas Pribyl, Sven Hammerschmidt, Eric W Deutsch, Samuel L Bader, Michael Hecker, Robert L Moritz, Ulrike Mäder, Uwe Völker, Frank Schmidt

Articles, Abstracts, and Reports

Data-independent acquisition mass spectrometry promises higher performance in terms of quantification and reproducibility compared to data-dependent acquisition mass spectrometry methods. To enable high-accuracy quantification of Staphylococcus aureus proteins, we have developed a global ion library for data-independent acquisition approaches employing high-resolution time of flight or Orbitrap instruments for this human pathogen. We applied this ion library resource to investigate the time-resolved adaptation of S. aureus to the intracellular niche in human bronchial epithelial cells and in a murine pneumonia model. In epithelial cells, abundance changes for more than 400 S. aureus proteins were quantified, revealing, e.g., the precise temporal regulation …


Maternal Hypothalamic-Pituitary-Adrenal Axis Response To Foraging Uncertainty: A Model Of Individual Vs. Social Allostasis And The "Superorganism Hypothesis", Jeremy D. Coplan, Nishant K. Gupta, Asif Karim, Anna Rozenboym, Eric L.P. Smith, John G. Kral, Leonard A. Rosenblum Sep 2017

Maternal Hypothalamic-Pituitary-Adrenal Axis Response To Foraging Uncertainty: A Model Of Individual Vs. Social Allostasis And The "Superorganism Hypothesis", Jeremy D. Coplan, Nishant K. Gupta, Asif Karim, Anna Rozenboym, Eric L.P. Smith, John G. Kral, Leonard A. Rosenblum

Publications and Research

Introduction: Food insecurity is a major global contributor to developmental origins of adult disease. The allostatic load of maternal food uncertainty from variable foraging demand (VFD) activates corticotropin-releasing factor (CRF) without eliciting hypothalamic-pituitary-adrenal (HPA) activation measured on a group level. Individual homeostatic adaptations of the HPA axis may subserve second-order homeostasis, a process we provisionally term “social allostasis.” We postulate that maternal food insecurity induces a “superorganism” state through coordination of individual HPA axis response.

Methods: Twenty-four socially-housed bonnet macaque maternal-infant dyads were exposed to 16 weeks of alternating two-week epochs of low or high foraging demand shown to compromise …


A Pilot Clinical Trial Of Recombinant Human Angiotensin-Converting Enzyme 2 In Acute Respiratory Distress Syndrome., Akram Khan, Cody Benthin, Brian Zeno, Timothy E Albertson, John Boyd, Jason D Christie, Richard Hall, Germain Poirier, Juan J Ronco, Mark Tidswell, Kelly Hardes, William M Powley, Tracey J Wright, Sarah K Siederer, David A Fairman, David A Lipson, Andrew I Bayliffe, Aili L Lazaar Sep 2017

A Pilot Clinical Trial Of Recombinant Human Angiotensin-Converting Enzyme 2 In Acute Respiratory Distress Syndrome., Akram Khan, Cody Benthin, Brian Zeno, Timothy E Albertson, John Boyd, Jason D Christie, Richard Hall, Germain Poirier, Juan J Ronco, Mark Tidswell, Kelly Hardes, William M Powley, Tracey J Wright, Sarah K Siederer, David A Fairman, David A Lipson, Andrew I Bayliffe, Aili L Lazaar

Trauma and Acute Care Articles

BACKGROUND: Renin-angiotensin system (RAS) signaling and angiotensin-converting enzyme 2 (ACE2) have been implicated in the pathogenesis of acute respiratory distress syndrome (ARDS). We postulated that repleting ACE2 using GSK2586881, a recombinant form of human angiotensin-converting enzyme 2 (rhACE2), could attenuate acute lung injury.

METHODS: We conducted a two-part phase II trial comprising an open-label intrapatient dose escalation and a randomized, double-blind, placebo-controlled phase in ten intensive care units in North America. Patients were between the ages of 18 and 80 years, had an American-European Consensus Criteria consensus diagnosis of ARDS, and had been mechanically ventilated for less than 72 h. …


Long-Term Impact Of Changing Childhood Malnutrition On Rotavirus Diarrhoea: Two Decades Of Adjusted Association With Climate And Socio-Demographic Factors From Urban Bangladesh, Sumon Kumar Das, Mohammod Jobayer Chisti, Mohammad Habibur Rahman Sarker, Jui Das, Shawnawaz Ahmed, K. M. Shahunja, Shamsun Nahar, Nora Gibbons, Tahmeed Ahmed, Abu Syed Golam Faruque, Mustafizur Rahman, George J. Fuchs Iii, Abdullah Al Mamun, Peter John Baker Sep 2017

Long-Term Impact Of Changing Childhood Malnutrition On Rotavirus Diarrhoea: Two Decades Of Adjusted Association With Climate And Socio-Demographic Factors From Urban Bangladesh, Sumon Kumar Das, Mohammod Jobayer Chisti, Mohammad Habibur Rahman Sarker, Jui Das, Shawnawaz Ahmed, K. M. Shahunja, Shamsun Nahar, Nora Gibbons, Tahmeed Ahmed, Abu Syed Golam Faruque, Mustafizur Rahman, George J. Fuchs Iii, Abdullah Al Mamun, Peter John Baker

Pediatrics Faculty Publications

Background

There is strong association between childhood rotavirus, diarrhoea, climate factors and malnutrition. Conversely, a significant nutritional transition (reduced under-nutrition) with a concurrent increasing trend of rotavirus infection in last decade was also observed among under 5 children, especially in developing countries including Bangladesh. Considering the pathophysiology of rotavirus, there might be an interaction of this nutrition transition which plays a pivotal role in increasing rotavirus infection in addition to climate and other man-made factors in urban areas such as Dhaka, Bangladesh.

Methods

Relevant monthly data from 1993–2012 were extracted from the archive of the Diarrhoeal Disease Surveillance System of …


Serum D-Dimer Test Is Promising For The Diagnosis Of Periprosthetic Joint Infection And Timing Of Reimplantation., Alisina Shahi, Michael M. Kheir, Majd Tarabichi, Hamid R.S. Hosseinzadeh, Timothy L. Tan, Javad Parvizi Sep 2017

Serum D-Dimer Test Is Promising For The Diagnosis Of Periprosthetic Joint Infection And Timing Of Reimplantation., Alisina Shahi, Michael M. Kheir, Majd Tarabichi, Hamid R.S. Hosseinzadeh, Timothy L. Tan, Javad Parvizi

Rothman Institute Papers

BACKGROUND: Despite the availability of a battery of tests, the diagnosis of periprosthetic joint infection (PJI) continues to be challenging. Serum D-dimer assessment is a widely available test that detects fibrinolytic activities that occur during infection. We hypothesized that patients with PJI may have a high level of circulating D-dimer and that the presence of a high level of serum D-dimer may be a sign of persistent infection in patients awaiting reimplantation.

METHODS: This prospective study was initiated to enroll patients undergoing primary and revision arthroplasty. Our cohort consisted of 245 patients undergoing primary arthroplasty (n = 23), revision for …


Emerging Therapies For Stage Iii Non-Small Cell Lung Cancer: Stereotactic Body Radiation Therapy And Immunotherapy, Sameera S. Kumar, Kristin A. Higgins, Ronald C. Mcgarry Sep 2017

Emerging Therapies For Stage Iii Non-Small Cell Lung Cancer: Stereotactic Body Radiation Therapy And Immunotherapy, Sameera S. Kumar, Kristin A. Higgins, Ronald C. Mcgarry

Radiation Medicine Faculty Publications

The current standard of care for locally advanced non-small cell lung cancer (NSCLC) includes radiation, chemotherapy, and surgery in certain individualized cases. In unresectable NSCLC, chemoradiation has been the standard of care for the past three decades. Local and distant failure remains high in this group of patients, so dose escalation has been studied in both single institution and national clinical trials. Though initial studies showed a benefit to dose escalation, phase III studies examining dose escalation using standard fractionation or hyperfractionation have failed to show a benefit. Over the last 17 years, stereotactic body radiation therapy (SBRT) has shown …


Cortical Activation During Action Observation, Action Execution, And Interpersonal Synchrony In Adults: A Functional Near-Infrared Spectroscopy (Fnirs) Study, Anjana Bhat, Michael Hoffman, Susanna Trost, Mckenzie Culotta, Jeffrey Eilbott, Daisuke Tsuzuki, Kevin A. Pelphrey Sep 2017

Cortical Activation During Action Observation, Action Execution, And Interpersonal Synchrony In Adults: A Functional Near-Infrared Spectroscopy (Fnirs) Study, Anjana Bhat, Michael Hoffman, Susanna Trost, Mckenzie Culotta, Jeffrey Eilbott, Daisuke Tsuzuki, Kevin A. Pelphrey

Psychiatry and Behavioral Sciences Faculty Publications

Introduction: Humans engage in Interpersonal Synchrony (IPS) as they synchronize their own actions with that of a social partner over time. When humans engage in imitation/IPS behaviors, multiple regions in the frontal, temporal, and parietal cortices are activated including the putative Mirror Neuron Systems (Iacoboni, 2005; Buxbaum et al., 2014). In the present study, we compared fNIRS-based cortical activation patterns across three conditions of action observation (“Watch” partner), action execution (“Do” on your own), and IPS (move “Together”).

Methods: Fifteen typically developing adults completed a reach and cleanup task with the right arm while cortical activation was …