Medicine and Health Sciences Commons^™

Utilization Of Hiv-1 Envelope V3 To Identify X4- And R5-Specific Tat And Ltr Sequence Signatures., Gregory C Antell, Will Dampier, Benjamas Aiamkitsumrit, Michael R Nonnemacher, Jeffrey M Jacobson, Vanessa Pirrone, Wen Zhong, Katherine Kercher, Shendra Passic, Jean W Williams, Gregory Schwartz, Uri Hershberg, Fred C Krebs, Brian Wigdahl

Department of Medicine Faculty Papers

BACKGROUND: HIV-1 entry is a receptor-mediated process directed by the interaction of the viral envelope with the host cell CD4 molecule and one of two co-receptors, CCR5 or CXCR4. The amino acid sequence of the third variable (V3) loop of the HIV-1 envelope is highly predictive of co-receptor utilization preference during entry, and machine learning predictive algorithms have been developed to characterize sequences as CCR5-utilizing (R5) or CXCR4-utilizing (X4). It was hypothesized that while the V3 loop is predominantly responsible for determining co-receptor binding, additional components of the HIV-1 genome may contribute to overall viral tropism and display sequence signatures …

Ips Cell Transplantation For Traumatic Spinal Cord Injury., Miguel Goulao, Angelo C Lepore

Farber Institute for Neuroscience Faculty Papers

A large body of work has been published on transplantation of a wide range of neural stem and progenitor cell types derived from the developing and adult CNS, as well as from pluripotent embryonic stem cells, in models of traumatic spinal cord injury (SCI). However, many of these cell-based approaches present practical issues for clinical translation such as ethical cell derivation, generation of potentially large numbers of homogenously prepared cells, and immune rejection. With the advent of induced Pluripotent Stem (iPS) cell technology, many of these issues may potentially be overcome. To date, a number of studies have demonstrated integration, …

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 …

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 …

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.

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.