Medical Specialties Commons^™

Clinical, Laboratory And Health-Related Quality Of Life Correlates Of Systemic Lupus Erythematosus Responder Index Response: A Post Hoc Analysis Of The Phase 3 Belimumab Trials, R. Furie, M. A. Petri, V. Strand, D. D. Gladman, Z. J. Zhong, W. W. Freimuth

Journal Articles

OBJECTIVE: Correlates of systemic lupus erythematosus (SLE) Responder Index (SRI) response with clinical trial end points were examined using pooled data from the Study of Belimumab in Subjects with SLE (BLISS) trials (N=1684). METHODS: Changes in clinical, laboratory and health-related quality of life measures from baseline at 52 weeks were compared between SRI responders (n=761) and non-responders (n=923). RESULTS: More SRI responders than non-responders had >/=4-point (100% vs 3.8%) and >/=7-point (40.3% vs 1.3%) Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index reductions, no new British Isles Lupus Assessment Group (BILAG) A and7.5 mg/d to7.5 …

Approaching The Next Revolution? Evolutionary Integration Of Neural And Immune Pathogen Sensing And Response, K. J. Tracey

Journal Articles

Mammalian immunity evolved by the process of natural selection that produced differential survival and reproduction advantages through combinations of hereditary traits underlying the response to pathogens. Primitive animals sense the presence of microbial pathogens through recognition of pathogen-derived molecules in their rudimentary immune and nervous systems. No molecular biological mechanism assigns primacy of pathogen sensing mechanisms to immune cells over neurons. Rather, in animals as diverse as Caenorhabditis elegans to mammals, neural reflexes are activated by the presence of pathogens and transduce neural mechanisms that control the development of immunity. A coming revolution in immunological thinking will require immunologists to …

Central Cholinergic Activation Of A Vagus Nerve-To-Spleen Circuit Alleviates Experimental Colitis, H. Ji, M. F. Rabbi, B. Labis, V. A. Pavlov, K. J. Tracey, J. E. Ghia

Journal Articles

The cholinergic anti-inflammatory pathway is an efferent vagus nerve-based mechanism that regulates immune responses and cytokine production through alpha 7 nicotinic acetylcholine receptor (alpha 7nAChR) signaling. Decreased efferent vagus nerve activity is observed in inflammatory bowel disease. We determined whether central activation of this pathway alters inflammation in mice with colitis and the mediating role of a vagus nerve-to-spleen circuit and alpha 7nAChR signaling. Two experimental models of colitis were used in C57BL/6 mice. Central cholinergic activation induced by the acetylcholinesterase inhibitor galantamine or a muscarinic acetylcholine receptor agonist treatments resulted in reduced mucosal inflammation associated with decreased major histocompatibility …

High-Mobility Group Box 1 Protein Initiates Postoperative Cognitive Decline By Engaging Bone Marrow-Derived Macrophages, S. Vacas, V. Degos, K. J. Tracey, M. Maze

Journal Articles

Background: Aseptic trauma engages the innate immune response to trigger a neuroinflammatory reaction that results in postoperative cognitive decline. The authors sought to determine whether high-mobility group box 1 protein (HMGB1), an ubiquitous nucleosomal protein, initiates this process through activation and trafficking of circulating bone marrow-derived macrophages to the brain. Methods: The effects of HMGB1 on memory (using trace fear conditioning) were tested in adult C57BL/6J male mice; separate cohorts were tested after bone marrow-derived macrophages were depleted by clodrolip. The effect of anti-HMGB1 neutralizing antibody on the inflammatory and behavioral responses to tibial surgery were investigated. Results: A single …

Lymphocyte Called Home: Beta2-Adreneric Neurotransmission Confines T Cells To Lymph Nodes To Suppress Inflammation, K J. Tracey

Journal Articles

No abstract provided.

Mapping Human Brain Networks With Cortico-Cortical Evoked Potentials, C. J. Keller, C. J. Honey, P. Megevand, L. Entz, I. Ulbert, A. D. Mehta

Journal Articles

The cerebral cortex forms a sheet of neurons organized into a network of interconnected modules that is highly expanded in humans and presumably enables our most refined sensory and cognitive abilities. The links of this network form a fundamental aspect of its organization, and a great deal of research is focusing on understanding how information flows within and between different regions. However, an often-overlooked element of this connectivity regards a causal, hierarchical structure of regions, whereby certain nodes of the cortical network may exert greater influence over the others. While this is difficult to ascertain non-invasively, patients undergoing invasive electrode …

Nanocomposite Scaffold For Chondrocyte Growth And Cartilage Tissue Engineering: Effects Of Carbon Nanotube Surface Functionalization, N. O. Chahine, N. M. Collette, C. B. Thomas, D. C. Genetos, G. G. Loots

Journal Articles

The goal of this study was to assess the long-term biocompatibility of single-wall carbon nanotubes (SWNTs) for tissue engineering of articular cartilage. We hypothesized that SWNT nanocomposite scaffolds in cartilage tissue engineering can provide an improved molecular-sized substrate for stimulation of chondrocyte growth, as well as structural reinforcement of the scaffold's mechanical properties. The effect of SWNT surface functionalization (-COOH or -PEG) on chondrocyte viability and biochemical matrix deposition was examined in two-dimensional cultures, in three-dimensional (3D) pellet cultures, and in a 3D nanocomposite scaffold consisting of hydrogels + SWNTs. Outcome measures included cell viability, histological and SEM evaluation, GAG …

Targeting A Heterogeneous Tumor: The Promise Of The Interleukin-13 Receptor Alpha2, I. Bodhinayake, M. Ottenhausen, J. A. Boockvar

Journal Articles

No abstract provided.

Transcranial Magnetic Stimulation Across The Menstrual Cycle: What Do Hormones Have To Do With It?, C. L. Harden

Journal Articles

No abstract provided.

Medical Management With Or Without Interventional Therapy For Unruptured Brain Arteriovenous Malformations (Aruba): A Multicentre, Non-Blinded, Randomised Trial, J. P. Mohr, M. K. Parides, C. Stapf, E. Moquete, C. S. Moy, J. R. Overbey, R. A. S. Salman, E. Vicaut, R. Libman, Aruba Investigators Int, +12 Additional Authors

Journal Articles

Background The clinical benefit of preventive eradication of unruptured brain arteriovenous malformations remains uncertain. A Randomised trial of Unruptured Brain Arteriovenous malformations (ARUBA) aims to compare the risk of death and symptomatic stroke in patients with an unruptured brain arteriovenous malformation who are allocated to either medical management alone or medical management with interventional therapy. Methods Adult patients (>= 18 years) with an unruptured brain arteriovenous malformation were enrolled into this trial at 39 clinical sites in nine countries. Patients were randomised (by web-based system, in a 1: 1 ratio, with random permuted block design [block size 2, 4, …

Blood Levels Of S-100 Calcium-Binding Protein B, High-Sensitivity C-Reactive Protein, And Interleukin-6 For Changes In Depressive Symptom Severity After Coronary Artery Bypass Grafting: Prospective Cohort Nested Within A Randomized, Controlled Trial, Daniel M. Pearlman, Jeremiah R. Brown, Todd A. Mackenzie, Felix, Jr. Hernandez, Souhel Najjar

Journal Articles

Background: Cross-sectional and retrospective studies have associated major depressive disorder with glial activation and injury as well as blood-brain barrier disruption, but these associations have not been assessed prospectively. Here, we aimed to determine the relationship between changes in depressive symptom severity and in blood levels of S-100 calcium-binding protein B (S-100B), high-sensitivity C-reactive protein, and interleukin-6 following an inflammatory challenge. Methods: Fifty unselected participants were recruited from a randomized, controlled trial comparing coronary artery bypass grafting procedures performed with versus without cardiopulmonary bypass for the risk of neurocognitive decline. Depressive symptom severity was measured at baseline, discharge, and six-month …

Sudden Unexpected Nocturnal Death In Chiari Type 1 Malformation And Potential Role Of Opioid Analgesics, F. Roohi, T. Gropen, R. W. Kula

Journal Articles

BACKGROUND: Chiari malformation type 1 (CM1) is a common congenital anomaly of the craniocervical junction. CM1 is reported to run a usually benign course and patients typically experience no symptoms or chronic, slowly progressive symptoms. However, recent reports indicate that a subset of patients with CM1 may present with acute deterioration and sudden unexpected death (SUD). We report a case of SUD during sleep in a young man with CM1, which we believe was related to the administration of common and therapeutic doses of narcotic analgesics for the management of pain. We will clarify the pathophysiology of acute deterioration and …

Middle Cerebral Artery Arrow Sign, Z. D. Levy, R. E. Temes, A. R. Dehdashti

Journal Articles

No abstract provided.

Central Muscarinic Cholinergic Activation Alters Interaction Between Splenic Dendritic Cell And Cd4(+)Cd25(-) T Cells In Experimental Colitis, P. Munyaka, M. F. Rabbi, V. A. Pavlov, K. J. Tracey, E. Khafipour, J. E. Ghia

Journal Articles

Background: The cholinergic anti-inflammatory pathway (CAP) is based on vagus nerve (VN) activity that regulates macrophage and dendritic cell responses in the spleen through alpha-7 nicotinic acetylcholine receptor (a7nAChR) signaling. Inflammatory bowel disease (IBD) patients present dysautonomia with decreased vagus nerve activity, dendritic cell and T cell over-activation. The aim of this study was to investigate whether central activation of the CAP alters the function of dendritic cells (DCs) and sequential CD4(+)/CD25(-)T cell activation in the context of experimental colitis. Methods: The dinitrobenzene sulfonic acid model of experimental colitis in C57BL/6 mice was used. Central, intracerebroventricular infusion of the M1 …

Head Impact Exposure In Male And Female Collegiate Ice Hockey Players, Bethany J. Wilcox, Jonathan G. Beckwith, Richard M. Greenwald, Jeffrey J. Chu, Thomas W. Mcallister, Laura A. Flashman, Arthur C. Maerlender, Ann-Christine Duhaime, Joseph J. Crisco

Department of Psychology: Faculty Publications

The purpose of this study was to quantify head impact exposure (frequency, location and magnitude of head impacts) for individual male and female collegiate ice hockey players and to investigate differences in exposure by sex, player position, session type, and team. Ninety-nine (41 male, 58 female) players were enrolled and 37,411 impacts were recorded over three seasons. Frequency of impacts varied significantly by sex (males: 287 per season, females: 170, p < 0.001) and helmet impact location (p < 0.001) but not by player position (p = 0.088). Head impact frequency also varied by session type; both male and female players sustained more impacts in games than in practices (p < 0.001), however the magnitude of impacts did not differ between session types. There was no difference in 95th percentile peak linear acceleration between sexes (males: 41.6 g, females: 40.8 g), but 95th percentile peak rotational acceleration and HITsp (a composite severity measure) were greater for males than females (4424, 3409 rad/s2, and 25.6, 22.3, respectively). Impacts to the back of the helmet resulted in the greatest 95th percentile peak linear accelerations for males (45.2 g) and females (50.4 g), while impacts to the side and back of the head were associated with the greatest 95th percentile peak rotational accelerations (males: 4719, 4256 rad/sec², females: 3567, 3784 rad/sec², respectively). It has been proposed that reducing an individual’s head impact exposure is a practical approach for reducing the risk of …

Development Of Status Epilepticus, Sustained Calcium Elevations And Neuronal Injury In A Rat Survival Model Of Lethal Paraoxon Intoxication, Laxmikant Sudhir Deshpande, Dawn S. Carter, Kristin Phillips, Robert E. Blair, Robert J. Delorenzo

Neurology Publications

Paraoxon (POX) is an active metabolite of organophosphate (OP) pesticide parathion that has been weaponized and used against civilian populations. Exposure to POX produces high mortality. OP poisoning is often associated with chronic neurological disorders. In this study, we optimize a rat survival model of lethal POX exposures in order to mimic both acute and long-term effects of POX intoxication. Male Sprague–Dawley rats injected with POX (4 mg/kg, ice-cold PBS, s.c.) produced a rapid cholinergic crisis that evolved into status epilepticus (SE) and death within 6–8 min. The EEG profile for POX induced SE was characterized and showed clinical and …

Seizure Detection, Seizure Prediction, And Closed-Loop Warning Systems In Epilepsy, S Ramgopal, S Thome-Souza, M Jackson, N E. Kadish, I Sanchez Fernandez, J Klehm, William Bosl, C Reinsberger, S Schachter, T Loddenkemper

Nursing and Health Professions Faculty Research and Publications

Nearly one-third of patients with epilepsy continue to have seizures despite optimal medication management. Systems employed to detect seizures may have the potential to improve outcomes in these patients by allowing more tailored therapies and might, additionally, have a role in accident and SUDEP prevention. Automated seizure detection and prediction require algorithms which employ feature computation and subsequent classification. Over the last few decades, methods have been developed to detect seizures utilizing scalp and intracranial EEG, electrocardiography, accelerometry and motion sensors, electrodermal activity, and audio/video captures. To date, it is unclear which combination of detection technologies yields the best results, …

Cerebral Pressure Passivity In Newborns With Encephalopathy Undergoing Therapeutic Hypothermia, Rathinaswamy B. Govindan, An Nguyen Massaro, Nickie N. Andescavage, Taeun Chang, Adre J. Du Plessis

Neurology Faculty Publications

We extended our recent modification of the power spectral estimation approach to quantify spectral coherence. We tested both the standard and the modified approaches on simulated data, which showed that the modified approach was highly specific and sensitive to the coupling introduced in the simulation while the standard approach lacked these features. We also applied the modified and standard approaches to quantify the pressure passivity in 4 infants receiving therapeutic hypothermia. This was done by measuring the coupling between continuous cerebral hemoglobin differences and mean arterial blood pressure. Our results showed that the modified approach identified a lower pressure passivity …

Lysosomal Abnormalities In Hereditary Spastic Paraplegia Types Spg15 And Spg11, Benoit Renvoise, Jaerak Chang, Rajat Singh, Sayuri Yonekawa, Edmond J. Fitzgibbon, Ami Mankodi, Adeline Vanderver, Alice B. Schindler, Camilo Toro, William A. Gahl, Don J. Mahuran, Craig Blackstone, Tyler Pierson

Neurology Faculty Publications

Objective

Hereditary spastic paraplegias (HSPs) are among the most genetically diverse inherited neurological disorders, with over 70 disease loci identified (SPG1-71) to date. SPG15 and SPG11 are clinically similar, autosomal recessive disorders characterized by progressive spastic paraplegia along with thin corpus callosum, white matter abnormalities, cognitive impairment, and ophthalmologic abnormalities. Furthermore, both have been linked to early-onset parkinsonism.

Methods

We describe two new cases of SPG15 and investigate cellular changes in SPG15 and SPG11 patient-derived fibroblasts, seeking to identify shared pathogenic themes. Cells were evaluated for any abnormalities in cell division, DNA repair, endoplasmic reticulum, endosomes, and lysosomes.

Results

Fibroblasts …

Implicit Sequence Learning In People With Parkinson's Disease, Katherine R. Gamble, Thomas J. Cummings, Steven E. Lo, Pritha T. Ghosh, James H. Howard, Darlene V. Howard

Neurology Faculty Publications

Implicit sequence learning involves learning about dependencies in sequences of events without intent to learn or awareness of what has been learned. Sequence learning is related to striatal dopamine levels, striatal activation, and integrity of white matter connections. People with Parkinson’s disease (PD) have degeneration of dopamine-producing neurons, leading to dopamine deficiency and therefore striatal deficits, and they have difficulties with sequencing, including complex language comprehension and postural stability. Most research on implicit sequence learning in PD has used motor-based tasks. However, because PD presents with motor deficits, it is difficult to assess whether learning itself is impaired in these …

Assessing Function And Endurance In Adults With Spinal And Bulbar Muscular Atrophy: Validity Of The Adult Myopathy Assessment Tool., Michael O. Harris-Love, Lindsay Fernandez-Rhodes, Galen Joe, Joseph A. Shrader, Angela Kokkinis, Alison La Pean Kirschner, Sungyoung Auh, Cheunju Chen, Li Li, Ellen Levy, Todd E. Davenport, Nicholas A. Di Prospero, Kenneth H. Fischbeck

Exercise and Nutrition Sciences Faculty Publications

Purpose. The adult myopathy assessment tool (AMAT) is a performance-based battery comprised of functional and endurance subscales that can be completed in approximately 30 minutes without the use of specialized equipment. The purpose of this study was to determine the construct validity and internal consistency of the AMAT with a sample of adults with spinal and bulbar muscular atrophy (SBMA).

Methods. AMAT validity was assessed in 56-male participants with genetically confirmed SBMA (mean age, 53 ± 10 years). The participants completed the AMAT and assessments for disease status, strength, and functional status. Results. Lower AMAT scores were associated with longer …

Examining A Link Between Paraquat, Alpha-Synuclein Fibrillation And Neurodegeneration: A Review, Nikhil Ailaney

AUCTUS: The Journal of Undergraduate Research and Creative Scholarship

Parkinson’s disease is a chronic and progressive motor system disorder that is caused by the degeneration of dopaminergic neurons in the central nervous system. At the molecular level, Parkinson’s disease works by decreasing the concentrations of the neurotransmitter dopamine, a chemical messenger involved in motor messaging, within the central nervous system. Low levels of dopamine in the central nervous system causes motor system dysfunction because the insufficient levels of dopamine lead to an inability for neurons to successfully transmit motor messages. At the organismal level, Parkinson’s disease causes tremors, Bradykinesia, and rigidity. These symptoms ultimately lead to a diminished quality …

Understanding And Managing Complications In Neurosurgery, Raza Sayyed, M Shahzad Shamim

Pakistan Journal of Neurological Sciences (PJNS)

It is a well-known surgical maxim that only two types of surgeons do not have surgical complications; those who do not operate, and those who lie. Surgical complications in other words, are unwanted but undeniable part of surgery. There is not one operation with a 0% complication rate and therefore statistically, if a surgeon does not have complications, he probably has not operated enough. Despite their inevitability, complications convey a sense of gravity to the public, health professionals, and the policy makers alike.

Delay In Diagnosis Of Motor Neuron Disease. A Tertiary Care Experience, Hazim Brohi, Naveed Uddin Ahmed, Rajesh Khatri, Ishaq Asghar

Pakistan Journal of Neurological Sciences (PJNS)

Motor Neuron Disease is a progressive neurological disorder with poor prognosis. Inability to correctly recognize the disease, leads to undue agony and diagnostic dilemma. Studies have been done to look at the average duration taken to diagnose the disease from the onset of symptoms. The literature shows that latency from symptom onset to diagnosis range from 10.6–17.5 months. No such study has been conducted in our region. We reviewed 62 patients referred to the neurophysiology lab from year 2009 to 2013 with quarry of MND. Only 40 patients were identified to fulfill the El Escorial criteria for MND. The median …

Assessing Interprofessional Continuing Education And Planning Ahead, Farhan Vakani, Mughis Sheerani

Pakistan Journal of Neurological Sciences (PJNS)

The purpose of this survey is to check the concept of Interprofessional education (IPE) to continuing education among working physicians.It assessed 150 randomly selected working physicians of the Aga Khan University Hospital. One -best type questionnaire was designed and piloted to check its completion within 90 seconds.Four quick questions were dedicated at C1 & C2 level focused to check the knowledge and understanding of the physicians to IPE. The results showed 100% response rate. Majority (i.e. > 80%) of the respondents were familiar with the term IPE.The next three items tested physicians understanding regarding the IPE ability to improve communication, teamwork, …

Crossed Cerebellar Diaschisis In Partial Status Epilepticus, Sahrish Aieshah Kazi, Rehmani Aniqah Jawad, Rashed Nazir, Shahid Ahmed Shah, Arsalan Ahmad

Pakistan Journal of Neurological Sciences (PJNS)

Crossed cerebellar diaschisis is a phenomena described as decrease in metabolism in the cerebellar hemisphere contralateral to the supratentorial lesion. A 61 year old man presented with status epilepticus. CT Brain showed small acute hemorrhage in left parietal lobe.MRI revealed diffusion restriction in right cerebral and left cerebellar hemispheres with hyperintensities on T2WI and FLAIR. However, CT perfusion was suggestive of increased perfusion in these areas. Periictal EEG showed frequent bursts of higher voltage spike and wave discharges over the right hemisphere. He was treated with IV antiepileptics. But he continued to deteriorate, and expired at 10th day of admission.

Neurostimulation For Refractory Primary Chronic Headache Disorders: A Review, Bindu Yoga, Modar Khalil, Hassan Zafar, Fayyaz Ahmed

Pakistan Journal of Neurological Sciences (PJNS)

Headache is the commonest symptom seen in both primary and secondary care. Vast majority are primary i.e. for which no underlying cause has been detected. Tension Headaches, Migraine and Cluster Headaches are the most common primary headache disorders in the population. Although most of the primary headache disorders can be satisfactorily treated with both acute and preventive medications, those that are refractory to conventional treatment pose a great challenge to the headache physician. Moreover some patients are not able to use traditional treatment due to intolerance and co-morbidities. Neurostimulation is a treatment modality that has been used in other neurological …

Can Prophylactic Antibiotics For Aspiration Improve Stroke Outcomes? The Pantheris Trial., Ayeesha Kamran Kamal, Quratulain Shaikh

Department of Medicine

No abstract provided.

Toward The Development Of The International Classification Of Functioning Core Sets For Children With Cerebral Palsy: A Global Expert Survey, Veronica Schiariti, Louise C. Masse, Alarcos Cieza, Anne F. Klassen, Karen Sauve, Robert Armstrong, Maureen O’Donnell

Paediatrics and Child Health, East Africa

The goal of the International Classification of Functioning is to standardize the classification of health and function of children around the world. To facilitate the application of this classification, International Classification of Functioning-based tools like the "Core Sets" are being developed. We conducted an international survey of professional experts to identify the most relevant areas of functioning in children with cerebral palsy. The questionnaire covered each component of the classification. In total, 193 professionals completed the survey (response rate 78%). Overall, 9706 answers were linked to the classification (pediatric version) by 2 professionals. From the experts' perspective, movement-related areas and …

Neurosurgery Literature Highlights & Psychiatry Literature Highlights, Muhammad Waqas Shaiq, Muhammad Shahzad Shamim

Pakistan Journal of Neurological Sciences (PJNS)

Today, a great challenge of our profession is to envision how we will deliver exemplary neurosurgical care in the future. To accomplish this requires anticipating how economic, political, and societal influences will affect our ability to provide the highest quality of patient care in an arena that will look increasingly different from today's world of medicine. Already, our profession is battling a relentless assault as numerous sectors implement change that impacts us and our community every day. Surviving this requires an effective strategy that will involve significant cultural change.