Other Medical Specialties Commons^™

Hospitalized Patients At High Risk For Obstructive Sleep Apnea Have More Rapid Response System Events And Intervention Is Associated With Reduced Events., Sunil Sharma, Md, Anindita Chowdhury, Lili Tang, Leslee Willes, Brian Glynn, Stuart F Quan

Department of Medicine Faculty Papers

BACKGROUND: Rapid response system (RRS) is a safety tool designed for early detection and intervention of a deteriorating patient on the general floor in the hospital. Obstructive sleep apnea (OSA) has been associated with significant cardiovascular complications. We hypothesized that patients with high-risk of OSA have higher rate of RRS events and intervention with positive airway pressure therapy in these patients can mitigate the RRS events.

METHODS: As part of a clinical pathway, during a 15 month period, patients with BMI ≥ 30 kg/m2 in select medical services were screened with a validated sleep questionnaire. Patients were characterized as high …

Dcc Mediates Functional Assembly Of Peripheral Auditory Circuits., Young J Kim, Sheng-Zhi Wang, Stephen Tymanskyj, Le Ma, Huizhong W Tao, Li I Zhang

Department of Neuroscience Faculty Papers

Proper structural organization of spiral ganglion (SG) innervation is crucial for normal hearing function. However, molecular mechanisms underlying the developmental formation of this precise organization remain not well understood. Here, we report in the developing mouse cochlea that deleted in colorectal cancer (Dcc) contributes to the proper organization of spiral ganglion neurons (SGNs) within the Rosenthal's canal and of SGN projections toward both the peripheral and central auditory targets. In Dcc mutant embryos, mispositioning of SGNs occurred along the peripheral auditory pathway with misrouted afferent fibers and reduced synaptic contacts with hair cells. The central auditory pathway simultaneously exhibited similar …

Evaluation Of Polymorphic Locus Sequence Typing For Candida Glabrata Epidemiology., Santosh Katiyar, Eric Shiffrin, Md, Celeste Shelton, Kelley Healey, John-Paul Vermitsky, Tom Edlind

Department of Medicine Faculty Papers

The opportunistic yeastCandida glabratais increasingly refractory to antifungal treatment or prophylaxis and relatedly is increasingly implicated in health care-associated infections. To elucidate the epidemiology of these infections, strain typing is required. Sequence-based typing provides multiple advantages over length-based methods, such as pulsed-field gel electrophoresis (PFGE); however, conventional multilocus sequence typing (targeting 6 conserved loci) and whole-genome sequencing are impractical for routine use. A commercial sequence-based typing service forC. glabratathat targets polymorphic tandem repeat-containing loci has recently been developed. These CgMT-J and CgMT-M services were evaluated with 56 epidemiologically unrelated isolates, 4 to 7 fluconazole-susceptible or fluconazole-resistant isolates from each of …

Conversion To Eslicarbazepine Acetate Monotherapy: A Pooled Analysis Of 2 Phase Iii Studies., Michael R Sperling, Jacqueline French, Mercedes P Jacobson, Ladislav Pazdera, Mallory Gough, Hailong Cheng, Todd Grinnell, David Blum

Department of Medicine Faculty Papers

OBJECTIVE: To assess the efficacy and safety of eslicarbazepine acetate (ESL) monotherapy.

METHODS: This post hoc pooled analysis of 2 randomized double-blind studies (093-045 and -046) included adults with partial-onset seizures medically uncontrolled by 1 or 2 antiepileptic drugs (AEDs). Following the baseline period (8 weeks), eligible patients were randomized 2:1 to receive ESL 1,600 mg or 1,200 mg once daily for 18 weeks; the primary endpoint was study exit by meeting predefined exit criteria (signifying worsening seizure control). In each study, treatment was considered effective if the upper 95% confidence limit for exit rate was lower than the historical …

Consequential Considerations When Mapping Trna Fragments., Aristeidis G Telonis, Phillipe Loher, Yohei Kirino, Phd, Isidore Rigoutsos

Computational Medicine Center Faculty Papers

We examine several of the choices that went into the design of tDRmapper, a recently reported tool for identifying transfer RNA (tRNA) fragments in deep sequencing data, evaluate them in the context of currently available knowledge, and discuss their potential impact on the output that the tool generates.

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

Department of Medicine Faculty Papers

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

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

Department of Physical Therapy Faculty Papers

No abstract provided.

Cannibalism, Kuru, And Mad Cows: Prion Disease As A "Choose-Your-Own-Experiment" Case Study To Simulate Scientific Inquiry In Large Lectures., Antonio Serrano, Jeffrey Liebner, Justin K Hines

Department of Medicine Faculty Papers

Despite significant efforts to reform undergraduate science education, students often perform worse on assessments of perceptions of science after introductory courses, demonstrating a need for new educational interventions to reverse this trend. To address this need, we created An Inexplicable Disease, an engaging, active-learning case study that is unusual because it aims to simulate scientific inquiry by allowing students to iteratively investigate the Kuru epidemic of 1957 in a choose-your-own-experiment format in large lectures. The case emphasizes the importance of specialization and communication in science and is broadly applicable to courses of any size and sub-discipline of the life sciences.

Cloning And Transcriptional Activity Of The Mouse Omi/Htra2 Gene Promoter., Dan Liu, Xin Liu, Ye Wu, Wen Wang, Xin-Liang Ma, Huirong Liu

Department of Medicine Faculty Papers

HtrA serine peptidase 2 (HtrA2), also named Omi, is a pro-apoptotic protein that exhibits dramatic changes in expression levels in a variety of disorders, including ischemia/reperfusion injury, cancer, and neurodegeneration. In our study, Omi/HtrA2 protein levels were high in the heart, brain, kidney and liver, with elevated heart/brain expression in aging mice. A similar expression pattern was observed at the mRNA level, which suggests that the regulation of Omi/HtrA2 is predominately transcriptional. Promoter binding by transcription factors is the main influencing factor of transcription, and to identify specific promoter elements that contribute to the differential expression of mouse Omi/HtrA2, we …

Reduction Of Ctrp9, A Novel Anti-Platelet Adipokine, Contributes To Abnormal Platelet Activity In Diabetic Animals., Wenqing Wang, Wayne Bond Lau, Yajing Wang, Xin-Liang Ma, Rong Li

Department of Medicine Faculty Papers

Platelet hyper-reactivity is a crucial cause of accelerated atherosclerosis increasing risk of thrombotic vascular events in diabetic patients. The mechanisms leading to abnormal platelet activity during diabetes are complex and not fully defined. The current study attempted to clarify the role of CTRP9, a novel adiponectin paralog, in enhanced platelet activity and determined whether CTRP9 may inhibit platelet activity. Adult male C57BL/6 J mice were randomized to receive high-fat diet (HFD) or normal diet (ND). 8 weeks after HFD, animals were sacrificed, and both plasma CTRP9 and platelet aggregation were determined. HFD-fed animals increased weight gain significantly, and became hyperglycemic …

Preparation And Biological Activity Of The Monoclonal Antibody Against The Second Extracellular Loop Of The Angiotensin Ii Type 1 Receptor, Mingming Wei, Chengrui Zhao, Suli Zhang, Li Wang, Huirong Liu, Xin-Liang Ma

Department of Medicine Faculty Papers

No abstract provided.

Neurovascular Disorders: Novel Perspectives On Pathogenesis, Diagnosis, And Treatment., David Hasan, Nohra Chalouhi, Md, Aaron S Dumont, Robert M Starke, Pascal Jabbour Md

Department of Neurosurgery Faculty Papers

No abstract provided.

Racemose Neurocysticercosis., Kristin Krupa, Kelly Krupa, Bs, Mary L Pisculli, Deena M Athas, Christopher J Farrell, Md

Department of Neurosurgery Faculty Papers

BACKGROUND: Neurocysticercosis (NCC) is an invasive parasitic infection of the central nervous system caused by the larval stage of the tapeworm Taenia solium. The clinical manifestations of NCC depend on the parasitic load and location of infection, as well as the developmental stage of the cysticerci and host immune response, with symptoms ranging from subclinical headaches to seizures, cerebrovascular events, and life-threatening hydrocephalus. Racemose NCC represents a particularly severe variant of extraparenchymal NCC characterized by the presence of multiple confluent cysts within the subarachnoid space and is associated with increased morbidity and mortality, as well as a decreased response to …

Vertebral Body Stapling Versus Bracing For Patients With High-Risk Moderate Idiopathic Scoliosis., Laury Cuddihy, Aina J Danielsson, Patrick J Cahill, Amer F Samdani, Harsh Grewal, John M Richmond, M J Mulcahey, John P Gaughan, M Darryl Antonacci, Randal R Betz

Department of Medicine Faculty Papers

Purpose. We report a comparison study of vertebral body stapling (VBS) versus a matched bracing cohort for immature patients with moderate (25 to 44°) idiopathic scoliosis (IS). Methods. 42 of 49 consecutive patients (86%) with IS were treated with VBS and followed for a minimum of 2 years. They were compared to 121 braced patients meeting identical inclusion criteria. 52 patients (66 curves) were matched according to age at start of treatment (10.6 years versus 11.1 years, resp. [P = 0.07]) and gender. Results. For thoracic curves 25-34°, VBS had a success rate (defined as curve progression

Interactions Of L-3,5,3′-Triiodothyronine, Allopregnanolone, And Ivermectin With The Gabaa Receptor: Evidence For Overlapping Intersubunit Binding Modes, Thomas Westergard, Reza Salari, Joseph V. Martin, Grace Brannigan

Department of Neuroscience Faculty Papers

No abstract provided.

Positive Allosteric Modulation Of Kv Channels By Sevoflurane: Insights Into The Structural Basis Of Inhaled Anesthetic Action., Qiansheng Liang, Warren D Anderson, Shelly T Jones, Caio S Souza, Juliana M Hosoume, Werner Treptow, Manuel Covarrubias

Department of Neuroscience Faculty Papers

Inhalational general anesthesia results from the poorly understood interactions of haloethers with multiple protein targets, which prominently includes ion channels in the nervous system. Previously, we reported that the commonly used inhaled anesthetic sevoflurane potentiates the activity of voltage-gated K+ (Kv) channels, specifically, several mammalian Kv1 channels and the Drosophila K-Shaw2 channel. Also, previous work suggested that the S4-S5 linker of K-Shaw2 plays a role in the inhibition of this Kv channel by n-alcohols and inhaled anesthetics. Here, we hypothesized that the S4-S5 linker is also a determinant of the potentiation of Kv1.2 and K-Shaw2 by sevoflurane. Following functional expression …

Deletion Of Cyclophilin D Impairs Β-Oxidation And Promotes Glucose Metabolism., Michele Tavecchio, Sofia Lisanti, Michael J Bennett, Lucia R Languino, Dario C Altieri

Department of Cancer Biology Faculty Papers

Cyclophilin D (CypD) is a mitochondrial matrix protein implicated in cell death, but a potential role in bioenergetics is not understood. Here, we show that loss or depletion of CypD in cell lines and mice induces defects in mitochondrial bioenergetics due to impaired fatty acid β-oxidation. In turn, CypD loss triggers a global compensatory shift towards glycolysis, with transcriptional upregulation of effectors of glucose metabolism, increased glucose consumption and higher ATP production. In vivo, the glycolytic shift secondary to CypD deletion is associated with expansion of insulin-producing β-cells, mild hyperinsulinemia, improved glucose tolerance, and resistance to high fat diet-induced liver …

Dna-Repair Defects And Olaparib In Metastatic Prostate Cancer., Joaquin Mateo, Suzanne Carreira, Shahneen Sandhu, Susana Miranda, Helen Mossop, Raquel Perez-Lopez, Daniel Nava Rodrigues, Dan Robinson, Aurelius Omlin, Nina Tunariu, Gunther Boysen, Nuria Porta, Penny Flohr, Alexa Gillman, Ines Figueiredo, Claire Paulding, George Seed, Suneil Jain, Christy Ralph, Andrew Protheroe, Syed Hussain, Robert Jones, Tony Elliott, Ursula Mcgovern, Diletta Bianchini, Jane Goodall, Zafeiris Zafeiriou, Chris T Williamson, Roberta Ferraldeschi, Ruth Riisnaes, Bernardette Ebbs, Gemma Fowler, Desamparados Roda, Wei Yuan, Yi-Mi Wu, Xuhong Cao, Rachel Brough, Helen Pemberton, Roger A'Hern, Amanda Swain, Lakshmi P Kunju, Rosalind Eeles, Gerhardt Attard, Christopher J Lord, Alan Ashworth, Mark A Rubin, Karen E Knudsen, Felix Y Feng, Arul M Chinnaiyan, Emma Hall, Johann S De Bono

Department of Medicine Faculty Papers

BACKGROUND: Prostate cancer is a heterogeneous disease, but current treatments are not based on molecular stratification. We hypothesized that metastatic, castration-resistant prostate cancers with DNA-repair defects would respond to poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibition with olaparib.

METHODS: We conducted a phase 2 trial in which patients with metastatic, castration-resistant prostate cancer were treated with olaparib tablets at a dose of 400 mg twice a day. The primary end point was the response rate, defined either as an objective response according to Response Evaluation Criteria in Solid Tumors, version 1.1, or as a reduction of at least 50% in the …

Does Metal Transfer Differ On Retrieved Ceramic And Cocr Femoral Heads?, Eliza K Fredette, Daniel W Macdonald, Richard J Underwood, Antonia F. Chen, Md, Mba, Michael A Mont, Gwo-Chin Lee, Gregg R Klein, Clare M Rimnac, Steven M Kurtz

Rothman Institute Papers

Metal transfer has been observed on retrieved THA femoral heads for both CoCr and ceramic bearing materials. In vitro wear testing has shown increased wear to polyethylene acetabular liners with the presence of metal transfer. This study sought to investigate the extent of metal transfer on the bearing surface of CoCr and ceramic femoral heads and identify prevalent morphologies. Three bearing couple cohorts: M-PE (n = 50), C-PE (n = 35), and C-C (n = 15), were derived from two previously matched collections (n = 50/group) of CoCr and ceramic femoral heads. From the three cohorts, 75% of the femoral …

Palbociclib In Hormone-Receptor-Positive Advanced Breast Cancer., Nicholas C Turner, Cynthia Huang Bartlett, Massimo Cristofanilli

Department of Medicine Faculty Papers

No abstract provided.

Emerging Novel Therapies For Heart Failure., Anthony M Szema, Sophia Dang, Jonathan C Li

Department of Medicine Faculty Papers

Heart function fails when the organ is unable to pump blood at a rate proportional to the body's need for oxygen or when this function leads to elevated cardiac chamber filling pressures (cardiogenic pulmonary edema). Despite our sophisticated knowledge of heart failure, even so-called ejection fraction-preserved heart failure has high rates of mortality and morbidity. So, novel therapies are sorely needed. This review discusses current standard therapies for heart failure and launches an exploration into emerging novel treatments on the heels of recently-approved sacubitril and ivbradine. For example, Vasoactive Intestinal Peptide (VIP) is protective of the heart, so in the …

Orphan Nuclear Receptor Nur77 Inhibits Cardiac Hypertrophic Response To Beta-Adrenergic Stimulation., Guijun Yan, Ni Zhu, Shengdong Huang, Bing Yi, Xiying Shang, Ming Chen, Nadan Wang, Guan-Xin Zhang, Jennifer A Talarico, Douglas G Tilley, Erhe Gao, Jianxin Sun

Center for Translational Medicine Faculty Papers

The orphan nuclear receptor Nur77 plays critical roles in cardiovascular diseases, and its expression is markedly induced in the heart after beta-adrenergic receptor (β-AR) activation. However, the functional significance of Nur77 in β-AR signaling in the heart remains unclear. By using Northern blot, Western blot, and immunofluorescent staining assays, we showed that Nur77 expression was markedly upregulated in cardiomyocytes in response to multiple hypertrophic stimuli, including isoproterenol (ISO), phenylephrine (PE), and endothelin-1 (ET-1). In a time- and dose-dependent manner, ISO increases Nur77 expression in the nuclei of cardiomyocytes. Overexpression of Nur77 markedly inhibited ISO-induced cardiac hypertrophy by inducing nuclear translocation …

Targeting The Mrna-Binding Protein Hur Impairs Malignant Characteristics Of Pancreatic Ductal Adenocarcinoma Cells., Masaya Jimbo, Fernando F Blanco, Yu-Hung Huang, Aristeidis G Telonis, Brad A Screnci, Gabriela L Cosma, Vitali Alexeev, Gregory E Gonye, Charles Yeo, Janet A Sawicki, Jordan M Winter, Jonathan Brody, Md

Computational Medicine Center Faculty Papers

Post-transcriptional regulation is a powerful mediator of gene expression, and can rapidly alter the expression of numerous transcripts involved in tumorigenesis. We have previously shown that the mRNA-binding protein HuR (ELAVL1) is elevated in human pancreatic ductal adenocarcinoma (PDA) specimens compared to normal pancreatic tissues, and its cytoplasmic localization is associated with increased tumor stage. To gain a better insight into HuR's role in PDA biology and to assess it as a candidate therapeutic target, we altered HuR expression in PDA cell lines and characterized the resulting phenotype in preclinical models. HuR silencing by short hairpin and small interfering RNAs …

Novel Targeted Sirna-Loaded Hybrid Nanoparticles: Preparation, Characterization And In Vitro Evaluation., Nneka Dim, Maryna Perepelyuk, Olukayode Gomes, Chellappagounder Thangavel, Yi Liu, Robert Den, Ashakumary Lakshmikuttyamma, Sunday A Shoyele

Department of Radiation Oncology Faculty Papers

BACKGROUND: siRNAs have a high potential for silencing critical molecular pathways that are pathogenic. Nevertheless, their clinical application has been limited by a lack of effective and safe nanotechnology-based delivery system that allows a controlled and safe transfection to cytosol of targeted cells without the associated adverse effects. Our group recently reported a very effective and safe hybrid nanoparticle delivery system composing human IgG and poloxamer-188 for siRNA delivery to cancer cells. However, these nanoparticles need to be optimized in terms of particle size, loading capacity and encapsulation efficiency. In the present study, we explored the effects of certain production …

Computerized Adaptive Tests Detect Change Following Orthopaedic Surgery In Youth With Cerebral Palsy., M J Mulcahey, Mary D Slavin, Pengsheng Ni, Lawrence C Vogel, Scott H Kozin, Stephen M Haley, Alan M Jette

Department of Occupational Therapy Faculty Papers

BACKGROUND: The Cerebral Palsy Computerized Adaptive Test (CP-CAT) is a parent-reported outcomes instrument for measuring lower and upper-extremity function, activity, and global health across impairment levels and a broad age range of children with cerebral palsy (CP). This study was performed to examine whether the Lower Extremity/Mobility (LE) CP-CAT detects change in mobility following orthopaedic surgery in children with CP.

METHODS: This multicenter, longitudinal study involved administration of the LE CP-CAT, the Pediatric Outcomes Data Collection Instrument (PODCI) Transfer/Mobility and Sports/Physical Functioning domains, and the Timed "Up & Go" test (TUG) before and after elective orthopaedic surgery in a convenience …

A Prospective Highlight On Exosomal Nanoshuttles And Cancer Immunotherapy And Vaccination., Mohammad Rafi, Yadollah Omidi

Department of Neurology Faculty Papers

INTRODUCTION: Exosomes (EXOs) and ectosomes (ECTOs) are nanoscale membranous extracellular vesicles (EVs) derived from different cells mediating various cellular communications. EXOs are liberated based on the exocytosis of multivesicular bodies, while ECTOs are ubiquitously released from the plasma membranes.

METHODS: Here, in this paper, we go over the extracellular vesicular machineries and concisely highlight their clinical importance in solid tumors and their possible applications in cancer immunotherapy/vaccination.

RESULTS: In various types of cancers, these vesicles play central roles delivering cancer cell messages to the target cells, as a result both of them seem to provide a novel useful means for …

Chimeric Cells Of Maternal Origin Do Not Appear To Be Pathogenic In The Juvenile Idiopathic Inflammatory Myopathies Or Muscular Dystrophy., Carol M Artlett, Sihem Sassi-Gaha, Ronald C Ramos, Frederick W Miller, Lisa G Rider

Department of Medicine Faculty Papers

INTRODUCTION: Microchimeric cells have been studied for over a decade, with conflicting reports on their presence and role in autoimmune and other inflammatory diseases. To determine whether microchimeric cells were pathogenic or mediating tissue repair in inflammatory myopathies, we phenotyped and quantified microchimeric cells in juvenile idiopathic inflammatory myopathies (JIIM), muscular dystrophy (MD), and noninflammatory control muscle tissues.

METHOD: Fluorescence immunophenotyping for infiltrating cells with sequential fluorescence in situ hybridization was performed on muscle biopsies from ten patients with JIIM, nine with MD and ten controls.

RESULTS: Microchimeric cells were significantly increased in MD muscle (0.079 ± 0.024 microchimeric cells/mm(2) …

Developments In Neurovascular Diseases And Treatments., Robert M Starke, Stephen J Monteith, Andrew M Southerland, R Webster Crowley, Nohra Chalouhi, Dale Ding, David M Hasan, Aaron S Dumont

Department of Neurosurgery Faculty Papers

No abstract provided.

Differential Host Immune Responses After Infection With Wild-Type Or Lab-Attenuated Rabies Viruses In Dogs., Clement W Gnanadurai, Yang Yang, Ying Huang, Zhenguang Li, Christina M Leyson, Tanya L Cooper, Simon R Platt, Stephen B Harvey, D Craig Hooper, Milosz Faber, Zhen F Fu

Department of Medical Genetics Faculty Papers

METHODOLOGY/PRINCIPAL FINDINGS: The experimental infection of dogs with TriGAS induced high levels of VNA in the serum, whereas wt RABV infection did not. Dogs infected with TriGAS developed antibodies against the virus including its glycoprotein, whereas dogs infected with DRV-NG11 only developed rabies antibodies that are presumably specific for the nucleoprotein, (N) and not the glycoprotein (G). We show that infection with TriGAS induces early activation of B cells in the draining lymph nodes and persistent activation of DCs and B cells in the blood. On the other hand, infection with DRV-NG11 fails to induce the activation of DCs and …

Inflammatory Muscle Diseases., Marinos Dalakas

Department of Medicine Faculty Papers

No abstract provided.