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Factors Leading To Meconium Aspiration Syndrome In Term- And Post-Term Neonates, Saroop Chand, Aamna Salman, Razia Mustafa Abbassi, Abdul Rehman Siyal, Fayaz Ahmed Memon, Abdul Lateef Leghari, Ashmal Sami Kabani, Sajid Ali Sep 2019

Factors Leading To Meconium Aspiration Syndrome In Term- And Post-Term Neonates, Saroop Chand, Aamna Salman, Razia Mustafa Abbassi, Abdul Rehman Siyal, Fayaz Ahmed Memon, Abdul Lateef Leghari, Ashmal Sami Kabani, Sajid Ali

Department of Paediatrics and Child Health

Background: Meconium aspiration syndrome (MAS) is considered a major cause of respiratory morbidity. It is a common issue encountered in the delivery room and newborn nursery. There is a need to identify the factors that lead to MAS to develop strategies to screen such patients at an early stage to decrease the mortality and morbidity. The objective of this study was to determine the factors leading to MAS in neonates delivered at ≥37 weeks of gestational age.
Methods: A cross-sectional study was conducted through non-probability consecutive sampling technique at Liaquat University Hospital, Hyderabad from August 2016 to February 2017. All …


Surgical Stress And Cancer Progression: The Twisted Tango., Zhiwei Chen, Peidong Zhang, Ya Xu, Jiahui Yan, Zixuan Liu, Wayne Bond Lau, Bonnie Lau, Ying Li, Xia Zhao, Yuquan Wei, Shengtao Zhou Sep 2019

Surgical Stress And Cancer Progression: The Twisted Tango., Zhiwei Chen, Peidong Zhang, Ya Xu, Jiahui Yan, Zixuan Liu, Wayne Bond Lau, Bonnie Lau, Ying Li, Xia Zhao, Yuquan Wei, Shengtao Zhou

Department of Emergency Medicine Faculty Papers

Surgical resection is an important avenue for cancer treatment, which, in most cases, can effectively alleviate the patient symptoms. However, accumulating evidence has documented that surgical resection potentially enhances metastatic seeding of tumor cells. In this review, we revisit the literature on surgical stress, and outline the mechanisms by which surgical stress, including ischemia/reperfusion injury, activation of sympathetic nervous system, inflammation, systemically hypercoagulable state, immune suppression and effects of anesthetic agents, promotes tumor metastasis. We also propose preventive strategies or resolution of tumor metastasis caused by surgical stress.


The Phosphatase Ubash3b/Sts-1 Is A Negative Regulator Of Bcr-Abl Kinase Activity And Leukemogenesis, Afsar Ali Mian, Ines Baumann, Marcus Liebermann, Florian Grebien, Giulio Superti-Furga, Martin Ruthardt, Oliver G. Ottmann, Oliver Hantschel Sep 2019

The Phosphatase Ubash3b/Sts-1 Is A Negative Regulator Of Bcr-Abl Kinase Activity And Leukemogenesis, Afsar Ali Mian, Ines Baumann, Marcus Liebermann, Florian Grebien, Giulio Superti-Furga, Martin Ruthardt, Oliver G. Ottmann, Oliver Hantschel

Centre for Regenerative Medicine & Stem Cell Research

No abstract provided.


Colostrum And Mature Breast Milk Analysis Of Serum Irisin And Sterol Regulatory Element-Binding Proteins-1c In Gestational Diabetes Mellitus, Syeda Sadia Fatima, Erum Khalid, Asma Akbar Ladak, Syed Adnan Ali Sep 2019

Colostrum And Mature Breast Milk Analysis Of Serum Irisin And Sterol Regulatory Element-Binding Proteins-1c In Gestational Diabetes Mellitus, Syeda Sadia Fatima, Erum Khalid, Asma Akbar Ladak, Syed Adnan Ali

Department of Biological & Biomedical Sciences

Background: We aimed to evaluate irisin and SREBP-1c levels in serum, colostrum and mature breast milk in women with and without gestational diabetes (GDM); and to relate them with maternal glucose, lipid profile and weight status of babies.
Methods: GDM positive women (n = 33) and normal glucose tolerant women (NGT) (n = 33) were recruited. Maternal blood samples were collected at 28th week of gestation and later at 6-week post-partum while breast milk samples of the lactating mothers were collected within 72 hours of birth (colostrum) and at 6 weeks post-partum (mature milk). Irisin and SREBP-1c levels were analyzed …


Collaborative International Research In Clinical And Longitudinal Experience Study In Nmosd., Lawrence J Cook, John W Rose, Jessica S Alvey, Anna Marie Jolley, Renee Kuhn, Brie Marron, Melissa Pederson, Rene Enriquez, Jeff Yearley, Stephen Mckechnie, May H Han, Anna J Tomczak, Michael Levy, Maureen A Mealy, Jessica Coleman, Jeffrey L Bennett, Ruth Johnson, Myka Barnes-Garcia, Anthony L Traboulsee, Robert L Carruthers, Lisa Eunyoung Lee, Julia J Schubert, Katrina Mcmullen, Ilya Kister, Zoe Rimler, Allyson Reid, Nancy L Sicotte, Sarah M Planchon, Jeffrey A Cohen, Diane Ivancic, Jennifer L Sedlak, Ilana Katz Sand, Pavle Repovic, Lilyana Amezcua, Ana Pruitt, Erika Amundson, Tanuja Chitnis, Devin S Mullin, Eric C Klawiter, Andrew W Russo, Claire S Riley, Kaho B Onomichi, Libby Levine, Katherine E Nelson, Nancy M Nealon, Casey Engel, Mason Kruse-Hoyer, Melanie Marcille, Leticia Tornes, Anne Rumpf, Angela Greer, Megan Kenneally Behne, Renee R Rodriguez, Daniel W Behne, Derek W Blackway, Brian Coords, Terrence F Blaschke, Judy Sheard, Terry J Smith, Jacinta M Behne, Michael R Yeaman Sep 2019

Collaborative International Research In Clinical And Longitudinal Experience Study In Nmosd., Lawrence J Cook, John W Rose, Jessica S Alvey, Anna Marie Jolley, Renee Kuhn, Brie Marron, Melissa Pederson, Rene Enriquez, Jeff Yearley, Stephen Mckechnie, May H Han, Anna J Tomczak, Michael Levy, Maureen A Mealy, Jessica Coleman, Jeffrey L Bennett, Ruth Johnson, Myka Barnes-Garcia, Anthony L Traboulsee, Robert L Carruthers, Lisa Eunyoung Lee, Julia J Schubert, Katrina Mcmullen, Ilya Kister, Zoe Rimler, Allyson Reid, Nancy L Sicotte, Sarah M Planchon, Jeffrey A Cohen, Diane Ivancic, Jennifer L Sedlak, Ilana Katz Sand, Pavle Repovic, Lilyana Amezcua, Ana Pruitt, Erika Amundson, Tanuja Chitnis, Devin S Mullin, Eric C Klawiter, Andrew W Russo, Claire S Riley, Kaho B Onomichi, Libby Levine, Katherine E Nelson, Nancy M Nealon, Casey Engel, Mason Kruse-Hoyer, Melanie Marcille, Leticia Tornes, Anne Rumpf, Angela Greer, Megan Kenneally Behne, Renee R Rodriguez, Daniel W Behne, Derek W Blackway, Brian Coords, Terrence F Blaschke, Judy Sheard, Terry J Smith, Jacinta M Behne, Michael R Yeaman

Articles, Abstracts, and Reports

Objective: To develop a resource of systematically collected, longitudinal clinical data and biospecimens for assisting in the investigation into neuromyelitis optica spectrum disorder (NMOSD) epidemiology, pathogenesis, and treatment.

Methods: To illustrate its research-enabling purpose, epidemiologic patterns and disease phenotypes were assessed among enrolled subjects, including age at disease onset, annualized relapse rate (ARR), and time between the first and second attacks.

Results: As of December 2017, the Collaborative International Research in Clinical and Longitudinal Experience Study (CIRCLES) had enrolled more than 1,000 participants, of whom 77.5% of the NMOSD cases and 71.7% of the controls continue in active follow-up. Consanguineous …


Diabetes-Related Amylin Dyshomeostasis: A Contributing Factor To Cerebrovascular Pathology And Dementia, Han Ly, Florin Despa Sep 2019

Diabetes-Related Amylin Dyshomeostasis: A Contributing Factor To Cerebrovascular Pathology And Dementia, Han Ly, Florin Despa

Pharmacology and Nutritional Sciences Faculty Publications

Type 2 diabetes (T2D) increases the risk for cerebrovascular disease (CVD) and dementia. The underlying molecular mechanisms remain elusive, which hampers the development of treatment or/and effective prevention strategies. Recent studies suggest that dyshomeostasis of amylin, a satiety hormone that forms pancreatic amyloid in patients with T2D, promotes accumulation of amylin in cerebral small blood vessels and interaction with Alzheimer's disease (AD) pathology. Overexpression of human amylin in rodents (rodent amylin does not form amyloid) leads to late-life onset T2D and neurologic deficits. In this Review, we discuss clinical evidence of amylin pathology in CVD and AD and identify critical …


The Effects Of Therapeutic Riding On Social Skills And Sensory Functioning In Children With Autism, Betsy Donahoe-Fillmore, Mary Insana Fisher, Christy Lee, Jordan Bevins, Cristin Carter, Stephanie Dailey, Kelsey Haynes, Allison Richard, Sarah Soboslay Sep 2019

The Effects Of Therapeutic Riding On Social Skills And Sensory Functioning In Children With Autism, Betsy Donahoe-Fillmore, Mary Insana Fisher, Christy Lee, Jordan Bevins, Cristin Carter, Stephanie Dailey, Kelsey Haynes, Allison Richard, Sarah Soboslay

Physical Therapy Faculty Publications

Purpose and Significance: Therapeutic riding (TR) is equine-assisted riding lessons that are adapted for people with a wide variety of impairments and is often used as an adjunct to traditional therapies. Previous research has shown that TR helped to improve sensory functioning, cognition and social skills in children with Autism Spectrum Disorder (ASD) but sessions have typically been for 10-12 weeks. The purpose of this study was to investigate if social skills and sensory functioning improved after only 8 weeks of TR.

Subjects: Children were recruited from a local TR center. Participants included seven children (5M, 2F) with a diagnosis …


Detection And Concentration Of Plasma Aflatoxin Is Associated With Detection Of Oncogenic Human Papillomavirus In Kenyan Women, Jianjun Zhang, Elkanah Omenge, Philip Tonui, Yan Tong, Titus Manai, Stephen Kiptoo, Kapten Muthoka, John Groopman, Joshua Smith, Erin Madeen Sep 2019

Detection And Concentration Of Plasma Aflatoxin Is Associated With Detection Of Oncogenic Human Papillomavirus In Kenyan Women, Jianjun Zhang, Elkanah Omenge, Philip Tonui, Yan Tong, Titus Manai, Stephen Kiptoo, Kapten Muthoka, John Groopman, Joshua Smith, Erin Madeen

Obstetrics and Gynaecology, East Africa

Background: Cervical cancer is common in Kenyan women. Cofactors in addition to infection with oncogenic human papillomavirus (HPV) are likely to be important in causing cervical cancer, because only a small percentage of HPV-infected women will develop this malignancy. Kenyan women are exposed to dietary aflatoxin, a potent carcinogen and immunosuppressive agent, which may be such a cofactor.

Methods: Demographics, behavioral data, plasma, and cervical swabs were collected from 88 human immunodeficiency virus-uninfected Kenyan women without cervical dysplasia. Human papillomavirus detection was compared between women with or without plasma aflatoxin B1-lysine (AFB1-lys) and evaluated in relation to AFB1-lys concentration.

Results: …


Vitamin D Status And Risk Of Incident Tuberculosis Disease: A Nested Case-Control Study, Systematic Review, And Individual-Participant Data Meta-Analysis, Omowunmi Aibana, Chuan-Chin Huang, Said Aboud, Alberto Arnedo-Pena, Mercedes C. Becerra, Juan Bautista Bellido-Blasco, Ramesh Bhosale, Roger Calderon, Rabia Hussain, Najeeha Talat Iqbal Sep 2019

Vitamin D Status And Risk Of Incident Tuberculosis Disease: A Nested Case-Control Study, Systematic Review, And Individual-Participant Data Meta-Analysis, Omowunmi Aibana, Chuan-Chin Huang, Said Aboud, Alberto Arnedo-Pena, Mercedes C. Becerra, Juan Bautista Bellido-Blasco, Ramesh Bhosale, Roger Calderon, Rabia Hussain, Najeeha Talat Iqbal

Department of Pathology and Laboratory Medicine

Background: Few studies have evaluated the association between preexisting vitamin D deficiency and incident tuberculosis (TB). We assessed the impact of baseline vitamins D levels on TB disease risk.
Methods and Findings: We assessed the association between baseline vitamin D and incident TB in a prospective cohort of 6,751 HIV-negative household contacts of TB patients enrolled between September 1, 2009, and August 29, 2012, in Lima, Peru. We screened for TB disease at 2, 6, and 12 months after enrollment. We defined cases as household contacts who developed TB disease at least 15 days after enrollment of the index patient. …


Nuclear Receptor Subfamily 4 Group A Member 2 Inhibits Activation Of Erk Signaling And Cell Growth In Response To Β-Adrenergic Stimulation In Adult Rat Cardiomyocytes, Sadia Ashraf, Yassmin K Hegazy, Romain Harmancey Sep 2019

Nuclear Receptor Subfamily 4 Group A Member 2 Inhibits Activation Of Erk Signaling And Cell Growth In Response To Β-Adrenergic Stimulation In Adult Rat Cardiomyocytes, Sadia Ashraf, Yassmin K Hegazy, Romain Harmancey

Faculty, Staff and Student Publications

Sustained elevation of sympathetic activity is an important contributor to pathological cardiac hypertrophy, ventricular arrhythmias, and left ventricular contractile dysfunction in chronic heart failure. The orphan nuclear receptor NR4A2 is an immediate early-response gene activated in the heart under β-adrenergic stimulation. The goal of this study was to identify the transcriptional remodeling events induced by increased NR4A2 expression in cardiomyocytes and their impact on the physiological response of those cells to sustained β-adrenergic stimulation. Treatment of adult rat ventricular myocytes with isoproterenol induced a rapid (<4 >h) increase in NR4A2 levels that was accompanied by a transient (<24 >h) increase …


Infant With Protein C Deficiency And Stroke In The Setting Of Iron Deficiency Anemia, Tahseen Jalal Karim, Dustin J Paul, Regina M Troxell, Rajan Patel, Ian J Butler Sep 2019

Infant With Protein C Deficiency And Stroke In The Setting Of Iron Deficiency Anemia, Tahseen Jalal Karim, Dustin J Paul, Regina M Troxell, Rajan Patel, Ian J Butler

Faculty, Staff and Student Publications

We report an 18-month-old infant with ischemic stroke, neurocognitive impairment, and psychomotor retardation in the setting of severe iron deficiency anemia. Although an uncommon outcome in anemic children, stroke is important to consider as a cause for developmental delay in children with iron deficiency anemia.


Vitamin D Status And Risk Of Incident Tuberculosis Disease: A Nested Case-Control Study, Systematic Review, And Individual-Participant Data Meta-Analysis, Omowunmi Aibana, Chuan-Chin Huang, Said Aboud, Alberto Arnedo-Pena, Mercedes C Becerra, Juan Bautista Bellido-Blasco, Ramesh Bhosale, Roger Calderon, Silvia Chiang, Carmen Contreras, Ganmaa Davaasambuu, Wafaie W Fawzi, Molly F Franke, Jerome T Galea, Daniel Garcia-Ferrer, Maria Gil-Fortuño, Barbará Gomila-Sard, Amita Gupta, Nikhil Gupte, Rabia Hussain, Jesus Iborra-Millet, Najeeha T Iqbal, Jose Vicente Juan-Cerdán, Aarti Kinikar, Leonid Lecca, Vidya Mave, Noemi Meseguer-Ferrer, Grace Montepiedra, Ferdinand M Mugusi, Olumuyiwa A Owolabi, Julie Parsonnet, Freddy Roach-Poblete, Maria Angeles Romeu-García, Stephen A Spector, Christopher R Sudfeld, Mark W Tenforde, Toyin O Togun, Rosa Yataco, Zibiao Zhang, Megan B Murray Sep 2019

Vitamin D Status And Risk Of Incident Tuberculosis Disease: A Nested Case-Control Study, Systematic Review, And Individual-Participant Data Meta-Analysis, Omowunmi Aibana, Chuan-Chin Huang, Said Aboud, Alberto Arnedo-Pena, Mercedes C Becerra, Juan Bautista Bellido-Blasco, Ramesh Bhosale, Roger Calderon, Silvia Chiang, Carmen Contreras, Ganmaa Davaasambuu, Wafaie W Fawzi, Molly F Franke, Jerome T Galea, Daniel Garcia-Ferrer, Maria Gil-Fortuño, Barbará Gomila-Sard, Amita Gupta, Nikhil Gupte, Rabia Hussain, Jesus Iborra-Millet, Najeeha T Iqbal, Jose Vicente Juan-Cerdán, Aarti Kinikar, Leonid Lecca, Vidya Mave, Noemi Meseguer-Ferrer, Grace Montepiedra, Ferdinand M Mugusi, Olumuyiwa A Owolabi, Julie Parsonnet, Freddy Roach-Poblete, Maria Angeles Romeu-García, Stephen A Spector, Christopher R Sudfeld, Mark W Tenforde, Toyin O Togun, Rosa Yataco, Zibiao Zhang, Megan B Murray

Faculty, Staff and Student Publications

BACKGROUND: Few studies have evaluated the association between preexisting vitamin D deficiency and incident tuberculosis (TB). We assessed the impact of baseline vitamins D levels on TB disease risk.

METHODS AND FINDINGS: We assessed the association between baseline vitamin D and incident TB in a prospective cohort of 6,751 HIV-negative household contacts of TB patients enrolled between September 1, 2009, and August 29, 2012, in Lima, Peru. We screened for TB disease at 2, 6, and 12 months after enrollment. We defined cases as household contacts who developed TB disease at least 15 days after enrollment of the index patient. …


Nuclear Receptor Subfamily 4 Group A Member 2 Inhibits Activation Of Erk Signaling And Cell Growth In Response To Β-Adrenergic Stimulation In Adult Rat Cardiomyocytes, Sadia Ashraf, Yassmin K Hegazy, Romain Harmancey Sep 2019

Nuclear Receptor Subfamily 4 Group A Member 2 Inhibits Activation Of Erk Signaling And Cell Growth In Response To Β-Adrenergic Stimulation In Adult Rat Cardiomyocytes, Sadia Ashraf, Yassmin K Hegazy, Romain Harmancey

Faculty, Staff and Student Publications

Sustained elevation of sympathetic activity is an important contributor to pathological cardiac hypertrophy, ventricular arrhythmias, and left ventricular contractile dysfunction in chronic heart failure. The orphan nuclear receptor NR4A2 is an immediate early-response gene activated in the heart under β-adrenergic stimulation. The goal of this study was to identify the transcriptional remodeling events induced by increased NR4A2 expression in cardiomyocytes and their impact on the physiological response of those cells to sustained β-adrenergic stimulation. Treatment of adult rat ventricular myocytes with isoproterenol induced a rapid (<4 >h) increase in NR4A2 levels that was accompanied by a transient (<24 >h) increase …


Science Of Lifestyle; Strategies For Change, Raza Ur Rahman Sep 2019

Science Of Lifestyle; Strategies For Change, Raza Ur Rahman

Pakistan Journal of Neurological Sciences (PJNS)

Since the start of 21st century the focus of medical treatment is changing from curative to the preventive medicine and now functional recovery and quality of life are the outcome of curative medicine. These new outcomes of modern medicine can be achieved through adopting the strategies that enhance wellness of patient. The methods of enhancing wellness are in practice since centuries and their effectiveness has been handed down through word of mouth and tradition. They continue to evolve and were first documented in 1970s, by Canyon Ranch1, as a strategy to improve health through the principles of a healthy lifestyle. …


What, When And For Whom Model Of Nutrition: A Health Management Approach, Muhammad Rafiq Sep 2019

What, When And For Whom Model Of Nutrition: A Health Management Approach, Muhammad Rafiq

Pakistan Journal of Neurological Sciences (PJNS)

Studies have shown that nutrition plays an important role in the pathophysiology of different health issues either physiological, or psychological. Nutrition is implicated in the development of health issues in different ways. The purpose of this mini review was to suggest a comprehensive model of nutrition, “What, When and for Whom Model of Nutrition”, in the light of existing literature. For this purpose, existing literature was explored to study the role of nutrition on mental health in perspective to, what type of nutrition, when it is consumed and/or who consumes it. Researchers concluded that it is not only what we …


Flecainide Toxicity Resulting In Pacemaker Latency And Intermittent Failure To Capture, John M. Suffredini, Joshua Rutland, Peter Akpunonu, Regan Baum, John Catanzaro, Claude S. Elayi Aug 2019

Flecainide Toxicity Resulting In Pacemaker Latency And Intermittent Failure To Capture, John M. Suffredini, Joshua Rutland, Peter Akpunonu, Regan Baum, John Catanzaro, Claude S. Elayi

Emergency Medicine Faculty Publications

BACKGROUND Flecainide is a class Ic antiarrhythmic agent used in the treatment of supraventricular and ventricular arrhythmias. It is associated with a potent adverse effect profile; however, the effects of flecainide toxicity in the setting of a pacemaker have not been well described. We describe a unique case of flecainide toxicity secondary to acute kidney injury in the setting of a dual-chamber pacemaker, resulting in ventricular capture latency and intermittent failure to capture.

CASE REPORT The patient was a 91-year-old female with a history of atrial fibrillation maintained in sinus rhythm on flecainide, who presented complaining of purple visual disturbances …


Activation Of Lxrβ Inhibits Tumor Respiration And Is Synthetically Lethal With Bcl-Xl Inhibition, Trang Thi Thu Nguyen, Chiaki Tsuge Ishida, Enyuan Shang, Chang Shu, Consuelo Torrini, Yiru Zhang, Elena Bianchetti, Maria J. Sanchez-Quintero, Giulio Kleiner, Catarina M. Quinzii, Mike-Andrew Westhoff, Georg Karpel-Massler, Peter Canoll, Markus D. Siegelin Aug 2019

Activation Of Lxrβ Inhibits Tumor Respiration And Is Synthetically Lethal With Bcl-Xl Inhibition, Trang Thi Thu Nguyen, Chiaki Tsuge Ishida, Enyuan Shang, Chang Shu, Consuelo Torrini, Yiru Zhang, Elena Bianchetti, Maria J. Sanchez-Quintero, Giulio Kleiner, Catarina M. Quinzii, Mike-Andrew Westhoff, Georg Karpel-Massler, Peter Canoll, Markus D. Siegelin

Publications and Research

Liver-X-receptor (LXR) agonists are known to bear anti-tumor activity. However, their efficacy is limited and additional insights regarding the underlying mechanism are necessary. By performing transcriptome analysis coupled with global polar metabolite screening, we show that LXR agonists, LXR623 and GW3965, enhance synergistically the anti-proliferative effect of BH3 mimetics in solid tumor malignancies, which is predominantly mediated by cell death with features of apoptosis and is rescued by exogenous cholesterol. Extracellular flux analysis and carbon tracing experiments (U-13C-glucose and U-13C-glutamine) reveal that within 5 h, activation of LXRβ results in reprogramming of tumor cell metabolism, leading …


Modeling Interval Timing By Recurrent Neural Nets, Theodore Raphan, Eugene Dorokhin, Andrew R. Delamater Aug 2019

Modeling Interval Timing By Recurrent Neural Nets, Theodore Raphan, Eugene Dorokhin, Andrew R. Delamater

Publications and Research

The purpose of this study was to take a new approach in showing how the central nervous system might encode time at the supra-second level using recurrent neural nets (RNNs). This approach utilizes units with a delayed feedback, whose feedback weight determines the temporal properties of specific neurons in the network architecture. When these feedback neurons are coupled, they form a multilayered dynamical system that can be used to model temporal responses to steps of input in multidimensional systems. The timing network was implemented using separate recurrent “Go” and “NoGo” neural processing units to process an individual stimulus indicating the …


Development Of Substrate Degradation Enzyme Therapy For Mucopolysaccharidosis Iva Murine Model., Kazuki Sawamoto, Shunji Tomatsu Aug 2019

Development Of Substrate Degradation Enzyme Therapy For Mucopolysaccharidosis Iva Murine Model., Kazuki Sawamoto, Shunji Tomatsu

Department of Pediatrics Faculty Papers

Mucopolysaccharidosis IVA (MPS IVA) is caused by a deficiency of the lysosomal enzyme N-acetylgalactosamine-6-sulfate sulfatase (GALNS). Conventional enzyme replacement therapy (ERT) is approved for MPS IVA. However, the fact that the infused enzyme cannot penetrate avascular lesions in cartilage leads to minimal impact on the bone lesion. Moreover, short half-life, high cost, instability, and narrow optimal pH range remain unmet challenges in ERT. Thermostable keratanase, endo-β-N-acetylglucosaminidase, has a unique character of a wide optimal pH range of pH 5.0-7.0. We hypothesized that this endoglycosidase degrades keratan sulfate (KS) polymer in circulating blood and, therefore, ameliorates the accumulation of KS in …


Evidence To Date: Ranibizumab And Its Potential In The Treatment Of Retinopathy Of Prematurity, Samir Patel, Michael A. Klufas Aug 2019

Evidence To Date: Ranibizumab And Its Potential In The Treatment Of Retinopathy Of Prematurity, Samir Patel, Michael A. Klufas

Wills Eye Hospital Papers

Retinopathy of prematurity (ROP) is a leading and preventable cause of childhood blindness worldwide. Although laser photocoagulation remains the gold standard for treatment, the off-label use of anti-vascular endothelial growth factor (anti-VEGF) therapy to treat ROP, particularly posterior zone I disease, is increasing. Although initial studies on anti-VEGF therapy for ROP have focused on bevacizumab, recent studies have proposed that ranibizumab may be a safer and more effective alternative for use in this population. This review updates recent evidence regarding the use of ranibizumab in the management of ROP.


Mice Exposed To Combined Chronic Low-Dose Irradiation And Modeled Microgravity Develop Long-Term Neurological Sequelae, Amber M. Paul, Eliah G. Overbey, William A. Da Silveira, Candice G.T. Tahimic, Sigrid S. Reinsch, Nathaniel Szewczyk, Seta Stanbouly, Charles Wang, Jonathan M. Galazka, Xiao Wen Mao Aug 2019

Mice Exposed To Combined Chronic Low-Dose Irradiation And Modeled Microgravity Develop Long-Term Neurological Sequelae, Amber M. Paul, Eliah G. Overbey, William A. Da Silveira, Candice G.T. Tahimic, Sigrid S. Reinsch, Nathaniel Szewczyk, Seta Stanbouly, Charles Wang, Jonathan M. Galazka, Xiao Wen Mao

Publications

Spaceflight poses many challenges for humans. Ground-based analogs typically focus on single parameters of spaceflight and their associated acute effects. This study assesses the long-term transcriptional effects following single and combination spaceflight analog conditions using the mouse model: simulated microgravity via hindlimb unloading (HLU) and/or low-dose γ-ray irradiation (LDR) for 21 days, followed by 4 months of readaptation. Changes in gene expression and epigenetic modifications in brain samples during readaptation were analyzed by whole transcriptome shotgun sequencing (RNA-seq) and reduced representation bisulfite sequencing (RRBS). The results showed minimal gene expression and cytosine methylation alterations at 4 months readaptation within single …


Generation Of An Oncolytic Adenovirus Targeting The Cxcr4 And Cxcr7 Chemokine Receptors In Breast Cancer, Samia Melissa O'Bryan Aug 2019

Generation Of An Oncolytic Adenovirus Targeting The Cxcr4 And Cxcr7 Chemokine Receptors In Breast Cancer, Samia Melissa O'Bryan

LSU Doctoral Dissertations

Breast cancer is the most diagnosed cancer in women under 60 and the second most diagnosed cancer in women over 60. While treatments for localized breast cancer are quite successful with high survival rates at 99%, advanced breast cancer remains hard to treat with a nearly 75% decrease in survival. Current treatments are inefficient at treating advanced stages of breast cancer, and thus, new therapies are sorely needed to address the complexity of advanced stage breast cancer. The ideal therapy would be capable of systemic administration, targets cancer cells and spares normal tissue. Oncolytic adenovirus is an ideal therapeutic vector …


Editorial: Cancer Ecosystems., Ubaldo E. Martinez-Outshoorn, Mireia Bartrons, Ramon Bartrons Aug 2019

Editorial: Cancer Ecosystems., Ubaldo E. Martinez-Outshoorn, Mireia Bartrons, Ramon Bartrons

Department of Medical Oncology Faculty Papers

No abstract provided.


Human Polyomavirus Jcpyv And Its Role In Progressive Multifocal Leukoencephalopathy And Oncogenesis, Luis Del Valle, Sergio Piña-Oviedo Aug 2019

Human Polyomavirus Jcpyv And Its Role In Progressive Multifocal Leukoencephalopathy And Oncogenesis, Luis Del Valle, Sergio Piña-Oviedo

School of Medicine Faculty Publications

The human neurotropic virus JCPyV, a member of the family, is the opportunistic infectious agent of Progressive Multifocal Leukoencephalopathy (PML), a fatal disease seen in severe immunosuppressive conditions and, during the last decade, in patients undergoing immunotherapy. JCPyV is a ubiquitous pathogen with up to 85% of the adult population word-wide exhibiting antibodies against it. Early experiments demonstrated that direct inoculation of JCPyV into the brain of different species resulted in the development of brain tumors and other neuroectodermal-derived neoplasias. Later, several reports showed the detection of viral sequences in medulloblastomas and glial tumors, as well as expression of the …


N-Glycosylation-Defective Splice Variants Of Neuropilin-1 Promote Metastasis By Activating Endosomal Signals, Xiuping Huang, Qing Ye, Min Chen, Aimin Li, Wenting Mi, Yuxin Fang, Yekaterina Y. Zaytseva, Kathleen L. O'Connor, Craig W. Vander Kooi, Side Liu, Qing-Bai She Aug 2019

N-Glycosylation-Defective Splice Variants Of Neuropilin-1 Promote Metastasis By Activating Endosomal Signals, Xiuping Huang, Qing Ye, Min Chen, Aimin Li, Wenting Mi, Yuxin Fang, Yekaterina Y. Zaytseva, Kathleen L. O'Connor, Craig W. Vander Kooi, Side Liu, Qing-Bai She

Markey Cancer Center Faculty Publications

Neuropilin-1 (NRP1) is an essential transmembrane receptor with a variety of cellular functions. Here, we identify two human NRP1 splice variants resulting from the skipping of exon 4 and 5, respectively, in colorectal cancer (CRC). Both NRP1 variants exhibit increased endocytosis/recycling activity and decreased levels of degradation, leading to accumulation on endosomes. This increased endocytic trafficking of the two NRP1 variants, upon HGF stimulation, is due to loss of N-glycosylation at the Asn150 or Asn261 site, respectively. Moreover, these NRP1 variants enhance interactions with the Met and β1-integrin receptors, resulting in Met/β1-integrin co-internalization and co-accumulation on endosomes. This provides persistent …


Response Of Human Small Intestinal Epithelium To Fractionated Irradiation: Dynamical Modeling Approach, Francis A. Cucinotta, Olga A. Smirnova Aug 2019

Response Of Human Small Intestinal Epithelium To Fractionated Irradiation: Dynamical Modeling Approach, Francis A. Cucinotta, Olga A. Smirnova

Health Physics and Diagnostic Sciences Faculty Research

A biologically motivated mathematical model of the dynamics of the small intestinal epithelium in humans treated with fractionated radiotherapy has been developed and is further investigated here. This model, originating from our previous work, is implemented as a system of nonlinear ordinary differential equations, in which the variables and parameters have a clear biological meaning. The model also includes, as input, the key parameters of fractionated irradiation. The modeling results on the dynamical response of the human normal small intestinal epithelium to fractionated radiation therapy regimens were in agreement with the corresponding empirical data, which, in turn, demonstrates the capability …


Meta-Analysis Of Cognitive Performance By Novel Object Recognition After Proton And Heavy Ion Exposures, Eliedonna Cacao, Francis A. Cucinotta Aug 2019

Meta-Analysis Of Cognitive Performance By Novel Object Recognition After Proton And Heavy Ion Exposures, Eliedonna Cacao, Francis A. Cucinotta

Health Physics and Diagnostic Sciences Faculty Research

Experimental studies of cognitive detriments in mice and rats after proton and heavy ion exposures have been performed by several laboratories to investigate possible risks to astronauts exposed to cosmic rays in space travel and patients treated for brain cancers with proton and carbon beams in Hadron therapy. However, distinct radiation types and doses, cognitive tests and rodent models have been used by different laboratories, while few studies have considered detailed dose-response characterizations, including estimates of relative biological effectiveness (RBE). Here we report on the first quantitative meta-analysis of the dose response for proton and heavy ion rodent studies of …


Advances In Gene Ontology Utilization Improve Statistical Power Of Annotation Enrichment, Eugene Waverly Hinderer Iii, Robert M. Flight, Rashmi Dubey, James N. Macleod, Hunter N. B. Moseley Aug 2019

Advances In Gene Ontology Utilization Improve Statistical Power Of Annotation Enrichment, Eugene Waverly Hinderer Iii, Robert M. Flight, Rashmi Dubey, James N. Macleod, Hunter N. B. Moseley

Maxwell H. Gluck Equine Research Center Faculty Publications

Gene-annotation enrichment is a common method for utilizing ontology-based annotations in gene and gene-product centric knowledgebases. Effective utilization of these annotations requires inferring semantic linkages by tracing paths through edges in the ontological graph, referred to as relations. However, some relations are semantically problematic with respect to scope, necessitating their omission or modification lest erroneous term mappings occur. To address these issues, we created the Gene Ontology Categorization Suite, or GOcats—a novel tool that organizes the Gene Ontology into subgraphs representing user-defined concepts, while ensuring that all appropriate relations are congruent with respect to scoping semantics. Here, we demonstrate the …


Equine Or Porcine Synovial Fluid As A Novel Ex Vivo Model For The Study Of Bacterial Free-Floating Biofilms That Form In Human Joint Infections, Jessica M. Gilbertie, Lauren V. Schnabel, Noreen J. Hickok, Megan E. Jacob, Brian P. Conlon, Irving Shapiro, Javad Parvizi, Thomas P. Schaer Aug 2019

Equine Or Porcine Synovial Fluid As A Novel Ex Vivo Model For The Study Of Bacterial Free-Floating Biofilms That Form In Human Joint Infections, Jessica M. Gilbertie, Lauren V. Schnabel, Noreen J. Hickok, Megan E. Jacob, Brian P. Conlon, Irving Shapiro, Javad Parvizi, Thomas P. Schaer

Department of Orthopaedic Surgery Faculty Papers

Bacterial invasion of synovial joints, as in infectious or septic arthritis, can be difficult to treat in both veterinary and human clinical practice. Biofilms, in the form of free-floating clumps or aggregates, are involved with the pathogenesis of infectious arthritis and periprosthetic joint infection (PJI). Infection of a joint containing an orthopedic implant can additionally complicate these infections due to the presence of adherent biofilms. Because of these biofilm phenotypes, bacteria within these infected joints show increased antimicrobial tolerance even at high antibiotic concentrations. To date, animal models of PJI or infectious arthritis have been limited to small animals such …


Imaging Of Glucose Metabolism By 13c-Mri Distinguishes Pancreatic Cancer Subtypes In Mice, Shun Kishimoto, Jeffrey R. Brender, Daniel R. Crooks, Shingo Matsumoto, Tomohiro Seki, Nobu Oshima, Hellmut Merkle, Penghui Lin, Galen Reed, Albert P. Chen, Jan Henrik Ardenkjaer-Larsen, Jeeva Munasinghe, Keita Saito, Kazutoshi Yamamoto, Peter L. Choyke, James Mitchell, Andrew N. Lane, Teresa W. M. Fan, W. Marston Linehan, Murali C. Krishna Aug 2019

Imaging Of Glucose Metabolism By 13c-Mri Distinguishes Pancreatic Cancer Subtypes In Mice, Shun Kishimoto, Jeffrey R. Brender, Daniel R. Crooks, Shingo Matsumoto, Tomohiro Seki, Nobu Oshima, Hellmut Merkle, Penghui Lin, Galen Reed, Albert P. Chen, Jan Henrik Ardenkjaer-Larsen, Jeeva Munasinghe, Keita Saito, Kazutoshi Yamamoto, Peter L. Choyke, James Mitchell, Andrew N. Lane, Teresa W. M. Fan, W. Marston Linehan, Murali C. Krishna

Center for Environmental and Systems Biochemistry Faculty Publications

Metabolic differences among and within tumors can be an important determinant in cancer treatment outcome. However, methods for determining these differences non-invasively in vivo is lacking. Using pancreatic ductal adenocarcinoma as a model, we demonstrate that tumor xenografts with a similar genetic background can be distinguished by their differing rates of the metabolism of 13C labeled glucose tracers, which can be imaged without hyperpolarization by using newly developed techniques for noise suppression. Using this method, cancer subtypes that appeared to have similar metabolic profiles based on steady state metabolic measurement can be distinguished from each other. The metabolic maps from …