Digital Commons Network^™

Indicators Of Psychological Distress And Body Image Disorders In Female Patients With Breast Cancer, Helena Van Oers, Lourens Schlebusch

Journal of Mind and Medical Sciences

Breast cancer patients are vulnerable to elevated stress related to receiving the diagnosis, unfamiliar and invasive treatment, and coping with the side-effects of treatment, which may find various forms of expression. Another common feature of this patient population is body image dysphoria. Both the disease and treatment lead to impairments in physical appearance and general bodily functioning. This study aimed to explore the differential manifestations of stress and the nature of body image dysphoria within a sample of female breast cancer patients (n=80), compared to female patients with other sites of disease (n=80) in order to examine differences in the …

Intestinal Microbiota – A Possible Contributor To Cardiovascular Diseases?, Roua Iorga, Ovidiu Gabriel Bratu, Nicolae Bacalbasa, Mihnea-Alexandru Gaman, Camelia Cristina Diaconu

Journal of Mind and Medical Sciences

The intestinal microbiota represents an interesting and emergent field of research, with already known implications in metabolic and immunological functions. Recently, there is increasing evidence that specific gut microbial populations are associated with cardiovascular diseases. Numerous completed and ongoing studies aim to evaluate the potential of intestinal microbiota assessment to improve the prevention, diagnosis, and therapeutic arsenal of cardiovascular diseases, considering dysbiosis as a cardiovascular risk factor. There is strong evidence for a correlation between intestinal flora imbalance and metabolic changes secondary to bacterial metabolites. In this minireview, we discuss recent data about the connections between intestinal microbiota and cardiovascular …

Hepatitis C Virus: Host, Environmental And Viral Factors Promoting Spontaneous Clearance, Sergiu Ioan Micu, Marilena Musat, Andrada Dumitru, Dan Nicolae Paduraru, Anca Rogoveanu, Anca Dumitriu, Stana Paunica, Cristian Balalau, Roxana Emanuela Popoiag

Journal of Mind and Medical Sciences

Hepatitis C virus (HCV) is a pathogenic entity which determines inflammation and liver damage through complex immune mechanisms. Although progress has been made in managing the disease course, chronic infection still remains a significant cause of morbidity and mortality to this day. Because both acute and chronic infection are often asymptomatic, chronic infection is frequently diagnosed when its complications have developed. In a small proportion of cases, the chronic infection does not develop, the immune system managing to cleanse the body from this silent pathogen in the absence of specific treatment, a process called spontaneous viral clearance, which occurs rarely, …

Diagnosis And Management Of Pericardial Effusion, Maria Manea, Ovidiu Gabriel Bratu, Nicolae Bacalbasa, Camelia Cristina Diaconu

Journal of Mind and Medical Sciences

Pericardial effusion is a common pathology in clinical practice. The etiology of pericardial effusion is diverse, from infectious diseases, malignancies, autoimmune diseases, chronic renal failure, to drug-related or after an invasive cardiac intervention. Clinical presentation of pericardial effusion is variable, depending on the volume of the fluid and the rate of accumulation. Clinical manifestations are dramatic if the pericardial fluid accumulates rapidly. Classical symptoms in pericardial effusion include pleuritic chest pain associated with dyspnea. In case of cardiac tamponade, orthopnea, jugular venous distension, pulsus paradoxus, hypotension, and shock appear. Transthoracic echocardiography is the gold standard investigation for the diagnosis of …

A Functional K+ Channel From Tetraselmis Virus 1, A Member Of The Mimiviridae, Kerri Kukovetz, Brigitte Hertel, Christopher R. Schvarcz, Andrea Saponaro, Mirja Manthey, Ulrike Burk, Timo Greiner, Grieg F. Steward, James L. Van Etten, Anna Moroni, Gerhard Thiel, Oliver Rauh

Nebraska Center for Virology: Faculty Publications

Potassium ion (K+) channels have been observed in diverse viruses that infect eukaryotic marine and freshwater algae. However, experimental evidence for functional K+ channels among these alga-infecting viruses has thus far been restricted to members of the family Phycodnaviridae, which are large, double-stranded DNA viruses within the phylum Nucleocytoviricota. Recent sequencing projects revealed that alga-infecting members of Mimiviridae, another family within this phylum, may also contain genes encoding K+ channels. Here we examine the structural features and the functional properties of putative K+ channels from four cultivated members of Mimiviridae. While all four proteins contain variations …

Elevated Serum Il-21 Levels Are Associated With Stable Immune Status In Kidney Transplant Recipients And A Mouse Model Of Kidney Transplantation, Luying Guo, Junhao Lv, Jian Zhang, Hao Deng, Shi Feng, Shuaihui Liu, Pengpeng Yan, Jingyi Zhou, Hui Chen, Meifang Wang, Qin Zhou, Huiping Wang, Jianghua Chen, Yu Kuang, Jia Shen, Rendwing Wang

School of Medicine Faculty Research

Allograft rejection after renal transplantation remains a challenge to overcome. Interleukin (IL)-21, a cytokine with pleiotropic effects, maintains immune homeostasis post-transplantation. Here, we report higher levels of IL-21 in kidney transplant recipients with non-rejection (NR) than in recipients with T cell-mediated rejection (TCMR, P < 0.001) and antibody-mediated rejection (ABMR, P = 0.005). We observed a negative correlation between IL-21 and creatinine (Cr) levels (P = 0.016). The receiving operating characteristic (ROC) curve showed a promising diagnostic value of IL-21 to identify acute rejection with an area under the curve (AUC) of 0.822 (P < 0.001). In contrast, exogenous administration of IL-21 accelerated acute rejection in a comparative translational kidney transplant (KT) mouse model. Reduced IL-21 levels in the peripheral blood were observed in KT mice after IL-21 injection. Further analysis revealed that increased IL-21 levels in the spleen induced proliferation of CD4+ T cells and CD19+ B cells after IL-21 treatment. Our findings suggest a critical function of IL-21 in kidney transplantation and the potential involvement of the IL-21/IL-21R pathway in acute rejection management.

Ontogeny Related Changes In The Pediatric Liver Metabolome., Christopher M. Wilson, Qian Li, R Gaedigk, Chengpeng Bi, Saskia N. De Wildt, J Steven Leeder, Brooke L. Fridley

Manuscripts, Articles, Book Chapters and Other Papers

Background: A major challenge in implementing personalized medicine in pediatrics is identifying appropriate drug dosages for children. The majority of drug dosing studies have been based on adult populations, often with modification of the dosing for children based on size and weight. However, the growth and development experienced by children between birth and adulthood represents a dynamically changing biological system, with implications for effective drug dosing, efficacy as well as potential drug toxicity. The purpose of this study was to apply a metabolomics approach to gain preliminary insights into the ontogeny of liver function from newborn to adolescent.

Methods: Metabolites …

Estrogen/Progesterone Receptor And Her2 Discordance Between Primary Tumor And Brain Metastases In Breast Cancer And Its Effect On Treatment And Survival, Ayal Aizer, Jason Chan, Steve Braunstein, Jessica Lee, John P Kirkpatrick, Will Breen, Paul D Brown, Diana Shi, Helen A Shih, Hany Soliman, Arjun Sahgal, Ryan Shanley, William Sperduto, Emil Lou, Ashlyn Everett, Drexell Hunter Boggs, Laura Masucci, David Roberge, Jill Remick, Kristin Plichta, John M Buatti, Supriya Jain, Laurie E Gaspar, Cheng-Chia Wu, Tony J C Wang, John Bryant, Michael Chuong, James Yu, Veronica Chiang, Toshimichi Nakano, Hidefumi Aoyama, Minesh P Mehta

Faculty, Staff and Student Publications

BACKGROUND: Breast cancer treatment is based on estrogen receptors (ERs), progesterone receptors (PRs), and human epidermal growth factor receptor 2 (HER2). At the time of metastasis, receptor status can be discordant from that at initial diagnosis. The purpose of this study was to determine the incidence of discordance and its effect on survival and subsequent treatment in patients with breast cancer brain metastases (BCBM).

METHODS: A retrospective database of 316 patients who underwent craniotomy for BCBM between 2006 and 2017 was created. Discordance was considered present if the ER, PR, or HER2 status differed between the primary tumor and the …

Knowledge And Practice Regarding Prostate Cancer Germline Testing Among Urologists: Gaps To Address For Optimal Implementation, Stacy Loeb, Nataliya Byrne, Dawn Walter, Danil V Makarov, David R Wise, Daniel Becker, Veda N Giri

Department of Medical Oncology Faculty Papers

BACKGROUND: Germline testing is recommended for all men with metastatic prostate cancer (PCa), and for some with localized PCa meeting specific histologic or family history criteria. Germline genetic evaluation has important implications for PCa prognosis and management, as well as implications for family members and cancer screening. Despite the importance of germline evaluation, its utilization in urologic practice is unknown.

MATERIALS AND METHODS: We conducted a 32-item survey of U.S. urologists to examine knowledge of germline testing guidelines and practice patterns. It was shared through email to 6 American Urological Association sections, the Veterans Affairs Urology Mailgroup, and social media. …

Integrated Multiparametric Radiomics And Informatics System For Characterizing Breast Tumor Characteristics With The Oncotypedx Gene Assay, Michael A. Jacobs, Christopher B. Umbricht, Vishwa S. Parekh, Riham H. El Khouli, Leslie Cope, Katarzyna J. Macura, Susan Harvey, Antonio C. Wolff

Radiology Faculty Publications

Optimal use of multiparametric magnetic resonance imaging (mpMRI) can identify key MRI parameters and provide unique tissue signatures defining phenotypes of breast cancer. We have developed and implemented a new machine-learning informatic system, termed Informatics Radiomics Integration System (IRIS) that integrates clinical variables, derived from imaging and electronic medical health records (EHR) with multiparametric radiomics (mpRad) for identifying potential risk of local or systemic recurrence in breast cancer patients. We tested the model in patients (n = 80) who had Estrogen Receptor positive disease and underwent OncotypeDX gene testing, radiomic analysis, and breast mpMRI. The IRIS method was trained …

Clinical Efficacy Of Direct-Acting Antiviral Therapy For Recurrent Hepatitis C Virus Infection After Liver Transplantation In Patients With Hepatocellular Carcinoma, Wael Ahmed Yousry, Maha Mohsen Kamal El-Din, Mohamed Mohamed Bahaa El-Din, Osama Aboelfotoh El Sayed, Ahmed Omar Kaseb, John Alan Goss, Fasiha Kanwal, Prasun Kumar Jalal

Faculty, Staff and Students Publications

BACKGROUND: Recurrent hepatitis C virus (HCV) infection of transplanted liver allografts is universal in patients with detectable HCV viremia at the time of transplantation. Direct-acting antiviral (DAA) therapy has been adopted as the standard of care for recurrent HCV infection in the post-transplant setting. However, there are insufficient data regarding its efficacy in liver transplant (LT) recipients with a history of hepatocellular carcinoma (HCC), and the risk of HCC recurrence after DAA therapy is unknown.

AIM: To demonstrate predictors of DAA treatment failure and HCC recurrence in LT recipients.

METHODS: A total of 106 LT recipients given DAAs for recurrent …

Tdp-43 Mediated Blood-Brain Barrier Permeability And Leukocyte Infiltration Promote Neurodegeneration In A Low-Grade Systemic Inflammation Mouse Model, Frank Zamudio, Anjanet R. Loon, Shayna Smeltzer, Khawla Benyamine, Nanda K. Navalpur Shanmugam, Nicholas J. F. Stewart, Daniel C. Lee, Kevin Nash, Maj-Linda B. Selenica

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Neuronal cytoplasmic inclusions containing TAR DNA-binding protein 43 (TDP-43) are a neuropathological feature of several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Alzheimer's Disease (AD). Emerging evidence also indicates that systemic inflammation may be a contributor to the pathology progression of these neurodegenerative diseases.

METHODS: To investigate the role of systemic inflammation in the progression of neuronal TDP-43 pathology, AAV9 particles driven by the UCHL1 promoter were delivered to the frontal cortex of wild-type aged mice via intracranial injections to overexpress TDP-43 or green fluorescent protein (GFP) in corticospinal motor neurons. Animals were then subjected …

An Approach To Classifying Subjective Cognitive Decline In Community-Dwelling Elders, Laura A. Rabin, Cuilling Wang, Jacqueline A. Mogle, Richard B. Lipton, Carol A. Derby, Mindy J. Katz

Publications and Research

Introduction: Subjective cognitive decline (SCD) may be an early symptomatic man- ifestation of Alzheimer’s disease, though published research largely neglects how to classify SCD in community-based studies.

Methods: In neuropsychologically intact Einstein Aging Study participants (n = 1115; meanage=78;63%female;30%non-White),weusedCoxmodelstoexaminetheasso- ciation between self-perceived cognitive functioning at baseline (using three different approaches) and incident amnestic mild cognitive impairment (aMCI) with covariates of age, sex, education, race/ethnicity, general (objective) cognition, depressive symp- toms, and four other SCD-related features.

Results: After a median of 3 years, 198 participants developed aMCI. In models that included all the variables, self-perceived cognitive functioning was consistently asso- ciated …

Rho Gtpases: Big Players In Breast Cancer Initiation, Metastasis And Therapeutic Responses, Brock Humphries, Zhishan Wang, Chengfeng Yang

Toxicology and Cancer Biology Faculty Publications

Rho GTPases, a family of the Ras GTPase superfamily, are key regulators of the actin cytoskeleton. They were originally thought to primarily affect cell migration and invasion; however, recent advances in our understanding of the biology and function of Rho GTPases have demonstrated their diverse roles within the cell, including membrane trafficking, gene transcription, migration, invasion, adhesion, survival and growth. As these processes are critically involved in cancer initiation, metastasis and therapeutic responses, it is not surprising that studies have demonstrated important roles of Rho GTPases in cancer. Although the majority of data indicates an oncogenic role of Rho GTPases, …

Matrine Inhibits Cns Autoimmunity Through An Ifn-Β-Dependent Mechanism, Yaojuan Chu, Wendi Ma, Rodolfo Thome, Jie Dan Ping, Fangzhou Liu, Mengru Wang, Mingliang Zhang, Guang-Xian Zhang, Lin Zhu

Department of Neurology Faculty Papers

Matrine (MAT), a quinolizidine alkaloid component derived from the root of Sophora flavescens, suppresses experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS), by inducing the production of immunomodulatory molecules, e.g., IL-10. In an effort to find the upstream pathway(s) of the mechanism underlying these effects, we have tested certain upregulated immunomodulatory molecules. Among them, we found increased levels of IL-27 and IFN-β, one of the first-line MS therapies. Indeed, while low levels of IFN-β production in sera and type I interferon receptor (IFNAR1) expression in spinal cord of saline-treated control EAE mice were detected, they were significantly …

Time For Some Drugs Or Drugs For Some Time, Linda Zhang, Lauren Wilson, Benjamin Pierce

Psychiatry

No abstract provided.

Atrial Myocyte Nlrp3/Camkii Nexus Forms A Substrate For Postoperative Atrial Fibrillation, Cristina E Molina, Henry Sutanto, Marcel Tekook, Qiongling Wang, Issam H Abu-Taha, Marcel Gorka, Stephan Künzel, Ali El-Armouche, Hermann Reichenspurner, Markus Kamler, Viacheslav Nikolaev, Ursula Ravens, Na Li, Stanley Nattel, Xander H T Wehrens, Dobromir Dobrev

Faculty, Staff and Students Publications

RATIONALE: Postoperative atrial fibrillation (POAF) is a common and troublesome complication of cardiac surgery. POAF is generally believed to occur when postoperative triggers act on a preexisting vulnerable substrate, but the underlying cellular and molecular mechanisms are largely unknown.

OBJECTIVE: To identify cellular POAF mechanisms in right atrial samples from patients without a history of atrial fibrillation undergoing open-heart surgery.

METHODS AND RESULTS: Multicellular action potentials, membrane ion-currents (perforated patch-clamp), or simultaneous membrane-current (ruptured patch-clamp) and [Ca

CONCLUSIONS: Preexisting Ca

Prevalence And Determinants Of Anemia Among Women Of Reproductive Age In Thatta Pakistan: Findings From A Cross-Sectional Study, Sumera Aziz Ali, Zahid Abbasi, Babar Shahid, Ghazal Moin, K Michael Hambidge, Nancy F. Krebs, Jamie E. Westcott, Elizabeth M. Mcclure, Robert L. Goldenberg, Sarah Saleem

Community Health Sciences

Background: Anemia is a major public health concern among women of reproductive age leading to high maternal mortality in low- and middle-income countries. Of the prior studies conducted in Pakistan, most focused on large urban areas and did not explore the determinants of anemia among women of reproductive age (WRA) across socio-demographic, dietary, reproductive, and biological domains. Thus, we aimed to study the prevalence and determinants of anemia among WRA in rural Pakistan.
Methods: We conducted a cross-sectional study in the Thatta district of Pakistan from September 2018 to January 2019 and enrolled 150 non-pregnant, married women. Data collectors administered …

Mesencephalic Astrocyte-Derived Neurotrophic Factor (Manf) Regulates Neurite Outgrowth Through The Activation Of Akt/Mtor And Erk/Mtor Signaling Pathways, Wen Wen, Yongchao Wang, Hui Li, Hong Xu, Mei Xu, Jacqueline A. Frank, Murong Ma, Jia Luo

Pharmacology and Nutritional Sciences Faculty Publications

Neurite outgrowth is essential for brain development and the recovery of brain injury and neurodegenerative diseases. In this study, we examined the role of the neurotrophic factor MANF in regulating neurite outgrowth. We generated MANF knockout (KO) neuro2a (N2a) cell lines using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 and demonstrated that MANF KO N2a cells failed to grow neurites in response to RA stimulation. Using MANF siRNA, this finding was confirmed in human SH-SY5Y neuronal cell line. Nevertheless, MANF overexpression by adenovirus transduction or addition of MANF into culture media facilitated the growth of longer neurites in RA-treated N2a …

Repurposing Anti-Inflammasome Nrtis For Improving Insulin Sensitivity And Reducing Type 2 Diabetes Development, Jayakrishna Ambati, Joseph Magagnoli, Hannah Leung, Shao-Bin Wang, Chris A. Andrews, Dongxu Fu, Akshat Pandey, Srabani Sahu, Siddharth Narendran, Shuichiro Hirahara, Shinichi Fukuda, Jian Sun, Lekha Pandya, Meenakshi Ambati, Felipe Pereira, Akhil Varshney, Tammy Cummings, James W. Hardin, Babatunde Edun, Charles L. Bennett, Kameshwari Ambati, Benjamin J. Fowler, Nagaraj Kerur, Christian Röver, Norbert Leitinger, Brian C. Werner, Joshua D. Stein, S. Scott Sutton, Bradley D. Gelfand

Ophthalmology and Visual Science Faculty Publications

Innate immune signaling through the NLRP3 inflammasome is activated by multiple diabetes-related stressors, but whether targeting the inflammasome is beneficial for diabetes is still unclear. Nucleoside reverse-transcriptase inhibitors (NRTI), drugs approved to treat HIV-1 and hepatitis B infections, also block inflammasome activation. Here, we show, by analyzing five health insurance databases, that the adjusted risk of incident diabetes is 33% lower in patients with NRTI exposure among 128,861 patients with HIV-1 or hepatitis B (adjusted hazard ratio for NRTI exposure, 0.673; 95% confidence interval, 0.638 to 0.710; P < 0.0001; 95% prediction interval, 0.618 to 0.734). Meanwhile, an NRTI, lamivudine, improves insulin sensitivity and reduces inflammasome activation in diabetic and insulin resistance-induced human cells, as well as in mice fed with high-fat chow; mechanistically, inflammasome-activating short interspersed nuclear element (SINE) transcripts are elevated, whereas SINE-catabolizing DICER1 is reduced, in diabetic cells and mice. These data suggest the possibility of repurposing an approved class of drugs for prevention of diabetes.

Organic Field-Effect Transistors As Flexible, Tissue-Equivalent Radiation Dosimeters In Medical Applications, Andrew M. Zeidell, Tong Ren, David S. Filston, Hamna F. Iqbal, Emma Holland, J. Daniel Bourland, John E. Anthony, Oana D. Jurchescu

Chemistry Faculty Publications

Radiation therapy is one of the most prevalent procedures for cancer treatment, but the risks of malignancies induced by peripheral beam in healthy tissues surrounding the target is high. Therefore, being able to accurately measure the exposure dose is a critical aspect of patient care. Here a radiation detector based on an organic field‐effect transistor (RAD‐OFET) is introduced, an in vivo dosimeter that can be placed directly on a patient's skin to validate in real time the dose being delivered and ensure that for nearby regions an acceptable level of low dose is being received. This device reduces the errors …

The Role Of Nerves In Skeletal Development, Adaptation, And Aging., Ryan E Tomlinson, Blaine A Christiansen, Adrienne A Giannone, Damian C Genetos

Department of Orthopaedic Surgery Faculty Papers

The skeleton is well-innervated, but only recently have the functions of this complex network in bone started to become known. Although our knowledge of skeletal sensory and sympathetic innervation is incomplete, including the specific locations and subtypes of nerves in bone, we are now able to reconcile early studies utilizing denervation models with recent work dissecting the molecular signaling between bone and nerve. In total, sensory innervation functions in bone much as it does elsewhere in the body-to sense and respond to stimuli, including mechanical loading. Similarly, sympathetic nerves regulate autonomic functions related to bone, including homeostatic remodeling and vascular …

Hepatic Lipocalin 2 Promotes Liver Fibrosis And Portal Hypertension, Jiegen Chen, Josepmaria Argemi, Gemma Odena, Ming-Jiang Xu, Yan Cai, Veronica Massey, Austin Parrish, Rajanikanth Vadigepalli, Jose Altamirano, Joaquin Cabezas, Pere Gines, Juan Caballeria, Natasha Snider, Pau Sancho-Bru, Shizuo Akira, Ivan Rusyn, Bin Gao, Ramon Bataller

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Advanced fibrosis and portal hypertension influence short-term mortality. Lipocalin 2 (LCN2) regulates infection response and increases in liver injury. We explored the role of intrahepatic LCN2 in human alcoholic hepatitis (AH) with advanced fibrosis and portal hypertension and in experimental mouse fibrosis. We found hepatic LCN2 expression and serum LCN2 level markedly increased and correlated with disease severity and portal hypertension in patients with AH. In control human livers, LCN2 expressed exclusively in mononuclear cells, while its expression was markedly induced in AH livers, not only in mononuclear cells but also notably in hepatocytes. Lcn2−/− mice were protected from liver …

Loss Of Speg Inhibitory Phosphorylation Of Ryanodine Receptor Type-2 Promotes Atrial Fibrillation, David Y Chiang, Carlos F Kramm, Tarah A Word, Sören Brandenburg, Mohit Hulsurkar, Katherina M Alsina, Hui-Bin Liu, Brian Martin, Dennis Uhlenkamp, Oliver M Moore, Satadru K Lahiri, Eleonora Corradini, Markus Kamler, Albert J R Heck, Stephan E Lehnart, Dobromir Dobrev, Xander H T Wehrens

Faculty, Staff and Students Publications

BACKGROUND: Enhanced diastolic calcium (Ca

METHODS: Western blotting was performed with right atrial biopsies from patients with paroxysmal AF. SPEG atrial knockout mice were generated using adeno-associated virus 9. In mice, AF inducibility was determined using intracardiac programmed electric stimulation, and diastolic Ca

RESULTS: Western blotting revealed decreased SPEG protein levels in atrial biopsies from patients with paroxysmal AF in comparison with patients in sinus rhythm. SPEG atrial-specific knockout mice exhibited increased susceptibility to pacing-induced AF by programmed electric stimulation and enhanced Ca

CONCLUSIONS: Unlike other kinases (PKA, CaMKII) that increase RyR2 activity, SPEG phosphorylation reduces RyR2-mediated sarcoplasmic reticulum Ca

Soluble Glycoprotein Vi Is A Predictor Of Major Bleeding In Patients With Suspected Heparin-Induced Thrombocytopenia, Allyson M Pishko, Robert K Andrews, Elizabeth E Gardiner, Daniel S Lefler, Adam Cuker

Department of Medical Oncology Faculty Papers

We have shown that patients with suspected heparin-induced thrombocytopenia (HIT) have a high incidence of major bleeding. Recent studies have implicated elevated soluble glycoprotein VI (sGPVI) levels as a potential risk factor for bleeding. We sought to determine if elevated sGPVI plasma levels are associated with major bleeding events in patients with suspected HIT. We used a cohort of 310 hospitalized adult patients with suspected HIT who had a blood sample collected at the time HIT was suspected. Plasma sGPVI levels were measured by using enzyme-linked immunosorbent assay. Patients were excluded who had received a platelet transfusion within 1 day …

Sphenopalatine Ganglion Stimulation Upregulates Transport Of Temozolomide Across The Blood-Brain Barrier, Thana N. Theofanis, Ankit K. Rochani, Richard F. Schmidt, Michael J. Lang, Geoffrey P. Stricsek, Robert H. Rosenwasswer, Ashwini D. Sharan, Gagan Kaushal, Lorraine Iacovitti

Department of Neurosurgery Faculty Papers

Sphenopalatine ganglion (SPG) stimulation has been shown to reversibly alter blood-brainbarrier (BBB) permeability. It is widely used for the treatment of cluster headaches in Europe and iswell tolerated in humans. The therapeutic potential for SPG stimulation in other central nervoussystem (CNS) diseases has yet to be explored. Glioblastoma Multiforme (GBM) remains one of themost difficult primary CNS neoplasms to treat, with an average survival of approximately 18 months atthe time of diagnosis. Since 2004, the gold standard of treatment for GBM in the United States includessurgery followed by treatment with temozolomide (TMZ) and radiation. We sought to determine ifSPG stimulation …

In Vitro Susceptibility Of Treponema Pallidum Subsp Pallidum To Doxycycline

Faculty, Staff and Student Publications

Doxycycline is regarded as an effective therapy for early syphilis, and there is increasing interest in using doxycycline for prophylaxis of this infection. However, the MIC of doxycycline for Treponema pallidum subsp. pallidum has not been reported previously. In this study, an in vitro culture system was utilized to determine that the MIC of doxycycline is 0.06 to 0.10 μg/ml for four strains of T. pallidum subsp. pallidum (Nichols, SS14, UW231B, and UW249B). The Nichols strain cultured in vitro with doxycycline was also tested for infectivity in rabbits, and the minimum bactericidal concentration (MBC) was found to be ≤0.1 μg/ml …

The Membrane-Associated Form Of Cyclin D1 Enhances Cellular Invasion, Ke Chen, Xuanmao Jiao, Anthony Ashton, Agnese Di Rocco, Timothy G Pestell, Yunguang Sun, Jun Zhao, Mathew C Casimiro, Zhiping Li, Michael P Lisanti, Peter Mccue, Duanwen Shen, Samuel Achilefu, Hallgeir Rui, Richard G Pestell

Department of Cancer Biology Faculty Papers

The essential G1-cyclin, CCND1, is a collaborative nuclear oncogene that is frequently overexpressed in cancer. D-type cyclins bind and activate CDK4 and CDK6 thereby contributing to G1-S cell-cycle progression. In addition to the nucleus, herein cyclin D1 was also located in the cytoplasmic membrane. In contrast with the nuclear-localized form of cyclin D1 (cyclin D1NL), the cytoplasmic membrane-localized form of cyclin D1 (cyclin D1MEM) induced transwell migration and the velocity of cellular migration. The cyclin D1MEM was sufficient to induce G1-S cell-cycle progression, cellular proliferation, and colony formation. The cyclin D1MEM was sufficient to induce phosphorylation of the serine threonine …

Intratumoral Translocation Positive Heterogeneity In Pediatric Alveolar Rhabdomyosarcoma Tumors Correlates To Patient Survival Prognosis, Katrina Gleditsch, Jorge Peñas, Danielle Mercer, Ayesha Umrigar, James Briscoe, Matthew Stark, Fern Tsien, Andrew D. Hollenbach

School of Medicine Faculty Publications

Alveolar rhabdomyosarcoma (ARMS) is characterized by one of three translocation states: t(2;13) (q35;q14) producing PAX3-FOXO1, t(1;13) (p36;q14) producing PAX7-FOXO1, or translocation-negative. Tumors with t(2;13) are associated with greater disease severity and mortality than t(1;13) positive or translocation negative patients. Consistent with this fact, previous work concluded that a molecular analysis of RMS translocation status is essential for the accurate determination of prognosis and diagnosis. However, despite this knowledge, most diagnoses rely on histology and in some cases utilize fluorescence in situ hybridization (FISH) probes unable to differentiate between translocation products. Along these same lines, diagnostic RT-PCR analysis, which can differentiate …

Microglial-Associated Responses To Comorbid Amyloid Pathology And Hyperhomocysteinemia In An Aged Knock-In Mouse Model Of Alzheimer's Disease, David J. Braun, Edgardo R. Dimayuga, Josh M. Morganti, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Elevated blood homocysteine levels, termed hyperhomocysteinemia (HHcy), is a prevalent risk factor for Alzheimer's disease (AD) in elderly populations. While dietary supplementation of B-vitamins is a generally effective method to lower homocysteine levels, there is little if any benefit to cognition. In the context of amyloid pathology, dietary-induced HHcy is known to enhance amyloid deposition and certain inflammatory responses. Little is known, however, about whether there is a more specific effect on microglia resulting from combined amyloid and HHcy pathologies.

METHODS: The present study used a knock-in mouse model of amyloidosis, aged to 12 months, given 8 weeks of …