Medicine and Health Sciences Commons^™

Higher And Lower Order Factor Analyses Of The Temperament In Middle Childhood Questionnaire., Yuliya Kotelnikova, Thomas M Olino, Daniel N Klein, Sarah V M Mackrell, Elizabeth P Hayden

Brain and Mind Institute Researchers' Publications

The Temperament in Middle Childhood Questionnaire (TMCQ) is a widely used parent-report measure of temperament. However, neither its lower nor higher order structures has been tested via a bottom-up, empirically based approach. We conducted higher and lower order exploratory factor analyses (EFAs) of the TMCQ in a large ( N = 654) sample of 9-year-olds. Item-level EFAs identified 92 items as suitable (i.e., with loadings ≥.40) for constructing lower order factors, only half of which resembled a TMCQ scale posited by the measure's authors. Higher order EFAs of the lower order factors showed that a three-factor structure (Impulsivity/Negative Affectivity, Negative …

Incidence Of Cognitively Defined Late-Onset Alzheimer's Dementia Subgroups From A Prospective Cohort Study., Paul K Crane, Emily Trittschuh, Shubhabrata Mukherjee, Andrew J Saykin, R Elizabeth Sanders, Eric B Larson, Susan M Mccurry, Wayne Mccormick, J D Bowen, Thomas Grabowski, Mackenzie Moore, Julianna Bauman, Alden L Gross, C Dirk Keene, Thomas D Bird, Laura E Gibbons, Jesse Mez

Articles, Abstracts, and Reports

INTRODUCTION: There may be biologically relevant heterogeneity within typical late-onset Alzheimer's dementia.

METHODS: We analyzed cognitive data from people with incident late-onset Alzheimer's dementia from a prospective cohort study. We determined individual averages across memory, visuospatial functioning, language, and executive functioning. We identified domains with substantial impairments relative to that average. We compared demographic, neuropathology, and genetic findings across groups defined by relative impairments.

RESULTS: During 32,286 person-years of follow-up, 869 people developed Alzheimer's dementia. There were 393 (48%) with no domain with substantial relative impairments. Some participants had isolated relative impairments in memory (148, 18%), visuospatial functioning (117, 14%), …

Nadph Oxidase 5 (Nox5)-Induced Reactive Oxygen Signaling Modulates Normoxic Hif-1Α And P27, Smitha Antony, Guojian Jiang, Yongzhong Wu, Jennifer L Meitzler, Hala R Makhlouf, Diana C Haines, Donna Butcher, Dave S B Hoon, Jiuping Ji, Yiping Zhang, Agnes Juhasz, Jiamo Lu, Han Liu, Iris Dahan, Mariam Konate, Krishnendu K Roy, James H Doroshow

Articles, Abstracts, and Reports

NADPH oxidase 5 (NOX5) generated reactive oxygen species (ROS) have been implicated in signaling cascades that regulate cancer cell proliferation. To evaluate and validate NOX5 expression in human tumors, we screened a broad range of tissue microarrays (TMAs), and report substantial overexpression of NOX5 in malignant melanoma and cancers of the prostate, breast, and ovary. In human UACC-257 melanoma cells that possesses high levels of functional endogenous NOX5, overexpression of NOX5 resulted in enhanced cell growth, increased numbers of BrdU positive cells, and increased γ-H2AX levels. Additionally, NOX5-overexpressing (stable and inducible) UACC-257 cells demonstrated increased normoxic HIF-1α expression and decreased …

Medicaid Managed Care And The Health Care Utilization Of Foster Children, Makayla Palmer, James Marton, Aaron Yelowitz, Jeffery Talbert

Economics Faculty Publications

A recent trend in state Medicaid programs is the transition of vulnerable populations into Medicaid managed care (MMC) who were initially carved out of such coverage, such as foster children or those with disabilities. The purpose of this article is to evaluate the impact of the transition of foster children from fee-for-service Medicaid coverage to MMC coverage on outpatient health care utilization. There is very little empirical evidence on the impact of managed care on the health care utilization of foster children because of the recent timing of these transitions as well as challenges associated with finding data sets large …

Physical Aggressiveness And Gray Matter Deficits In Ventromedial Prefrontal Cortex, David S. Chester, Donald R. Lynam, Richard Milich, C. Nathan Dewall

Psychology Faculty Publications

What causes individuals to hurt others? Since the famous case of Phineas Gage, lesions of the ventromedial prefrontal cortex (VMPFC) have been reliably linked to physically aggressive behavior. However, it is unclear whether naturally-occurring deficits in VMPFC, among normal individuals, might have widespread consequences for aggression. Using voxel based morphometry, we regressed gray matter density from the brains of 138 normal female and male adults onto their dispositional levels of physical aggression, verbal aggression, and sex, simultaneously. Physical, but not verbal, aggression was associated with reduced gray matter volume in the VMPFC and to a lesser extent, frontopolar cortex. Participants …

Influence Of Dietary Salt Knowledge, Perceptions, And Beliefs On Consumption Choices After Stroke In Uganda, Martin N. Kaddumukasa, Elly Katabira, Martha Sajatovic, Svetlana Pundik, Mark Kaddumukasa, Larry B. Goldstein

Neurology Faculty Publications

Background

Previous research on Uganda's poststroke population revealed that their level of dietary salt knowledge did not lead to healthier consumption choices.

Purpose

Identify barriers and motivators for healthy dietary behaviors and evaluate the understanding of widely accepted salt regulation mechanisms among poststroke patients in Uganda.

Methods

Convergent parallel mixed methods triangulation design comprised a cross-sectional survey (n = 81) and 8 focus group discussions with 7-10 poststroke participants in each group. We assessed participant characteristics and obtained insights into their salt consumption attitudes, perceptions, and knowledge. Qualitative responses were analyzed using an inductive approach with thematic analytic procedures. Relationships …

Buspirone Maintenance Does Not Alter The Reinforcing, Subjective, And Cardiovascular Effects Of Intranasal Methamphetamine, Anna R. Reynolds, Justin Charles Strickland, William W. Stoops, Joshua A. Lile, Craig R. Rush

Pharmaceutical Sciences Faculty Publications

Background—Medications development efforts for methamphetamine-use disorder have targeted central monoamines because these systems are directly involved in the effects of methamphetamine. Buspirone is a dopamine autoreceptor and D3 receptor antagonist and partial agonist at serotonin 1A receptors, making it a logical candidate medication for methamphetamine-use disorder. Buspirone effects on abuse-related behaviors of methamphetamine have been mixed in clinical and preclinical studies. Experimental research using maintenance dosing, which models therapeutic use, is limited. This study evaluated the influence of buspirone maintenance on the reinforcing effects of methamphetamine using a self-administration procedure, which has predictive validity for clinical efficacy. The impact …

Cognitive Trajectory Changes Over 20 Years Before Dementia Diagnosis: A Large Cohort Study., Ge Li, Eric B Larson, Jane B Shofer, Paul K Crane, Laura E Gibbons, Wayne Mccormick, J D Bowen, Mary Lou Thompson

Articles, Abstracts, and Reports

BACKGROUND/OBJECTIVES: Longitudinal studies have shown an increase in cognitive decline many years before clinical diagnosis of dementia. We sought to estimate changes, relative to "normal" aging, in the trajectory of scores on a global cognitive function test-the Cognitive Abilities Screening Instrument (CASI).

DESIGN: A prospective cohort study.

SETTING: Community-dwelling members of a U.S. health maintenance organization.

PARTICIPANTS: Individuals aged 65 and older who had no dementia diagnosis at baseline and had at least two visits with valid CASI test score (N = 4,315).

MEASUREMENTS: Average longitudinal trajectories, including changes in trajectory before clinical diagnosis in those who would be diagnosed …

Ecog-Acrin (E4805) Randomized Phase Ii Study To Determine The Effect Of 2 Different Doses Of Aflibercept In Patients With Metastatic Renal Cell Carcinoma, Roberto Pili, Opeyemi Jegede, Michael A. Carducci, Judith Manola, David L. Groteluschen, Leonard L. Appleman, Glenn Liu, James C. Shanks, Shaker R. Dakhil, Janice Dutcher, Robert S. Dipaola

Internal Medicine Faculty Publications

Background—Aflibercept is a recombinantly-produced fusion protein that has potent anti-VEGF activity. We tested whether aflibercept has clinical activity in clear cell renal cell carcinoma (ccRCC). The recommended Phase 2 dose was 4 mg/kg but several patients treated at 1 mg/kg demonstrated prolonged progression-free survival (PFS). We therefore tested both doses in a parallel group randomized trial.

Methods—Eligible patients (pts) had histologically confirmed advanced or metastatic ccRCC and previous treatments including prior exposure to a VEGF RTKI. Patients received aflibercept (either 1 mg/kg or 4 mg/kg) day 1 of a 14-day cycle until progression. Patients randomized to 1 mg/kg …

Measuring Heightened Attention To Alcohol In A Naturalistic Setting: A Validation Study, Ramey G. Monem, Mark T. Fillmore

Psychology Faculty Publications

Attentional bias to alcohol-related stimuli is believed to be an important contributor to the development and maintenance of drug abuse. There is a considerable body of research examining attentional bias, much of which has typically utilized image-display tasks as a means to assess the phenomenon. Little, however, is known about the nature of this bias in an individual’s natural environment. The current study sought to implement a novel approach to assessing attentional bias in vivo. Participants wore portable eye-tracking glasses that recorded video from their point of view and measured fixation time to objects they observed. They entered a room …

Effects Of Environmental Enrichment On Self-Administration Of The Short-Acting Opioid Remifentanil In Male Rats, Rebecca S. Hofford, Jonathan J. Chow, Joshua S. Beckmann, Michael T. Bardo

Psychology Faculty Publications

Background

Opioid abuse is a major problem around the world. Identifying environmental factors that contribute to opioid abuse and addiction is necessary for decreasing this epidemic. In rodents, environmental enrichment protects against the development of low dose stimulant self-administration, but studies examining the effect of enrichment and isolation (compared to standard housing) on the development of intravenous opioid self-administration have not been conducted. The present study investigated the role of environmental enrichment on self-administration of the short-acting μ-opioid remifentanil.

Methods

Rats were raised in an enriched condition (Enr), standard condition (Std), or isolated condition (Iso) beginning at 21 days of …

Common Tdp1 Polymorphisms In Relation To Survival Among Small Cell Lung Cancer Patients: A Multicenter Study From The International Lung Cancer Consortium, Pawadee Lohavanichbutr, Lori C. Sakoda, Christopher I. Amos, Susanne M. Arnold, David C. Christiani, Michael P. A. Davies, John K. Field, Eric B. Haura, Rayjean J Hung, Takashi Kohno, Maria Teresa Landi, Geoffrey Liu, Yi Liu, Michael W. Marcus, Grainne M. O'Kane, Matthew B. Schabath, Kouya Shiraishi, Stacey A. Slone, Adonina Tardón, Ping Yang, Kazushi Yoshida, Ruyang Zhang, Xuchen Zong, Gary E. Goodman, Noel S. Weiss, Chu Chen

Internal Medicine Faculty Publications

Background—DNA topoisomerase inhibitors are commonly used for treating small-cell lung cancer (SCLC). Tyrosyl-DNA phosphodiesterase (TDP1) repairs DNA damage caused by this class of drugs and may therefore influence treatment outcome. In this study, we investigated whether common TDP1 single-nucleotide polymorphisms (SNP) are associated with overall survival among SCLC patients.

Methods—Two TDP1 SNPs (rs942190 and rs2401863) were analyzed in 890 patients from 10 studies in the International Lung Cancer Consortium (ILCCO). The Kaplan–Meier method and Cox regression analyses were used to evaluate genotype associations with overall mortality at 36 months postdiagnosis, adjusting for age, sex, race, and tumor stage. …

Successful Reversal Of Furosemide-Induced Secondary Hyperparathyroidism With Cinacalcet., Tarak Srivastava, Shahryar Jafri, William E. Truog, Judith Sebestyen Vansickle, Winston M. Manimtim, Uri S. Alon

Manuscripts, Articles, Book Chapters and Other Papers

Secondary hyperparathyroidism (SHPT) is a rare complication of furosemide therapy that can occur in patients treated with the loop diuretic for a long period of time. We report a 6-month-old 28-weeks premature infant treated chronically with furosemide for his bronchopulmonary dysplasia, who developed hypocalcemia and severe SHPT, adversely affecting his bones. Discontinuation of the loop diuretic and the addition of supplemental calcium and calcitriol only partially reversed the SHPT, bringing serum parathyroid hormone level down from 553 to 238 pg/mL. After introduction of the calcimimetic Cinacalcet, we observed a sustained normalization of parathyroid hormone concentration at 27 to 63 pg/mL …

Serum Microrna-27b As A Screening Biomarker For Left Ventricular Hypertrophy, Yan Wang, Shuyan Chen, Yanhong Gao, Song Zhang

The Texas Heart Institute Journal

MicroRNA-27b (miR-27b) is frequently upregulated in pressure-overloaded hypertrophic hearts. The clinical implications of aberrant circulating miR-27b in the diagnosis and management of left ventricular hypertrophy warrant study. We investigated whether serum miR-27b is a biomarker for left ventricular hypertrophy (LVH).

We used stem-loop reverse-transcription quantitative polymerase chain reaction techniques to analyze serum miR-27b levels in 200 hypertensive patients with LVH, 100 hypertensive patients without LVH, and 100 healthy volunteers. We found that serum miR-27b levels were significantly higher in the hypertensive patients with LVH than in the hypertensive patients without LVH and in the healthy volunteers. Upon receiver operating characteristic …

Automated Ecological Assessment Of Physical Activity: Advancing Direct Observation., Jordan A. Carlson, Bo Liu, James F. Sallis, Jacqueline Kerr, J Aaron Hipp, Vincent S. Staggs, Amy Papa, Kelsey Dean, Nuno M. Vasconcelos

Manuscripts, Articles, Book Chapters and Other Papers

Technological advances provide opportunities for automating direct observations of physical activity, which allow for continuous monitoring and feedback. This pilot study evaluated the initial validity of computer vision algorithms for ecological assessment of physical activity. The sample comprised 6630 seconds per camera (three cameras in total) of video capturing up to nine participants engaged in sitting, standing, walking, and jogging in an open outdoor space while wearing accelerometers. Computer vision algorithms were developed to assess the number and proportion of people in sedentary, light, moderate, and vigorous activity, and group-based metabolic equivalents of tasks (MET)-minutes. Means and standard deviations (SD) …

Surgical Approaches To Adenocarcinoma Of The Gastroesophageal Junction: The Siewert Ii Conundrum., Andrew M. Brown, Danica N. Giugliano, Adam C. Berger, Michael J. Pucci, Francesco Palazzo

Department of Surgery Faculty Papers

BACKGROUND: The Siewert classification system for gastroesophageal junction adenocarcinoma has provided morphological and topographical information to help guide surgical decision-making. Evidence has shown that Siewert I and III tumors are distinct entities with differing epidemiologic and histologic characteristics and distinct patterns of disease progression, requiring different treatment. Siewert II tumors share some of the characteristics of type I and III lesions, and the surgical approach is not universally agreed upon. Appropriate surgical options include transthoracic esophagogastrectomy, transhiatal esophagectomy, and transabdominal extended total gastrectomy.

PURPOSE: A review of the available evidence of the surgical management of Siewert II tumors is presented. …

Fremanezumab For The Preventive Treatment Of Chronic Migraine., Stephen D. Silberstein, David W. Dodick, Marcelo E. Bigal, Paul P. Yeung, Peter J. Goadsby, Tricia Blankenbiller, Melissa Grozinski-Wolff, Ronghua Yang, Yuju Ma, Ernesto Aycardi

Department of Neurology Faculty Papers

BACKGROUND: Fremanezumab, a humanized monoclonal antibody targeting calcitonin gene-related peptide (CGRP), is being investigated as a preventive treatment for migraine. We compared two fremanezumab dose regimens with placebo for the prevention of chronic migraine.

METHODS: In this phase 3 trial, we randomly assigned patients with chronic migraine (defined as headache of any duration or severity on ≥15 days per month and migraine on ≥8 days per month) in a 1:1:1 ratio to receive fremanezumab quarterly (a single dose of 675 mg at baseline and placebo at weeks 4 and 8), fremanezumab monthly (675 mg at baseline and 225 mg at …

Linkage, Whole Genome Sequence, And Biological Data Implicate Variants In Rab10 In Alzheimer's Disease Resilience., Perry G Ridge, Celeste M Karch, Simon Hsu, Ivan Arano, Craig C Teerlink, Mark T W Ebbert, Josue D Gonzalez Murcia, James M Farnham, Anna R Damato, Mariet Allen, Xue Wang, Oscar Harari, Victoria M Fernandez, Rita Guerreiro, Jose Bras, John Hardy, Ronald Munger, Maria Norton, Celeste Sassi, Andrew Singleton, Steven G Younkin, Dennis W Dickson, Todd E Golde, Nathan D Price, Nilüfer Ertekin-Taner, Carlos Cruchaga, Alison M Goate, Christopher Corcoran, Joann Tschanz, Lisa A Cannon-Albright, John S K Kauwe

Articles, Abstracts, and Reports

BACKGROUND: While age and the APOE ε4 allele are major risk factors for Alzheimer's disease (AD), a small percentage of individuals with these risk factors exhibit AD resilience by living well beyond 75 years of age without any clinical symptoms of cognitive decline.

METHODS: We used over 200 "AD resilient" individuals and an innovative, pedigree-based approach to identify genetic variants that segregate with AD resilience. First, we performed linkage analyses in pedigrees with resilient individuals and a statistical excess of AD deaths. Second, we used whole genome sequences to identify candidate SNPs in significant linkage regions. Third, we replicated SNPs …

Top2a And Ezh2 Provide Early Detection Of An Aggressive Prostate Cancer Subgroup., David P. Labbé, Christopher J. Sweeney, Myles Brown, Phillip Galbo, Spencer Rosario, Kristine M. Wadosky, Sheng-Yu Ku, Martin Sjöström, Mohammed Alshalalfa, Nicholas Erho, Elai Davicioni, R. Jeffrey Karnes, Edward M. Schaeffer, Robert B. Jenkins, Robert B. Den, Ashley E. Ross, Michaela Bowden, Ying Huang, Kathryn P. Gray, Felix Y. Feng, Daniel E. Spratt, David W. Goodrich, Kevin H. Eng, Leigh Ellis

Department of Radiation Oncology Faculty Papers

Purpose: Current clinical parameters do not stratify indolent from aggressive prostate cancer. Aggressive prostate cancer, defined by the progression from localized disease to metastasis, is responsible for the majority of prostate cancer–associated mortality. Recent gene expression profiling has proven successful in predicting the outcome of prostate cancer patients; however, they have yet to provide targeted therapy approaches that could inhibit a patient's progression to metastatic disease. Experimental Design: We have interrogated a total of seven primary prostate cancer cohorts (n = 1,900), two metastatic castration-resistant prostate cancer datasets (n = 293), and one prospective cohort (n = 1,385) to assess …

Reducing Symptom Distress In Patients With Advanced Cancer Using An E-Alert System For Caregivers: Pooled Analysis Of Two Randomized Clinical Trials, David H. Gustafson, Lori L. Dubenske, Amy K. Atwood, Ming-Yuan Chih, Roberta A. Johnson, Fiona Mctavish, Andrew Quanbeck, Roger L. Brown, James F. Cleary, Dhavan Shah

Health and Clinical Sciences Faculty Publications

Background: Symptom distress in patients toward the end of life can change rapidly. Family caregivers have the potential to help patients manage those symptoms, as well as their own stress, if they are equipped with the proper resources. Electronic health (eHealth) systems may be able to provide those resources. Very sick patients may not be able to use such systems themselves to report their symptoms but family caregivers could.

Objective: The aim of this paper was to assess the effects on cancer patient symptom distress of an eHealth system that alerts clinicians to significant changes in the patient’s symptoms, as …

Cardiovascular Health Is Associated With Physical Function Among Older Community Dwelling Men And Women., Yichen Jin, Toshiko Tanaka, Yan Ma, Stefania Bandinelli, Luigi Ferrucci, Sameera A Talegawkar

Exercise and Nutrition Sciences Faculty Publications

Background

Age related decline in physical function is a significant concern affecting the quality of life of older individuals.

Methods

We examined the associations between baseline overall cardiovascular health (CVH), its components, and physical function in 906 men and women from the InCHIANTI cohort. Physical function was assessed using the Short Performance Physical Battery and poor physical function was defined as an Short Performance Physical Battery score less than 10. Overall CVH score, ranging from 0 to 12 in the cohort, was operationalized using adherence to ideal levels for health behaviors including smoking status, physical activity, body mass index, and …

Precision Newborn Screening For Lysosomal Disorders, Melissa M. Minter Baerg, Stephanie D. Stoway, Jeremy Hart, Lea Mott, Dawn S. Peck, Stephanie L. Nett, Jason S. Eckerman, Jean M. Lacey, Coleman T. Turgeon, Dimitar Gavrilov, Devin Oglesbee, Kimiyo Raymond, Silvia Tortorelli, Dietrich Matern, Lars Mørkrid, Piero Rinaldo

Pathology and Laboratory Medicine Faculty Publications

Purpose: The implementation of newborn screening for lysosomal disorders has uncovered overall poor specificity, psychosocial harm experienced by caregivers, and costly follow-up testing of false-positive cases. We report an informatics solution proven to minimize these issues.

Methods: The Kentucky Department for Public Health outsourced testing for mucopolysaccharidosis type I (MPS I) and Pompe disease, conditions recently added to the recommended uniform screening panel, plus Krabbe disease, which was added by legislative mandate. A total of 55,161 specimens were collected from infants born over 1 year starting from February 2016. Testing by tandem mass spectrometry was integrated with multivariate pattern recognition …

Low Arousal Positive Emotional Stimuli Attenuate Aberrant Working Memory Processing In Persons With Mild Cognitive Impairment, Lucas S. Broster, Shonna L. Jenkins, Sarah D. Holmes, Gregory A. Jicha, Yang Jiang

Behavioral Science Faculty Publications

Emotional enhancement effects on memory have been reported to mitigate the pathophysiology of Alzheimer’s disease (AD). However, relative to their manifestation in persons without pathologic aging, these effects may be reduced in magnitude or even deleterious, especially in tasks that more closely model ecologic memory performance. Based upon a synthesis of such reports, we hypothesized that in persons with AD low arousal positive stimuli would evoke relatively intact emotional enhancement effects, but that high arousal negative stimuli would evoke disordered emotional enhancement effects. To assess this, participants with and without mild cognitive impairment (MCI) presumed to be due to AD …

Tobacco's Minor Alkaloids: Effects On Place Conditioning And Nucleus Accumbens Dopamine Release In Adult And Adolescent Rats, Julie A. Marusich, Mahesh Darna, A. George Wilson, Emily D. Denehy, Amanda Ebben, Agripina G. Deaciuc, Linda P. Dwoskin, Michael T. Bardo, Timothy W. Lefever, Jenny L. Wiley, Chad J. Reissig, Kia J Jackson

Pharmaceutical Sciences Faculty Publications

Tobacco products are some of the most commonly used psychoactive drugs worldwide. Besides nicotine, alkaloids in tobacco include cotinine, myosmine, and anatabine. Scientific investigation of these constituents and their contribution to tobacco dependence is less well developed than for nicotine. The present study evaluated the nucleus accumbens dopamine-releasing properties and rewarding and/or aversive properties of nicotine (0.2-0.8 mg/kg), cotinine (0.5-5.0 mg/kg), anatabine (0.5-5.0 mg/kg), and myosmine (5.0-20.0 mg/kg) through in vivo microdialysis and place conditioning, respectively, in adult and adolescent male rats. Nicotine increased dopamine release at both ages, and anatabine and myosmine increased dopamine release in adults, but not …

Deficiency Of Klf4 Compromises The Lung Function In An Acute Mouse Model Of Allergic Asthma, Jeanette A. Nimpong, Wintana Gebregziabher, Udai P. Singh, Prakash Nagarkatti, Mitzi Nagarkatti, Johnie Hodge, Chunming Liu, Daping Fan, Walden Ai

Molecular and Cellular Biochemistry Faculty Publications

Asthma is a chronic inflammatory disease of the airways and the mechanisms are not fully understood. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of monocytes, granulocyte and myeloid cells at early stage of differentiation. They possess phenotypic plasticity and regulate airway inflammation. We recently reported that Kruppel-like factor 4 (KLF4) regulates MDSC differentiation into fibrocytes, emerging effectors in chronic inflammation. However, the role of KLF4 in asthma is not known. Thymic stromal lymphopoietin (TSLP) is an epithelial cell-derived cytokine and a key initiator of allergic airway inflammation. Given the fact that TSLP promotes Th2 cytokine production that increases MDSC …

Differential Impact Of Serial Measurement Of Nonplatelet Thromboxane Generation On Long-Term Outcome After Cardiac Surgery., Nikolaos Kakouros, Tyler J Gluckman, John V Conte, Thomas S Kickler, Katherine Laws, Bruce A Barton, Jeffrey J Rade

Articles, Abstracts, and Reports

BACKGROUND: Systemic thromboxane generation, not suppressible by standard aspirin therapy and likely arising from nonplatelet sources, increases the risk of atherothrombosis and death in patients with cardiovascular disease. In the RIGOR (Reduction in Graft Occlusion Rates) study, greater nonplatelet thromboxane generation occurred early compared with late after coronary artery bypass graft surgery, although only the latter correlated with graft failure. We hypothesize that a similar differential association exists between nonplatelet thromboxane generation and long-term clinical outcome.

METHODS AND RESULTS: Five-year outcome data were analyzed for 290 RIGOR subjects taking aspirin with suppressed platelet thromboxane generation. Multivariable modeling was performed to …

Hypotonia And Intellectual Disability Without Dysmorphic Features In A Patient With Pign-Related Disease., Isabelle Thiffault, Britton Zuccarelli, Holly Welsh, Xuan Yuan, Emily Farrow, Lee Zellmer, Neil Miller, Sarah Soden, Ahmed Abdelmoity, Robert A Brodsky, Carol Saunders

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Defects in the human glycosylphosphatidylinositol anchor biosynthetic pathway are associated with inherited glycosylphosphatidylinositol (GPI)-deficiencies characterized by a broad range of clinical phenotypes including multiple congenital anomalies, dysmorphic faces, developmental delay, hypotonia, and epilepsy. Biallelic variants in PIGN, encoding phosphatidylinositol-glycan biosynthesis class N have been recently associated with multiple congenital anomalies hypotonia seizure syndrome.

CASE PRESENTATION: Our patient is a 2 year old male with hypotonia, global developmental delay, and focal epilepsy. Trio whole-exome sequencing revealed heterozygous variants in PIGN, c.181G > T (p.Glu61*) and c.284G > A (p.Arg95Gln). Analysis of FLAER and anti-CD59 by flow-cytometry demonstrated a shift in this patient's …

Identification Of A Novel Synaptic Protein, Tmtc3, Involved In Periventricular Nodular Heterotopia With Intellectual Disability And Epilepsy, Sali M K Farhan, Kevin C J Nixon, Michelle Everest, Tara N Edwards, Shirley Long, Dmitri Segal, Maria J Knip, Heleen H Arts, Rana Chakrabarti, Jian Wang, John F Robinson, Donald Lee, Seyed M Mirsattari, C Anthony Rupar, Victoria M Siu, Forge Canada Consortium, Michael O Poulter, Robert A Hegele, Jamie M Kramer

Paediatrics Publications

Defects in neuronal migration cause brain malformations, which are associated with intellectual disability (ID) and epilepsy. Using exome sequencing, we identified compound heterozygous variants (p.Arg71His and p. Leu729ThrfsTer6) in TMTC3, encoding transmembrane and tetratricopeptide repeat containing 3, in four siblings with nocturnal seizures and ID. Three of the four siblings have periventricular nodular heterotopia (PVNH), a common brain malformation caused by failure of neurons to migrate from the ventricular zone to the cortex. Expression analysis using patient-derived cells confirmed reduced TMTC3 transcript levels and loss of the TMTC3 protein compared to parental and control cells. As TMTC3 function is currently …

Disparities In Rate, Triggers, And Management In Pediatric And Adult Cases Of Suspected Drug-Induced Anaphylaxis In Canada, Sofianne Gabrielli, Ann E Clarke, Harley Eisman, Judy Morris, Lawrence Joseph, Sebastien La Vieille, Peter Small, Rodrick Lim, Paul Enarson, Michal Zelcer, Edmond S Chan, Chris Mill, Moshe Ben-Shoshan

Paediatrics Publications

Introduction

Data is sparse on drug-induced anaphylaxis (DIA) and there have not been studies assessing the differences in clinical characteristics and management of DIA between adults and children.

Objective

We assessed the percentage, diagnosis, and management of DIA among all anaphylaxis visits in three pediatric and one adult emergency departments (ED) across Canada.

Methods

Children presenting to the Montreal Children's Hospital (MCH), British Columbia Children's Hospital (BCCH), and Children's Hospital at London Health Sciences Center and adults presenting to Hôpital du Sacré-Coeur with anaphylaxis were recruited as part of the Cross-Canada Anaphylaxis Registry. A standardized data form documenting the reaction …

Disruption Of Hippocampal Multisynaptic Networks By General Anesthetics., Min-Ching Kuo, L Stan Leung

Physiology and Pharmacology Publications

BACKGROUND: Previous studies showed that synaptic transmission is affected by general anesthetics, but an anesthetic dose response in freely moving animals has not been done. The hippocampus provides a neural network for the evaluation of isoflurane and pentobarbital on multisynaptic transmission that is relevant to memory function.

METHODS: Male Long-Evans rats were implanted with multichannel and single electrodes in the hippocampus. Spontaneous local field potentials and evoked field potentials were recorded in freely behaving rats before (baseline) and after various doses of isoflurane (0.25 to 1.5%) and sodium pentobarbital (10 mg/kg intraperitoneal).

RESULTS: Monosynaptic population excitatory postsynaptic potentials at the …