Medical Sciences Commons^™

Current Understanding Of The Mechanism Of Action Of The Antiepileptic Drug Lacosamide, Michael A. Rogawski, Azita Tofighy, H Steve White, Alain Matagne, Christian Wolff

Michael A. Rogawski

The antiepileptic drug lacosamide [(R)-2-acetamido-N-benzyl-3-methoxypropanamide], a chiral functionalized amino acid, was originally identified by virtue of activity in the mouse and rat maximal electroshock (MES) test. Attention was drawn to lacosamide because of its high oral potency and stereoselectivity. Lacosamide is also active in the 6 Hz seizure model but inactive against clonic seizures in rodents induced by subcutaneous pentylenetetrazol, bicuculline and picrotoxin. It is also ineffective in genetic models of absence epilepsy. At doses greater than those required to confer protection in the MES test, lacosamide inhibits behavioral and electrographic seizures in hippocampal kindled rats. It also effectively ...

Ngo's Bpa Report Intended To Frighten, Not Enlighten., Robert L. Brent Dr.

The Selected Works of Robert Brent

None

Validated Automatic Brain Extraction Of Head Ct Images, John Muschelli Iii, Natalie L. Ullman, Daniel F. Hanley, Paul Vespa, Ciprian M. Crainiceanu

John Muschelli III

Background

X-ray Computed Tomography (CT) imaging of the brain is commonly used in diagnostic settings. Al- though CT scans are primarily used in clinical practice, they are increasingly used in research. A fundamental processing step in brain imaging research is brain extraction – the process of separating the brain tissue from all other tissues. Methods for brain extraction have either been validated but not fully automated, or have been fully automated and informally proposed, but never formally validated.

Aim

To systematically analyze and validate the performance of FSL’s brain extraction tool (BET) on head CT images of patients with intracranial ...

Breast Cancer Screening: Early Detection Is Not Enough, Judy A. Tjoe

Journal of Patient-Centered Research and Reviews

N/A

Association Between Body Surface Area And Outcomes After Percutaneous Coronary Intervention, Kambiz Shetabi, Tonga Nfor, Fengyi Shen, Anjan Gupta, Tanvir Bajwa, Suhail Allaqaband

Journal of Patient-Centered Research and Reviews

Purpose

Obesity is a well-known risk factor for adverse cardiovascular events, but some studies suggest higher body mass index (BMI) is associated with better outcomes after ST-segment elevation myocardial infarction (STEMI). We sought to determine the effect of body surface area (BSA) on adverse events after primary percutaneous coronary intervention (PCI) for STEMI and how this relates to the reported obesity paradox theory.

Methods

We analyzed a prospective registry of patients with STEMI who underwent primary PCI at a tertiary care hospital from 2003 to 2009. Post-PCI complications and 1-year all-cause mortality were compared across BSA quartiles. Relationship with 1-year ...

Skeletal Muscle Fibrosis In The Mdx/Utrn+/- Mouse Validates Its Suitability As A Murine Model Of Duchenne Muscular Dystrophy, Lisa M. Hoffman, William T. Hrinivich, Kelly M. Gutpell

Medical Biophysics Publications

Various therapeutic approaches have been studied for the treatment of Duchenne muscular dystrophy (DMD), but none of these approaches have led to significant long-term effects in patients. One reason for this observed inefficacy may be the use of inappropriate animal models for the testing of therapeutic agents. The mdx mouse is the most widely used murine model of DMD, yet it does not model the fibrotic progression observed in patients. Other murine models of DMD are available that lack one or both alleles of utrophin, a functional analog of dystrophin. The aim of this study was to compare fibrosis and ...

Pyruvate Carboxylase Is Critical For Non-Small-Cell Lung Cancer Proliferation, Katherine Sellers, Matthew P. Fox, Michael Bousamra Ii, Stephen P. Slone, Richard M. Higashi, Donald M. Miller, Yali Wang, Jun Yan, Mariia O. Yuneva, Rahul Deshpande, Andrew N. Lane, Teresa W-M Fan

Toxicology and Cancer Biology Faculty Publications

Anabolic biosynthesis requires precursors supplied by the Krebs cycle, which in turn requires anaplerosis to replenish precursor intermediates. The major anaplerotic sources are pyruvate and glutamine, which require the activity of pyruvate carboxylase (PC) and glutaminase 1 (GLS1), respectively. Due to their rapid proliferation, cancer cells have increased anabolic and energy demands; however, different cancer cell types exhibit differential requirements for PC- and GLS-mediated pathways for anaplerosis and cell proliferation. Here, we infused patients with early-stage non-small-cell lung cancer (NSCLC) with uniformly 13C-labeled glucose before tissue resection and determined that the cancerous tissues in these patients had enhanced PC activity ...

Surfactant And Matrix Metalloproteinase 3 In The Pathogenesis Of Acute Lung Injury, Valeria Puntorieri

University of Western Ontario - Electronic Thesis and Dissertation Repository

Acute lung injury (ALI) is a pulmonary inflammatory disorder resulting in respiratory failure that is initiated by a number of different insults to the lung. Despite very high mortality, there are still no effective treatments for this disease, and the main supportive therapy, mechanical ventilation, can further lung injury and contribute to ALI progression. The overall objective of this work was therefore to evaluate the role of two key players in the disease process, such as: i) lung surfactant, a material essential for minimizing the work of breathing and for pulmonary immunomodulation, and ii) matrix metalloproteinase 3 (MMP-3), protease involved ...

The Cell's Antenna And Bending With The Flow, Surya M. Nauli, Kimberly F. Atkinson, Sarmed H. Kathem

Pharmacy Faculty Articles and Research

Polycystic kidney disease (PKD) is the most common life-threatening genetic disease worldwide – affecting about 12.5 million people. Patients with the condition have multiple fluid-filled cysts in their kidneys that lead to a massive enlargement of the organ and gradual worsening of its function, as well as complete failure in many cases. The lack of available treatment means patients may eventually require regular dialysis or a kidney transplant.

Two Potential Hookworm Daf-16 Target Genes, Snr-3 And Lpp-1: Gene Structure, Expression Profile, And Implications Of A Cis-Regulatory Element In The Regulation Of Gene Expression, Xin Gao, Kevin Goggin, Camille Dowling, Jason Qian, John Hawdon

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background

Hookworms infect nearly 700 million people, causing anemia and developmental stunting in heavy infections. Little is known about the genomic structure or gene regulation in hookworms, although recent publication of draft genome assemblies has allowed the first investigations of these topics to be undertaken. The transcription factor DAF-16 mediates multiple developmental pathways in the free living nematode Caenorhabditis elegans, and is involved in the recovery from the developmentally arrested L3 in hookworms. Identification of downstream targets of DAF-16 will provide a better understanding of the molecular mechanism of hookworm infection.

Methods

Genomic Fragment 2.23 containing a DAF-16 binding ...

Feasibility Of Simultaneous Whole-Brain Imaging On An Integrated Pet-Mri System Using An Enhanced 2-Point Dixon Attenuation Correction Method., Udunna C Anazodo, Jonathan D Thiessen, Tracy Ssali, Jonathan Mandel, Matthias Günther, John Butler, William Pavlosky, Frank S Prato, R Terry Thompson, Keith S St Lawrence

Medical Biophysics Publications

PURPOSE: To evaluate a potential approach for improved attenuation correction (AC) of PET in simultaneous PET and MRI brain imaging, a straightforward approach that adds bone information missing on Dixon AC was explored.

METHODS: Bone information derived from individual T1-weighted MRI data using segmentation tools in SPM8, were added to the standard Dixon AC map. Percent relative difference between PET reconstructed with Dixon+bone and with Dixon AC maps were compared across brain regions of 13 oncology patients. The clinical potential of the improved Dixon AC was investigated by comparing relative perfusion (rCBF) measured with arterial spin labeling to relative ...

Expression Of Interferon Gamma By A Recombinant Rabies Virus Strongly Attenuates The Pathogenicity Of The Virus Via Induction Of Type I Interferon., Darryll A Barkhouse, Samantha A Garcia, Emily K Bongiorno, Aurore Lebrun, Milosz Faber, D Craig Hooper, Phd

Department of Cancer Biology Faculty Papers

UNLABELLED: Previous animal model experiments have shown a correlation between interferon gamma (IFN-γ) expression and both survival from infection with attenuated rabies virus (RABV) and reduction of neurological sequelae. Therefore, we hypothesized that rapid production of murine IFN-γ by the rabies virus itself would induce a more robust antiviral response than would occur naturally in mice. To test this hypothesis, we used reverse engineering to clone the mouse IFN-γ gene into a pathogenic rabies virus backbone, SPBN, to produce the recombinant rabies virus designated SPBNγ. Morbidity and mortality were monitored in mice infected intranasally with SPBNγ or SPBN(-) control virus ...

Influence Of Planning Resources On Gait Control In Parkinson’S Disease, Frederico P. Faria

Theses and Dissertations (Comprehensive)

Movement disturbances in individuals with Parkinson’s disease (PD) have been associated with difficulties to plan complex actions. Performance of simple and complex actions overloads resources for individuals with Parkinson’s disease (PD). However, it is unclear if central resources required to plan gait adjustments while walking exacerbate gait disturbances of patients with PD. More specifically, it is unclear how gait impairments, sensory processing, and the dopaminergic system influence the load on processing resources (e.g. cognitive load) during the planning of step modifications. In order to investigate the relative influence of these factors on cognitive load and its impact ...

'Vitamin D And Cognition In Older Adults': Updated International Recommendations., C Annweiler, E Dursun, F Féron, D Gezen-Ak, A V Kalueff, T Littlejohns, D J Llewellyn, P Millet, T Scott, K L Tucker, S Yilmazer, O Beauchet

Medical Biophysics Publications

BACKGROUND: Hypovitaminosis D, a condition that is highly prevalent in older adults aged 65 years and above, is associated with brain changes and dementia. Given the rapidly accumulating and complex contribution of the literature in the field of vitamin D and cognition, clear guidance is needed for researchers and clinicians.

METHODS: International experts met at an invitational summit on 'Vitamin D and Cognition in Older Adults'. Based on previous reports and expert opinion, the task force focused on key questions relating to the role of vitamin D in Alzheimer's disease and related disorders. Each question was discussed and voted ...

Hippocampal Volume, Early Cognitive Decline And Gait Variability: Which Association?, Olivier Beauchet, Cyrille P Launay, Cédric Annweiler, Gilles Allali

Medical Biophysics Publications

BACKGROUND: In contrast to its prominent function in cognition, the involvement of the hippocampus in gait control is still a matter of debate. The present study aimed to examine the association of the hippocampal volume with mean values and coefficients of variation (CoV) of spatio-temporal gait parameters among cognitively healthy individuals (CHI) and patients with mild cognitive impairment (MCI).

METHODS: A total of 90 individuals (47 CHI with a mean age of 69.7±3.6years and 48.9% women, and 43 MCI individuals with a mean age of 70.2±3.7years and 62.8% women) were included in ...

Inhibitory Control Efficiency In Successful Weight Loss Participants, Kathryn Curran Olds

Graduate College Dissertations and Theses

Eating unhealthy foods and eating past satiety are inappropriate behaviors that promote obesity. The ability to effectively inhibit an inappropriate behavior is a key component of cognitive restraint and its impairment has been previously linked to obesity. In this study, a Go/No-Go fMRI task was completed by a cohort of adult women that had experienced initial weight loss followed by various levels of weight regain or continued weight loss. Region of interest fMRI analysis revealed that greater total weight loss was significantly related to decreasing activation in the right inferior frontal gyrus and the right superior frontal gyrus. These ...

Unified Voxel- And Tensor-Based Morphometry (Uvtbm) Using Registration Confidence., Ali R Khan, Lei Wang, Mirza Faisal Beg

Medical Biophysics Publications

Voxel-based morphometry (VBM) and tensor-based morphometry (TBM) both rely on spatial normalization to a template and yet have different requirements for the level of registration accuracy. VBM requires only global alignment of brain structures, with limited degrees of freedom in transformation, whereas TBM performs best when the registration is highly deformable and can achieve higher registration accuracy. In addition, the registration accuracy varies over the whole brain, with higher accuracy typically observed in subcortical areas and lower accuracy seen in cortical areas. Hence, even the determinant of Jacobian of registration maps is spatially varying in their accuracy, and combining these ...

Validation Of Volumetric And Single-Slice Mri Adipose Analysis Using A Novel Fully Automated Segmentation Method., Bryan T Addeman, Shelby Kutty, Thomas G Perkins, Abraam S Soliman, Curtis N Wiens, Colin M Mccurdy, Melanie D Beaton, Robert A Hegele, Charles Mckenzie

Medical Biophysics Publications

PURPOSE: To validate a fully automated adipose segmentation method with magnetic resonance imaging (MRI) fat fraction abdominal imaging. We hypothesized that this method is suitable for segmentation of subcutaneous adipose tissue (SAT) and intra-abdominal adipose tissue (IAAT) in a wide population range, easy to use, works with a variety of hardware setups, and is highly repeatable.

MATERIALS AND METHODS: Analysis was performed comparing precision and analysis time of manual and automated segmentation of single-slice imaging, and volumetric imaging (78-88 slices). Volumetric and single-slice data were acquired in a variety of cohorts (body mass index [BMI] 15.6-41.76) including healthy ...

Pretreatment Of Human Cerebrovascular Endothelial Cells With Co-Releasing Molecule-3 Interferes With Jnk/Ap-1 Signaling And Suppresses Lps-Induced Proadhesive Phenotype., Fukashi Serizawa, Eric Patterson, Richard F Potter, Douglas D Fraser, Gediminas Cepinskas

Medical Biophysics Publications

OBJECTIVE: Exogenously administered CO interferes with PMN recruitment to the inflamed organs. The mechanisms of CO-dependent modulation of vascular proadhesive phenotype, a key step in PMN recruitment, are unclear.

METHODS: We assessed the effects/mechanisms of CO liberated from a water-soluble CORM-3 on modulation of the proadhesive phenotype in hCMEC/D3 in an in vitro model of endotoxemia. To this end, hCMEC/D3 were stimulated with LPS (1 μg/mL) for six hours. In some experiments hCMEC/D3 were pretreated with CORM-3 (200 μmol/L) before LPS-stimulation. PMN rolling/adhesion to hCMEC/D3 were assessed under conditions of laminar shear ...

Detective Quantum Efficiency Of Photon-Counting X-Ray Detectors., Jesse Tanguay, Seungman Yun, Ho Kyung Kim, Ian A Cunningham

Medical Biophysics Publications

PURPOSE: Single-photon-counting (SPC) x-ray imaging has the potential to improve image quality and enable novel energy-dependent imaging methods. Similar to conventional detectors, optimizing image SPC quality will require systems that produce the highest possible detective quantum efficiency (DQE). This paper builds on the cascaded-systems analysis (CSA) framework to develop a comprehensive description of the DQE of SPC detectors that implement adaptive binning.

METHODS: The DQE of SPC systems can be described using the CSA approach by propagating the probability density function (PDF) of the number of image-forming quanta through simple quantum processes. New relationships are developed to describe PDF transfer ...