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The Utility Of Surgical Simulation In Student Education, Jared Raikin Feb 2020

The Utility Of Surgical Simulation In Student Education, Jared Raikin

Gibbon Surgical Review

The use of simulation in the field of surgery has become a heavily researched topic over the last few decades, but it is by no means a new concept. The first recorded use of surgical simulation dates back 2,500 years with evidence of nasal models for flap reconstruction made of leaf and clay.1 But simulation as we know it today did not take shape until the 1980s with the invention of the Comprehensive Anesthesia Simulation Environment (CASE) mannequins. The use of nonorganic simulation tools revolutionized the field and continues to play a large role in medical education. These modalities have …


Proton Pump Inhibitor Use Affects Pseudarthrosis Rates And Influences Patient-Reported Outcomes., John J. Mangan, Srikanth N. Divi, James Mckenzie, Justin D. Stull, William Conaway, David S. Casper, Dhruv K.C. Goyal, Kristen J. Nicholson, Matthew S. Galetta, Scott C. Wagner, I. David Kaye, Mark Kurd, Barrett I. Woods, Kristen E. Radcliff, Jeffrey A. Rihn, D. Greg Anderson, Alan S. Hilibrand, Alex R. Vaccaro, Gregory D. Schroeder, Christopher K. Kepler Feb 2020

Proton Pump Inhibitor Use Affects Pseudarthrosis Rates And Influences Patient-Reported Outcomes., John J. Mangan, Srikanth N. Divi, James Mckenzie, Justin D. Stull, William Conaway, David S. Casper, Dhruv K.C. Goyal, Kristen J. Nicholson, Matthew S. Galetta, Scott C. Wagner, I. David Kaye, Mark Kurd, Barrett I. Woods, Kristen E. Radcliff, Jeffrey A. Rihn, D. Greg Anderson, Alan S. Hilibrand, Alex R. Vaccaro, Gregory D. Schroeder, Christopher K. Kepler

Department of Orthopaedic Surgery Faculty Papers

Study Design: Retrospective cohort review.

Objectives: Cervical pseudarthrosis is a frequent cause of need for revision anterior cervical discectomy and fusion (ACDF) and may lead to worse patient-reported outcomes. The effect of proton pump inhibitors on cervical fusion rates are unknown. The purpose of this study was to determine if patients taking PPIs have higher rates of nonunion after ACDF.

Methods: A retrospective cohort review was performed to compare patients who were taking PPIs preoperatively with those not taking PPIs prior to ACDF. Patients younger than 18 years of age, those with less than 1-year follow-up, and those undergoing surgery …


The Identification Of Xylazine In A Patient Who Presented For Heroin Withdrawal, Colin Appleford, Michael J. Smith Feb 2020

The Identification Of Xylazine In A Patient Who Presented For Heroin Withdrawal, Colin Appleford, Michael J. Smith

Conference Presentation Abstracts

Learning Overview: The goal of this presentation is to present a recent case of a patient whose toxicology studies revealed the presence of xylazine and to inform the audience about xylazine as a drug adulterant and drug of abuse. Impact on the Forensic Science Community: This presentation will impact the forensic science community by raising awareness about a less well-known veterinary medicine and providing information about how to detect the drug in human samples. Introduction: It is important not to overlook veterinary medications as possible drugs of abuse. Having an awareness of these medications is crucial for physicians, forensic pathologists, …


Losartan Rescues Inflammation-Related Mucociliary Dysfunction In Relevant Models Of Cystic Fibrosis, Michael D Kim, Nathalie Baumlin, Makoto Yoshida, Deepika Polineni, Sebastian F Salathe, Joseph K David, Charles A Peloquin, Adam Wanner, John S Dennis, Juliette Sailland, Philip Whitney, Frank T Horrigan, Juan R Sabater, William M Abraham, Matthias Salathe Feb 2020

Losartan Rescues Inflammation-Related Mucociliary Dysfunction In Relevant Models Of Cystic Fibrosis, Michael D Kim, Nathalie Baumlin, Makoto Yoshida, Deepika Polineni, Sebastian F Salathe, Joseph K David, Charles A Peloquin, Adam Wanner, John S Dennis, Juliette Sailland, Philip Whitney, Frank T Horrigan, Juan R Sabater, William M Abraham, Matthias Salathe

Faculty, Staff and Students Publications

Rationale: Despite therapeutic progress in treating cystic fibrosis (CF) airway disease, airway inflammation with associated mucociliary dysfunction remains largely unaddressed. Inflammation reduces the activity of apically expressed large-conductance Ca2+-activated and voltage-dependent K+ (BK) channels, critical for mucociliary function in the absence of CFTR (CF transmembrane conductance regulator).

Objectives: To test losartan as an antiinflammatory therapy in CF using CF human bronchial epithelial cells and an ovine model of CF-like airway disease.

Methods: Losartan’s antiinflammatory effectiveness to rescue BK activity and thus mucociliary function was tested in vitro using primary, fully redifferentiated human airway epithelial cells homozygous for …


Impaired Meningeal Lymphatic Vessel Development Worsens Stroke Outcome, Pavel Yanev, Katherine Poinsatte, Devon Hominick, Noor Khurana, Kielen R. Zuurbier, Marcus Berndt, Erik J. Plautz, Michael T. Dellinger, Ann M. Stowe Feb 2020

Impaired Meningeal Lymphatic Vessel Development Worsens Stroke Outcome, Pavel Yanev, Katherine Poinsatte, Devon Hominick, Noor Khurana, Kielen R. Zuurbier, Marcus Berndt, Erik J. Plautz, Michael T. Dellinger, Ann M. Stowe

Neurology Faculty Publications

The discovery of meningeal lymphatic vessels (LVs) has sparked interest in identifying their role in diseases of the central nervous system. Similar to peripheral LVs, meningeal LVs depend on vascular endothelial growth factor receptor-3 (VEGFR3) signaling for development. Here we characterize the effect of stroke on meningeal LVs, and the impact of meningeal lymphatic hypoplasia on post-stroke outcomes. We show that photothrombosis (PT), but not transient middle cerebral artery occlusion (tMCAo), induces meningeal lymphangiogenesis in young male C57Bl/J6 mice. We also show that Vegfr3wt/mut mice develop significantly fewer meningeal LVs than Vegfr3wt/wt mice. Again, meningeal lymphangiogenesis occurs in …


Conventional And Contemporary Approaches Of Splinting Traumatized Teeth: A Review Article, Shizrah Jamal, Momina Motiwala, Rabia Ghafoor Feb 2020

Conventional And Contemporary Approaches Of Splinting Traumatized Teeth: A Review Article, Shizrah Jamal, Momina Motiwala, Rabia Ghafoor

Section of Dental-Oral Maxillofacial Surgery

Trauma moves a tooth from its original position which needs to be repositioned for optimum healing and better outcomes. To stabilize the traumatically displaced teeth, splinting is specified as the gold standard. In this article we have discussed about various old and modern techniques based on the type of material to splint teeth with dentoalveolar trauma. As per recommendation of IADT, providing flexible splint is beneficial for good healing. A biologically favourable splint should not just be user friendly but also should be convenient in terms of removal. Every technique has its merits and demerits. Iatrogenic trauma to the teeth …


Ablation Of Refractory Papillary Muscle Ventricular Tachycardia Warranting Multiple Adjunctive Ablation Techniques: A Combined Approach For Success, Mark Pollet, Ben Jenny, Adwait Mehta, Austin Howard, Nilesh Mathuria Feb 2020

Ablation Of Refractory Papillary Muscle Ventricular Tachycardia Warranting Multiple Adjunctive Ablation Techniques: A Combined Approach For Success, Mark Pollet, Ben Jenny, Adwait Mehta, Austin Howard, Nilesh Mathuria

Faculty, Staff and Student Publications

A 27-year-old male presented to our institution with recurrent unifocal premature ventricular contraction/nonsustained ventricular tachycardia (VT) with associated cardiomyopathy. The patient had undergone three prior ablation procedures with continued arrhythmia. Mapping led to identification of the VT arising from the basal aspect of the left ventricular anterolateral papillary muscle. Conventional ablation techniques were unsuccessful. We incorporated adjunctive ablation techniques in this case that ultimately led to a successful outcome. The present discussion covers the roles of intracardiac echocardiography, induced apnea, and low-ionic irrigation.


Assessing Lymphatic Route Of Csf Outflow And Peripheral Lymphatic Contractile Activity During Head-Down Tilt Using Near-Infrared Fluorescence Imaging, John C Rasmussen, Sunkuk Kwon, Amanda Pinal, Alexander Bareis, Fred C Velasquez, Christopher F Janssen, John R Morrow, Caroline E Fife, Ron J Karni, Eva M Sevick-Muraca Feb 2020

Assessing Lymphatic Route Of Csf Outflow And Peripheral Lymphatic Contractile Activity During Head-Down Tilt Using Near-Infrared Fluorescence Imaging, John C Rasmussen, Sunkuk Kwon, Amanda Pinal, Alexander Bareis, Fred C Velasquez, Christopher F Janssen, John R Morrow, Caroline E Fife, Ron J Karni, Eva M Sevick-Muraca

Faculty, Staff and Student Publications

Evidence overwhelmingly suggests that the lymphatics play a critical role in the clearance of cerebrospinal fluid (CSF) from the cranial space. Impairment of CSF outflow into the lymphatics is associated with a number of pathological conditions including spaceflight-associated neuro-ocular syndrome (SANS), a problem that limits long-duration spaceflight. We used near-infrared fluorescence lymphatic imaging (NIRFLI) to dynamically visualize the deep lymphatic drainage pathways shared by CSF outflow and disrupted during head-down tilt (HDT), a method used to mimic the cephalad fluid shift that occurs in microgravity. After validating CSF clearance into the lymph nodes of the neck in swine, a pilot …


Toward Actionable Practice Parameters For "Dual Diagnosis": Principles Of Assessment And Management For Co-Occurring Psychiatric And Intellectual/Developmental Disability., John N. Constantino, Shae Strom, Michael Bunis, Cy Nadler, Teresa Rodgers, Julia Lepage, Connie Cahalan, Amber Stockreef, Lucas Evans, Rachel Jones, Alyssa Wilson Feb 2020

Toward Actionable Practice Parameters For "Dual Diagnosis": Principles Of Assessment And Management For Co-Occurring Psychiatric And Intellectual/Developmental Disability., John N. Constantino, Shae Strom, Michael Bunis, Cy Nadler, Teresa Rodgers, Julia Lepage, Connie Cahalan, Amber Stockreef, Lucas Evans, Rachel Jones, Alyssa Wilson

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE OF REVIEW: Although treatment algorithms and parameters for best practice are readily available for all major syndromes of psychiatric impairment, the occurrence of psychiatric syndromes in individuals with intellectual and developmental disability (IDD) invokes serious contextual challenges for interpretation of symptoms, diagnosis, and optimization of treatment, both for clinicians and for the service sectors in which care and support of individuals with IDD are delivered. Recognizing that there exist very few definitive resources for best practice under the circumstance of this form of "dual diagnosis," the Missouri Department of Mental Health convened an expert panel to conduct a focused …


Changing Face Of Trauma And Surgical Training In A Developing Country: A Literature Review, Qamar Riaz, Sabah Uddin Saqib, Rehan Nasir Khan, Nadeem Ahmed Siddiqui Feb 2020

Changing Face Of Trauma And Surgical Training In A Developing Country: A Literature Review, Qamar Riaz, Sabah Uddin Saqib, Rehan Nasir Khan, Nadeem Ahmed Siddiqui

Department of Surgery Docs

Trauma continues to be the major cause of disability and death globally and surgeons are often involved in immediate care. However there has been an exponential decrease in the number of the trained trauma surgeons. The purpose of the current review article is to summarize the published literature pertaining to trauma education in postgraduate surgical training programmes internationally and in a developing country as Pakistan. Several electronic databases like MEDLINE, PubMed, Google scholar and PakMediNet were searched using the keywords 'trauma education' or 'trauma training' AND 'postgraduate medical education', 'surgery residency training', 'surgery residents' and 'surgeons'. The current training in …


A Review Of Teen And Adolescent Attitudes Regarding E-Cigarettes And Their Relevance To Education, Maury Grebenau Jan 2020

A Review Of Teen And Adolescent Attitudes Regarding E-Cigarettes And Their Relevance To Education, Maury Grebenau

Journal of Adolescent and Family Health

Over the last ten years, while teenage use of cigarettes has diminished, their use of electronic nicotine delivery systems (e-cigarettes) has increased. Adolescent e-cigarette use includes risks and challenges which are unique and different from adolescent use of traditional cigarettes. Many of the risks of e-cigarettes are not well known or well understood, especially by the teen population. A robust understanding of what entices adolescents and teens to use e-cigarettes is critical for schools in crafting an effective response. This paper reviews the literature on teen and adolescent perspectives on e-cigarettes and provides suggestions for using this information to guide …


Solving The Sepsis Puzzle: Every Minute Counts, Jamie Roney, Amber Cline Jan 2020

Solving The Sepsis Puzzle: Every Minute Counts, Jamie Roney, Amber Cline

Articles, Abstracts, and Reports

SPEMS Pre-Conference Course Sepsis Class


Evaluation Of The Effect Of Gm-Csf Blocking On The Phenotype And Function Of Human Monocytes, Noushin Lotfi, Guang-Xian Zhang, Nafiseh Esmaeil, Mohamad Rostami Jan 2020

Evaluation Of The Effect Of Gm-Csf Blocking On The Phenotype And Function Of Human Monocytes, Noushin Lotfi, Guang-Xian Zhang, Nafiseh Esmaeil, Mohamad Rostami

Department of Neurology Faculty Papers

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a multipotent cytokine that prompts the proliferation of bone marrow-derived macrophages and granulocytes. In addition to its effects as a growth factor, GM-CSF plays an important role in chronic inflammatory autoimmune diseases such as multiple sclerosis and rheumatoid arthritis. Reports have identified monocytes as the primary target of GM-CSF; however, its effect on monocyte activation has been under-estimated. Here, using flow cytometry and ELISA we show that GM-CSF induces an inflammatory profile in human monocytes, which includes an upregulated expression of HLA-DR and CD86 molecules and increased production of TNF-α and IL-1β. Conversely, blockage of …


Evaluation Of The Effect Of Gm-Csf Blocking On The Phenotype And Function Of Human Monocytes., Noushin Lotfi, Guang-Xian Zhang, Nafiseh Esmaeil, Mohamad Rostami Jan 2020

Evaluation Of The Effect Of Gm-Csf Blocking On The Phenotype And Function Of Human Monocytes., Noushin Lotfi, Guang-Xian Zhang, Nafiseh Esmaeil, Mohamad Rostami

Department of Neurology Faculty Papers

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a multipotent cytokine that prompts the proliferation of bone marrow-derived macrophages and granulocytes. In addition to its effects as a growth factor, GM-CSF plays an important role in chronic inflammatory autoimmune diseases such as multiple sclerosis and rheumatoid arthritis. Reports have identified monocytes as the primary target of GM-CSF; however, its effect on monocyte activation has been under-estimated. Here, using flow cytometry and ELISA we show that GM-CSF induces an inflammatory profile in human monocytes, which includes an upregulated expression of HLA-DR and CD86 molecules and increased production of TNF-α and IL-1β. Conversely, blockage of …


Potential Use Of Biotherapeutic Bacteria To Target Colorectal Cancer-Associated Taxa, Gareth Lawrence, Maire Begley, Paul D. Cotter, Caitríona M. Guinane Jan 2020

Potential Use Of Biotherapeutic Bacteria To Target Colorectal Cancer-Associated Taxa, Gareth Lawrence, Maire Begley, Paul D. Cotter, Caitríona M. Guinane

Department of Biological Sciences Publications

The role of the gut microbiome in human health and disease is the focus of much attention. It has been widely agreed upon that our gut bacteria play a role in host immunity, nutrient absorption, digestion, metabolism, and other key drivers of health. Furthermore, certain microbial signatures and specific taxa have also been associated with the development of diseases, such as obesity; inflammatory bowel disease; and, indeed, colorectal cancer (CRC), which is the focus of this review. By extension, such taxa represent potential therapeutic targets. In particular, the emerging human pathogen Fusobacterium nucleatum represents an important agent in CRC development …


Short-Chain Fatty Acids Improve Poststroke Recovery Via Immunological Mechanisms, Rebecca Sadler, Julia V. Cramer, Steffanie Heindl, Sarantos Kostidis, Dene Betz, Kielen R. Zuurbier, Bernd H. Northoff, Marieke Heijink, Mark P. Goldberg, Erik J. Plautz, Stefan Roth, Rainer Malik, Martin Dichgans, Lesca M. Holdt, Corinne Benakis, Martin Giera, Ann M. Stowe, Arthur Liesz Jan 2020

Short-Chain Fatty Acids Improve Poststroke Recovery Via Immunological Mechanisms, Rebecca Sadler, Julia V. Cramer, Steffanie Heindl, Sarantos Kostidis, Dene Betz, Kielen R. Zuurbier, Bernd H. Northoff, Marieke Heijink, Mark P. Goldberg, Erik J. Plautz, Stefan Roth, Rainer Malik, Martin Dichgans, Lesca M. Holdt, Corinne Benakis, Martin Giera, Ann M. Stowe, Arthur Liesz

Neurology Faculty Publications

Recovery after stroke is a multicellular process encompassing neurons, resident immune cells, and brain-invading cells. Stroke alters the gut microbiome, which in turn has considerable impact on stroke outcome. However, the mechanisms underlying gut–brain interaction and implications for long-term recovery are largely elusive. Here, we tested the hypothesis that short-chain fatty acids (SCFAs), key bioactive microbial metabolites, are the missing link along the gut–brain axis and might be able to modulate recovery after experimental stroke. SCFA supplementation in the drinking water of male mice significantly improved recovery of affected limb motor function. Using in vivo wide-field calcium imaging, we observed …


Metabolic Dysregulation In The Atp7b-/- Wilson's Disease Mouse Model, Clavia Ruth Wooton-Kee, Matthew Robertson, Ying Zhou, Bingning Dong, Zhen Sun, Kang Ho Kim, Hailan Liu, Yong Xu, Nagireddy Putluri, Pradip Saha, Cristian Coarfa, David D Moore, Alli M Nuotio-Antar Jan 2020

Metabolic Dysregulation In The Atp7b-/- Wilson's Disease Mouse Model, Clavia Ruth Wooton-Kee, Matthew Robertson, Ying Zhou, Bingning Dong, Zhen Sun, Kang Ho Kim, Hailan Liu, Yong Xu, Nagireddy Putluri, Pradip Saha, Cristian Coarfa, David D Moore, Alli M Nuotio-Antar

Faculty, Staff and Students Publications

Inactivating mutations in the copper transporter Atp7b result in Wilson’s disease. The Atp7b−/− mouse develops hallmarks of Wilson’s disease. The activity of several nuclear receptors decreased in Atp7b−/− mice, and nuclear receptors are critical for maintaining metabolic homeostasis. Therefore, we anticipated that Atp7b−/− mice would exhibit altered progression of diet-induced obesity, fatty liver, and insulin resistance. Following 10 wk on a chow or Western-type diet (40% kcal fat), parameters of glucose and lipid homeostasis were measured. Hepatic metabolites were measured by liquid chromatography–mass spectrometry and correlated with transcriptomic data. Atp7b−/− mice fed a chow diet presented …


Cryptococcal Antigen Testing In An Integrated Medical System: Eastern Wisconsin, Marianne Klumph, Brian Hoeynck, Dennis J. Baumgardner Jan 2020

Cryptococcal Antigen Testing In An Integrated Medical System: Eastern Wisconsin, Marianne Klumph, Brian Hoeynck, Dennis J. Baumgardner

Journal of Patient-Centered Research and Reviews

Cryptococcosis is a serious environmentally acquired endemic fungal infection commonly associated with immunocompromised hosts. Little is known regarding frequency or distribution in Wisconsin. We explored the geodemographic and clinical features of patients tested with cryptococcal antigen tests (CrAg) — previously shown to be >90% sensitive and >90% specific — within a large health care system located in eastern Wisconsin. To examine this, we retrospectively analyzed 1465 CrAg tests on 1211 unique patients (female: 50.2%; white race: 73.9%; mean age: 53.7 ± 16.5 years). At least one CrAg result was positive in 23 of 1211 patients (1.9%). From these, 21 of …


Implications Of C1q/Tnf-Related Protein Superfamily In Patients With Coronary Artery Disease., Yanwei Zhang, Caihong Liu, Jing Liu, Rui Guo, Zheyi Yan, Wenxia Liu, Wayne Bond Lau, Xiangying Jiao, Jimin Cao, Kun Xu, Yongping Jia, Xin-Liang Ma, Yajing Wang Jan 2020

Implications Of C1q/Tnf-Related Protein Superfamily In Patients With Coronary Artery Disease., Yanwei Zhang, Caihong Liu, Jing Liu, Rui Guo, Zheyi Yan, Wenxia Liu, Wayne Bond Lau, Xiangying Jiao, Jimin Cao, Kun Xu, Yongping Jia, Xin-Liang Ma, Yajing Wang

Department of Emergency Medicine Faculty Papers

The C1q complement/TNF-related protein superfamily (CTRPs) displays differential effects on the regulation of metabolic homeostasis, governing cardiovascular function. However, whether and how they may serve as predictor/pro-diagnosis factors for assessing the risks of coronary artery disease (CAD) remains controversial. Therefore, we performed a clinical study to elaborate on the implication of CTRPs (CTRP1, CTRP5, CTRP7, and CTRP15) in CAD. CTRP1 were significantly increased, whereas CTRP7 and CTRP15 levels were decreased in CAD patients compared to the non-CAD group. Significant differences in CTRP1 levels were discovered between the single- and triple-vascular-vessel lesion groups. ROC analysis revealed that CTRP7 and CTRP15 may …


Rhoa-Rock Signaling As A Therapeutic Target In Traumatic Brain Injury, Shalaka Mulherkar, Kimberley F Tolias Jan 2020

Rhoa-Rock Signaling As A Therapeutic Target In Traumatic Brain Injury, Shalaka Mulherkar, Kimberley F Tolias

Faculty, Staff and Students Publications

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. TBIs, which range in severity from mild to severe, occur when a traumatic event, such as a fall, a traffic accident, or a blow, causes the brain to move rapidly within the skull, resulting in damage. Long-term consequences of TBI can include motor and cognitive deficits and emotional disturbances that result in a reduced quality of life and work productivity. Recovery from TBI can be challenging due to a lack of effective treatment options for repairing TBI-induced neural damage and alleviating functional impairments. Central nervous system (CNS) …


Utility Of Ultrasound And Mammography In Detection Of Negative Axillary Nodal Metastasis In Breast Cancer, Anam Khan, Imrana Masroor, Kumail Khandwala, Summar Un-Nisa Abbasi, Muhammad Usman Tariq Jan 2020

Utility Of Ultrasound And Mammography In Detection Of Negative Axillary Nodal Metastasis In Breast Cancer, Anam Khan, Imrana Masroor, Kumail Khandwala, Summar Un-Nisa Abbasi, Muhammad Usman Tariq

Department of Radiology

Objective: The status of axillary lymph nodes is one of the most important prognostic factors in patients with breast cancer. A precise noninvasive evaluation of axillary lymph node status preoperatively, although challenging, is vital for optimization of the treatment plan for patients. The objective of our study was to assess the utility of ultrasound and mammography in detecting the absence of axillary lymph nodal metastasis in patients of breast cancer, taking histopathology as gold standard.
Methods: A cross-sectional study was conducted in the Department of Radiology, Aga Khan University Hospital, Karachi. All female patients between 20 and 95 years of …


Biogeographic Study Of Human Gut-Associated Crassphage Suggests Impacts From Industrialization And Recent Expansion, Tanvi P/ Honap, Krithivasan Sankaranarayanan, Stephanie L. Schnorr, Andrew T. Ozga, Christina Warinner, Cecil M. Lewis Jr. Jan 2020

Biogeographic Study Of Human Gut-Associated Crassphage Suggests Impacts From Industrialization And Recent Expansion, Tanvi P/ Honap, Krithivasan Sankaranarayanan, Stephanie L. Schnorr, Andrew T. Ozga, Christina Warinner, Cecil M. Lewis Jr.

Anthropology Faculty Research

CrAssphage (cross-assembly phage) is a bacteriophage that was first discovered in human gut metagenomic data. CrAssphage belongs to a diverse family of crAss-like bacteriophages thought to infect gut commensal bacteria belonging to Bacteroides species. However, not much is known about the biogeography of crAssphage and whether certain strains are associated with specific human populations. In this study, we screened publicly available human gut metagenomic data from 3,341 samples for the presence of crAssphage sensu stricto (NC_024711.1). We found that crAssphage prevalence is low in traditional, hunter-gatherer populations, such as the Hadza from Tanzania and Matses from Peru, as compared to …


Foxd3 Regulates Vista Expression In Melanoma., Sheera R. Rosenbaum, Meghan Knecht, Mehri Mollaee, Zhijiu Zhong, Dan A. Erkes, Peter A. Mccue, Chervoneva, Adam C. Berger, Jennifer A. Lo, David E. Fisher, Jeffrey E. Gershenwald, Michael A. Davies, Timothy J. Purwin, Andrew E. Aplin Jan 2020

Foxd3 Regulates Vista Expression In Melanoma., Sheera R. Rosenbaum, Meghan Knecht, Mehri Mollaee, Zhijiu Zhong, Dan A. Erkes, Peter A. Mccue, Chervoneva, Adam C. Berger, Jennifer A. Lo, David E. Fisher, Jeffrey E. Gershenwald, Michael A. Davies, Timothy J. Purwin, Andrew E. Aplin

Department of Cancer Biology Faculty Papers

Immune checkpoint inhibitors have improved patient survival in melanoma, but the innate resistance of many patients necessitates the investigation of alternative immune targets. Many immune checkpoint proteins lack proper characterization, including V-domain Ig suppressor of T cell activation (VISTA). VISTA expression on immune cells can suppress T cell activity; however, few studies have investigated its expression and regulation in cancer cells. In this study, we observe that VISTA is expressed in melanoma patient samples and cell lines. Tumor cell-specific expression of VISTA promotes tumor onset in vivo, associated with increased intratumoral T regulatory cells, and enhanced PDL-1 expression on tumor-infiltrating …


Spotlight On Icosapent Ethyl For Cardiovascular Risk Reduction: Evidence To Date, Xiaoming Jia, Stephanie Koh, Mahmoud Al Rifai, Roger S. Blumenthal, Salim S. Virani Jan 2020

Spotlight On Icosapent Ethyl For Cardiovascular Risk Reduction: Evidence To Date, Xiaoming Jia, Stephanie Koh, Mahmoud Al Rifai, Roger S. Blumenthal, Salim S. Virani

Office of the Provost

Icosapent ethyl is a highly purified formulation of eicosapentaenoic acid, a type of omega-3 fatty acid contained in fish oil. While omega-3 fatty acids have long been thought to have cardioprotective benefits, the Reduction of Cardiovascular Events with EPA-Intervention Trial (REDUCE-IT) has helped to establish icosapent ethyl as an evidence-based therapy for risk reduction of atherosclerotic cardiovascular disease (ASCVD). REDUCE-IT, however, was by no means an overnight success story. Close examination of the evidence shows that the trial was a culmination of many lessons learned from previous studies. The purpose of this manuscript is to review contemporary evidence of icosapent …


Sevoflurane Pre-Conditioning Ameliorates Diabetic Myocardial Ischemia/Reperfusion Injury Via Differential Regulation Of P38 And Erk., Dina Xie, Jianli Zhao, Rui Guo, Liyuan Jiao, Yanqing Zhang, Wayne Bond Lau, Bernard Lopez, Theodore Christopher, Erhe Gao, Jimin Cao, Xin-Liang Ma, Yajing Wang Jan 2020

Sevoflurane Pre-Conditioning Ameliorates Diabetic Myocardial Ischemia/Reperfusion Injury Via Differential Regulation Of P38 And Erk., Dina Xie, Jianli Zhao, Rui Guo, Liyuan Jiao, Yanqing Zhang, Wayne Bond Lau, Bernard Lopez, Theodore Christopher, Erhe Gao, Jimin Cao, Xin-Liang Ma, Yajing Wang

Department of Emergency Medicine Faculty Papers

Diabetes mellitus (DM) significantly increases myocardial ischemia/reperfusion (MI/R) injury. During DM, cardioprotection induced by conventional pre-conditioning (PreCon) is decreased due to impaired AMP-activated protein kinase (AMPK) signaling. The current study investigated whether PreCon with inhaled anesthetic sevoflurane (SF-PreCon) remains cardioprotective during DM, and identified the involved mechanisms. Normal diet (ND) and high-fat diet (HFD)-induced DM mice were randomized into control and SF-PreCon (3 cycles of 15-minute period exposures to 2% sevoflurane) groups before MI/R. SF-PreCon markedly reduced MI/R injury in DM mice, as evidenced by improved cardiac function (increased LVEF and ±Dp/dt), decreased infarct size, and decreased apoptosis. To determine …


A New Regulatory Mechanism Of Protein Phosphatase 2a Activity Via Set In Acute Myeloid Leukemia., Elena Arriazu, Carmen Vicente, Raffaella Pippa, Irene Peris, Elena Martínez-Balsalobre, Patricia García-Ramírez, Nerea Marcotegui, Ana Igea, Diego Alignani, José Rifón, María C. Mateos, María L. Cayuela, Angel R. Nebreda, María D. Odero Jan 2020

A New Regulatory Mechanism Of Protein Phosphatase 2a Activity Via Set In Acute Myeloid Leukemia., Elena Arriazu, Carmen Vicente, Raffaella Pippa, Irene Peris, Elena Martínez-Balsalobre, Patricia García-Ramírez, Nerea Marcotegui, Ana Igea, Diego Alignani, José Rifón, María C. Mateos, María L. Cayuela, Angel R. Nebreda, María D. Odero

Department of Medical Oncology Faculty Papers

Acute myeloid leukemia (AML) is an aggressive hematologic malignancy. Although novel emerging drugs are available, the overall prognosis remains poor and new therapeutic approaches are required. PP2A phosphatase is a key regulator of cell homeostasis and is recurrently inactivated in AML. The anticancer activity of several PP2A-activating drugs (e.g., FTY720) depends on their interaction with the SET oncoprotein, an endogenous PP2A inhibitor that is overexpressed in 30% of AML cases. Elucidation of SET regulatory mechanisms may therefore provide novel targeted therapies for SET-overexpressing AMLs. Here, we show that upregulation of protein kinase p38β is a common event in AML. We …


Immune-Mediated Genetic Pathways Resulting In Pulmonary Function Impairment Increase Lung Cancer Susceptibility, Linda Kachuri, Mattias Johansson, Sara R. Rashkin, Rebecca E. Graff, Yohan Bossé, Venkata Manem, Neil E. Caporaso, Maria Teresa Landi, David C. Christiani, Paolo Vineis, Geoffrey Liu, Ghislaine Scelo, David Zaridze, Sanjay S Shete, Demetrius Albanes, Melinda C. Aldrich, Adonina Tardón, Gad Rennert, Chu Chen, Gary E. Goodman, Jennifer A. Doherty, Heike Bickeböller, John K. Field, Michael P Davies, M. Dawn Teare, Lambertus A. Kiemeney, Stig E. Bojesen, Aage Haugen, Shanbeh Zienolddiny, Stephen Lam, Loïc Le Marchand, Iona Cheng, Matthew B. Schabath, Eric J. Duell, Angeline S. Andrew, Jonas Manjer, Philip Lazarus, Susanne M. Arnold, James D. Mckay, Nima C. Emami, Matthew T. Warkentin, Yonathan Brhane, Ma'en Obeidat, Richard M. Martin, Caroline Relton, George Davey Smith, Philip C. Haycock, Christopher I. Amos, Paul Brennan, John S. Witte, Rayjean J. Hung Jan 2020

Immune-Mediated Genetic Pathways Resulting In Pulmonary Function Impairment Increase Lung Cancer Susceptibility, Linda Kachuri, Mattias Johansson, Sara R. Rashkin, Rebecca E. Graff, Yohan Bossé, Venkata Manem, Neil E. Caporaso, Maria Teresa Landi, David C. Christiani, Paolo Vineis, Geoffrey Liu, Ghislaine Scelo, David Zaridze, Sanjay S Shete, Demetrius Albanes, Melinda C. Aldrich, Adonina Tardón, Gad Rennert, Chu Chen, Gary E. Goodman, Jennifer A. Doherty, Heike Bickeböller, John K. Field, Michael P Davies, M. Dawn Teare, Lambertus A. Kiemeney, Stig E. Bojesen, Aage Haugen, Shanbeh Zienolddiny, Stephen Lam, Loïc Le Marchand, Iona Cheng, Matthew B. Schabath, Eric J. Duell, Angeline S. Andrew, Jonas Manjer, Philip Lazarus, Susanne M. Arnold, James D. Mckay, Nima C. Emami, Matthew T. Warkentin, Yonathan Brhane, Ma'en Obeidat, Richard M. Martin, Caroline Relton, George Davey Smith, Philip C. Haycock, Christopher I. Amos, Paul Brennan, John S. Witte, Rayjean J. Hung

Markey Cancer Center Faculty Publications

Impaired lung function is often caused by cigarette smoking, making it challenging to disentangle its role in lung cancer susceptibility. Investigation of the shared genetic basis of these phenotypes in the UK Biobank and International Lung Cancer Consortium (29,266 cases, 56,450 controls) shows that lung cancer is genetically correlated with reduced forced expiratory volume in one second (FEV1: rg = 0.098, p = 2.3 × 10-8) and the ratio of FEV1 to forced vital capacity (FEV1/FVC: rg = 0.137, p = 2.0 × 10-12). Mendelian randomization analyses demonstrate that …


Musical Expertise Generalizes To Superior Temporal Scaling In A Morse Code Tapping Task, Matthew A. Slayton, Juan L. Romero-Sosa, Katrina Shore, Dean V. Buonomano, Indre Viskontas Jan 2020

Musical Expertise Generalizes To Superior Temporal Scaling In A Morse Code Tapping Task, Matthew A. Slayton, Juan L. Romero-Sosa, Katrina Shore, Dean V. Buonomano, Indre Viskontas

Psychology

A key feature of the brain’s ability to tell time and generate complex temporal patterns is its capacity to produce similar temporal patterns at different speeds. For example, humans can tie a shoe, type, or play an instrument at different speeds or tempi—a phenomenon referred to as temporal scaling. While it is well established that training improves timing precision and accuracy, it is not known whether expertise improves temporal scaling, and if so, whether it generalizes across skill domains. We quantified temporal scaling and timing precision in musicians and non-musicians as they learned to tap a Morse code sequence. We …


Preoperative Maximization To Reduce Complications In Spinal Surgery, Sukanta Maitra, Christopher Mikhail, Samuel K. Cho, Michael D. Daubs Jan 2020

Preoperative Maximization To Reduce Complications In Spinal Surgery, Sukanta Maitra, Christopher Mikhail, Samuel K. Cho, Michael D. Daubs

School of Medicine Faculty Research

Study design: Invited narrative review. Objectives: The aim of this review was to summarize current literature regarding risk factors that surgeons can optimize in the preoperative setting in the spinal surgery patient, in order to reduce complications and improve patient-reported outcomes. Methods: Review of the relevant literature by the authors. Results: Modifiable risk factors identified relative to the patient include obesity, malnutrition/nutrient deficiency, diabetes/hyperglycemia, preoperative anemia, vitamin D/DEXA (dual-energy radiograph absorptiometry), nicotine use/smoking, and opioid use/psychosocial factors. Conclusion: By maximizing a patient's physiological and psychological status prior to elective spine surgery, we may move closer to achieving the goals of …


Prenatal Choline Supplementation During High-Fat Feeding Improves Long-Term Blood Glucose Control In Male Mouse Offspring, Hunter W. Korsmo, Kaydine Edwards, Bhoomi Dave, Chauntelle Jack-Roberts, Huanling Yu, Anjana Saxena, Marie Salvador, Moshe Dembitzer, Jaskomal Phagoora, Xinyin Jiang Jan 2020

Prenatal Choline Supplementation During High-Fat Feeding Improves Long-Term Blood Glucose Control In Male Mouse Offspring, Hunter W. Korsmo, Kaydine Edwards, Bhoomi Dave, Chauntelle Jack-Roberts, Huanling Yu, Anjana Saxena, Marie Salvador, Moshe Dembitzer, Jaskomal Phagoora, Xinyin Jiang

Publications and Research

Maternal obesity increases the risk of metabolic dysregulation in rodent offspring, especially when offspring are exposed to a high-fat (HF), obesogenic diet later in life. We previously demonstrated that maternal choline supplementation (MCS) in HF-fed mouse dams during gestation prevents fetal overgrowth and excess adiposity. In this study, we examined the long-term metabolic influence of MCS. C57BL/6J mice were fed a HF diet with or without choline supplementation prior to and during gestation. After weaning, their pups were exposed to either a HF or control diet for 6 weeks before measurements. Prenatal and post-weaning dietary treatments led to sexually dimorphic …