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Distinct Lymphocyte Antigens 6 (Ly6) Family Members Ly6d, Ly6e, Ly6k And Ly6h Drive Tumorigenesis And Clinical Outcome., Linlin Luo, Peter Mcgarvey, Subha Madhavan, Rakesh Kumar, Yuriy Gusev, Geeta Upadhyay Feb 2016

Distinct Lymphocyte Antigens 6 (Ly6) Family Members Ly6d, Ly6e, Ly6k And Ly6h Drive Tumorigenesis And Clinical Outcome., Linlin Luo, Peter Mcgarvey, Subha Madhavan, Rakesh Kumar, Yuriy Gusev, Geeta Upadhyay

Biochemistry and Molecular Medicine Faculty Publications

Stem cell antigen-1 (Sca-1) is used to isolate and characterize tumor initiating cell populations from tumors of various murine models [1]. Sca-1 induced disruption of TGF-β signaling is required in vivo tumorigenesis in breast cancer models [2, 3-5]. The role of human Ly6 gene family is only beginning to be appreciated in recent literature [6-9]. To study the significance of Ly6 gene family members, we have visualized one hundred thirty gene expression omnibus (GEO) dataset using Oncomine (Invitrogen) and Georgetown Database of Cancer (G-DOC). This analysis showed that four different members Ly6D, Ly6E, Ly6H or Ly6K have increased gene expressed …


Lambda Red-Mediated Recombineering In The Attaching And Effacing Pathogen Escherichia Albertii., Marisa Egan, Jasmine Ramirez, Christian Xander, Chirag Upreti, Shantanu Bhatt Feb 2016

Lambda Red-Mediated Recombineering In The Attaching And Effacing Pathogen Escherichia Albertii., Marisa Egan, Jasmine Ramirez, Christian Xander, Chirag Upreti, Shantanu Bhatt

Department of Medicine Faculty Papers

BACKGROUND: The ability to introduce site-specific mutations in bacterial pathogens is essential towards understanding their molecular mechanisms of pathogenicity. This has been greatly facilitated by the genetic engineering technique of recombineering. In recombineering, linear double- or single-stranded DNA molecules with two terminal homology arms are electroporated into hyperrecombinogenic bacteria that express a phage-encoded recombinase. The recombinase catalyzes the replacement of the endogenous allele with the exogenous allele to generate selectable or screenable recombinants. In particular, lambda red recombinase has been instrumental in engineering mutations to characterize the virulence arsenal of the attaching and effacing (A/E) pathogens enteropathogenic Escherichia coli (EPEC), …


Curcumin Nanoformulation For Cervical Cancer Treatment, Mohd S. Zaman, Neeraj Chauhan, Murali M. Yallapu, Rishi K. Gara, Diane M. Maher, Sonam Kumari, Mohammed Sikander, Sheema Khan, Nadeem Zafar, Meena Jaggi, Subhash C. Chauhan Feb 2016

Curcumin Nanoformulation For Cervical Cancer Treatment, Mohd S. Zaman, Neeraj Chauhan, Murali M. Yallapu, Rishi K. Gara, Diane M. Maher, Sonam Kumari, Mohammed Sikander, Sheema Khan, Nadeem Zafar, Meena Jaggi, Subhash C. Chauhan

School of Medicine Publications

Cervical cancer is one of the most common cancers among women worldwide. Current standards of care for cervical cancer includes surgery, radiation, and chemotherapy. Conventional chemotherapy fails to elicit therapeutic responses and causes severe systemic toxicity. Thus, developing a natural product based, safe treatment modality would be a highly viable option. Curcumin (CUR) is a well-known natural compound, which exhibits excellent anti-cancer potential by regulating many proliferative, oncogenic, and chemo-resistance associated genes/proteins. However, due to rapid degradation and poor bioavailability, its translational and clinical use has been limited. To improve these clinically relevant parameters, we report a poly(lactic-co-glycolic acid) based …


Tom Curran, Phd, Frs, Named Executive Director Of Children's Research Institute, Children's Mercy Hospital Feb 2016

Tom Curran, Phd, Frs, Named Executive Director Of Children's Research Institute, Children's Mercy Hospital

Our Story Continues

Tom Curran, PhD, FRS, has been named Chief Scientific Officer and Executive Director of the Children’s Mercy Children’s Research Institute (CRI), effective Feb. 1 [2016]

The Children’s Research Institute at Children’s Mercy Kansas City was established last year to build on the hospital’s century-long history in pediatric research and to focus the hospital’s future research efforts in four key areas:

  • Pediatric Genomic Medicine
  • Clinical Pharmacology
  • Health Services and Outcomes
  • Health Care Delivery


The Role Of Ng2 Proteoglycan In Glioma., Sridevi Yadavilli, Eugene I Hwang, Roger J. Packer, Javad Nazarian Feb 2016

The Role Of Ng2 Proteoglycan In Glioma., Sridevi Yadavilli, Eugene I Hwang, Roger J. Packer, Javad Nazarian

Neurology Faculty Publications

Neuron glia antigen-2 ((NG2), also known as chondroitin sulphate proteoglycan 4, or melanoma-associated chondroitin sulfate proteoglycan) is a type-1 membrane protein expressed by many central nervous system (CNS) cells during development and differentiation and plays a critical role in proliferation and angiogenesis. 'NG2' often references either the protein itself or the highly proliferative and undifferentiated glial cells expressing high levels of NG2 protein. NG2 glia represent the fourth major type of neuroglia in the mammalian nervous system and are classified as oligodendrocyte progenitor cells by virtue of their committed oligodendrocyte generation in developing and adult brain. Here, we discuss NG2 …


Dnah6 And Its Interactions With Pcd Genes In Heterotaxy And Primary Ciliary Dyskinesia., You Li, Hisato Yagi, Ezenwa Obi Onuoha, Rama Rao Damerla, Richard Francis, Yoshiyuki Furutani, Iman Sami, Linda Leatherbury, +13 Additional Authors Feb 2016

Dnah6 And Its Interactions With Pcd Genes In Heterotaxy And Primary Ciliary Dyskinesia., You Li, Hisato Yagi, Ezenwa Obi Onuoha, Rama Rao Damerla, Richard Francis, Yoshiyuki Furutani, Iman Sami, Linda Leatherbury, +13 Additional Authors

Pediatrics Faculty Publications

Heterotaxy, a birth defect involving left-right patterning defects, and primary ciliary dyskinesia (PCD), a sinopulmonary disease with dyskinetic/immotile cilia in the airway are seemingly disparate diseases. However, they have an overlapping genetic etiology involving mutations in cilia genes, a reflection of the common requirement for motile cilia in left-right patterning and airway clearance. While PCD is a monogenic recessive disorder, heterotaxy has a more complex, largely non-monogenic etiology. In this study, we show mutations in the novel dynein gene DNAH6 can cause heterotaxy and ciliary dysfunction similar to PCD. We provide the first evidence that trans-heterozygous interactions between DNAH6 and …


A Telehealth Behavioral Coaching Intervention For Neurocognitive Disorder Family Carers., Ann Steffen, Judith Gant Feb 2016

A Telehealth Behavioral Coaching Intervention For Neurocognitive Disorder Family Carers., Ann Steffen, Judith Gant

Psychology Faculty Works

No abstract provided.


Spatially Selective 2d Rf Inner Field Of View (Ifov) Diffusion Kurtosis Imaging (Dki) Of The Pediatric Spinal Cord, Chris J. Conklin, Devon M. Middleton, Mehdi Alizadeh, Jürgen Finsterbusch, David L. Raunig, Scott H. Faro, Pallav N. Shah, Laura Krisa, Rebecca Sinko, Ms, Otr/L, Joan Z. Delalic, M. J. Mulcahey, Feroze B. Mohamed Feb 2016

Spatially Selective 2d Rf Inner Field Of View (Ifov) Diffusion Kurtosis Imaging (Dki) Of The Pediatric Spinal Cord, Chris J. Conklin, Devon M. Middleton, Mehdi Alizadeh, Jürgen Finsterbusch, David L. Raunig, Scott H. Faro, Pallav N. Shah, Laura Krisa, Rebecca Sinko, Ms, Otr/L, Joan Z. Delalic, M. J. Mulcahey, Feroze B. Mohamed

Department of Physical Therapy Faculty Papers

No abstract provided.


Factors Affecting Depression Among Married Women Living In Urban Squatter Settlements Of Karachi, Pakistan, Shireen Shehzad, Salima Farooq, Yasmin Parpio, Rozina Karmaliani Professor, Nargis Asad, Iqbal Azam Syed, Omrana Pasha Feb 2016

Factors Affecting Depression Among Married Women Living In Urban Squatter Settlements Of Karachi, Pakistan, Shireen Shehzad, Salima Farooq, Yasmin Parpio, Rozina Karmaliani Professor, Nargis Asad, Iqbal Azam Syed, Omrana Pasha

School of Nursing & Midwifery

Background: Depression is one of the growing public health concerns among women worldwide. This is one of the most under-recognized and under-treated mental illnesses worldwide. Women of developing countries are inexplicably affecting with depression. Purpose: The purpose of study is to assess the prevalence and associative factors of depression among women of aged 20 to 40 years living in urban squatter settlements of Karachi, Pakistan. The identification of all the potential determinants will potentially help in formulating preventive strategies in order to decline the prevalence of depression among women and improve the well being of women.
Methods: An analytical cross-sectional …


The Effects Of Acidified Pepsin On Porcine Vocal Fold Tissue: Developing A Porcine Model Of Laryngopharyngeal Reflux Disease, Abigail Cox Durkes Feb 2016

The Effects Of Acidified Pepsin On Porcine Vocal Fold Tissue: Developing A Porcine Model Of Laryngopharyngeal Reflux Disease, Abigail Cox Durkes

Open Access Dissertations

Approximately 7.5 million Americans are affected by a voice disorder. In the last year, 7.2% of people missed one or more days of work due to a voice problem. For professional voice users, such as teachers, the rate increases to 20% and an annual cost of $2.5 billion. Voice disorders are complex and multi-faceted, as well as difficult to diagnose and treat. Prospective animal studies are necessary to study the pathophysiology of voice disorders, optimize our understanding of laryngeal pathology, and improve treatment outcomes. The pig provides a unique opportunity to test hypotheses relating to laryngeal disease because porcine vocal …


Malt Lymphoma Of The Base Of The Tongue: A Rare Case Entity, Haissan Iftikhar, Moghira Siddiqui, Khurram Minhas Feb 2016

Malt Lymphoma Of The Base Of The Tongue: A Rare Case Entity, Haissan Iftikhar, Moghira Siddiqui, Khurram Minhas

Department of Surgery Docs

Abstract

Lymphoma is a malignant tumour arising from lymphoid tissue, with the majority of cases being in the lymph nodes, however, in 1/4th of cases, these tumours are found in extralymphoid tissue. Lymphoid tissue is also found in organs having mucosa, such as the digestive tract, salivary gland and in tracheal tissue. This collection of lymphoid tissue is known as mucosa-associated lymphoid tissue (MALT), and non-Hodgkin lymphoma involving this extralymphoidal lymph tissue is known as MALT lymphoma. It was first reported by Isaacson and Wright in 1983, however, it was not included as a working diagnosis in clinical use until …


Down-Regulation Of Placental Neuropilin-1 In Fetal Growth Restriction., Dev Maulik, Alok De, Louis Ragolia, Jodi Evans, Dmitry Grigoryev, Kamani Lankachandra, David Mundy, Jolene Muscat, Mary M. Gerkovich, Shui Qing Ye Feb 2016

Down-Regulation Of Placental Neuropilin-1 In Fetal Growth Restriction., Dev Maulik, Alok De, Louis Ragolia, Jodi Evans, Dmitry Grigoryev, Kamani Lankachandra, David Mundy, Jolene Muscat, Mary M. Gerkovich, Shui Qing Ye

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Fetal growth restriction (FGR) is associated with adverse outcomes extending from fetal to adult life, and thus, constitutes a major health care challenge. Fetuses with progressive growth restriction show increasing impedance in the umbilical artery flow, which may become absent during end-diastole. Absent end-diastolic flow (AEDF) is associated with adverse perinatal outcomes including stillbirths and perinatal asphyxia. Placentas from such pregnancies demonstrate deficient fetoplacental vascular branching. Current evidence, moreover, indicates an antiangiogenic state in maternal circulation in several pregnancy complications including preeclampsia, small-for-gestational-age births, fetal death, and preterm labor. The angiogenic mediators in maternal circulation are predominantly of placental …


Differences And Similarities In The Clinicopathological Features Of Pancreatic Neuroendocrine Tumors In China And The United States: A Multicenter Study, Li-Ming Zhu, Laura Tang, Xin-Wei Qiao, Edward M. Wolin, Nicholas N. Nissen, Deepti Dhall, Jie Chen, Lin Shen, Yihebali Chi, Yao-Zong Yuan, Qi-Wen Ben, Bin Lv, Ya-Ru Zhou, Chun-Mei Bai, Jie Chen, Yu-Li Song, Tian-Tian Song, Chong-Mei Lu, Run Yu, Yuan-Jia Chen Feb 2016

Differences And Similarities In The Clinicopathological Features Of Pancreatic Neuroendocrine Tumors In China And The United States: A Multicenter Study, Li-Ming Zhu, Laura Tang, Xin-Wei Qiao, Edward M. Wolin, Nicholas N. Nissen, Deepti Dhall, Jie Chen, Lin Shen, Yihebali Chi, Yao-Zong Yuan, Qi-Wen Ben, Bin Lv, Ya-Ru Zhou, Chun-Mei Bai, Jie Chen, Yu-Li Song, Tian-Tian Song, Chong-Mei Lu, Run Yu, Yuan-Jia Chen

Markey Cancer Center Faculty Publications

The presentation, pathology, and prognosis of pancreatic neuroendocrine tumors (PNETs) in Asian patients have not been studied in large cohorts. We hypothesized that the clinicopathological features of PNETs of Chinese patients might be different from those of US patients. The objectives of this study were to address whether PNETs in Chinese patients exhibit unique clinicopathological features and natural history, and can be graded and staged using the WHO/ENETS criteria.

This is a retrospective review of medical records of patients with PNETs in multiple academic medical centers in China (7) and the United States (2). Tumor grading and staging were based …


Genetic Loci Associated With Renal Function Measures And Chronic Kidney Disease In Children: The Pediatric Investigation For Genetic Factors Linked With Renal Progression Consortium., Matthias Wuttke, Craig S. Wong, Elke Wühl, Daniel Epting, Li Luo, Anselm Hoppmann, Anke Doyon, Yong Li, Gkdgen Consortium, Betül Sözeri, Daniela Thurn, Martin Helmstädter, Tobias B. Huber, Tom D. Blydt-Hansen, Albrecht Kramer-Zucker, Otto Mehls, Anette Melk, Uwe Querfeld, Susan L. Furth, Bradley A. Warady, Franz Schaefer, Anna Köttgen Feb 2016

Genetic Loci Associated With Renal Function Measures And Chronic Kidney Disease In Children: The Pediatric Investigation For Genetic Factors Linked With Renal Progression Consortium., Matthias Wuttke, Craig S. Wong, Elke Wühl, Daniel Epting, Li Luo, Anselm Hoppmann, Anke Doyon, Yong Li, Gkdgen Consortium, Betül Sözeri, Daniela Thurn, Martin Helmstädter, Tobias B. Huber, Tom D. Blydt-Hansen, Albrecht Kramer-Zucker, Otto Mehls, Anette Melk, Uwe Querfeld, Susan L. Furth, Bradley A. Warady, Franz Schaefer, Anna Köttgen

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Chronic kidney disease (CKD) in children is characterized by rapid progression and a high incidence of end-stage renal disease and therefore constitutes an important health problem. While unbiased genetic screens have identified common risk variants influencing renal function and CKD in adults, the presence and identity of such variants in pediatric CKD are unknown.

METHODS: The international Pediatric Investigation for Genetic Factors Linked with Renal Progression (PediGFR) Consortium comprises three pediatric CKD cohorts: Chronic Kidney Disease in Children (CKiD), Effect of Strict Blood Pressure Control and ACE Inhibition on the Progression of CRF in Pediatric Patients (ESCAPE) and Cardiovascular …


Squamous Cell Carcinoma Of Oral Tongue In Young Patients — A 10 Years Tertiary Care Experience, Shakeel Uz Zaman, Muhammad Adeel, Anwar Suhail Feb 2016

Squamous Cell Carcinoma Of Oral Tongue In Young Patients — A 10 Years Tertiary Care Experience, Shakeel Uz Zaman, Muhammad Adeel, Anwar Suhail

Department of Surgery Docs

Abstract

OBJECTIVE:

To evaluate the clinical and pathological profile of young patients with squamous cell carcinoma of tongue.

METHODS:

The retrospective study was conducted at Aga Khan University Hospital, Karachi, and comprised record of patients20.

RESULTS:

Of the 29 patients, 17(58.6%) were men and 12(41.3%) were women. The overall mean age at presentation was 29.6+/-4.4 years. All patients (100%) had some sort of addiction, with 15(51.7%) having more than one addiction. Of the total, 20(68.9%) patients had moderately differentiated carcinoma. At presentation, 20(68.9%) had advanced stage (III-IV) disease. Surgery was the primary modality used in all the patients (100%). Median …


Geographic Access To Working Family Planning Centers And Unintended Pregnancies Among Married Women: A Community Based Nested Case Control Study., Sumera Aziz Ali, Sarah Saleem, Neelofar Sami, Mir Shabbar, Muhammad Ahmed, Shafquat Rozi, Robert L. Goldenberg, Margo S. Harrison, Omrana Pasha Feb 2016

Geographic Access To Working Family Planning Centers And Unintended Pregnancies Among Married Women: A Community Based Nested Case Control Study., Sumera Aziz Ali, Sarah Saleem, Neelofar Sami, Mir Shabbar, Muhammad Ahmed, Shafquat Rozi, Robert L. Goldenberg, Margo S. Harrison, Omrana Pasha

Community Health Sciences

Background:

Unintended pregnancies pose substantial risk to mothers and children. In Pakistan, unintended pregnancies account for 46% of all pregnancies. Lack of geographic access to open and well-supplied family planning (FP) centers may be related to the occurrence of such pregnancies, particularly in rural areas.

Objective:

The objective of this analysis is to determine if geographic access to family planning centers in the Thatta district of Pakistan is related to unintended pregnancy rates among married women.

Methods:

We conducted a community-based, nested case-control study of 800 pregnant women identified from the database of an active surveillance system, which registers and …


Endosteal Biologic Augmentation For Surgical Fixation Of Displaced Femoral Neck Fractures, Lionel E Lazaro, Jacqueline F Birnbaum, Nadja A Farshad-Amacker, David L Helfet, Hollis G Potter, Dean G Lorich Feb 2016

Endosteal Biologic Augmentation For Surgical Fixation Of Displaced Femoral Neck Fractures, Lionel E Lazaro, Jacqueline F Birnbaum, Nadja A Farshad-Amacker, David L Helfet, Hollis G Potter, Dean G Lorich

Faculty, Staff and Student Publications

OBJECTIVES: To report outcomes of a cohort with displaced femoral neck fractures (FNFs) treated with a length/angle-stable construct augmented with an endosteal fibular allograft serving as a biologic dowel.

DESIGN: Prospective.

SETTING: Level I Trauma Center.

PATIENTS: The study group consists of 27 patients with isolated FNF surgically treated by a single surgeon.

INTERVENTION: Open reduction of the femoral neck, fixed with a length- and angle-stable construct of 2 fully threaded cannulated screws augmented with an endosteal fibular allograft serving as a biologic dowel.

MAIN OUTCOME MEASUREMENTS: Clinical and radiographic outcomes of the fixation construct and the viability of both …


Evaluation Of A Pacap Peptide Analogue Labeled With (68)Ga Using Two Different Chelating Agents., Pardeep Kumar, Sushil Kumar Tripathi, Chang-Po Chen, Neil Mehta, Bishnuhari Paudyal, Eric Wickstrom, Mathew L. Thakur Feb 2016

Evaluation Of A Pacap Peptide Analogue Labeled With (68)Ga Using Two Different Chelating Agents., Pardeep Kumar, Sushil Kumar Tripathi, Chang-Po Chen, Neil Mehta, Bishnuhari Paudyal, Eric Wickstrom, Mathew L. Thakur

Department of Radiology Faculty Papers

OBJECTIVE: The authors have conjugated chelating agents (DOTA and NODAGA) with a peptide (pituitary adenylate cyclase-activating peptide [PACAP] analogue) that has a high affinity for VPAC1 receptors expressed on cancer cells. To determine a suitable chelating agent for labeling with (68)Ga, they have compared the labeling kinetics and stability of these peptide conjugates.

METHODS: For labeling, (68)GaCl3 was eluted in 0.1 M HCl from a [(68)Ge-(68)Ga] generator. The influences of peptide concentration, pH, and temperature on the radiolabeling efficiency were studied. The stability was evaluated in saline, human serum, DTPA, transferrin, and metallic ions (FeCl3, CaCl2, and ZnCl2). Cell binding …


Human Igg1 Antibodies Suppress Angiogenesis In A Target-Independent Manner, Sasha Bogdanovich, Younghee Kim, Takeshi Mizutani, Reo Yasuma, Laura Tudisco, Valeria Cicatiello, Ana Bastos-Carvalho, Nagaraj Kerur, Yoshio Hirano, Judit Z. Baffi, Valeria Tarallo, Shengjian Li, Tetsuhiro Yasuma, Parthasarathy Arpitha, Benjamin James Fowler, Charles B. Wright, Ivana Apicella, Adelaide Greco, Arturo Brunetti, Menotti Ruvo, Annamaria Sandomenico, Miho Nozaki, Ryo Ijima, Hiroki Kaneko, Yuichiro Ogura, Hiroko Terasaki, Balamurali K. Ambati, Jeanette H. W. Leusen, Wallace Y. Langdon, Michael R. Clark, Bradley D. Gelfand, Jayakrishna Ambati Jan 2016

Human Igg1 Antibodies Suppress Angiogenesis In A Target-Independent Manner, Sasha Bogdanovich, Younghee Kim, Takeshi Mizutani, Reo Yasuma, Laura Tudisco, Valeria Cicatiello, Ana Bastos-Carvalho, Nagaraj Kerur, Yoshio Hirano, Judit Z. Baffi, Valeria Tarallo, Shengjian Li, Tetsuhiro Yasuma, Parthasarathy Arpitha, Benjamin James Fowler, Charles B. Wright, Ivana Apicella, Adelaide Greco, Arturo Brunetti, Menotti Ruvo, Annamaria Sandomenico, Miho Nozaki, Ryo Ijima, Hiroki Kaneko, Yuichiro Ogura, Hiroko Terasaki, Balamurali K. Ambati, Jeanette H. W. Leusen, Wallace Y. Langdon, Michael R. Clark, Bradley D. Gelfand, Jayakrishna Ambati

Ophthalmology and Visual Science Faculty Publications

Aberrant angiogenesis is implicated in diseases affecting nearly 10% of the world’s population. The most widely used anti-angiogenic drug is bevacizumab, a humanized IgG1 monoclonal antibody that targets human VEGFA. Although bevacizumab does not recognize mouse Vegfa, it inhibits angiogenesis in mice. Here we show bevacizumab suppressed angiogenesis in three mouse models not via Vegfa blockade but rather Fc-mediated signaling through FcγRI (CD64) and c-Cbl, impairing macrophage migration. Other approved humanized or human IgG1 antibodies without mouse targets (adalimumab, alemtuzumab, ofatumumab, omalizumab, palivizumab and tocilizumab), mouse IgG2a, and overexpression of human IgG1-Fc or mouse IgG2a-Fc, also inhibited angiogenesis in wild-type …


Antimetabolite Ttl-315 Selectively Kills Glucose-Deprived Cancer Cells And Enhances Responses To Cytotoxic Chemotherapy In Preclinical Models Of Cancer., James Duhadaway, George C Prendergast Jan 2016

Antimetabolite Ttl-315 Selectively Kills Glucose-Deprived Cancer Cells And Enhances Responses To Cytotoxic Chemotherapy In Preclinical Models Of Cancer., James Duhadaway, George C Prendergast

Kimmel Cancer Center Faculty Papers

Maintaining thiol homeostasis is an imperative for cancer cell survival in the nutrient-deprived microenvironment of solid tumors. Despite this metabolic vulnerability, a selective approach has yet to be developed to disrupt thiol homeostasis in solid tumors for therapeutic purposes. In this study, we report the identification of 2-mercaptopropionyl glycine disulfide (TTL-315) as a novel antimetabolite that blocks cell survival in a manner conditional on glucose deprivation. In the presence of glucose, TTL-315 lacks cytotoxic effects in normal cells where it is detoxified by reduction to 2-mercaptopropionyl glycine, a compound with known clinical pharmacologic and safety profiles. In several rodent models …


Utilization Of The Clinical Laboratory For The Implementation Of Concussion Biomarkers In Collegiate Football And The Necessity Of Personalized And Predictive Athlete Specific Reference Intervals, Stefanie Podlog (Nee Schulte), Natalie N. Rasmussen, Joseph W. Mcbeth, Patrick Q. Richards, Eric Yochem, David J. Petron, Frederick G. Strathmann Jan 2016

Utilization Of The Clinical Laboratory For The Implementation Of Concussion Biomarkers In Collegiate Football And The Necessity Of Personalized And Predictive Athlete Specific Reference Intervals, Stefanie Podlog (Nee Schulte), Natalie N. Rasmussen, Joseph W. Mcbeth, Patrick Q. Richards, Eric Yochem, David J. Petron, Frederick G. Strathmann

Athletic Training Collection

Background: A continued interest in concussion biomarkers makes the eventual implementation of identified biomarkers into routine concussion assessment an eventual reality. We sought to develop and test an interdisciplinary approach that could be used to integrate blood-based biomarkers into the established concussion management program for a collegiate football team.

Methods: We used a CLIA-certified laboratory for all testing and chose biomarkers where clinically validated testing was available as would be required for results used in clinical decision making. We summarized the existing methods and results for concussion assessment across an entire season to identify and demonstrate the challenges with the …


Gap Junction Mediated Mirna Intercellular Transfer And Gene Regulation: A Novel Mechanism For Intercellular Genetic Communication, Liang Zong, Yan Zhu, Ruqiang Liang, Hong-Bo Zhao Jan 2016

Gap Junction Mediated Mirna Intercellular Transfer And Gene Regulation: A Novel Mechanism For Intercellular Genetic Communication, Liang Zong, Yan Zhu, Ruqiang Liang, Hong-Bo Zhao

Otolaryngology--Head & Neck Surgery Faculty Publications

Intercellular genetic communication is an essential requirement for coordination of cell proliferation and differentiation and has an important role in many cellular processes. Gap junction channels possess large pore allowing passage of ions and small molecules between cells. MicroRNAs (miRNAs) are small regulatory RNAs that can regulate gene expression broadly. Here, we report that miRNAs can pass through gap junction channels in a connexin-dependent manner. Connexin43 (Cx43) had higher permeability, whereas Cx30 showed little permeability to miRNAs. In the tested connexin cell lines, the permeability to miRNAs demonstrated: Cx43 > Cx26/30 > Cx26 > Cx31 > Cx30 = Cx-null. However, consistent with a uniform …


Biodistribution And Pharmacokinetics Study Of Sirna-Loaded Anti-Ntsr1-Mab-Functionalized Novel Hybrid Nanoparticles In A Metastatic Orthotopic Murine Lung Cancer Model., Maryna Perepelyuk, Chellappagounder Thangavel, Yi Liu, Robert B. Den, Bo Lu, Adam E. Snook, Sunday A. Shoyele Jan 2016

Biodistribution And Pharmacokinetics Study Of Sirna-Loaded Anti-Ntsr1-Mab-Functionalized Novel Hybrid Nanoparticles In A Metastatic Orthotopic Murine Lung Cancer Model., Maryna Perepelyuk, Chellappagounder Thangavel, Yi Liu, Robert B. Den, Bo Lu, Adam E. Snook, Sunday A. Shoyele

Department of Radiation Oncology Faculty Papers

Small interfering RNA (siRNA) is effective in silencing critical molecular pathways in cancer. The use of this tool as a treatment modality is limited by lack of an intelligent carrier system to enhance the preferential delivery of this molecule to specific targets in vivo. In the present study, the in vivo behavior of novel anti-NTSR1-mAb-functionalized antimutant K-ras siRNA-loaded hybrid nanoparticles, delivered by i.p. injection to non-small-cell lung cancer in mice models, was investigated and compared to that of a naked siRNA formulation. The siRNA in anti-NTSR1-mAb-functionalized hybrid nanoparticles was preferentially accumulated in tumor-bearing lungs and metastasized tumor for at least …


Neurocognitive Dysfunction In Brain Tumor Patients Following Radiation Therapy: A Review Of Biological Hypotheses, Current Treatment Outcomes, And Novel Therapeutic Strategies, Raj Singh Jan 2016

Neurocognitive Dysfunction In Brain Tumor Patients Following Radiation Therapy: A Review Of Biological Hypotheses, Current Treatment Outcomes, And Novel Therapeutic Strategies, Raj Singh

Marshall Journal of Medicine

Given the difficulty of surgical resection of brain neoplasms located adjacent to vital structures of the brain as well as the challenges posed by the blood-brain-barrier for the efficacy of chemotherapeutic agents, whole brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS) are often turned to for patients with brain metastases as well as primary brain neoplasms. Though radiation therapy may be successful in local control of these tumors, many patients experience treatment-related neurocognitive issues later in life. In this review, we examine cognitive dysfunction in brain tumor patients following radiation therapy, with an emphasis on the pediatric population. Articles were …


Neural Substrate Expansion For The Restoration Of Brain Function., H Isaac Chen, Dennis Jgamadze, Mijail Serruya, D Kacy Cullen, John A Wolf, Douglas H Smith Jan 2016

Neural Substrate Expansion For The Restoration Of Brain Function., H Isaac Chen, Dennis Jgamadze, Mijail Serruya, D Kacy Cullen, John A Wolf, Douglas H Smith

Department of Neurology Faculty Papers

Restoring neurological and cognitive function in individuals who have suffered brain damage is one of the principal objectives of modern translational neuroscience. Electrical stimulation approaches, such as deep-brain stimulation, have achieved the most clinical success, but they ultimately may be limited by the computational capacity of the residual cerebral circuitry. An alternative strategy is brain substrate expansion, in which the computational capacity of the brain is augmented through the addition of new processing units and the reconstitution of network connectivity. This latter approach has been explored to some degree using both biological and electronic means but thus far has not …


Human Polyomaviruses And Incidence Of Cutaneous Squamous Cell Carcinoma In The New Hampshire Skin Cancer Study, Anala Gossai, Tim Waterboer, Anne G. Hoen, Shohreh F. Farzan, Heather Nelson, Angelika Michel, Martina Willhauck-Fleckenstein, Brock Christensen, Ann Perry, Michael Pawlita, Margaret Karagas Jan 2016

Human Polyomaviruses And Incidence Of Cutaneous Squamous Cell Carcinoma In The New Hampshire Skin Cancer Study, Anala Gossai, Tim Waterboer, Anne G. Hoen, Shohreh F. Farzan, Heather Nelson, Angelika Michel, Martina Willhauck-Fleckenstein, Brock Christensen, Ann Perry, Michael Pawlita, Margaret Karagas

Dartmouth Scholarship

Squamous cell carcinoma (SCC) of the skin is a malignancy arising from epi- thelial keratinocytes. Experimental and epidemiologic evidence raise the possibility that human polyomaviruses (PyV) may be associated with the occurrence of SCC. To investigate whether the risk for SCC was associated with PyV infection, seropositivity to 10 PyV types was assessed following diagnosis in a population- based case–control study conducted in the United States. A total of 253 SCC cases and 460 age group and gender-matched controls were included. Antibody response against each PyV was measured using a multiplex serology-based glu- tathione S-transferase capture assay of recombinantly expressed …


Evidence And Knowledge Gaps On The Disease Burden In Sexual And Gender Minorities: A Review Of Systematic Reviews, Karel Blondeel, Lale Say, Doris Chou, Igor Toskin, Rajat Khosla, Elisa Scolaro, Marleen Temmerman Jan 2016

Evidence And Knowledge Gaps On The Disease Burden In Sexual And Gender Minorities: A Review Of Systematic Reviews, Karel Blondeel, Lale Say, Doris Chou, Igor Toskin, Rajat Khosla, Elisa Scolaro, Marleen Temmerman

Obstetrics and Gynaecology, East Africa

Sexual and gender minorities (SGM) include individuals with a wide range of sexual orientations, physical characteristics, and gender identities and expressions. Data suggest that people in this group face a significant and poorly understood set of additional health risks and bear a higher burden of some diseases compared to the general population. A large amount of data is available on HIV/AIDS, but far less on other health problems. In this review we aimed to synthesize the knowledge on the burden of communicable and non-communicable diseases, mental health conditions and violence experienced by SGM, based on available systematic reviews. We conducted …


Reducing Gastrointestinal Anastomotic Leak Rates: Review Of Challenges And Solutions, Benjamin Philllips Jan 2016

Reducing Gastrointestinal Anastomotic Leak Rates: Review Of Challenges And Solutions, Benjamin Philllips

Department of Surgery Faculty Papers

Various techniques and interventions have been developed in an effort to obviate gastrointestinal anastomotic leaks. This review is intended to delineate potential modifications that can be made to reduce the risk of anastomotic leaks following gastrointestinal surgery. It may also serve to aid in identifying patients who are at increased risk of anastomotic leak. Modifiable risk factors for leak discussed include malnutrition, smoking, steroid use, bowel preparation, chemotherapy, duration of surgery, use of pressors, intravenous fluid administration, blood transfusion, and surgical anastomotic technique. Based upon literature review, operative techniques should include minimizing operative time, reducing ischemia, and utilizing stapled anastomoses. …


Models For Hsv Shedding Must Account For Two Levels Of Overdispersion, Amalia Magaret Jan 2016

Models For Hsv Shedding Must Account For Two Levels Of Overdispersion, Amalia Magaret

UW Biostatistics Working Paper Series

We have frequently implemented crossover studies to evaluate new therapeutic interventions for genital herpes simplex virus infection. The outcome measured to assess the efficacy of interventions on herpes disease severity is the viral shedding rate, defined as the frequency of detection of HSV on the genital skin and mucosa. We performed a simulation study to ascertain whether our standard model, which we have used previously, was appropriately considering all the necessary features of the shedding data to provide correct inference. We simulated shedding data under our standard, validated assumptions and assessed the ability of 5 different models to reproduce the …


Hyaluronidase And Hyaluronan Oligosaccharides Promote Neurological Recovery After Intraventricular Hemorrhage, Govindaiah Vinukonda, Preeti Dohare, Arslan Arshad, Muhammad T. Zia, Sanjeet Panda, Ritesh Korumilli, Praveen Ballabh Jan 2016

Hyaluronidase And Hyaluronan Oligosaccharides Promote Neurological Recovery After Intraventricular Hemorrhage, Govindaiah Vinukonda, Preeti Dohare, Arslan Arshad, Muhammad T. Zia, Sanjeet Panda, Ritesh Korumilli, Praveen Ballabh

NYMC Faculty Publications

Intraventricular hemorrhage (IVH) in premature infants results in inflammation, arrested oligodendrocyte progenitor cell (OPC) maturation, and reduced myelination of the white matter. Hyaluronan (HA) inhibits OPC maturation and complexes with the heavy chain (HC) of glycoprotein inter-α-inhibitor to form pathological HA (HC-HA complex), which exacerbates inflammation. Therefore, we hypothesized that IVH would result in accumulation of HA, and that either degradation of HA by hyaluronidase treatment or elimination of HCs from pathological HA by HA oligosaccharide administration would restore OPC maturation, myelination, and neurological function in survivors with IVH. To test these hypotheses, we used the preterm rabbit model of …