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Efficient Remyelination Requires Dna Methylation, Sarah Moyon, Dan Ma, Jimmy L. Huynh, David J.C. Coutts, Chao Zhao, Patrizia Casaccia, Robin J. M. Franklin Mar 2017

Efficient Remyelination Requires Dna Methylation, Sarah Moyon, Dan Ma, Jimmy L. Huynh, David J.C. Coutts, Chao Zhao, Patrizia Casaccia, Robin J. M. Franklin

Advanced Science Research Center

Oligodendrocyte progenitor cells (OPCs) are the principal source of new myelin in the central nervous system. A better understanding of how they mature into myelin-forming cells is of high relevance for remyelination. It has recently been demonstrated that during developmental myelination, the DNA methyltransferase 1 (DNMT1), but not DNMT3A, is critical for regulating proliferation and differentiation of OPCs into myelinating oligodendrocytes (OLs). However, it remains to be determined whether DNA methylation is also critical for the differentiation of adult OPCs during remyelination. After lysolecithin-induced demyelination in the ventrolateral spinal cord white matter of adult mice of either sex, we detected …


Galactose And Its Metabolites Deteriorate Metaphase Ii Mouse Oocyte Quality And Subsequent Embryo Development By Disrupting The Spindle Structure, Mili Thakur, Faten Shaeib, Sana N. Khan, Hamid-Reza Kohan-Ghader, Roohi Jeelani, Sarah R. Aldhaheri, Bernard Gonik, Husam M. Abu-Soud Mar 2017

Galactose And Its Metabolites Deteriorate Metaphase Ii Mouse Oocyte Quality And Subsequent Embryo Development By Disrupting The Spindle Structure, Mili Thakur, Faten Shaeib, Sana N. Khan, Hamid-Reza Kohan-Ghader, Roohi Jeelani, Sarah R. Aldhaheri, Bernard Gonik, Husam M. Abu-Soud

C.S. Mott Center Research Publications

Premature ovarian insufficiency (POI) is a frequent long-term complication of classic galactosemia. The majority of women with this disorder develop POI, however rare spontaneous pregnancies have been reported. Here, we evaluate the effect of D-galactose and its metabolites, galactitol and galactose 1-phosphate, on oocyte quality as well as embryo development to elucidate the mechanism through which these compounds mediate oocyte deterioration. Metaphase II mouse oocytes (n=240), with and without cumulus cells (CCs), were exposed for 4hours to D-galactose (2μM), galactitol (11μM) and galactose 1-phosphate (0.1mM), (corresponding to plasma concentrations in patients on galactoserestricted diet) and compared to controls. The treated …


Coccolithoviruses: A Review Of Cross-Kingdom Genomic Thievery And Metabolic Thuggery, Jozef I. Nissimov, António Pagarete, Fangrui Ma, Sean Cody, David D. Dunigan, Susan A. Kimmance, Michael J. Allen Mar 2017

Coccolithoviruses: A Review Of Cross-Kingdom Genomic Thievery And Metabolic Thuggery, Jozef I. Nissimov, António Pagarete, Fangrui Ma, Sean Cody, David D. Dunigan, Susan A. Kimmance, Michael J. Allen

Nebraska Center for Virology: Faculty Publications

Coccolithoviruses (Phycodnaviridae) infect and lyse the most ubiquitous and successful coccolithophorid in modern oceans, Emiliania huxleyi. So far, the genomes of 13 of these giant lytic viruses (i.e., Emiliania huxleyi viruses—EhVs) have been sequenced, assembled, and annotated. Here, we performed an in-depth comparison of their genomes to try and contextualize the ecological and evolutionary traits of these viruses. The genomes of these EhVs have from 444 to 548 coding sequences (CDSs). Presence/absence analysis of CDSs identified putative genes with particular ecological significance, namely sialidase, phosphate permease, and sphingolipid biosynthesis. The viruses clustered into distinct clades, based on their DNA polymerase …


Effects Of Cetp Inhibition With Anacetrapib On Metabolism Of Vldl-Tg And Plasma Apolipoproteins C-Ii, C-Iii, And E, John S. Millar, Michael E. Lassman, Tiffany Thomas, Rajasekhar Ramakrishnan, Patricia Jumes, Richard L. Dunbar, Emil M. Degoma, Amanda L. Baer, Wahida Karmally, Daniel S. Donovan, Hashmi Rafeek, John A. Wagner, Stephen Holleran, Joseph Obunike, Yang Liu, Soumia Aoujil, Taylor Standiford, David E. Gutstein, Henry N. Ginsberg, Daniel J. Rader, Gissette Reyes-Soffer Mar 2017

Effects Of Cetp Inhibition With Anacetrapib On Metabolism Of Vldl-Tg And Plasma Apolipoproteins C-Ii, C-Iii, And E, John S. Millar, Michael E. Lassman, Tiffany Thomas, Rajasekhar Ramakrishnan, Patricia Jumes, Richard L. Dunbar, Emil M. Degoma, Amanda L. Baer, Wahida Karmally, Daniel S. Donovan, Hashmi Rafeek, John A. Wagner, Stephen Holleran, Joseph Obunike, Yang Liu, Soumia Aoujil, Taylor Standiford, David E. Gutstein, Henry N. Ginsberg, Daniel J. Rader, Gissette Reyes-Soffer

Publications and Research

Cholesteryl ester transfer protein (CETP) mediates the transfer of HDL cholesteryl esters for triglyceride (TG) in VLDL/LDL. CETP inhibition, with anacetrapib, increases HDL-cholesterol, reduces LDL-cholesterol, and lowers TG levels. This study describes the mechanisms responsible for TG lowering by examining the kinetics of VLDL-TG, apoC-II, apoC-III, and apoE. Mildly hypercholesterolemic subjects were randomized to either placebo (N = 10) or atorvastatin 20 mg/qd (N = 29) for 4 weeks (period 1) followed by 8 weeks of anacetrapib, 100 mg/qd (period 2). Following each period, subjects underwent stable isotope metabolic studies to determine the fractional catabolic rates (FCRs) and production rates …


Vestibular Activation Habituates The Vasovagal Response In The Rat, Bernard Cohen, Giorgio P. Martinelli, Yongqing Xiang, Theodore Raphan, Sergei B. Yakushin Mar 2017

Vestibular Activation Habituates The Vasovagal Response In The Rat, Bernard Cohen, Giorgio P. Martinelli, Yongqing Xiang, Theodore Raphan, Sergei B. Yakushin

Publications and Research

Vasovagal syncope is a significant medical problem without effective therapy, postulated to be related to a collapse of baroreflex function. While some studies have shown that repeated static tilts can block vasovagal syncope, this was not found in other studies. Using anesthetized, male Long–Evans rats that were highly susceptible to generation of vasovagal responses, we found that repeated activation of the vestibulosympathetic reflex (VSR) with ±2 and ±3 mA, 0.025 Hz sinusoidal galvanic vestibular stimulation (sGVS) caused incremental changes in blood pressure (BP) and heart rate (HR) that blocked further generation of vasovagal responses. Initially, BP and HR fell ≈20–50 …


Dynamic Transcriptomes Identify Biogenic Amines And Insect-Like Hormonal Regulation For Mediating Reproduction In Schistosoma Japonicum., Jipeng Wang, Ying Yu, Haimo Shen, Tao Qing, Yuanting Zheng, Qing Li, Xiaojin Mo, Shuqi Wang, Nana Li, Riyi Chai, Bin Xu, Mu Liu, Paul J Brindley, Donald P Mcmanus, Zheng Feng, Leming Shi, Wei Hu Mar 2017

Dynamic Transcriptomes Identify Biogenic Amines And Insect-Like Hormonal Regulation For Mediating Reproduction In Schistosoma Japonicum., Jipeng Wang, Ying Yu, Haimo Shen, Tao Qing, Yuanting Zheng, Qing Li, Xiaojin Mo, Shuqi Wang, Nana Li, Riyi Chai, Bin Xu, Mu Liu, Paul J Brindley, Donald P Mcmanus, Zheng Feng, Leming Shi, Wei Hu

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Eggs produced by the mature female parasite are responsible for the pathogenesis and transmission of schistosomiasis. Female schistosomes rely on a unique male-induced strategy to accomplish reproductive development, a process that is incompletely understood. Here we map detailed transcriptomic profiles of male and female Schistosoma japonicum across eight time points throughout the sexual developmental process from pairing to maturation. The dynamic gene expression pattern data reveal clear sex-related characteristics, indicative of an unambiguous functional division between males and females during their interplay. Cluster analysis, in situ hybridization and RNAi assays indicate that males likely use biogenic amine neurotransmitters through the …


Relationship Of The Median And Radial Nerves At The Elbow: Application To Avoiding Injury During Venipuncture Or Other Invasive Procedures Of The Cubital Fossa., Vlad Voin, Joe Iwanaga, Juan P Sardi, Christian Fisahn, Marios Loukas, Rod J Oskouian, R Shane Tubbs Mar 2017

Relationship Of The Median And Radial Nerves At The Elbow: Application To Avoiding Injury During Venipuncture Or Other Invasive Procedures Of The Cubital Fossa., Vlad Voin, Joe Iwanaga, Juan P Sardi, Christian Fisahn, Marios Loukas, Rod J Oskouian, R Shane Tubbs

Articles, Abstracts, and Reports

INTRODUCTION: The median and radial nerves are two important neural structures found in the cubital fossa. The trajectory and landmarks used to identify their location are important when procedures are done in this area.

METHODS AND MATERIALS: Ten fresh-frozen cadavers were dissected (20 upper limbs) and measurements were taken from the medial epicondyle to the median and radial nerves as well as to the lateral epicondyle of each limb.

RESULTS: The distance between the medial epicondyle and the median nerve was found to be three centimeters with a range of 2.1 to four centimeters and the distance from the medial …


Spotlight On Blisibimod And Its Potential In The Treatment Of Systemic Lupus Erythematosus: Evidence To Date, Aleksander Lenert, Timothy B. Niewold, Petar Lenert Mar 2017

Spotlight On Blisibimod And Its Potential In The Treatment Of Systemic Lupus Erythematosus: Evidence To Date, Aleksander Lenert, Timothy B. Niewold, Petar Lenert

Internal Medicine Faculty Publications

B cells in general and BAFF (B cell activating factor of the tumor necrosis factor [TNF] family) in particular have been primary targets of recent clinical trials in systemic lupus erythematosus (SLE). In 2011, belimumab, a monoclonal antibody against BAFF, became the first biologic agent approved for the treatment of SLE. Follow-up studies have shown excellent long-term safety and tolerability of belimumab. In this review, we critically analyze blisibimod, a novel BAFF-neutralizing agent. In contrast to belimumab that only blocks soluble BAFF trimer but not soluble 60-mer or membrane BAFF, blisibimod blocks with high affinity all three forms of BAFF. …


Tuning Up The Old Brain With New Tricks: Attention Training Via Neurofeedback, Yang Jiang, Reza Abiri, Xiaopeng Zhao Mar 2017

Tuning Up The Old Brain With New Tricks: Attention Training Via Neurofeedback, Yang Jiang, Reza Abiri, Xiaopeng Zhao

Sanders-Brown Center on Aging Faculty Publications

Neurofeedback (NF) is a form of biofeedback that uses real-time (RT) modulation of brain activity to enhance brain function and behavioral performance. Recent advances in Brain-Computer Interfaces (BCI) and cognitive training (CT) have provided new tools and evidence that NF improves cognitive functions, such as attention and working memory (WM), beyond what is provided by traditional CT. More published studies have demonstrated the efficacy of NF, particularly for treating attention deficit hyperactivity disorder (ADHD) in children. In contrast, there have been fewer studies done in older adults with or without cognitive impairment, with some notable exceptions. The focus of this …


The Role Of Adenosine Signaling In Headache: A Review., Nathan T. Fried, Melanie B. Elliott, Michael L. Oshinsky Mar 2017

The Role Of Adenosine Signaling In Headache: A Review., Nathan T. Fried, Melanie B. Elliott, Michael L. Oshinsky

Department of Neurology Faculty Papers

Migraine is the third most prevalent disease on the planet, yet our understanding of its mechanisms and pathophysiology is surprisingly incomplete. Recent studies have built upon decades of evidence that adenosine, a purine nucleoside that can act as a neuromodulator, is involved in pain transmission and sensitization. Clinical evidence and rodent studies have suggested that adenosine signaling also plays a critical role in migraine headache. This is further supported by the widespread use of caffeine, an adenosine receptor antagonist, in several headache treatments. In this review, we highlight evidence that supports the involvement of adenosine signaling in different forms of …


Pulmonary Surfactant Fortified With Cath-2 As A Novel Therapy For Bacterial Pneumonia, Brandon J. Baer Mar 2017

Pulmonary Surfactant Fortified With Cath-2 As A Novel Therapy For Bacterial Pneumonia, Brandon J. Baer

Western Research Forum

Background: Bacterial pneumonia is a leading cause of death worldwide, with high mortality rates persisting even after antibiotic treatment. Current treatments for pneumonia involve administration of antibiotics, however after the bacteria are killed they release toxic substances that induce inflammation and lung dysfunction. Host defense peptides represent a potential solution to this problem through their ability to down regulate inflammation. However, effective delivery to the lung is difficult because of the complex branching structure of the airways. My study addresses this delivery problem by using exogenous surfactant, a pulmonary delivery vehicle capable of improving spreading of these peptides throughout the …


The Soy-Derived Peptide Lunasin Inhibits Invasive Potential Of Melanoma Initiating Cells, Chris Shidal, Jun-Ichi Inaba, Kavitha Yaddanapudi, Keith R. Davis Mar 2017

The Soy-Derived Peptide Lunasin Inhibits Invasive Potential Of Melanoma Initiating Cells, Chris Shidal, Jun-Ichi Inaba, Kavitha Yaddanapudi, Keith R. Davis

Plant Pathology Faculty Publications

Lunasin is a 44 amino acid peptide with multiple functional domains including an aspartic acid tail, an RGD domain, and a chromatin-binding helical domain. We recently showed that Lunasin induced a phenotype switch of cancer initiating cells (CIC) out of the stem compartment by inducing melanocyte-associated differentiation markers while simultaneously reducing stem-cell-associated transcription factors. In the present study, we advance the hypothesis that Lunasin can reduce pools of melanoma cells with stem cell-like properties, and demonstrate that Lunasin treatment effectively inhibits the invasive potential of CICs in vitro as well as in vivo in a mouse experimental metastasis model. Mice …


Bioactive Lipids And Circulating Progenitor Cells In Patients With Cardiovascular Disease, Salim S. Hayek, Yuri Klyachkin, Ahmed Asfour, Nima Ghasemzadeh, Mosaab Awad, Iraj Hesaroieh, Hina Ahmed, Brandon Gray, Jinhee Kim, Edmund K. Waller, Arshed A. Quyyumi, Ahmed K. Abdel-Latif Mar 2017

Bioactive Lipids And Circulating Progenitor Cells In Patients With Cardiovascular Disease, Salim S. Hayek, Yuri Klyachkin, Ahmed Asfour, Nima Ghasemzadeh, Mosaab Awad, Iraj Hesaroieh, Hina Ahmed, Brandon Gray, Jinhee Kim, Edmund K. Waller, Arshed A. Quyyumi, Ahmed K. Abdel-Latif

Internal Medicine Faculty Publications

Bone marrow-derived progenitor cells are mobilized into the peripheral blood after acute myocardial injury and in chronic ischemic heart disease. However, the mechanisms responsible for this mobilization are poorly understood. We examined the relationship between plasma levels of bioactive lipids and number of circulating progenitor cells (CPCs) in patients (N = 437) undergoing elective or emergent cardiac catheterization. Plasma levels of sphingosine-1 phosphate (S1P) and ceramide-1 phosphate (C1P) were quantified using mass spectrometry. CPCs were assessed using flow cytometry. S1P levels correlated with the numbers of CD34+, CD34+/CD133+, and CD34+/CXCR4+ CPCs even after adjustment for potential confounding factors. However, …


A Murine Model To Study Epilepsy And Sudep Induced By Malaria Infection., Paddy Ssentongo, Anna E Robuccio, Godfrey Thuku, Derek G Sim, Ali Nabi, Fatemeh Bahari, Balaji Shanmugasundaram, Myles W Billard, Andrew Geronimo, Kurt W Short, Patrick J Drew, Jennifer Baccon, Steven L Weinstein, Frank G Gilliam, José A Stoute, Vernon M Chinchilli, Andrew F Read, Bruce J Gluckman, Steven J Schiff Mar 2017

A Murine Model To Study Epilepsy And Sudep Induced By Malaria Infection., Paddy Ssentongo, Anna E Robuccio, Godfrey Thuku, Derek G Sim, Ali Nabi, Fatemeh Bahari, Balaji Shanmugasundaram, Myles W Billard, Andrew Geronimo, Kurt W Short, Patrick J Drew, Jennifer Baccon, Steven L Weinstein, Frank G Gilliam, José A Stoute, Vernon M Chinchilli, Andrew F Read, Bruce J Gluckman, Steven J Schiff

Neurology Faculty Publications

One of the largest single sources of epilepsy in the world is produced as a neurological sequela in survivors of cerebral malaria. Nevertheless, the pathophysiological mechanisms of such epileptogenesis remain unknown and no adjunctive therapy during cerebral malaria has been shown to reduce the rate of subsequent epilepsy. There is no existing animal model of postmalarial epilepsy. In this technical report we demonstrate the first such animal models. These models were created from multiple mouse and parasite strain combinations, so that the epilepsy observed retained universality with respect to genetic background. We also discovered spontaneous sudden unexpected death in epilepsy …


Beta Oscillatory Changes And Retention Of Motor Skills During Practice In Healthy Subjects And In Patients With Parkinson’S Disease, Aaron B. Nelson, Clara Moisello, Jing Lin, Priya Panday, Serena Ricci, Andrea Canessa, Alessandro Di Rocco, Angelo Quartarone, Giuseppe Frazzitta, Ioannis U. Isaias, Giulio Tononi, Chiara Cirelli, M. Felice Ghilardi Mar 2017

Beta Oscillatory Changes And Retention Of Motor Skills During Practice In Healthy Subjects And In Patients With Parkinson’S Disease, Aaron B. Nelson, Clara Moisello, Jing Lin, Priya Panday, Serena Ricci, Andrea Canessa, Alessandro Di Rocco, Angelo Quartarone, Giuseppe Frazzitta, Ioannis U. Isaias, Giulio Tononi, Chiara Cirelli, M. Felice Ghilardi

Publications and Research

Recently we found that modulation depth of beta power during movement increases with practice over sensory-motor areas in normal subjects but not in patients with Parkinson’s disease (PD). As such changesmight reflect use-dependentmodifications, we concluded that reduction of beta enhancement in PD represents saturation of cortical plasticity. A few questions remained open: What is the relation between these EEG changes and retention of motor skills? Would a second task exposure restore beta modulation enhancement in PD? Do practice-induced increases of beta modulation occur within each block? We thus recorded EEG in patients with PD and age-matched controls in two consecutive …


Atr Mutations Promote The Growth Of Melanoma Tumors By Modulating The Immune Microenvironment., Chi-Fen Chen, Rolando Ruiz-Vega, Priya Vasudeva, Francisco Espitia, Tatiana B Krasieva, Sebastien De Feraudy, Bruce J Tromberg, Sharon Huang, Chad P Garner, Jie Wu, Dave S B Hoon, Anand K Ganesan Mar 2017

Atr Mutations Promote The Growth Of Melanoma Tumors By Modulating The Immune Microenvironment., Chi-Fen Chen, Rolando Ruiz-Vega, Priya Vasudeva, Francisco Espitia, Tatiana B Krasieva, Sebastien De Feraudy, Bruce J Tromberg, Sharon Huang, Chad P Garner, Jie Wu, Dave S B Hoon, Anand K Ganesan

Articles, Abstracts, and Reports

Melanomas accumulate a high burden of mutations that could potentially generate neoantigens, yet somehow suppress the immune response to facilitate continued growth. In this study, we identify a subset of human melanomas that have loss-of-function mutations in ATR, a kinase that recognizes and repairs UV-induced DNA damage and is required for cellular proliferation. ATR mutant tumors exhibit both the accumulation of multiple mutations and the altered expression of inflammatory genes, resulting in decreased T cell recruitment and increased recruitment of macrophages known to spur tumor invasion. Taken together, these studies identify a mechanism by which melanoma cells modulate the immune …


Gastrointestinal-Renal Axis: Role In The Regulation Of Blood Pressure., Jian Yang, Pedro A Jose, Chunyu Zeng Mar 2017

Gastrointestinal-Renal Axis: Role In The Regulation Of Blood Pressure., Jian Yang, Pedro A Jose, Chunyu Zeng

Medicine Faculty Publications

Hypertension is one of the most common and important health problems worldwide.1 It has been estimated that 29% of the world's adult population, or 1.56 billion people, will have hypertension by the year 2025.2The prevalence of high blood pressure and its adverse consequences result in a heavy burden for hypertensive patients from high‐, middle‐, and low‐income countries.2, 3 Many monogenic causes of hypertension have been reported. However, determining the causes of essential hypertension has been hampered because it is a complex disorder with genetic, epigenetic, and environmental determinants. Among numerous environmental factors, sodium intake is …


Zoledronic Acid Alters Hematopoiesis And Generates Breast Tumor-Suppressive Bone Marrow Cells., Jessalyn M. Ubellacker, Marie-Therese Haider, Molly J. Decristo, Gloria Allocca, Nicola J. Brown, Daniel P. Silver, Ingunn Holen, Sandra S. Mcallister Mar 2017

Zoledronic Acid Alters Hematopoiesis And Generates Breast Tumor-Suppressive Bone Marrow Cells., Jessalyn M. Ubellacker, Marie-Therese Haider, Molly J. Decristo, Gloria Allocca, Nicola J. Brown, Daniel P. Silver, Ingunn Holen, Sandra S. Mcallister

Department of Medical Oncology Faculty Papers

BACKGROUND: The bone-targeting agent zoledronic acid (ZOL) increases breast cancer survival in subsets of patients, but the underlying reasons for this protective effect are unknown. ZOL modulates the activity of osteoclasts and osteoblasts, which form hematopoietic stem cell niches, and therefore may affect hematopoietic cells that play a role in breast cancer progression.

METHOD: Immunocompetent and immunocompromised strains of mice commonly used for breast cancer research were injected with a single, clinically relevant dose of ZOL (100 μg/kg) or vehicle control. The effects of ZOL on the bone marrow microenvironment (bone volume, bone cell number/activity, extracellular matrix composition) were established …


Effect Of Duration Of Symptoms On Orchiectomy Rates In Testicular Torsion In Patients Under 25: Important Prognostic Trends, Lior Taich, Marc Zeffren, Muhammad Choudhury Mar 2017

Effect Of Duration Of Symptoms On Orchiectomy Rates In Testicular Torsion In Patients Under 25: Important Prognostic Trends, Lior Taich, Marc Zeffren, Muhammad Choudhury

NYMC Student Posters

The purpose of this study is to explore the relationship between duration of symptoms in testicular torsion and the effect on orchiectomy rates, with the intention of establishing an updated timeline for clinical management and surgical urgency.


The Role Of Estradiol Metabolism In Urogenital Schistosomiasis-Induced Bladder Cancer, Nuno Vale, Maria Gouveia, Gabriel Rinaldi, Julio Santos, Lucio Lara Santos, Paul J. Brindley, Jose Correia Da Costa Mar 2017

The Role Of Estradiol Metabolism In Urogenital Schistosomiasis-Induced Bladder Cancer, Nuno Vale, Maria Gouveia, Gabriel Rinaldi, Julio Santos, Lucio Lara Santos, Paul J. Brindley, Jose Correia Da Costa

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Urogenital schistosomiasis is a neglected tropical disease that can lead to bladder cancer. How urogenital schistosomiasis induces carcinogenesis remains unclear, although there is evidence that the human blood fluke Schistosoma haematobium, the infectious agent of urogenital schistosomiasis, releases estradiol-like metabolites. These kind of compounds have been implicated in other cancers. Aiming for enhanced understanding of the pathogenesis of the urogenital schistosomiasisinduced bladder cancer, here we review, interpret, and discuss findings of estradiol-like metabolites detected in both the parasite and in the human urine during urogenital schistosomiasis. Moreover, we predict pathways and enzymes that are involved in the production of these …


Prevention Of Recurrent Affective Episodes Using Extinction Training In The Reconsolidation Window: A Testable Psychotherapeutic Strategy., Robert M Post, Robert Kegan Mar 2017

Prevention Of Recurrent Affective Episodes Using Extinction Training In The Reconsolidation Window: A Testable Psychotherapeutic Strategy., Robert M Post, Robert Kegan

Psychiatry and Behavioral Sciences Faculty Publications

Stressors may initially precipitate affective episodes, but with sufficient numbers of recurrences, episodes can occur more autonomously. It is postulated the memory engram for these recurrent depressions moves from the conscious representational memory system to the unconscious habit memory system encoded in the striatum. If this were the case, cognitive behavior therapy targeted toward extinction of habit memories could be an effective maneuver for helping reverse the automaticity of affective episode recurrence. Extinction training in the reconsolidation window (which opens about 5 min to 1 h after active memory recall) can revise, reverse, or eliminate the long term memories associated …


Using A Multifaceted Approach To Working With Children Who Have Differences In Sensory Processing And Integration, Stacey Reynolds, Tara J. Glennon, Karla Ausderau, Roxanna M. Bendixen, Heather Miller-Kuhaneck, Beth Pfeiffer, Renee Watling, Kimberly Wilkinson, Stefanie C. Bodison Mar 2017

Using A Multifaceted Approach To Working With Children Who Have Differences In Sensory Processing And Integration, Stacey Reynolds, Tara J. Glennon, Karla Ausderau, Roxanna M. Bendixen, Heather Miller-Kuhaneck, Beth Pfeiffer, Renee Watling, Kimberly Wilkinson, Stefanie C. Bodison

Occupational Therapy Faculty Publications

Pediatric occupational therapy practitioners frequently provide interventions for children with differences in sensory processing and integration. Confusion exists regarding how best to intervene with these children and about how to describe and document methods. Some practitioners hold the misconception that Ayres Sensory Integration intervention is the only approach that can and should be used with this population. The issue is that occupational therapy practitioners must treat the whole client in varied environments; to do so effectively, multiple approaches to intervention often are required. This article presents a framework for conceptualizing interventions for children with differences in sensory processing and integration …


Mri-Guided Stereotactic Biopsy Of Murine Gbm For Spatiotemporal Molecular Genomic Assessment, Stefanie Galban, Waid Al-Holou, Hanxiao Wang, Amanda Welton, Kevin Heist, Yuan Zhu, +Several Additional Authors Mar 2017

Mri-Guided Stereotactic Biopsy Of Murine Gbm For Spatiotemporal Molecular Genomic Assessment, Stefanie Galban, Waid Al-Holou, Hanxiao Wang, Amanda Welton, Kevin Heist, Yuan Zhu, +Several Additional Authors

Pediatrics Faculty Publications

Brain tumor biopsies that are routinely performed in clinical settings significantly aid in diagnosis and staging. The aim of this study is to develop and evaluate a methodological image-guided approach that would allow for routine sampling of glioma tissue from orthotopic mouse brain tumor models. A magnetic resonance imaging-guided biopsy method is presented to allow for spatially precise stereotaxic sampling of a murine glioma coupled with genome-scale technology to provide unbiased characterization of intra- and intertumoral clonal heterogeneity. Longitudinal and multiregional sampling of intracranial tumors allows for successful collection of tumor biopsy samples, thus allowing for a pathway-enrichment analysis and …


Nutritional Approaches To Achieve Weight Loss In Nonalcoholic Fatty Liver Disease., Christine C Hsu, Erik Ness, Kris V Kowdley Mar 2017

Nutritional Approaches To Achieve Weight Loss In Nonalcoholic Fatty Liver Disease., Christine C Hsu, Erik Ness, Kris V Kowdley

Articles, Abstracts, and Reports

Nonalcoholic fatty liver disease (NAFLD) can range in spectrum from simple hepatic steatosis to nonalcoholic steatohepatitis (NASH), which is characterized by lipotoxicity, hepatocellular ballooning, and inflammation and can progress to cirrhosis. Weight loss is the cornerstone treatment for NAFLD and NASH. Various randomized controlled trials have shown that weight loss of ≥5-10% leads to significant improvements in hepatic steatosis. Diets high in sodium and fructose have been implicated in the pathogenesis of NAFLD. Although some clinical studies suggest that an isocaloric high-fructose diet does not worsen NAFLD, these clinical studies are often short in duration. More recently, the Dietary Approaches …


Labrad : Vol 43, Issue 1 - March 2017, Aga Khan University Hospital, Karachi Mar 2017

Labrad : Vol 43, Issue 1 - March 2017, Aga Khan University Hospital, Karachi

LABRAD - Departments of Pathology & Laboratory Medicine and Radiology Archives

  • Chikungunya
  • Rapid Molecular Diagnosis of Chlamydia Trachomatis (CT) and Neisseria Gonorrhoeae (NG) Urethritis
  • Overview of Rubella Testing
  • Most Common Bone and Soft Tissue Infections Seen in our Practice
  • Diagnosis of Helicobacter Pylori Infection in Developing Countries- Pros & Cons
  • Screening for Neonatal Infections with TORCH Profile
  • Blood and Bone Marrow Changes in Viral Infections
  • Malaria
  • World Rare Disease Day
  • Radiology Pathology Correlation


Endothelin Signaling In Bone, Jasmin Kristianto, Michael Johnson, Rafia Afzal, Robert D. Blank Mar 2017

Endothelin Signaling In Bone, Jasmin Kristianto, Michael Johnson, Rafia Afzal, Robert D. Blank

Department of Anaesthesia

The endothelin (ET) system includes 3 small peptide hormones and a pair of G-protein-coupled receptors. This review first outlines the ET signaling pathway and ET metabolism. Next, it summarizes the role of ET1 signaling in craniofacial development. Then, it discusses observations relating ET signaling to osteoblastic and other osteosclerotic processes in cancer. Finally, it describes recent work in our laboratory that points to endothelin signaling as an upstream mediator of WNT signaling, promoting bone matrix synthesis and mineralization. It concludes with a statement of some remaining gaps in knowledge and proposals for future research.


Differentiated State Of Initiating Tumor Cells Is Key To Distinctive Immune Responses Seen In H-Ras, Michael A Podolsky, Jacob T Bailey, Andrew J Gunderson, Carrie J Oakes, Kyle Breech, Adam B Glick Mar 2017

Differentiated State Of Initiating Tumor Cells Is Key To Distinctive Immune Responses Seen In H-Ras, Michael A Podolsky, Jacob T Bailey, Andrew J Gunderson, Carrie J Oakes, Kyle Breech, Adam B Glick

Articles, Abstracts, and Reports

Heterogeneity in tumor immune responses is a poorly understood yet critical parameter for successful immunotherapy. In two doxycycline-inducible models where oncogenic H-RasG12V is targeted either to the epidermal basal/stem cell layer with a Keratin14-rtTA transgene (K14Ras), or committed progenitor/suprabasal cells with an Involucrin-tTA transgene (InvRas), we observed strikingly distinct tumor immune responses. On threshold doxycycline levels yielding similar Ras expression, tumor latency, and numbers, tumors from K14Ras mice had an immunosuppressed microenvironment, whereas InvRas tumors had a proinflammatory microenvironment. On a Rag1-/- background, InvRas mice developed fewer and smaller tumors that regressed over time, whereas K14Ras mice developed more …


Relb Expression Determines The Differential Effects Of Ascorbic Acid In Normal And Cancer Cells, Xiaowei Wei, Yong Xu, Fang Fang Xu, Luksana Chaiswing, David M. Schnell, Teresa Noel, Chi Wang, Jinfei Chen, Daret K. St. Clair, William H. St. Clair Mar 2017

Relb Expression Determines The Differential Effects Of Ascorbic Acid In Normal And Cancer Cells, Xiaowei Wei, Yong Xu, Fang Fang Xu, Luksana Chaiswing, David M. Schnell, Teresa Noel, Chi Wang, Jinfei Chen, Daret K. St. Clair, William H. St. Clair

Toxicology and Cancer Biology Faculty Publications

Cancer cells typically experience higher oxidative stress than normal cells, such that elevating pro-oxidant levels can trigger cancer cell death. Although pre-exposure to mild oxidative agents will sensitize cancer cells to radiation, this pre-exposure may also activate the adaptive stress defense system in normal cells. Ascorbic acid is a prototype redox modulator that when infused intravenously appears to kill cancers without injury to normal tissues; however, the mechanisms involved remain elusive. In this study, we show how ascorbic acid kills cancer cells and sensitizes prostate cancer to radiation therapy while also conferring protection upon normal prostate epithelial cells against radiation-induced …


Effect Of Cigarette Smoke Exposure And Mutant Kras Overexpression On Pancreatic Cell Proliferation, Howard P. Glauert, R. Scott Elliott, Sung Gu Han, Mark Athey, Eun Young Lee, C. Gary Gairola Mar 2017

Effect Of Cigarette Smoke Exposure And Mutant Kras Overexpression On Pancreatic Cell Proliferation, Howard P. Glauert, R. Scott Elliott, Sung Gu Han, Mark Athey, Eun Young Lee, C. Gary Gairola

Pharmacology and Nutritional Sciences Faculty Publications

Pancreatic cancer is the fourth leading cause of cancer‑associated mortality. The major risk factor for pancreatic cancer is cigarette smoking. Kras mutations are commonly observed in human pancreatic cancers. The present study examined the hypothesis that exposure to cigarette smoke and overexpression of a mutant Kras gene in the pancreas affects pancreatic cell proliferation in mice. Mice overexpressing the mutant Kras gene (KRasG12D) in the pancreas as well as wild‑type mice were exposed to environmental tobacco smoke for 2 weeks. Overexpression of mutant Kras increased cell proliferation in pancreatic ductal, acinar and islet cells. Notably, cigarette smoke exposure …


A Meta-Analysis Of Neuropsychological Tests Utilized In Evaluations For Post-Operative Cognitive Dysfunction In Adult Surgery Patients, Joanna H. Swartz Mar 2017

A Meta-Analysis Of Neuropsychological Tests Utilized In Evaluations For Post-Operative Cognitive Dysfunction In Adult Surgery Patients, Joanna H. Swartz

Doctor of Psychology (PsyD)

Cognitive dysfunction post-surgery has a significant impact on patients’ quality of life during recovery and afterward. Several studies have been completed on post-operative cognitive dysfunction (POCD), but since studies are varied in their methodologies and designs a metaanalysis is helpful to synthesize the current available research. The present study took a metaanalysis approach to examine neuropsychological tests most sensitive to POCD in adult surgery patients, and determine implications this would have for developing a battery of tests to evaluate for POCD pre and post-surgery. Although some assessment batteries have been proposed for certain populations (e.g., cardiac patients), little research has …