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Molecular Characterization Of Nrxn1 Deletions From 19,263 Clinical Microarray Cases Identifies Exons Important For Neurodevelopmental Disease Expression, Chelsea Lowther, Marsha Speevak, Christine M Armour, Elaine S Goh, Gail E Graham, Chumei Li, Susan Zeesman, Malgorzata J M Nowaczyk, Lee-Anne Schultz, Antonella Morra, Rob Nicolson, Peter Bikangaga, Dawa Samdup, Mostafa Zaazou, Kerry Boyd, Jack H Jung, Victoria Siu, Manjulata Rajguru, Sharan Goobie, Mark A Tarnopolsky, Chitra Prasad, Paul T Dick, Asmaa S Hussain, Margreet Walinga, Renske G Reijenga, Matthew Gazzellone, Anath C Lionel, Christian R Marshall, Stephen W Scherer, Dimitri J Stavropoulos, Elizabeth Mccready, Anne S Bassett Jan 2017

Molecular Characterization Of Nrxn1 Deletions From 19,263 Clinical Microarray Cases Identifies Exons Important For Neurodevelopmental Disease Expression, Chelsea Lowther, Marsha Speevak, Christine M Armour, Elaine S Goh, Gail E Graham, Chumei Li, Susan Zeesman, Malgorzata J M Nowaczyk, Lee-Anne Schultz, Antonella Morra, Rob Nicolson, Peter Bikangaga, Dawa Samdup, Mostafa Zaazou, Kerry Boyd, Jack H Jung, Victoria Siu, Manjulata Rajguru, Sharan Goobie, Mark A Tarnopolsky, Chitra Prasad, Paul T Dick, Asmaa S Hussain, Margreet Walinga, Renske G Reijenga, Matthew Gazzellone, Anath C Lionel, Christian R Marshall, Stephen W Scherer, Dimitri J Stavropoulos, Elizabeth Mccready, Anne S Bassett

Paediatrics Publications

PURPOSE: The purpose of the current study was to assess the penetrance of NRXN1 deletions.

METHODS: We compared the prevalence and genomic extent of NRXN1 deletions identified among 19,263 clinically referred cases to that of 15,264 controls. The burden of additional clinically relevant copy-number variations (CNVs) was used as a proxy to estimate the relative penetrance of NRXN1 deletions.

RESULTS: We identified 41 (0.21%) previously unreported exonic NRXN1 deletions ascertained for developmental delay/intellectual disability that were significantly greater than in controls (odds ratio (OR) = 8.14; 95% confidence interval (CI): 2.91-22.72; P < 0.0001). Ten (22.7%) of these had a second clinically relevant CNV. Subjects with a deletion near the 3' end of NRXN1 were significantly more likely to have a second rare CNV than subjects with a 5' NRXN1 deletion (OR = 7.47; 95% CI: 2.36-23.61; P = 0.0006). The prevalence of intronic NRXN1 deletions was not statistically different between cases and controls (P = 0.618). The majority (63.2%) of intronic NRXN1 deletion cases had a second rare CNV at a prevalence twice as high as that for exonic NRXN1 deletion cases (P = 0.0035).

CONCLUSIONS: The results support the importance of exons …


Brainstem Shape Is Affected By Clinical Course In The Neonatal Intensive Care Unit, Marcus Lo, Leire Zubiaurre-Elorza, Conor Wild, Annika C Linke, David S C Lee, Victor K Han, Rhodri Cusack Jan 2017

Brainstem Shape Is Affected By Clinical Course In The Neonatal Intensive Care Unit, Marcus Lo, Leire Zubiaurre-Elorza, Conor Wild, Annika C Linke, David S C Lee, Victor K Han, Rhodri Cusack

Paediatrics Publications

The brainstem, critical for motor function, autonomic regulation, and many neurocognitive functions, undergoes rapid development from the third trimester. Accordingly, we hypothesized it would be vulnerable to insult during this period, and that a difficult clinical course in the neonatal intensive care unit (NICU) would affect development, and be reflected through atypical shape. Our study population consisted of 66 neonates - all inpatients from the NICU at Victoria Hospital, London Health Sciences Centre, ON, Canada, of which 45 entered the final analysis. The cohort varied in gestational age (GA) and ranged from neurologically healthy to severely brain-injured. Structural MRI was …


Pediatric Emergency Care Capacity In A Low-Resource Setting: An Assessment Of District Hospitals In Rwanda, Celestin Hategeka, Jean Shoveller, Lisine Tuyisenge, Cynthia Kenyon, David F Cechetto, Larry D Lynd Jan 2017

Pediatric Emergency Care Capacity In A Low-Resource Setting: An Assessment Of District Hospitals In Rwanda, Celestin Hategeka, Jean Shoveller, Lisine Tuyisenge, Cynthia Kenyon, David F Cechetto, Larry D Lynd

Paediatrics Publications

BACKGROUND: Health system strengthening is crucial to improving infant and child health outcomes in low-resource countries. While the knowledge related to improving newborn and child survival has advanced remarkably over the past few decades, many healthcare systems in such settings remain unable to effectively deliver pediatric advance life support management. With the introduction of the Emergency Triage, Assessment and Treatment plus Admission care (ETAT+)-a locally adapted pediatric advanced life support management program-in Rwandan district hospitals, we undertook this study to assess the extent to which these hospitals are prepared to provide this pediatric advanced life support management. The results of …


Identification Of Epigenetic Signature Associated With Alpha Thalassemia/Mental Retardation X-Linked Syndrome, Laila C Schenkel, Kristin D Kernohan, Arran Mcbride, Ditta Reina, Amanda Hodge, Peter J Ainsworth, David I Rodenhiser, Guillaume Pare, Nathalie G Bérubé, Cindy Skinner, Kym M Boycott, Charles Schwartz, Bekim Sadikovic Jan 2017

Identification Of Epigenetic Signature Associated With Alpha Thalassemia/Mental Retardation X-Linked Syndrome, Laila C Schenkel, Kristin D Kernohan, Arran Mcbride, Ditta Reina, Amanda Hodge, Peter J Ainsworth, David I Rodenhiser, Guillaume Pare, Nathalie G Bérubé, Cindy Skinner, Kym M Boycott, Charles Schwartz, Bekim Sadikovic

Paediatrics Publications

BACKGROUND: Alpha thalassemia/mental retardation X-linked syndrome (ATR-X) is caused by a mutation at the chromatin regulator gene

RESULTS: We performed genome-wide DNA methylation assessment of the peripheral blood samples from 18 patients with ATR-X and compared it to 210 controls. We demonstrated the evidence of a unique and highly specific DNA methylation "epi-signature" in the peripheral blood of ATRX patients, which was corroborated by targeted bisulfite sequencing experiments. Although genomically represented, differentially methylated regions showed evidence of preferential clustering in pericentromeric and telometric chromosomal regions, areas where ATRX has multiple functions related to maintenance of heterochromatin and genomic integrity.

CONCLUSION: …


Desynchronization Of Autonomic Response And Central Autonomic Network Connectivity In Posttraumatic Stress Disorder, Janine Thome, Maria Densmore, Paul A Frewen, Margaret C Mckinnon, Jean Théberge, Andrew A Nicholson, Julian Koenig, Julian F Thayer, Ruth A Lanius Jan 2017

Desynchronization Of Autonomic Response And Central Autonomic Network Connectivity In Posttraumatic Stress Disorder, Janine Thome, Maria Densmore, Paul A Frewen, Margaret C Mckinnon, Jean Théberge, Andrew A Nicholson, Julian Koenig, Julian F Thayer, Ruth A Lanius

Department of Medicine Publications

OBJECTIVES: Although dysfunctional emotion regulatory capacities are increasingly recognized as contributing to posttraumatic stress disorder (PTSD), little work has sought to identify biological markers of this vulnerability. Heart rate variability (HRV) is a promising biomarker that, together with neuroimaging, may assist in gaining a deeper understanding of emotion dysregulation in PTSD. The objective of the present study was, therefore, to characterize autonomic response patterns, and their related neuronal patterns in individuals with PTSD at rest.

METHODS: PTSD patients (N = 57) and healthy controls (N = 41) underwent resting-state fMRI. Connectivity patterns of key regions within the central autonomic network …


Impact Of Age On Cerebrovascular Dilation Versus Reactivity To Hypercapnia., Nicole S Coverdale, Mark B Badrov, J Kevin Shoemaker Jan 2017

Impact Of Age On Cerebrovascular Dilation Versus Reactivity To Hypercapnia., Nicole S Coverdale, Mark B Badrov, J Kevin Shoemaker

Kinesiology Publications

This study quantified the effect of age on cerebrovascular reactivity and cerebrovascular conductance while accounting for differences in grey matter volume in younger (YA: n = 12; 24 ± 4 years, six females) and older adults (OA: n = 10; 66 ± 7 years; five females). Cerebral blood flow velocity (CBFV; transcranial Doppler) in the middle cerebral artery (MCA), MCA cross-sectional area (CSA), intracranial volumes (magnetic resonance imaging), and mean arterial pressure (MAP; Finometer), were measured under normocapnic and hypercapnic (6% carbon dioxide) conditions. Cerebral blood flow (CBF) was quantified from CBFV and MCA CSA and normalized to grey matter …


Clinician's Commentary On Patterson Et Al., Sue Peters Jan 2017

Clinician's Commentary On Patterson Et Al., Sue Peters

Physical Therapy Publications

No abstract provided.


Testing Students’ E-Learning Via Facebook Through Bayesian Structural Equation Modeling, H. Salarzadeh Jenatabadi, S. Moghavvemi, C.W.J. Wan Mohamed Radzi, P. Babashamsi, M. Arashi Jan 2017

Testing Students’ E-Learning Via Facebook Through Bayesian Structural Equation Modeling, H. Salarzadeh Jenatabadi, S. Moghavvemi, C.W.J. Wan Mohamed Radzi, P. Babashamsi, M. Arashi

Research Publications (2016 to 2020)

Learning is an intentional activity, with several factors affecting students’ intention to use new learning technology. Researchers have investigated technology acceptance in different contexts by developing various theories/models and testing them by a number of means. Although most theories/models developed have been examined through regression or structural equation modeling, Bayesian analysis offers more accurate data analysis results. To address this gap, the unified theory of acceptance and technology use in the context of e-learning via Facebook are re-examined in this study using Bayesian analysis. The data (S1 Data) were collected from 170 students enrolled in a business statistics course at …


Sustained Nitric Oxide-Releasing Nanoparticles Interfere With Methicillin-Resistant Staphylococcus Aureus Adhesion And Biofilm Formation In A Rat Central Venous Catheter Model., Mircea Radu Mihu, Vitor Cabral, Rodney Pattabhi, Moses T Tar, Kelvin P Davies, Adam J Friedman, Luis R Martinez, Joshua D Nosanchuk Jan 2017

Sustained Nitric Oxide-Releasing Nanoparticles Interfere With Methicillin-Resistant Staphylococcus Aureus Adhesion And Biofilm Formation In A Rat Central Venous Catheter Model., Mircea Radu Mihu, Vitor Cabral, Rodney Pattabhi, Moses T Tar, Kelvin P Davies, Adam J Friedman, Luis R Martinez, Joshua D Nosanchuk

Dermatology Faculty Publications

Staphylococcus aureus is frequently isolated in the setting of infections of indwelling medical devices, which are mediated by the microbe's ability to form biofilms on a variety of surfaces. Biofilm-embedded bacteria are more resistant to antimicrobial agents than their planktonic counterparts and often cause chronic infections and sepsis, particularly in patients with prolonged hospitalizations. In this study, we demonstrate that sustained nitric oxide-releasing nanoparticles (NO-np) interfere with S. aureus adhesion and prevent biofilm formation on a rat central venous catheter (CVC) model of infection. Confocal and scanning electron microscopy showed that NO-np-treated staphylococcal biofilms displayed considerably reduced thicknesses and bacterial …


Variability In Objective And Subjective Measures Affects Baseline Values In Studies Of Patients With Copd, Wayne H. Anderson, Jae Wook Ha, David J. Couper, Wanda K. O'Neal, R. Graham Barr, Eugene R. Bleecker, Elizabeth E. Carretta, Christopher B. Cooper, Claire M. Doerschuk, M. Bradley Drummond, Meilan K. Han, Nadia N. Hansel, Victor Kim, Eric C. Kleerup, Fernando J. Martinez, Stephen I. Rennard, Donald Tashkin, Prescott G. Woodruff, Robert Paine, Jeffrey L. Curtis, Richard W. Kanner, Spiromics Research Group Jan 2017

Variability In Objective And Subjective Measures Affects Baseline Values In Studies Of Patients With Copd, Wayne H. Anderson, Jae Wook Ha, David J. Couper, Wanda K. O'Neal, R. Graham Barr, Eugene R. Bleecker, Elizabeth E. Carretta, Christopher B. Cooper, Claire M. Doerschuk, M. Bradley Drummond, Meilan K. Han, Nadia N. Hansel, Victor Kim, Eric C. Kleerup, Fernando J. Martinez, Stephen I. Rennard, Donald Tashkin, Prescott G. Woodruff, Robert Paine, Jeffrey L. Curtis, Richard W. Kanner, Spiromics Research Group

Journal Articles: Pulmonary & Critical Care Med

RATIONALE: Understanding the reliability and repeatability of clinical measurements used in the diagnosis, treatment and monitoring of disease progression is of critical importance across all disciplines of clinical practice and in clinical trials to assess therapeutic efficacy and safety.

OBJECTIVES: Our goal is to understand normal variability for assessing true changes in health status and to more accurately utilize this data to differentiate disease characteristics and outcomes.

METHODS: Our study is the first study designed entirely to establish the repeatability of a large number of instruments utilized for the clinical assessment of COPD in the same subjects over the same …


Foxc1 Is Associated With Estrogen Receptor Alpha And Affects Sensitivity Of Tamoxifen Treatment In Breast Cancer., Jinhua Wang, Yali Xu, Li Li, Lin Wang, Ru Yao, Qiang Sun, Guanhua Du Jan 2017

Foxc1 Is Associated With Estrogen Receptor Alpha And Affects Sensitivity Of Tamoxifen Treatment In Breast Cancer., Jinhua Wang, Yali Xu, Li Li, Lin Wang, Ru Yao, Qiang Sun, Guanhua Du

Articles, Abstracts, and Reports

FOXC1 is a member of Forkhead box transcription factors that participates in embryonic development and tumorigenesis. Our previous study demonstrated that FOXC1 was highly expressed in triple-negative breast cancer. However, it remains unclear what is the relation between FOXC1 and ERα and if FOXC1 regulates expression of ERα. To explore relation between FOXC1 and ERα and discover regulation of ERα expression by FOXC1 in breast cancer, we analyzed data assembled in the Oncomine and TCGA, and found that there was significantly higher FOXC1 expression in estrogen receptor-negative breast cancer than that in estrogen receptor-positive breast cancer. Overexpression of FOXC1 reduced …


Sting Expression And Response To Treatment With Sting Ligands In Premalignant And Malignant Disease., Jason R Baird, Zipei Feng, Hong D Xiao, David Friedman, Ben Cottam, Bernard A Fox, Gwen Kramer, Rom S Leidner, Richard Bryan Bell, Kristina H Young, Marka R Crittenden, Michael J Gough Jan 2017

Sting Expression And Response To Treatment With Sting Ligands In Premalignant And Malignant Disease., Jason R Baird, Zipei Feng, Hong D Xiao, David Friedman, Ben Cottam, Bernard A Fox, Gwen Kramer, Rom S Leidner, Richard Bryan Bell, Kristina H Young, Marka R Crittenden, Michael J Gough

Articles, Abstracts, and Reports

Human papilloma virus positive (HPV+) tumors represent a large proportion of anal, vulvar, vaginal, cervical and head and neck squamous carcinomas (HNSCC) and late stage invasive disease is thought to originate from a premalignant state. Cyclic dinucleotides that activate STimulator of INterferon Genes (STING) have been shown to cause rapid regression of a range of advanced tumors. We aimed to investigate STING ligands as a novel treatment for papilloma. We tested therapies in a spontaneous mouse model of papilloma of the face and anogenital region that histologically resembles human HPV-associated papilloma. We demonstrate that STING ligands cause rapid regression of …


The Cosmological Liveliness Of Terril Calder's The Lodge: Animating Our Relations And Unsettling Our Cinematic Spaces, Salma Monani Jan 2017

The Cosmological Liveliness Of Terril Calder's The Lodge: Animating Our Relations And Unsettling Our Cinematic Spaces, Salma Monani

Environmental Studies Faculty Publications

I first saw Métis artist Terril Calder's 2014 stop-frame feature, The Lodge, an independently made, relatively small- budget film, at its premiere at the ImagineNative Film + Media Arts festival, held annually in Toronto, Canada. The feature-length animation played to a full house at the Light-box Theater downtown. Many were there to attend the five-day festival, which is dedicated to Indigenous media made by and for Indigenous people. Others were there because as members of Toronto's general public they wanted to catch a movie during a night out in the city. Since then The Lodge has shown at various other …


The Distinct Metabolic Phenotype Of Lung Squamous Cell Carcinoma Defines Selective Vulnerability To Glycolytic Inhibition, Justin Goodwin, Michael L. Neugent, Shin Yup Lee, Joshua H. Choe, Hyunsung Choi, Dana M. R. Jenkins, Robin J. Ruthenborg, Maddox W. Robinson, Ji Yun Jeong, Masaki Wake, Hajime Abe, Norihiko Takeda, Hiroko Endo, Masahiro Inoue, Zhenyu Xuan, Hyuntae Yoo, Min Chen, Jung-Mo Ahn, John D. Minna, Kristi L. Helke, Pankaj K. Singh, David B. Shackelford, Jung-Whan Kim Jan 2017

The Distinct Metabolic Phenotype Of Lung Squamous Cell Carcinoma Defines Selective Vulnerability To Glycolytic Inhibition, Justin Goodwin, Michael L. Neugent, Shin Yup Lee, Joshua H. Choe, Hyunsung Choi, Dana M. R. Jenkins, Robin J. Ruthenborg, Maddox W. Robinson, Ji Yun Jeong, Masaki Wake, Hajime Abe, Norihiko Takeda, Hiroko Endo, Masahiro Inoue, Zhenyu Xuan, Hyuntae Yoo, Min Chen, Jung-Mo Ahn, John D. Minna, Kristi L. Helke, Pankaj K. Singh, David B. Shackelford, Jung-Whan Kim

Journal Articles: Eppley Institute

Adenocarcinoma (ADC) and squamous cell carcinoma (SqCC) are the two predominant subtypes of non-small cell lung cancer (NSCLC) and are distinct in their histological, molecular and clinical presentation. However, metabolic signatures specific to individual NSCLC subtypes remain unknown. Here, we perform an integrative analysis of human NSCLC tumour samples, patient-derived xenografts, murine model of NSCLC, NSCLC cell lines and The Cancer Genome Atlas (TCGA) and reveal a markedly elevated expression of the GLUT1 glucose transporter in lung SqCC, which augments glucose uptake and glycolytic flux. We show that a critical reliance on glycolysis renders lung SqCC vulnerable to glycolytic inhibition, …


Body Mass Index Change In Gastrointestinal Cancer And Chronic Obstructive Pulmonary Disease Is Associated With Dedicator Of Cytokinesis 1, Merry-Lynn Noelle Mcdonald, Sungho Won, Manuel Mattheisen, Peter J. Castaldi, Michael H. Cho, Erica Rutten, Megan Hardin, Wai-Ki Yip, Stephen I. Rennard, David A. Lomas, Emiel F.M. Wouters, Alvar Agusti, Richard Casaburi, Christoph P. Lange, George O'Connor, Craig P. Hersh, Edwin K. Silverman Jan 2017

Body Mass Index Change In Gastrointestinal Cancer And Chronic Obstructive Pulmonary Disease Is Associated With Dedicator Of Cytokinesis 1, Merry-Lynn Noelle Mcdonald, Sungho Won, Manuel Mattheisen, Peter J. Castaldi, Michael H. Cho, Erica Rutten, Megan Hardin, Wai-Ki Yip, Stephen I. Rennard, David A. Lomas, Emiel F.M. Wouters, Alvar Agusti, Richard Casaburi, Christoph P. Lange, George O'Connor, Craig P. Hersh, Edwin K. Silverman

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: There have been a number of candidate gene association studies of cancer cachexia-related traits, but no genome-wide association study (GWAS) has been published to date. Cachexia presents in patients with a number of complex traits, including both cancer and COPD. The objective of the current investigation was to search for a shared genetic aetiology for change in body mass index (ΔBMI) among cancer and COPD by using GWAS data in the Framingham Heart Study.

METHODS: A linear mixed effects model accounting for age, sex, and change in smoking status was used to calculate ΔBMI in participants over 40 years …


Reliability Of Medical Records In Diagnosing Inflammatory Breast Cancer In Egypt, Lynne Le, Catherine Schairer, Ahmed Hablas, Jane L. Meza, Shinobu Watanabe-Galloway, Mohamed Ramadan, Sofia D. Merajver, Ibrahim A. Seifeldin, Amr S. Soliman Jan 2017

Reliability Of Medical Records In Diagnosing Inflammatory Breast Cancer In Egypt, Lynne Le, Catherine Schairer, Ahmed Hablas, Jane L. Meza, Shinobu Watanabe-Galloway, Mohamed Ramadan, Sofia D. Merajver, Ibrahim A. Seifeldin, Amr S. Soliman

Journal Articles: Epidemiology

BACKGROUND: Inflammatory breast cancer (IBC) is a rare, aggressive breast cancer diagnosed clinically by the presence of diffuse erythema, peau d'orange, and edema that arise quickly in the affected breast. This study evaluated the validity of medical records in Gharbiah, Egypt in identifying clinical signs/symptoms of IBC. For 34 IBC cases enrolled in a case-control study at the Gharbiah Cancer Society and Tanta Cancer Center, Egypt (2009-2010), we compared signs/symptoms of IBC noted in medical records to those recorded on a standardized form at the time of IBC diagnosis by clinicians participating in the case-control study. We calculated the sensitivity …


Nephrology And Telehealth: Now? Or Now!, Sandeep Soman, Jerry Yee Jan 2017

Nephrology And Telehealth: Now? Or Now!, Sandeep Soman, Jerry Yee

Nephrology Articles

No abstract provided.


Bid-Induced Release Of Aif/Endog From Mitochondria Causes Apoptosis Of Macrophages During Infection With, Wei-Lin Hu, Hai-Yan Dong, Yang Li, David M. Ojcius, Shi-Jun Li, Jie Yan Jan 2017

Bid-Induced Release Of Aif/Endog From Mitochondria Causes Apoptosis Of Macrophages During Infection With, Wei-Lin Hu, Hai-Yan Dong, Yang Li, David M. Ojcius, Shi-Jun Li, Jie Yan

All Dugoni School of Dentistry Faculty Articles

Leptospirosis is a global zoonotic infectious disease caused by pathogenic Leptospira species. Leptospire-induced macrophage apoptosis through the Fas/FasL-caspase-8/3 pathway plays an important role in the survival and proliferation of the pathogen in hosts. Although, the release of mitochondrial apoptosis-inducing factor (AIF) and endonuclease G (EndoG) in leptospire-infected macrophages has been described, the mechanisms linking caspase and mitochondrion-related host-cell apoptosis has not been determined. Here, we demonstrated that leptospire-infection induced apoptosis through mitochondrial damages in macrophages. Apoptosis was caused by the mitochondrial release and nuclear translocation of AIF and/or EndoG, leading to nuclear DNA fragmentation. However, the mitochondrion-related CytC-caspase-9/3 pathway was …


Mononuclear-Macrophages But Not Neutrophils Act As Major Infiltrating Anti-Leptospiral Phagocytes During Leptospirosis., Xu Chen, Shi-Jun Li, David M. Ojcius, Ai-Hua Sun, Wei-Lin Hu, Xu'ai Lin, Jie Yan Jan 2017

Mononuclear-Macrophages But Not Neutrophils Act As Major Infiltrating Anti-Leptospiral Phagocytes During Leptospirosis., Xu Chen, Shi-Jun Li, David M. Ojcius, Ai-Hua Sun, Wei-Lin Hu, Xu'ai Lin, Jie Yan

All Dugoni School of Dentistry Faculty Articles

OBJECTIVE: To identify the major infiltrating phagocytes during leptospirosis and examine the killing mechanism used by the host to eliminate Leptospira interrogans.

METHODS: Major infiltrating phagocytes in Leptospira-infected C3H/HeJ mice were detected by immunohistochemistry. Chemokines and vascular endothelial cell adhesion molecules (VECAMs) of Leptospira-infected mice and leptospirosis patients were detected by microarray and immunohistochemistry. Leptospira-phagocytosing and -killing abilities of human or mouse macrophages and neutrophils, and the roles of intracellular ROS, NO and [Ca2+]i in Leptospira-killing process were evaluated by confocal microscopy and spectrofluorimetry.

RESULTS: Peripheral blood mononuclear-macrophages rather than neutrophils were the main infiltrating phagocytes in the lungs, liver …


Pathogenic Determinants And Mechanisms Of Als/Ftd Linked To Hexanucleotide Repeat Expansions In The C9orf72 Gene., Xinmei Wen, Thomas Westergard, Piera Pasinelli, Davide Trotti Jan 2017

Pathogenic Determinants And Mechanisms Of Als/Ftd Linked To Hexanucleotide Repeat Expansions In The C9orf72 Gene., Xinmei Wen, Thomas Westergard, Piera Pasinelli, Davide Trotti

Department of Neuroscience Faculty Papers

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two apparently distinct neurodegenerative diseases, the former characterized by selective loss of motor neurons in the brain and spinal cord and the latter characterized by selective atrophy of frontal and temporal lobes. Over the years, however, growing evidence from clinical, pathological and genetic findings has suggested that ALS and FTD belong to the same clinic-pathological spectrum disorder. This concept has been further supported by the identification of the most common genetic cause for both diseases, an aberrantly expanded hexanucleotide repeat GGGGCC/ CCCCGG sequence located in a non-coding region of the gene …


Intimate Partner Violence And Women's Cancer Quality Of Life, Ann L. Coker, Diane R. Follingstad, Lisandra S. Garcia, Heather M. Bush Jan 2017

Intimate Partner Violence And Women's Cancer Quality Of Life, Ann L. Coker, Diane R. Follingstad, Lisandra S. Garcia, Heather M. Bush

CRVAW Faculty Journal Articles

Purpose

Because intimate partner violence (IPV) may disproportionately impact women’s quality of life (QOL) when undergoing cancer treatment, women experiencing IPV were hypothesized to have (a) more symptoms of depression or stress and (b) lower QOL as measured with the Functional Assessment of Cancer Therapy (FACT-B) and Functional Assessment of Chronic Illness Therapy—Spiritual Well-being (FACIT-SP) Scales relative to those never experiencing IPV.

Methods

Women, aged 18–79, who were included in one of two state cancer registries from 2009 to 2015 with a recent incident, primary, invasive biopsy-confirmed cancer diagnosis were recruited and asked to complete a phone interview, within 12 …


Dealing With Pre-Exposure Prophylaxis-Associated Condom Migration: Changing The Paradigm For Men Who Have Sex With Men, Richard A. Crosby Jan 2017

Dealing With Pre-Exposure Prophylaxis-Associated Condom Migration: Changing The Paradigm For Men Who Have Sex With Men, Richard A. Crosby

Health, Behavior & Society Faculty Publications

The behavioural aspects of pre-exposure prophylaxis (PrEP) are challenging, particularly the issue of condom migration. Three vital questions are: (1) at the population-level, will condom migration lead to increases in non-viral sexually transmissible infections?; (2) how can clinic-based counselling best promote the dual use of condoms and PrEP?; and (3) in future PrEP trials, what are the ‘best practices’ that should be used to avoid type 1 and type 2 errors that arise without accounting for condom use behaviours? This communication piece addresses each question and suggests the risk of a ‘PrEP only’ focus to widening health disparities.


Mental Health Treatment Seeking Patterns And Preferences Of Appalachian Women With Depression, Claire Snell-Rood, Emily Hauenstein, Carl G. Leukefeld, Frances Feltner, Amber Marcum, Nancy E. Schoenberg Jan 2017

Mental Health Treatment Seeking Patterns And Preferences Of Appalachian Women With Depression, Claire Snell-Rood, Emily Hauenstein, Carl G. Leukefeld, Frances Feltner, Amber Marcum, Nancy E. Schoenberg

Behavioral Science Faculty Publications

This qualitative study explored social-cultural factors that shape treatment seeking behaviors among depressed rural, low-income women in Appalachia—a region with high rates of depression and a shortage of mental health services. Recent research shows that increasingly rural women are receiving some form of treatment and identifying their symptoms as depression. Using purposive sampling, investigators recruited 28 depressed low-income women living in Appalachian Kentucky and conducted semistructured interviews on participants’ perceptions of depression and treatment seeking. Even in this sample of women with diverse treatment behaviors (half reported current treatment), participants expressed ambivalence about treatment and its potential to promote recovery. …


Early Mutation Bursts In Colorectal Tumors., Junsong Zhao, Matthew P Salomon, Darryl Shibata, Christina Curtis, Kimberly Siegmund, Paul Marjoram Jan 2017

Early Mutation Bursts In Colorectal Tumors., Junsong Zhao, Matthew P Salomon, Darryl Shibata, Christina Curtis, Kimberly Siegmund, Paul Marjoram

Articles, Abstracts, and Reports

Tumor growth is an evolutionary process involving accumulation of mutations, copy number alterations, and cancer stem cell (CSC) division and differentiation. As direct observation of this process is impossible, inference regarding when mutations occur and how stem cells divide is difficult. However, this ancestral information is encoded within the tumor itself, in the form of intratumoral heterogeneity of the tumor cell genomes. Here we present a framework that allows simulation of these processes and estimation of mutation rates at the various stages of tumor development and CSC division patterns for single-gland sequencing data from colorectal tumors. We parameterize the mutation …


Differential Phenotypes Of Memory Cd4 And Cd8 T Cells In The Spleen And Peripheral Tissues Following Immunostimulatory Therapy., Gail D Sckisel, Annie Mirsoian, Christine M Minnar, Marka R Crittenden, Brendan Curti, Jane Q Chen, Bruce R Blazar, Alexander D Borowsky, Arta M Monjazeb, William J Murphy Jan 2017

Differential Phenotypes Of Memory Cd4 And Cd8 T Cells In The Spleen And Peripheral Tissues Following Immunostimulatory Therapy., Gail D Sckisel, Annie Mirsoian, Christine M Minnar, Marka R Crittenden, Brendan Curti, Jane Q Chen, Bruce R Blazar, Alexander D Borowsky, Arta M Monjazeb, William J Murphy

Articles, Abstracts, and Reports

BACKGROUND: Studies assessing immune parameters typically utilize human PBMCs or murine splenocytes to generate data that is interpreted as representative of immune status. Using splenocytes, we have shown memory CD4-T cells that expand following systemic immunostimulatory therapies undergo rapid IFNg-mediated activation induced cell death (AICD) resulting in a net loss of total CD4-T cells which correlates with elevated PD-1 expression. This is in contrast to CD8-T cells which expand with minimal PD-1 upregulation and apoptosis. In this study we expand upon our previous work by evaluating CD4 and CD8-T cell phenotype and distribution in peripheral organs which are more representative …


Persuasive Interventions For Controversial Cancer Screening Recommendations: Testing A Novel Approach To Help Patients Make Evidence-Based Decisions., Barry Saver, Kathleen M Mazor, Roger Luckmann, Sarah L Cutrona, Marcela Hayes, Tatyana Gorodetsky, Nancy Esparza, Gonzalo Bacigalupe Jan 2017

Persuasive Interventions For Controversial Cancer Screening Recommendations: Testing A Novel Approach To Help Patients Make Evidence-Based Decisions., Barry Saver, Kathleen M Mazor, Roger Luckmann, Sarah L Cutrona, Marcela Hayes, Tatyana Gorodetsky, Nancy Esparza, Gonzalo Bacigalupe

Articles, Abstracts, and Reports

PURPOSE: We wanted to evaluate novel decision aids designed to help patients trust and accept the controversial, evidence-based, US Preventive Services Task Force recommendations about prostate cancer screening (from 2012) and mammography screening for women aged 40 to 49 years (from 2009).

METHODS: We created recorded vignettes of physician-patient discussions about prostate cancer screening and mammography, accompanied by illustrative slides, based on principles derived from preceding qualitative work and behavioral science literature. We conducted a randomized crossover study with repeated measures with 27 men aged 50 to 74 years and 35 women aged 40 to 49 years. All participants saw …


Astrocytes Promote Progression Of Breast Cancer Metastases To The Brain Via A Kiss1-Mediated Autophagy., Natalya Kaverina, Anton V Borovjagin, Zaira Kadagidze, Anatoly Baryshnikov, Maria Baryshnikova, Dmitry Malin, Dhimankrishhna Ghosh, Nameeta Shah, Danny R Welch, Patrik Gabikian, Apollon Karseladze, Charles Cobbs, Ilya V Ulasov Jan 2017

Astrocytes Promote Progression Of Breast Cancer Metastases To The Brain Via A Kiss1-Mediated Autophagy., Natalya Kaverina, Anton V Borovjagin, Zaira Kadagidze, Anatoly Baryshnikov, Maria Baryshnikova, Dmitry Malin, Dhimankrishhna Ghosh, Nameeta Shah, Danny R Welch, Patrik Gabikian, Apollon Karseladze, Charles Cobbs, Ilya V Ulasov

Articles, Abstracts, and Reports

Formation of metastases, also known as cancer dissemination, is an important stage of breast cancer (BrCa) development. KISS1 expression is associated with inhibition of metastases development. Recently we have demonstrated that BrCa metastases to the brain exhibit low levels of KISS1 expression at both mRNA and protein levels. By using multicolor immunofluorescence and coculture techniques here we show that normal adult astrocytes in the brain are capable of promoting metastatic transformation of circulating breast cancer cells localized to the brain through secretion of chemokine CXCL12. The latter was found in this study to downregulate KISS1 expression at the post-transcriptional level …


Individual Fluid Plans Versus Ad Libitum On Hydration Status In Minor Professional Ice Hockey Players, Dawn M. Emerson, Toni Torres-Mcgehee, Charles C. Emerson, Teri L. Lasalle Jan 2017

Individual Fluid Plans Versus Ad Libitum On Hydration Status In Minor Professional Ice Hockey Players, Dawn M. Emerson, Toni Torres-Mcgehee, Charles C. Emerson, Teri L. Lasalle

Faculty Publications

BACKGROUND: Despite exercising in cool environments, ice hockey players exhibit several dehydration risk factors. Individualized fluid plans (IFPs) are designed to mitigate dehydration by matching an individual's sweat loss in order to optimize physiological systems and performance. METHODS: A randomized control trial was used to examine IFP versus ad libitum fluid ingestion on hydration in 11 male minor professional ice hockey players (mean age = 24.4 ± 2.6 years, height = 183.0 ± 4.6 cm, weight = 92.9 ± 7.8 kg). Following baseline measures over 2 practices, participants were randomly assigned to either control (CON) or intervention (INT) for 10 …


Mutational Landscapes Of Smoking-Related Cancers In Caucasians And African Americans: Precision Oncology Perspectives At Wake Forest Baptist Comprehensive Cancer Center., Ville Kytola, Umit Topaloglu, Lance D Miller, Rhonda L Bitting, Michael M Goodman, Ralph B D Agostino, Rodwige J Desnoyers, Carol Albright, George Yacoub, Shadi A Qasem, Barry Deyoung, Vesteinn Thorsson, Ilya Shmulevich, Meng Yang, Anastasia Shcherban, Matthew Pagni, Liang Liu, Matti Nykter, Kexin Chen, Gregory A Hawkins, Stefan C Grant, W Jeffrey Petty, Angela Tatiana Alistar, Edward A Levine, Edgar D Staren, Carl D Langefeld, Vincent Miller, Gaurav Singal, Robin M Petro, Mac Robinson, William Blackstock, Bayard L Powell, Lynne I Wagner, Kristie L Foley, Edward Abraham, Boris Pasche, Wei Zhang Jan 2017

Mutational Landscapes Of Smoking-Related Cancers In Caucasians And African Americans: Precision Oncology Perspectives At Wake Forest Baptist Comprehensive Cancer Center., Ville Kytola, Umit Topaloglu, Lance D Miller, Rhonda L Bitting, Michael M Goodman, Ralph B D Agostino, Rodwige J Desnoyers, Carol Albright, George Yacoub, Shadi A Qasem, Barry Deyoung, Vesteinn Thorsson, Ilya Shmulevich, Meng Yang, Anastasia Shcherban, Matthew Pagni, Liang Liu, Matti Nykter, Kexin Chen, Gregory A Hawkins, Stefan C Grant, W Jeffrey Petty, Angela Tatiana Alistar, Edward A Levine, Edgar D Staren, Carl D Langefeld, Vincent Miller, Gaurav Singal, Robin M Petro, Mac Robinson, William Blackstock, Bayard L Powell, Lynne I Wagner, Kristie L Foley, Edward Abraham, Boris Pasche, Wei Zhang

Articles, Abstracts, and Reports

Background: Cancers related to tobacco use and African-American ancestry are under-characterized by genomics. This gap in precision oncology research represents a major challenge in the health disparities in the United States. Methods: The Precision Oncology trial at the Wake Forest Baptist Comprehensive Cancer Center enrolled 431 cancer patients from March 2015 to May 2016. The composition of these patients consists of a high representation of tobacco-related cancers (e.g., lung, colorectal, and bladder) and African-American ancestry (13.5%). Tumors were sequenced to identify mutations to gain insight into genetic alterations associated with smoking and/or African-American ancestry. Results: Tobacco-related cancers exhibit a high …


Does Gated Beam Delivery Impact Delivery Accuracy On An Elekta Linac?, Mohammed Jermoumi, Roger Xie, Daliang Cao, David J Housley, David M Shepard Jan 2017

Does Gated Beam Delivery Impact Delivery Accuracy On An Elekta Linac?, Mohammed Jermoumi, Roger Xie, Daliang Cao, David J Housley, David M Shepard

Articles, Abstracts, and Reports

In this study, we evaluated the performance of an Elekta linac in the delivery of gated radiotherapy. Delivery accuracy was examined with an emphasis on the impact of using short gating windows (low monitor unit beam-on segments) or long beam hold times. The performance was assessed using a 20cm by 20cm open field with the radiation delivered using a range of beam-on and beam-off time periods. Gated delivery measurements were also performed for two SBRT plans delivered using volumetric modulated arc therapy (VMAT). Tests included both free-breathing based gating (covering a variety of gating windows) and simulated breath-hold based gating. …