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The Role Of Ezh2 In The Regulation Of The Activity Of Matrix Metalloproteinases In Prostate Cancer Cells., Yong Jae Shin, Jeong-Ho Kim

Biochemistry and Molecular Medicine Faculty Publications

Degradation of the extracellular matrix (ECM), a critical step in cancer metastasis, is determined by the balance between MMPs (matrix metalloproteinases) and their inhibitors TIMPs (tissue inhibitors of metalloproteinases). In cancer cells, this balance is shifted towards MMPs, promoting ECM degradation. Here, we show that EZH2 plays an active role in this process by repressing the expression of TIMP2 and TIMP3 in prostate cancer cells. The TIMP genes are derepressed by knockdown of EZH2 expression in human prostate cancer cells but repressed by overexpression of EZH2 in benign human prostate epithelial cells. EZH2 catalyzes H3K27 trimethylation and subsequent DNA methylation …

Examining Fatigue In Copd: Development, Validity And Reliability Of A Modified Version Of Facit-F Scale, Khaled Al-Shair, Hana Muellerova, Janelle Yorke, Stephen I. Rennard, Emiel F.M. Wouters, Nicola A. Hanania, Amir Sharafkhaneh, Jørgen Vestbo, Eclipse Investigators

Journal Articles: Pulmonary & Critical Care Med

INTRODUCTION: Fatigue is a disruptive symptom that inhibits normal functional performance of COPD patients in daily activities. The availability of a short, simple, reliable and valid scale would improve assessment of the characteristics and influence of fatigue in COPD.

METHODS: At baseline, 2107 COPD patients from the ECLIPSE cohort completed the Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) scale. We used well-structured classic method, the principal components analysis (PCA) and Rasch analysis for structurally examining the 13-item FACIT-F.

RESULTS: Four items were less able to capture fatigue characteristics in COPD and were deleted. PCA was applied to the remaining …

Effects Of Inhaled Corticosteroids On Airway Inflammation In Chronic Obstructive Pulmonary Disease: A Systematic Review And Meta-Analysis, Rachel Jen, Stephen I. Rennard, Don D. Sin

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation in the small airways. The effect of inhaled corticosteroids (ICS) on lung inflammation in COPD remains uncertain. We sought to determine the effects of ICS on inflammatory indices in bronchial biopsies and bronchoalveolar lavage fluid of patients with COPD.

METHODS: We searched Medline, Embase, Cinahl, and the Cochrane database for randomized, controlled clinical trials that used bronchial biopsies and bronchoalveolar lavage to evaluate the effects of ICS in stable COPD. For each chosen study, we calculated the mean differences in the concentrations of inflammatory cells before and after treatment …

The Long And Short Of It: The Role Of Telomeres In Fetal Origins Of Adult Disease., Stephanie E Hallows, Timothy Regnault, Dean H Betts

Paediatrics Publications

Placental insufficiency, maternal malnutrition, and other causes of intrauterine growth restriction (IUGR) can significantly affect short-term growth and long-term health. Following IUGR, there is an increased risk for cardiovascular disease and Type 2 Diabetes. The etiology of these diseases is beginning to be elucidated, and premature aging or cellular senescence through increased oxidative stress and DNA damage to telomeric ends may be initiators of these disease processes. This paper will explore the areas where telomere and telomerase biology can have significant effects on various tissues in the body in IUGR outcomes.

Hyperpolarized 3he Functional Magnetic Resonance Imaging Of Bronchoscopic Airway Bypass In Chronic Obstructive Pulmonary Disease., Lindsay Mathew, Miranda Kirby, Donald Farquhar, Christopher Licskai, Giles Santyr, Roya Etemad-Rezai, Grace Parraga, David G Mccormack

Medical Biophysics Publications

A 73-year-old exsmoker with Global initiative for chronic Obstructive Lung Disease stage III chronic obstructive pulmonary disease underwent airway bypass (AB) as part of the Exhale Airway Stents for Emphysema (EASE) trial, and was the only EASE subject to undergo hyperpolarized 3He magnetic resonance imaging for evaluation of lung function pre- and post-AB. 3He magnetic resonance imaging was acquired twice previously (32 and eight months pre-AB) and twice post-AB (six and 12 months post-AB). Six months post-AB, his increase in forced vital capacity was

Chest Mri In Children: Why Bother?, Amir M Owrangi, Grace Parraga

Medical Biophysics Publications

In this issue of Respirology, Montella and colleagues ask this question: How does high‐field chest MRI compare with CT of children with non‐cystic fibrosis (CF) lung disease? In an important extension of the first description of this study where they compared MRI and CT with pulmonary function measurements, the authors evaluated how widely‐used chest CT and almost never‐utilized lung MRI compare for diagnostic imaging of chronic lung disease. Here they show that high‐field (3Tesla as compared with the 1.5Tesla clinical standard) thoracic MRI has high reliability and good‐to‐excellent agreement with CT, definitively answering the important question at hand; their results …

Discriminating Famous From Fictional Names Based On Lifetime Experience: Evidence In Support Of A Signal-Detection Model Based On Finite Mixture Distributions., Ben Bowles, Iain M Harlow, Melissa M Meeking, Stefan Köhler

Brain and Mind Institute Researchers' Publications

It is widely accepted that signal-detection mechanisms contribute to item-recognition memory decisions that involve discriminations between targets and lures based on a controlled laboratory study episode. Here, the authors employed mathematical modeling of receiver operating characteristics (ROC) to determine whether and how a signal-detection mechanism contributes to discriminations between moderately famous and fictional names based on lifetime experience. Unique to fame judgments is a lack of control over participants' previous exposure to the stimuli deemed "targets" by the experimenter; specifically, if they pertain to moderately famous individuals, participants may have had no prior exposure to a substantial proportion of the …

Neural Network Diagnostic System For Dengue Patients Risk Classification, T. Faisal, M.N. Taib, Fatimah Ibrahim

Research Publications (2011 to 2015)

With the dramatic increase of the worldwide threat of dengue disease, it has been very crucial to correctly diagnose the dengue patients in order to decrease the disease severity. However, it has been a great challenge for the physicians to identify the level of risk in dengue patients due to overlapping of the medical classification criteria. Therefore, this study aims to construct a noninvasive diagnostic system to assist the physicians for classifying the risk in dengue patients. Systematic producers have been followed to develop the system. Firstly, the assessment of the significant predictors associated with the level of risk in …

Full-Forward And, Macho Homos : Toward A Masculist Reframing Of Male Homosexuality, Kristian Guagliardo

Theses : Honours

The following work explores the nexus of male homosexuality and traditional masculinity.

The creative work examines the ways in which both patriarchal and popular, purportedly feminist or queer theorist cultures arbitrarily assign allegedly immanent feminine qualities to homosexual males even when these characteristics are not congruent with the male subject. This facet of western, and specifically Australian, culture is explored through the prism of a hegemonically masculine ‘country boy’ who finds that despite his own comportment and identity, he becomes culturally and socially feminised by virtue of his homosexuality alone. He experiences isolation, angst, anger and cognitive dissonance as he …

Association Of Ireb2 And Chrna3 Polymorphisms With Airflow Obstruction In Severe Alpha-1 Antitrypsin Deficiency., Woo Jin Kim, Alice M. Wood, Alan F. Barker, Mark L. Brantly, Edward J. Campbell, Edward Eden, Gerard Mcelvaney, Stephen I. Rennard, Robert A. Sandhaus, James M. Stocks, James K. Stoller, Charlie Strange, Gerard Turino, Edwin K. Silverman, Robert A. Stockley, Dawn L. Demeo

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: The development of COPD in subjects with alpha-1 antitrypsin (AAT) deficiency is likely to be influenced by modifier genes. Genome-wide association studies and integrative genomics approaches in COPD have demonstrated significant associations with SNPs in the chromosome 15q region that includes CHRNA3 (cholinergic nicotine receptor alpha3) and IREB2 (iron regulatory binding protein 2).We investigated whether SNPs in the chromosome 15q region would be modifiers for lung function and COPD in AAT deficiency.

METHODS: The current analysis included 378 PIZZ subjects in the AAT Genetic Modifiers Study and a replication cohort of 458 subjects from the UK AAT Deficiency National …

Malaria And Related Outcomes In Patients With Intestinal Helminths: A Cross-Sectional Study, Abraham Degarege, Mengistu Legesse, Girmay Medhin, Abebe Animut, Berhanu Erko

Journal Articles: Epidemiology

BACKGROUND: The effects of helminth co-infection on malaria in humans remain uncertain. This study aimed to evaluate the nature of association of intestinal helminths with prevalence and clinical outcomes of Plasmodium infection.

METHODS: A cross-sectional study involving 1,065 malaria suspected febrile patients was conducted at Dore Bafeno Health Center, Southern Ethiopia, from December 2010 to February 2011. Plasmodium and intestinal helminth infections were diagnosed using Giemsa-stained blood films and Kato-Katz technique, respectively. Haemoglobin level was determined using a haemocue machine.

RESULTS: Among 1,065 malaria suspected febrile patients, 28.8% were positive for Plasmodium parasites (P. falciparum =13.0%, P. vivax =14.5%, P. …

Ceria-Engineered Nanomaterial Distribution In, And Clearance From, Blood: Size Matters, Mo Dan, Peng Wu, Eric A. Grulke, Uschi M. Graham, Jason M. Unrine, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

AIMS: Characterize different sized ceria-engineered nanomaterial (ENM) distribution in, and clearance from, blood (compared to the cerium ion) following intravenous infusion.

MATERIALS & METHODS: Cerium (Ce) was quantified in whole blood, serum and clot (the formed elements) up to 720 h.

RESULTS: Traditional pharmacokinetic modeling showed best fit for 5 nm ceria ENM and the cerium ion. Ceria ENMs larger than 5 nm were rapidly cleared from blood. After initially declining, whole blood 15 and 30 nm ceria increased (results that have not been well-described by traditional pharmacokinetic modeling). The cerium ion and 5 and 55 nm ceria did not …

Positive Behavior Intervention And Support: An Alternative Approach, Lucy Bridges

Dissertations

The purpose of this study is to examine the effects of PBIS on behavior in relation to the number of office discipline referrals, suspensions, and expulsions. Because of the current school discipline policies, black male students have been overrepresented in the exclusionary practices of office discipline referrals, suspensions, and expulsions. PBIS offers a viable alternative to current school discipline practices.

Use Of Robotics In Spinal Cord Injury: A Case Report., Lori Siedziewski, Roseann C. Schaaf, Julie Mount

Department of Occupational Therapy Faculty Papers

OBJECTIVE: We examined the use of robotics to treat upper-extremity (UE) dysfunction in tetraplegic patients with spinal cord injury (SCI).

METHOD: a 51-yr-old man with incomplete SCI participated in an occupational therapy program that combined traditional occupational therapy with Reo Go®, a comprehensive therapy platform that includes a robotic guide featuring a telescopic arm to enable high repetitions of functionally relevant UE exercises.

RESULTS: The participant demonstrated measurable improvements in active range of motion, muscle strength as measured through manual muscle testing, perceived right UE function, and self-care performance as measured by the FIM™.

CONCLUSION: The findings from this case …

Sexual Dimorphism In Periapical Inflammation And Bone Loss From Map Kinase Phosphatase-1 Deficient Mice, Justin Mcabee

MUSC Theses and Dissertations

Introduction: Mitogen Activating Protein (MAPK) kinase phosphatase-1 (MKP-1) has been shown to be a key negative regulator of the MAP kinase pathways of the innate immune system. The impact of MKP-1 in an endodontic model has yet to be studied. Thus, the purpose of this study was to determine the role of MKP-1 in a bacterial-driven model of pathological endodontic bone loss. Methods: Pulps were exposed in both lower 1st molars of 10-week old Dusp-1+1+IMKP-1 +1+ and Dusp-1-1-IMKP-1-1- mice and left open to the oral environment for either 3 or 8 weeks. At sacrifice, mandibles were harvested and scanned by …

The Female And Male Adolescent Breast, Donald E. Greydanus, Stephanie Stockburger, Hatim A. Omar, Colleen B. Dodich

Pediatrics Faculty Publications

The breast is an important organ system for the adolescent female and occasionally for the adolescent male as well. This chapter reviews basic principles of breast concerns and disorders including congenital anomalies, asymmetric breast development, underdeveloped breasts, virginal hypertrophy, breast masses, mastaglia, galactorrhea, gynecomastia in males, and others. Clinicians should be attuned to issues and concerns for this important structure in adolescents.

Using An Established Telehealth Model To Train Urban Primary Care Providers On Hypertension Management, Christopher Masi, Tamara Hamlish, Andrew Davis, Kristine Bordenave, Stephen Brown, Brenda Perea, Glen Aduana, Marcus Wolfe, George Bakris, Daniel Johnson

Project ECHO Bibliography

The objective of this study was to determine whether a videoconference-based telehealth network can increase hypertension management knowledge and self-assessed competency among primary care providers (PCPs) working in urban Federally Qualified Health Centers (FQHCs). We created a telehealth network among 6 urban FQHCs and our institution to support a 12-session educational program designed to teach state-of-the-art hypertension management. Each 1-hour session included a brief lecture by a university-based hypertension specialist, case presentations by PCPs, and interactive discussions among the specialist and PCPs. Twelve PCPs (9 intervention and 3 controls) were surveyed at baseline and immediately following the curriculum. The mean …

Depression, Anxiety, And Symptom Profiles Among Female And Male Victims Of Sexual Violence, Ekta Choudhary, Merideth Smith, Robert M. Bossarte

Faculty & Staff Scholarship

No abstract provided.

Age Before Stage: Insulin Resistance Rises Before The Onset Of Puberty: A 9-Year Longitudinal Study (Earlybird 26)., An Jeffery, Bs Metcalf, J Hosking, Aj Streeter, Ld Voss, Tj Wilkin

Peninsula Medical School

OBJECTIVE: Insulin resistance (IR) is associated with diabetes. IR is higher during puberty in both sexes, with some studies showing the increase to be independent of changes in adiposity. Few longitudinal studies have reported on children, and it remains unclear when the rise in IR that is often attributed to puberty really begins. We sought to establish from longitudinal data its relationship to pubertal onset, and interactions with age, sex, adiposity, and IGF-1. RESEARCH DESIGN AND METHODS: The EarlyBird Diabetes study is a longitudinal prospective cohort study of healthy children aged 5-14 years. Homeostasis model assessment (HOMA-IR), skinfolds (SSF), adiposity …

Effects Of Two Contrast Training Programs On Jump Performance In Rugby Union Players During A Competition Phase, C K Argus, N D Gill, J W Keogh, Michael Mcguigan, W G Hopkins

Research outputs 2012

Purpose: There is little literature comparing contrast training programs typically performed by team-sport athletes within a competitive phase. We compared the effects of two contrast training programs on a range of measures in high-level rugby union players during the competition season. Methods: The programs consisted of a higher volume-load (strength-power) or lower volume-load (speed-power) resistance training; each included a tapering of loading (higher force early in the week, higher velocity later in the week) and was performed twice a week for 4 wk. Eighteen players were assessed for peak power during a bodyweight countermovement jump (BWCMJ), bodyweight squat jump (BWSJ), …

Chronic Low Back Pain Is Associated With Reduced Vertebral Bone Mineral Measures In Community-Dwelling Adults, Andrew Briggs, Leon Straker, Angus Burnett, John Wark

Research outputs 2012

Background: Chronic low back pain (CLBP) experienced in middle-age may have important implications for vertebral bone health, although this issue has not been investigated as a primary aim previously. This study investigated the associations between CLBP and dual energy X-ray absorptiometry (DXA)-derived vertebral bone mineral measures acquired from postero-anterior and lateral-projections, among community-dwelling, middle-aged adults. Methods. Twenty-nine adults with CLBP (11 male, 18 female) and 42 adults with no history of LBP in the preceding year (17 male, 25 female) were evaluated. Self-reported demographic and clinical data were collected via questionnaires. Areal bone mineral density (aBMD) was measured in the …

Drug Education In Victorian Schools (Devs): The Study Protocol For A Harm Reduction Focused School Drug Education Trial, Richard Midford, Helen Cahill, David Foxcroft, Leanne Lester, Lynne Venning, Robyn Ramsden, Michelle Pose

Research outputs 2012

Background: This study seeks to extend earlier Australian school drug education research by developing and measuring the effectiveness of a comprehensive, evidence-based, harm reduction focused school drug education program for junior secondary students aged 13 to 15 years. The intervention draws on the recent literature as to the common elements in effective school curriculum. It seeks to incorporate the social influence of parents through home activities. It also emphasises the use of appropriate pedagogy in the delivery of classroom lessons. Methods/Design. A cluster randomised school drug education trial will be conducted with 1746 junior high school students in 21 Victorian …

Adjusting For Under-Identification Of Aboriginal And/Or Torres Strait Islander Births In Time Series Produced From Birth Records: Using Record Linkage Of Survey Data And Administrative Data Sources, D Lawrence, D Christensen, F Mitrou, Glenn Draper, G Davis, S Mckeown, Daniel Mcaullay, G Pearson, S R Zubrick

Research outputs 2012

Background: Statistical time series derived from administrative data sets form key indicators in measuring progress in addressing disadvantage in Aboriginal and Torres Strait Islander populations in Australia. However, inconsistencies in the reporting of Indigenous status can cause difficulties in producing reliable indicators. External data sources, such as survey data, provide a means of assessing the consistency of administrative data and may be used to adjust statistics based on administrative data sources. Methods. We used record linkage between a large-scale survey (the Western Australian Aboriginal Child Health Survey), and two administrative data sources (the Western Australia (WA) Register of Births and …

Prolonged Sedentary Time And Physical Activity In Workplace And Non-Work Contexts: A Cross-Sectional Study Of Office, Customer Service And Call Centre Employees, A A Thorp, G N Healy, E Winkler, B K Clark, P A Gardiner, N Owen, David Dunstan

Research outputs 2012

Background: To examine sedentary time, prolonged sedentary bouts and physical activity in Australian employees from different workplace settings, within work and non-work contexts.Methods: A convenience sample of 193 employees working in offices (131), call centres (36) and customer service (26) was recruited. Actigraph GT1M accelerometers were used to derive percentages of time spent sedentary (<100 counts per>minute; cpm), in prolonged sedentary bouts (≥20 minutes or ≥30 minutes), light-intensity activity (100-1951 cpm) and moderate-to-vigorous physical activity (MVPA; ≥1952 cpm). Using mixed models adjusted for confounders, these were compared for: work days versus non-work days; work hours versus non-work hours (work days only); …

Intense Physical Activity Is Associated With Cognitive Performance In The Elderly, Belinda Brown, Jeremiah Peiffer, Hamid Sohrabi, Alinda Mondal, Veer Bala Gupta, Stephanie Rainey-Smith, Kevin Taddei, S Burnham, K Ellis, C Szoeke, C L Masters, D Ames, C Rowe, Ralph Martins

Research outputs 2012

Numerous studies have reported positive impacts of physical activity on cognitive function. However, the majority of these studies have utilised physical activity questionnaires or surveys, thus results may have been influenced by reporting biases. Through the objective measurement of routine levels of physical activity via actigraphy, we report a significant association between intensity, but not volume, of physical activity and cognitive functioning. A cohort of 217 participants (aged 60-89 years) wore an actigraphy unit for 7 consecutive days and underwent comprehensive neuropsychological assessment. The cohort was stratified into tertiles based on physical activity intensity. Compared with individuals in the lowest …

Maternal Work Hours In Early To Middle Childhood Link To Later Adolescent Diet Quality, Jianghong Li, Therese O'Sullivan, Sarah Johnson, Fiona Stanley, Wendy H. Oddy

Research outputs 2012

Objective: Previous studies on maternal work hours and child diet quality have reported conflicting findings possibly due to differences in study design, lack of a comprehensive measure of diet quality and differing ages of the children under investigation. The present study aimed to prospectively examine the impact of parental work hours from age 1 year to age 14 years on adolescent diet quality.

Design: Multivariate linear regression models were used to examine independent associations between parents' work hours at each follow-up and across 14 years and adolescent diet quality at age 14 years. A diet quality index was based on …

Altered Expression Of Alzheimer's Disease-Related Proteins In Male Hypogonadal Mice, Eleanor S. Drummond, Ralph Martins, D J Handelsman, A R Harvey

Research outputs 2012

Age-related depletion of estrogens and androgens is associated with an increase in Alzheimer's disease (AD) brain pathology and diminished cognitive function. Here we investigated AD-associated molecular and cellular changes in brains of aged hypogonadal (hpg) male and female mice. hpg Mice have a spontaneous, inactivating genetic mutation in the GnRH gene resulting in lifelong deficiency of gonadotropins and gonadal sex hormones. Western blot analysis revealed low levels of amyloid precursor protein and high levels of presenilin 1, amyloid precursor protein C-terminal fragment, and β-amyloid 42 in brains of aged male, but not female, hpg mice. Changes were confined to the …

Clinical And Biomarker Changes In Dominantly Inherited Alzheimer's Disease, R J Bateman, C Xiong, T L Benzinger, A M Fagan, A Goate, N C Fox, D S Marcus, N J Cairns, X Xie, T M Blazey, D M Holtzman, A Santacruz, V Buckles, A Oliver, K Moulder, P M Aisen, B Ghetti, W M Klunk, E Mcdade, Ralph Martins, C M Masters, R Mayeux, J M Ringman, M M Rossor, P M Schofield, R M Sperling, S Salloway, J M Morris

Research outputs 2012

Background: The order and magnitude of pathologic processes in Alzheimer's disease are not well understood, partly because the disease develops over many years. Autosomal dominant Alzheimer's disease has a predictable age at onset and provides an opportunity to determine the sequence and magnitude of pathologic changes that culminate in symptomatic disease.

Methods: In this prospective, longitudinal study, we analyzed data from 128 participants who underwent baseline clinical and cognitive assessments, brain imaging, and cerebrospinal fluid (CSF) and blood tests. We used the participant's age at baseline assessment and the parent's age at the onset of symptoms of Alzheimer's disease to …

Early Versus Delayed Decompression For Traumatic Cervical Spinal Cord Injury: Results Of The Surgical Timing In Acute Spinal Cord Injury Study (Stascis)., Michael G Fehlings, Alex R. Vaccaro, Jefferson R Wilson, Anoushka Singh, David W Cadotte, James Harrop, Bizhan Aarabi, Christopher Shaffrey, Marcel Dvorak, Charles Fisher, Paul Arnold, Eric M Massicotte, Stephen Lewis, Raja Rampersaud

Department of Orthopaedic Surgery Faculty Papers

BACKGROUND: There is convincing preclinical evidence that early decompression in the setting of spinal cord injury (SCI) improves neurologic outcomes. However, the effect of early surgical decompression in patients with acute SCI remains uncertain. Our objective was to evaluate the relative effectiveness of early (injury) versus late (≥ 24 hours after injury) decompressive surgery after traumatic cervical SCI.

METHODS: We performed a multicenter, international, prospective cohort study (Surgical Timing In Acute Spinal Cord Injury Study: STASCIS) in adults aged 16-80 with cervical SCI. Enrolment occurred between 2002 and 2009 at 6 North American centers. The primary outcome was ordinal change …

Absence Of Altered Expression Of Optineurin In Primary Open Angle Glaucoma Patients., Khaled K Abu-Amero, Taif Anwar Azad, George L Spaeth, Jonathan Myers, L Jay Katz, Marlene Moster, Thomas M Bosley

Wills Eye Hospital Papers

PURPOSE: To investigate the expression level of the optineurin gene (OPTN) in the blood of primary open angle glaucoma (POAG) patients to determine if altered expression is playing a role in primary open angle glaucoma systemically.

METHODS: Patients (n=47) were eligible for inclusion if they met standard clinical criteria for POAG, including age greater than 40 years, intraocular pressure ≥21 mmHg in at least one eye before treatment, normal-appearing anterior chamber angles bilaterally on gonioscopy, and optic nerve injury characteristic of POAG. Control subjects (n=27) were recruited who were free from glaucoma by examination. DNA from patient was sequenced to …