Medical Specialties Commons^™

Mice Exposed To Combined Chronic Low-Dose Irradiation And Modeled Microgravity Develop Long-Term Neurological Sequelae, Amber M. Paul, Eliah G. Overbey, William A. Da Silveira, Candice G.T. Tahimic, Sigrid S. Reinsch, Nathaniel Szewczyk, Seta Stanbouly, Charles Wang, Jonathan M. Galazka, Xiao Wen Mao

Publications

Spaceflight poses many challenges for humans. Ground-based analogs typically focus on single parameters of spaceflight and their associated acute effects. This study assesses the long-term transcriptional effects following single and combination spaceflight analog conditions using the mouse model: simulated microgravity via hindlimb unloading (HLU) and/or low-dose γ-ray irradiation (LDR) for 21 days, followed by 4 months of readaptation. Changes in gene expression and epigenetic modifications in brain samples during readaptation were analyzed by whole transcriptome shotgun sequencing (RNA-seq) and reduced representation bisulfite sequencing (RRBS). The results showed minimal gene expression and cytosine methylation alterations at 4 months readaptation within single …

First-In-Human Study Of Tk-Positive Oncolytic Vaccinia Virus Delivered By Adipose Stromal Vascular Fraction Cells., Boris R Minev, Elliot Lander, John F Feller, Mark Berman, Bernadette M Greenwood, Ivelina Minev, Antonio F Santidrian, Duong Nguyen, Dobrin Draganov, Mehmet O Killinc, Anna Vyalkova, Santosh Kesari, Edward Mcclay, Gabriel Carabulea, Francesco M Marincola, Lisa H Butterfield, Aladar A Szalay

Articles, Abstracts, and Reports

BACKGROUND: ACAM2000, a thymidine kinase (TK)-positive strain of vaccinia virus, is the current smallpox vaccine in the US. Preclinical testing demonstrated potent oncolytic activity of ACAM2000 against several tumor types. This Phase I clinical trial of ACAM2000 delivered by autologous adipose stromal vascular fraction (SVF) cells was conducted to determine the safety and feasibility of such a treatment in patients with advanced solid tumors or acute myeloid leukemia (AML).

METHODS: Twenty-four patients with solid tumors and two patients with AML participated in this open-label, non-randomized dose-escalation trial. All patients were treated with SVF derived from autologous fat and incubated for …

Human Polyomavirus Jcpyv And Its Role In Progressive Multifocal Leukoencephalopathy And Oncogenesis, Luis Del Valle, Sergio Piña-Oviedo

School of Medicine Faculty Publications

The human neurotropic virus JCPyV, a member of the family, is the opportunistic infectious agent of Progressive Multifocal Leukoencephalopathy (PML), a fatal disease seen in severe immunosuppressive conditions and, during the last decade, in patients undergoing immunotherapy. JCPyV is a ubiquitous pathogen with up to 85% of the adult population word-wide exhibiting antibodies against it. Early experiments demonstrated that direct inoculation of JCPyV into the brain of different species resulted in the development of brain tumors and other neuroectodermal-derived neoplasias. Later, several reports showed the detection of viral sequences in medulloblastomas and glial tumors, as well as expression of the …

Analysis Of Manganese Accumulation In The Pituitary Gland And Hippocampus Of Smelters Using High Resolution 3-D T1-Weighted Mri, Alison Jeffries, Zeinab Aly, Molly Cromer

The Journal of Purdue Undergraduate Research

No abstract provided.

The Effects Of Aging On Sleep Parameters In A Healthy, Melatonin-Competent Mouse Model, Jiffin K. Paulose, Chanung Wang, Bruce F. O'Hara, Vincent M. Cassone

Biology Faculty Publications

Background: Sleep disturbances are common maladies associated with human age. Sleep duration is decreased, sleep fragmentation is increased, and the timing of sleep onset and sleep offset is earlier. These disturbances have been associated with several neurodegenerative diseases. Mouse models for human sleep disturbances can be powerful due to the accessibility to neuroscientific and genetic approaches, but these are hampered by the fact that most mouse models employed in sleep research have spontaneous mutations in the biosynthetic pathway(s) regulating the rhythmic production of the pineal hormone melatonin, which has been implicated in human sleep.

Purpose and method: The present study …

Timing Of Postoperative Magnetic Resonance Imaging (Mri) Following Glioma Resection: Shattering The 72 Hour Window, Syed Sarmad Bukhari, Muhammad Shahzad Shamim, Fatima Mubarak

Section of Neurosurgery

Extent of enhancing tumour resection is correlated with progression free survival following glioma surgery. Historically, a contrast enhanced MRI has been recommended within 72 hours following surgery to evaluate for residual disease. This theoretical window was established amidst conflicting evidence to avoid reactive enhancement. Recent studies with better designs and better imaging quality have sought to challenge this window with a more pragmatic method of evaluating residual disease.

Commentary: Recognizing Pupillary Dysfunction In Diabetic Autonomic Neuropathy, Padmaja Sudhakar

Ophthalmology and Visual Science Faculty Publications

No abstract provided.

Moving Toward The Future: Online Only., Jeffrey C Wang, Jens R Chapman, Karsten Wiechert

Articles, Abstracts, and Reports

No abstract provided.

Association Of Office And Ambulatory Blood Pressure With Mortality And Cardiovascular Outcomes, Wen-Yi Yang, Jesus D. Melgarejo, Lutgarde Thijs, Zhen-Yu Zhang, José Boggia, Fang-Fei Wei, Tine W. Hansen, Kei Asayama, Gladys E. Maestre, Takayoshi Ohkubo

School of Medicine Publications

Importance Blood pressure (BP) is a known risk factor for overall mortality and cardiovascular (CV)-specific fatal and nonfatal outcomes. It is uncertain which BP index is most strongly associated with these outcomes.

Objective To evaluate the association of BP indexes with death and a composite CV event.

Design, Setting, and Participants Longitudinal population-based cohort study of 11 135 adults from Europe, Asia, and South America with baseline observations collected from May 1988 to May 2010 (last follow-ups, August 2006-October 2016).

Exposures Blood pressure measured by an observer or an automated office machine; measured for 24 hours, during the day or …

Oxidative Phosphorylation: A Critical Feature And Novel Therapeutic Target In Melanoma Brain Metastases, Grant Fischer

Dissertations and Theses (Open Access)

We recently showed via RNA-sequencing (RNA-seq) analysis of clinical samples that melanoma brain metastases (MBMs) have higher expression of oxidative phosphorylation (OXPHOS) genes (including PPARGC1A or PGC1α) than patient-matched extracranial metastases (ECMs). Thus, the central hypothesis of this dissertation is that OXPHOS plays a critical role in the pathogenesis of MBMs.

RNA-seq analysis identified increased expression of OXPHOS genes in intracranial (ICr) vs. subcutaneous (SQ) xenografts of 4 different human melanoma cell lines. Increased OXPHOS in the ICr xenografts was confirmed by direct metabolite analysis and [U-¹³C]-glucose tracing analysis. Together, these studies indicate that the brain TME …

Spectrum Of Neurological Disorders In Neurology Outpatients Clinics In Urban And Rural Sindh, Pakistan: A Cross Sectional Study, Safia Awan, Alam Ibrahim Siddiqi, Ahmed Asif, Naveeduddin Ahmed, Hazim Brohi, Sajad Jalban, Mohammad Wasay

Section of Neurology

Background: Neurological disorders are the most common cause of morbidity and mortality in developing countries. Available evidence on urban–rural differences on neurological diseases is scare in such countries. Our study objective was to determine the prevalence of neurological diseases in urban and rural tertiary care hospitals of Sindh, Pakistan.

Methods: This was a cross sectional study conducted in selected urban and rural region of tertiary care hospitals of Sindh, Pakistan. The outpatients medical records of adults (18 years and above) was obtained from January 1st, 2014 to December 31st, 2014.

Results: A total of 10,786 outpatients visit were recorded in …

Prevalence Of Dyskinesia And Off By 30-Minute Intervals Through The Day And Assessment Of Daily Episodes Of Dyskinesia And Off: Novel Analyses Of Diary Data From Gocovri Pivotal Trials., Robert A. Hauser, Daniel Kremens, Lawrence W. Elmer, David L. Kreitzman, Ryan R. Walsh, Reed Johnson, Robert Howard, Jack T. Nguyen, Rajiv Patni

Department of Neurology Faculty Papers

BACKGROUND: Parkinson's disease (PD) patients using levodopa commonly develop dyskinesia and OFF episodes that reduce quality of life.

OBJECTIVE: Evaluate prevalence of troublesome dyskinesia and OFF through the day, assessed by 30-minute intervals, as well as the mean number and duration of troublesome dyskinesia and OFF episodes, transitions between PD states, and effects of Gocovri® (amantadine) extended release capsules on these episodes.

METHODS: Evaluate diary data from pooled Gocovri phase 3, placebo-controlled trials-analyzed for 17 hours following wake-up-at baseline and week 12.

RESULTS: Diaries were evaluable for 162 patients. At baseline, 67% of patients woke up OFF, with prevalence decreasing …

Emergency Care Surveillance And Emergency Care Registries In Low-Income And Middle-Income Countries: Conceptual Challenges And Future Directions For Research, Hani Mowaf, Christine Ngaruiya, Gerard O'Reilly, Olive Kobusingye, Vikas Kapil, Andres Rubiano, Marcus Ong, Juan Carlos Puyana, Akm Fazlur Rahman, Rashid Jooma, Blythe Beecrof, Junaid Razzak

Section of Neurosurgery

Despite the fact that the 15 leading causes of global deaths and disability-adjusted life years are from conditions amenable to emergency care, and that this burden is highest in low-income and middle-income countries (LMICs), there is a paucity of research on LMIC emergency care to guide policy making, resource allocation and service provision. A literature review of the 550 articles on LMIC emergency care published in the 10-year period from 2007 to 2016 yielded 106 articles for LMIC emergency care surveillance and registry research. Few articles were from established longitudinal surveillance or registries and primarily composed of short-term data collection. …

Short Amylin Receptor Antagonist Peptides Improve Memory Deficits In Alzheimer’S Disease Mouse Model, Rania Soudy, Ryoichi Kimura, Aarti Patel, Wen Fu, Kamaljit Kaur, David Westaway, Jing Yang, Jack Jhamandas

Pharmacy Faculty Articles and Research

Recent evidence supports involvement of amylin and the amylin receptor in the pathogenesis of Alzheimer’s disease (AD). We have previously shown that amylin receptor antagonist, AC253, improves spatial memory in AD mouse models. Herein, we generated and screened a peptide library and identified two short sequence amylin peptides (12–14 aa) that are proteolytically stable, brain penetrant when administered intraperitoneally, neuroprotective against Aβ toxicity and restore diminished levels of hippocampal long term potentiation in AD mice. Systemic administration of the peptides for five weeks in aged 5XFAD mice improved spatial memory, reduced amyloid plaque burden, and neuroinflammation. The common residue SQELHRLQTY …

Endoscopic Transsphenoidal Surgery For Cushing's Disease: A Review, Mirza Zain Baig, Altaf Ali Laghari, Aneela Darbar, Umme E Hani Abdullah, Sumiya Abbasi

Section of Neurosurgery

Ever since the 1960s, transsphenoidal surgery has been the modality of choice for treating Cushing's disease. Subsequent visualization of the pituitary fossa and sphenoid sinus may be done either with the operating microscope or with the relatively new endoscope. The endoscope due to its panoramic view allows greater visualization as compared to the operating microscope. It confers greater access to the cavernous sinus, sella, suprasellar, and parasellar regions and accommodates higher magnifications. It is bi-dimensional, however as opposed to the operating microscope that provides a three-dimensional view and allows greater depth perception. This article provides a comprehensive review of the …

White Matter Hyperintensity Regression: Comparison Of Brain Atrophy And Cognitive Profiles With Progression And Stable Groups, Omar M. Al-Janabi, Christopher E. Bauer, Larry B. Goldstein, Richard R. Murphy, Ahmed A. Bahrani, Charles D. Smith, Donna M. Wilcock, Brian T. Gold, Gregory A. Jicha

Sanders-Brown Center on Aging Faculty Publications

Subcortical white matter hyperintensities (WMHs) in the aging population frequently represent vascular injury that may lead to cognitive impairment. WMH progression is well described, but the factors underlying WMH regression remain poorly understood. A sample of 351 participants from the Alzheimer’s Disease Neuroimaging Initiative 2 (ADNI2) was explored who had WMH volumetric quantification, structural brain measures, and cognitive measures (memory and executive function) at baseline and after approximately 2 years. Selected participants were categorized into three groups based on WMH change over time, including those that demonstrated regression (n = 96; 25.5%), stability (n = 72; 19.1%), and …

Mdivi-1, A Mitochondrial Fission Inhibitor, Modulates T Helper Cells And Suppresses The Development Of Experimental Autoimmune Encephalomyelitis., Yan-Hua Li, Fang Xu, Rodolfo Thome, Min-Fang Guo, Man-Luan Sun, Guo-Bin Song, Rui-Lan Li, Zhi Chai, Bogoljub Ciric, A. M. Rostami, Mark T. Curtis, Cun-Gen Ma, Guang-Xian Zhang

Department of Neurology Faculty Papers

BACKGROUND: Unrestrained activation of Th1 and Th17 cells is associated with the pathogenesis of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). While inactivation of dynamin-related protein 1 (Drp1), a GTPase that regulates mitochondrial fission, can reduce EAE severity by protecting myelin from demyelination, its effect on immune responses in EAE has not yet been studied.

METHODS: We investigated the effect of Mdivi-1, a small molecule inhibitor of Drp1, on EAE. Clinical scores, inflammation, demyelination and Drp1 activation in the central nervous system (CNS), and T cell responses in both CNS and periphery were determined.

RESULTS: Mdivi-1 effectively …

Distinct Patterns Of Default Mode And Executive Control Network Circuitry Contribute To Present And Future Executive Function In Older Adults, Christopher A. Brown, Frederick A. Schmitt, Charles D. Smith, Brian T. Gold

Neuroscience Faculty Publications

Executive function (EF) performance in older adults has been linked with functional and structural profiles within the executive control network (ECN) and default mode network (DMN), white matter hyperintensities (WMH) burden and levels of Alzheimer's disease (AD) pathology. Here, we simultaneously explored the unique contributions of these factors to baseline and longitudinal EF performance in older adults. Thirty-two cognitively normal (CN) older adults underwent neuropsychological testing at baseline and annually for three years. Neuroimaging and AD pathology measures were collected at baseline. Separate linear regression models were used to determine which of these variables predicted composite EF scores at baseline …

Scurvy Presenting With Limp And Weakness: A Case Report., Robin M. Lund, Mara L. Becker, Steven Shapiro, Tyler Allison, Julia G. Harris

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Scurvy is one of the oldest diseases known to mankind. Although presently rare in the developed world, scurvy was a common potentially fatal disease. In recent times, the most common risk factors for scurvy include alcoholism, low socioeconomic status, and severely poor nutrition or dietary restriction secondary to psychiatric illness or developmental disorders. Our case demonstrates the importance of having a high index of clinical suspicion of an uncommon disease in developed countries and emphasizes the necessity of a dietary screening that could potentially reduce extensive work-up in patients with nonspecific complaints.

CASE PRESENTATION: We report a case of …

Key Inflammatory Pathway Activations In The Mci Stage Of Alzheimer’S Disease, Jagan A. Pillai, Sean Maxwell, Lynn M. Bekris, Stephen M. Rao, Mark R. Chance, James B. Leverenz

Faculty Scholarship

Objective: To determine the key inflammatory pathways that are activated in the peripheral and CNS compartments at the mild cognitive impairment (MCI) stage of Alzheimer’s disease (AD). Methods: A cross-sectional study of patients with clinical and biomarker characteristics consistent with MCI-AD in a discovery cohort, with replication in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. Inflammatory analytes were measured in the CSF and plasma with the same validated multiplex analyte platform in both cohorts and correlated with AD biomarkers (CSF Aβ42, total tau (t-tau), phosphorylated tau (p-tau) to identify key inflammatory pathway activations. The pathways were additionally validated by evaluating …

Agency And Neuroscience: A Conversation Between Philosophy And Psychology, Kevin Timpe, James Van Slyke

University Faculty Publications and Creative Works

No abstract provided.

Dysphagia Screening To Prevent Hospital-Acquired Pneumonia Rates, Namneet Sekhon

Dissertations

Problem Pneumonia is a leading cause of death worldwide and affects all ages. Pneumonia may be acquired by aspiration and a bedside nursing dysphagia screen may reduce hospital acquired pneumonia (HAP) rates for stroke patients. The aim of this study was to evaluate use of the dysphagia screen for all patients receiving a computed tomography (CT) scan of the head in the emergency department (ED).

Method An observational, descriptive design for all patients who received a CT of the head in the ED and admitted over a 60-day period. The rate of dysphagia screening with the DePaul Hospital Swallow Screen …

Case Study: Effects Of Psychosocial Factors On A Geriatric Patient With Guillain Barré Syndrome, Keane Evangelista, Mary Pent Hunter, Jessica Phung, Aum Tejani, Lee Anne H. Robotta

San Marcos, Summer 2019

The purpose of this case report is to determine how a change in intrinsic motivation and environmental factors help physical and functional improvements in a 77-year-old male patient with Guillain Barré Syndrome (GBS) in the geriatric population. Interventions to promote this change included patient education about lifestyle choices along with endurance and balance exercises.

Patient psychological state, community access, and general education about interventions/dosing had an effect on the patient's participation in his prescribed HEP. His comorbidities hindered his overall progress over the course of his treatment and should be addressed to improve patient outcomes. Activities that were more salient …

Effect Of Pregnancy On Growth Of Intracranial Meningiomas, Ayesha Quddusi, Muhammad Shahzad Shamim, Quratulain Virani

Section of Neurosurgery

Meningiomas are the most common benign primary intracranial tumours in adults. Their rapid growth during pregnancy has been well reported. Moreover, the relationship of increased progesterone expression during pregnancy and extensive tumour growth has been debated. In this review, we discuss not only the effect of progesterone on meningiomal growth but also other mechanisms involved in gestational meningiomas.

Ossification Of The Cruciform Ligament Of Atlas; A Rare Cause Of Cervical Myelopathy: Case Report And Review Of Literature, Muhammad Waqas Saeed Baqai, Gohar Javed, Mirza Zain Baig

Section of Neurosurgery

We present a case of cervical myelopathy secondary to ossification of the cruciform ligament (also known as cruciate ligament). This is a rare phenomenon that, to the best of our knowledge, has only been reported 16 times previously in literature. We have added a review of literature after our case presentation. We hope that by doing so, we may aid clinicians reach early diagnosis so as to be able to better manage this rare disease.

Perianal Necrotizing Fasciitis With Retroperitoneal Extension: A Case Report From Pakistan, Mirza Zain Baig, Abeer Aziz, Umme E Hani Abdullah, Muhammad Salman Khalil, Sumiya Abbasi

Section of Neurosurgery

Necrotizing fasciitis is a rare but potentially fatal condition. It is defined as a rapidly spreading infection of the subcutaneous soft tissue. Extension into the retroperitoneum may further complicate this deadly condition. We report a case of a 45-year-old gentleman who presented to our institute with perianal necrotizing fasciitis with extension into the retroperitoneum. He was managed with antibiotics and prompt surgical debridement. Our patient had a positive outcome which may be due to the fact that we had a high clinical suspicion, on the basis of which we opted for early operative management rather than delaying definitive treatment by …

Invasive Cryptococcal Meningitis Presenting As A Skull Base Mass In An Immunocompetent Host: A Case Report., Joshua Prickett, Juan J Altafulla, Anna Knisely, Zachary Litvack

Articles, Abstracts, and Reports

No abstract provided.

Global Spinal Deformity From The Upper Cervical Perspective. What Is "Abnormal" In The Upper Cervical Spine?, Peter G Passias, Haddy Alas, Renaud Lafage, Bassel G Diebo, Irene Chern, Christopher P Ames, Paul Park, Khoi D Than, Alan H Daniels, D Kojo Hamilton, Douglas C Burton, Robert A Hart, Shay Bess, Breton G Line, Eric O Klineberg, Christopher I Shaffrey, Justin S Smith, Frank J Schwab, Virginie Lafage

Articles, Abstracts, and Reports

Hypothesis: Reciprocal changes in the upper cervical spine correlate with adult TL deformity modifiers.

Design: This was a retrospective review.

Introduction: The upper cervical spine has remarkable adaptability to wide ranges of thoracolumbar (TL) deformity.

Methods: Patients >18 years with adult spinal deformity (ASD) and complete radiographic data at baseline (BL) and 1 year were identified. Patients were grouped into component types of the Roussouly classification system (Type 1: Pelvic incidence [PI]

Results: A total of 343 ASD patients were analyzed. When grouped by BL Schwab and Roussouly, Group

Conclusions: Our study suggests that upper cervical alignment remains relatively stable …

The Impact Of Osteotomy Grade And Location On Regional And Global Alignment Following Cervical Deformity Surgery., Peter G Passias, Samantha R Horn, Tina Raman, Avery E Brown, Virginie Lafage, Renaud Lafage, Justin S Smith, Cole A Bortz, Frank A Segreto, Katherine E Pierce, Haddy Alas, Breton G Line, Bassel G Diebo, Alan H Daniels, Han Jo Kim, Alex Soroceanu, Gregory M Mundis, Themistocles S Protopsaltis, Eric O Klineberg, Douglas C Burton, Robert A Hart, Frank J Schwab, Shay Bess, Christopher I Shaffrey, Christopher P Ames

Articles, Abstracts, and Reports

Introduction: Correction of cervical deformity (CD) often involves different types of osteotomies to address sagittal malalignment. This study assessed the relationship between osteotomy grade and vertebral level on alignment and clinical outcomes.

Methods: Retrospective review of a multi-center prospectively collected CD database. CD was defined as at least one of the following: C2-C7 Cobb >10°, cervical lordosis (CL) >10°, C2-C7 sagittal vertical axis (cSVA) >4 cm, and chin-brow vertical angle > 25°. Patients were evaluated for level and type of cervical osteotomy.

Results: 86 CD patients were included (61.4 ± 10.6 years, 66.3% female, body mass index 29.1 kg/m

Conclusions: CD …

A Technique For Approximating Transition Rates From Published Survival Analyses, Markian A. Pahuta, Joel Werier, Eugene K. Wai, Roy A. Patchell, Doug Coyle

Neurology Faculty Publications

Background: Quality-adjusted-life-years (QALYs) are used to concurrently quantify morbidity and mortality within a single parameter. For this reason, QALYs can facilitate the discussion of risks and benefits during patient counseling regarding treatment options. QALYs are often calculated using partitioned-survival modelling. Alternatively, QALYs can be calculated using more flexible and informative state-transition models populated with transition rates estimated using multistate modelling (MSM) techniques. Unfortunately the latter approach is considered not possible when only progression-free survival (PFS) and overall survival (OS) analyses are reported.

Methods: We have developed a method that can be used to estimate approximate transition rates from published PFS …