Medicine and Health Sciences Commons^™

Prevention Of Recurrent Affective Episodes Using Extinction Training In The Reconsolidation Window: A Testable Psychotherapeutic Strategy., Robert M Post, Robert Kegan

Psychiatry and Behavioral Sciences Faculty Publications

Stressors may initially precipitate affective episodes, but with sufficient numbers of recurrences, episodes can occur more autonomously. It is postulated the memory engram for these recurrent depressions moves from the conscious representational memory system to the unconscious habit memory system encoded in the striatum. If this were the case, cognitive behavior therapy targeted toward extinction of habit memories could be an effective maneuver for helping reverse the automaticity of affective episode recurrence. Extinction training in the reconsolidation window (which opens about 5 min to 1 h after active memory recall) can revise, reverse, or eliminate the long term memories associated …

Relb Expression Determines The Differential Effects Of Ascorbic Acid In Normal And Cancer Cells, Xiaowei Wei, Yong Xu, Fang Fang Xu, Luksana Chaiswing, David M. Schnell, Teresa Noel, Chi Wang, Jinfei Chen, Daret K. St. Clair, William H. St. Clair

Toxicology and Cancer Biology Faculty Publications

Cancer cells typically experience higher oxidative stress than normal cells, such that elevating pro-oxidant levels can trigger cancer cell death. Although pre-exposure to mild oxidative agents will sensitize cancer cells to radiation, this pre-exposure may also activate the adaptive stress defense system in normal cells. Ascorbic acid is a prototype redox modulator that when infused intravenously appears to kill cancers without injury to normal tissues; however, the mechanisms involved remain elusive. In this study, we show how ascorbic acid kills cancer cells and sensitizes prostate cancer to radiation therapy while also conferring protection upon normal prostate epithelial cells against radiation-induced …

Outpatient Parenteral Antimicrobial Therapy In Pediatric Medicaid Enrollees., Jennifer Goldman, Troy Richardson, Jason G. Newland, Brian R. Lee, Jeffrey S. Gerber, Matt Hall, Matthew Kronman, Adam L. Hersh

Manuscripts, Articles, Book Chapters and Other Papers

Background: Outpatient parenteral antimicrobial therapy (OPAT) is overused in cases where highly bioavailable oral alternatives would be equally effective. However, the scope of OPAT use for children nationwide is poorly understood. Our objective was to characterize OPAT use and clinical outcomes for a large population of pediatric Medicaid enrollees treated with OPAT.

Methods: We analyzed the Truven MarketScan Medicaid claims database between 2009 and 2012. An OPAT episode was identified by capturing children with claims data indicating home infusion therapy for an intravenous antimicrobial. We characterized OPAT use by describing patient demographics, diagnoses, and antimicrobials prescribed. We categorized an antimicrobial …

Longitudinal Cardiovascular Outcomes Of Sleep Disordered Breathing In Children: A Meta-Analysis And Systematic Review., Zarmina Ehsan, Stacey L. Ishman, Thomas R. Kimball, Nanhua Zhang, Yuanshu Zou, Raouf S. Amin

Manuscripts, Articles, Book Chapters and Other Papers

Objectives: The presence of sleep disordered breathing (SDB) is known to impact long-term cardiovascular morbidity in adults; however, the long-term effects in children are poorly understood. We aimed to systematically review and synthesize studies published to date on the long-term effects of SDB in children.

Study Design: Meta-analysis and systematic review using PubMed, CINAHL, Embase, and Scopus (all indexed years).

Methods: We searched for English-language articles containing original human data from prospective studies, with ≥7 participants, in children ≤18 years of age. Data regarding study design, demographics, clinical characteristics, outcomes, level of evidence, and risk of bias were obtained. Articles …

Parvovirus B19 Ns1 Protein Induces Cell Cycle Arrest At G2-Phase By Activating The Atr-Cdc25c-Cdk1 Pathway., Peng Xu, Zhe Zhou, Min Xiong, Wei Zou, Xuefeng Deng, Safder S. Ganaie, Steve Kleiboeker, Jianxin Peng, Kaiyu Liu, Shengqi Wang, Shui Qing Ye, Jianming Qiu

Manuscripts, Articles, Book Chapters and Other Papers

Human parvovirus B19 (B19V) infection of primary human erythroid progenitor cells (EPCs) arrests infected cells at both late S-phase and G2-phase, which contain 4N DNA. B19V infection induces a DNA damage response (DDR) that facilitates viral DNA replication but is dispensable for cell cycle arrest at G2-phase; however, a putative C-terminal transactivation domain (TAD2) within NS1 is responsible for G2-phase arrest. To fully understand the mechanism underlying B19V NS1-induced G2-phase arrest, we established two doxycycline-inducible B19V-permissive UT7/Epo-S1 cell lines that express NS1 or NS1mTAD2, and examined the function of the TAD2 domain during G2-phase arrest. The results confirm that the …

Assessment Of Dietary Intake Of Children With Chronic Kidney Disease., Wun Fung Hui, Aisha Betoko, Jonathan D. Savant, Alison G. Abraham, Larry A. Greenbaum, Bradley A. Warady, Marva M. Moxey-Mims, Susan L. Furth

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: Our aim was to characterize the nutrient intake of children with chronic kidney disease (CKD) relative to recommended intake levels.

METHODS: We conducted a cross-sectional study of dietary intake assessed by Food Frequency Questionnaire (FFQ) in The North American Chronic Kidney Disease in Children (CKiD) prospective cohort study. Nutrient intake was analyzed to estimate the daily consumption levels of various nutrients and compared with national guidelines for intake.

RESULTS: There were 658 FFQs available for analysis; 69.9 % of respondents were boys, with a median age [Interquartile range (IQR)] of 11 years (8-15). Median daily sodium, potassium, and phosphorus …

Nutritional Approaches To Achieve Weight Loss In Nonalcoholic Fatty Liver Disease., Christine C Hsu, Erik Ness, Kris V Kowdley

Articles, Abstracts, and Reports

Nonalcoholic fatty liver disease (NAFLD) can range in spectrum from simple hepatic steatosis to nonalcoholic steatohepatitis (NASH), which is characterized by lipotoxicity, hepatocellular ballooning, and inflammation and can progress to cirrhosis. Weight loss is the cornerstone treatment for NAFLD and NASH. Various randomized controlled trials have shown that weight loss of ≥5-10% leads to significant improvements in hepatic steatosis. Diets high in sodium and fructose have been implicated in the pathogenesis of NAFLD. Although some clinical studies suggest that an isocaloric high-fructose diet does not worsen NAFLD, these clinical studies are often short in duration. More recently, the Dietary Approaches …

Evaluating The Accountable Health Communities Demonstration Project., Laura Gottlieb, Jeffrey D. Colvin, Eric Fleegler, Danielle Hessler, Arvin Garg, Nancy Adler

Manuscripts, Articles, Book Chapters and Other Papers

Despite substantial evidence documenting the social patterning of disease, relatively little information is available on how the health care system can best intervene on social determinants to impact individual and population health. Announced in January 2016, the Centers for Medicare and Medicaid Innovation's (CMMI) Accountable Health Communities (AHC) initiative provides an important opportunity to improve the evidence base around integrated social and medical care delivery. To maximize learning from this large-scale demonstration, comprehensive evaluation efforts should focus on effectiveness and implementation research by supporting local, regional, and national studies across a range of outcomes. Findings from this demonstration could transform …

Substance Use And Treatment Outcomes Among Spanish-Speaking Latino/As From Four Acculturation Types., Kelly Serafini, Dennis C Wendt, India J Ornelas, Suzanne R Doyle, Dennis M Donovan

Articles, Abstracts, and Reports

The purpose of this study was to examine the association of acculturation with substance use treatment outcomes in a sample of treatment-seeking Latino/as (N = 405). The study used data from a multisite randomized controlled trial of a culturally adapted version of Motivational Enhancement Therapy delivered in Spanish. Berry, Kim, Minde, and Mok's (1987) acculturation model was used to divide the sample into 4 types (integrated, assimilated, separated, marginalized), based on Bicultural Involvement Questionnaire scores. One-way analyses of variance, chi-squared tests, and repeated-measures regression were used to examine baseline acculturation, posttreatment outcomes, and follow-up outcomes. All participants were of Latino/a …

Mucopolysaccharidosis Type I Newborn Screening: Best Practices For Diagnosis And Management., Lorne A. Clarke, Andrea M. Atherton, Barbara K. Burton, Debra L. Day-Salvatore, Paige Kaplan, Nancy D. Leslie, C Ronald Ronald Scott, David W. Stockton, Janet A. Thomas, Joseph Muenzer

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.

The Art And Skill Of Delivering Culturally Responsive Trauma-Focused Cognitive Behavioral Therapy In Tanzania And Kenya., Briana Woods-Jaeger, Christine M. Kava, Christopher F. Akiba, Leah Lucid, Shannon Dorsey

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: This study explored the facilitators, barriers, and strategies used to deliver a child mental health evidence-based treatment (EBT), trauma-focused cognitive behavioral therapy (TF-CBT), in a culturally responsive manner. In low- and middle-income countries most individuals with mental health problems do not receive treatment due to a shortage of mental health professionals. One approach to addressing this problem is task-sharing, in which lay counselors are trained to deliver mental health treatment. Combining this approach with a focus on EBT provides a strategy for bridging the mental health treatment gap. However, little is known about how western-developed EBTs are delivered in …

Ethical Concerns When Minors Act As Standardized Patients., Erwin Jiayuan Khoo, Robert Schremmer, Douglas S. Diekema, John Lantos

Manuscripts, Articles, Book Chapters and Other Papers

When minors are asked to assist medical educators by acting as standardized patients (SPs), there is a potential for the minors to be exploited. Minors deserve protection from exploitation. Such protection has been written into regulations governing medical research and into child labor laws. But there are no similar guidelines for minors' work in medical education. This article addresses the question of whether there should be rules. Should minors be required to give their informed consent or assent? Are there certain practices that could cause harm for the children who become SPs? We present a controversial case and ask a …

Osteoporosis Treatment Efficacy For Men: A Systematic Review And Meta-Analysis., Smita Nayak, Susan L Greenspan

Articles, Abstracts, and Reports

OBJECTIVES: To evaluate the efficacy of treatment options to reduce osteoporotic fracture risk in men.

DESIGN: Systematic review and meta-analysis.

SETTING: Randomized clinical trials that evaluated the efficacy of a treatment for osteoporosis or low bone mineral density for adult men and reported fracture outcomes.

PARTICIPANTS: Men.

MEASUREMENTS: PubMed, Embase, and the Cochrane Library databases were searched for relevant studies. Information was extracted from included studies on participant sociodemographic characteristics, number of male participants, treatment evaluated, comparator for evaluated treatment, study duration, and fracture outcomes. Risk of bias of individual studies was assessed using measures recommended by the Cochrane Collaboration. …

High Resolution Time-Course Mapping Of Early Transcriptomic, Molecular And Cellular Phenotypes In Huntington's Disease Cag Knock-In Mice Across Multiple Genetic Backgrounds., Seth A Ament, Jocelynn R Pearl, Andrea Grindeland, Jason St Claire, John C Earls, Marina Kovalenko, Tammy Gillis, Jayalakshmi Mysore, James F Gusella, Jong-Min Lee, Seung Kwak, David Howland, Min Young Lee, David Baxter, Kelsey Scherler, Kai Wang, Donald Geman, Jeffrey B Carroll, Marcy E Macdonald, George Carlson, Vanessa C Wheeler, Nathan D Price, Leroy Hood

Articles, Abstracts, and Reports

Huntington's disease is a dominantly inherited neurodegenerative disease caused by the expansion of a CAG repeat in the HTT gene. In addition to the length of the CAG expansion, factors such as genetic background have been shown to contribute to the age at onset of neurological symptoms. A central challenge in understanding the disease progression that leads from the HD mutation to massive cell death in the striatum is the ability to characterize the subtle and early functional consequences of the CAG expansion longitudinally. We used dense time course sampling between 4 and 20 postnatal weeks to characterize early transcriptomic, …

Rehabilitation Therapy In Older Acute Heart Failure Patients (Rehab-Hf) Trial: Design And Rationale., Gordon R. Reeves, David J. Whellan, Pamela Duncan, Christopher M. O'Connor, Amy M. Pastva, Joel D. Eggebeen, Leigh Ann Hewston, Timothy M. Morgan, Shelby D. Reed, W. Jack Rejeski, Robert J. Mentz, Paul B. Rosenberg, Dalane W. Kitzman

Division of Cardiology Faculty Papers

BACKGROUND: Acute decompensated heart failure (ADHF) is a leading cause of hospitalization in older persons in the United States. Reduced physical function and frailty are major determinants of adverse outcomes in older patients with hospitalized ADHF. However, these are not addressed by current heart failure (HF) management strategies and there has been little study of exercise training in older, frail HF patients with recent ADHF.

HYPOTHESIS: Targeting physical frailty with a multi-domain structured physical rehabilitation intervention will improve physical function and reduce adverse outcomes among older patients experiencing a HF hospitalization.

STUDY DESIGN: REHAB-HF is a multi-center clinical trial in …

Gvhd After Umbilical Cord Blood Transplantation For Acute Leukemia: An Analysis Of Risk Factors And Effect On Outcomes, Y Chen, T Wang, Michael T. Hemmer, A Alousi, J Pidala, Mitchell Cairo, C Cutler

NYMC Faculty Publications

Using the Center for International Blood and Marrow Transplant Research (CIBMTR) registry, we analyzed 1404 umbilical cord bloodtransplantation (UCBT) patients (single (<18 years)=810, double (⩾18 years)=594) with acute leukemia to define the incidence of acuteGvHD (aGvHD) and chronic GvHD (cGvHD), analyze clinical risk factors and investigate outcomes. After single UCBT, 100-day incidence of grade II-IV aGvHD was 39% (95% confidence interval (CI), 36-43%), grade III-IV aGvHD was 18% (95% CI, 15-20%) and 1-year cGvHD was 27% (95% CI, 24-30%). After double UCBT, 100-day incidence of grade II-IV aGvHD was 45% (95% CI, 41-49%), grade III-IV aGvHD was 22% (95% CI, 19-26%) and …

Childhood Obesity: The Role Of The Mental Health Professional, Barry Panzer

NYMC Faculty Publications

This work consists of two major components: understanding the nature of childhood obesity and providing clinical services. Factors responsible for the current epidemic will be outlined, as will the current definition of the disorder. Statistical data regarding the epidemiology of weight disorders in childhood will be provided in order to give a perspective of the problem. Various obesity trajectories and their differential diagnostic and treatment issues will be thoroughly explored. The intervention section intends to help clinicians to evaluate salient factors in assessing the obese child and to identify appropriate goals and treatment methods. The course will provide vital information …

Respiratory Syncytial Virus Hospitalization Risk In The Second Year Of Life By Specific Congenital Heart Disease Diagnoses, Deborah Friedman, J Fryzek, X Jiang, A Bloomfield, C Ambrose, P Wong

NYMC Faculty Publications

Children with hemodynamically significant congenital heart disease (CHD) are at elevated risk of morbidity and mortality due to respiratory syncytial virus (RSV) disease compared to their healthy peers. Previous studies have demonstrated lower RSV hospitalization risk among all children with CHD at 12-23 months of age versus 0-11 months of age. However, RSV hospitalization risk at 12-23 months of age by specific CHD diagnosis has not been characterized. Both case-control and cohort studies were conducted using data from the US National Inpatient Sample from 1997 to 2013 to characterize relative risk of RSV hospitalization among children 12-23 months of age …

Changes In Underlying Determinants Explain Rapid Increases In Child Linear Growth In Alive & Thrive Study Areas Between 2010 And 2014 In Bangladesh And Vietnam, Phuong Hong Nguyen, Derek Headey, Edward A. Frongillo Jr., Lan Mai Tran, Rahul Rawat, Marie T. Ruel, Purnima Menon

Faculty Publications

Background: Child linear growth sometimes improves in both intervention and comparison groups in evaluations of nutrition interventions, possibly because of spillover intervention effects to nonintervention areas or improvements in underlying determinants of nutritional change in both areas.

Objective: We aimed to understand what changes in underlying socioeconomic characteristics and behavioral factors are important in explaining improvements in child linear growth.

Methods: Baseline (2010) and endline (2014) surveys from the Alive & Thrive impact evaluation were used to identify the underlying determinants of height-for-age z scores (HAZs) among children aged 24–48 mo in Bangladesh (n = 4311) and 24–59 mo …

Efficacy And Tolerability Of Adjunctive Brivaracetam In Patients With Prior Antiepileptic Drug Exposure: A Post-Hoc Study., Ali A. Asadi-Pooya, Michael R. Sperling, Steve Chung, Pavel Klein, Anyzeila Diaz, Sami Elmoufti, Jimmy Schiemann, John Whitesides

Department of Neurology Faculty Papers

Brivaracetam (BRV), a selective, high-affinity ligand for synaptic vesicle protein 2A, is a new antiepileptic drug (AED) for adjunctive treatment of focal (partial-onset) seizures in adults with epilepsy. This post-hoc analysis was conducted to explore the efficacy of adjunctive BRV in patients with prior levetiracetam (LEV) exposure and whether changes in efficacy were related to the similar mechanism of action of these two drugs. Data were pooled from three Phase III studies (NCT00490035; NCT00464269; NCT01261325) of adults with focal seizures taking 1-2 AEDs who received placebo or BRV 50-200mg/day without titration over a 12-week treatment period. Patients taking concomitant LEV …

High-Dose Immunosuppressive Therapy And Autologous Hct For Relapsing-Remitting Ms., Richard A Nash, George J Hutton, Michael K Racke, Uday Popat, Steven M Devine, Kaitlyn C Steinmiller, Linda M Griffith, Paolo A Muraro, Harry Openshaw, Peter H Sayre, Olaf Stuve, Douglas L Arnold, Mark H Wener, George E Georges, Annette Wundes, George H Kraft, J D Bowen

Articles, Abstracts, and Reports

OBJECTIVE: To evaluate the safety, efficacy, and durability of multiple sclerosis (MS) disease stabilization after high-dose immunosuppressive therapy (HDIT) and autologous hematopoietic cell transplantation (HCT).

METHODS: High-Dose Immunosuppression and Autologous Transplantation for Multiple Sclerosis (HALT-MS) is a phase II clinical trial of HDIT/HCT for patients with relapsing-remitting (RR) MS who experienced relapses with disability progression (Expanded Disability Status Scale [EDSS] 3.0-5.5) while on MS disease-modifying therapy. The primary endpoint was event-free survival (EFS), defined as survival without death or disease activity from any one of: disability progression, relapse, or new lesions on MRI. Participants were evaluated through 5 years posttransplant. …

A Systematic Study Of Dysregulated Microrna In Type 2 Diabetes Mellitus., Yuqing He, Yuanlin Ding, Biyu Liang, Juanjuan Lin, Taek-Kyun Kim, Haibing Yu, Hanwei Hang, Kai Wang

Articles, Abstracts, and Reports

MicroRNAs (miRNAs) are small noncoding RNAs that modulate the cellular transcriptome at the post-transcriptional level. miRNA plays important roles in different disease manifestation, including type 2 diabetes mellitus (T2DM). Many studies have characterized the changes of miRNAs in T2DM, a complex systematic disease; however, few studies have integrated these findings and explored the functional effects of the dysregulated miRNAs identified. To investigate the involvement of miRNAs in T2DM, we obtained and analyzed all relevant studies published prior to 18 October 2016 from various literature databases. From 59 independent studies that met the inclusion criteria, we identified 158 dysregulated miRNAs in …

Genetic Drivers Of Kidney Defects In The Digeorge Syndrome., Esther Lopez-Rivera, Yangfan P. Liu, Miguel Verbitsky, Blair R. Anderson, Valentina P. Capone, Edgar A. Otto, Zhonghai Yan, Adele Mitrotti, Jeremiah Martino, Nicholas J. Steers, David A. Fasel, Katarina Vukojevic, Rong Deng, Silvia E. Racedo, Qingxue Liu, Max Werth, Rik Westland, Asaf Vivante, Gabriel S. Makar, Monica Bodria, Matthew G. Sampson, Christopher E. Gillies, Virginia Vega-Warner, Mariarosa Maiorana, Donald S. Petrey, Barry Honig, Vladimir J. Lozanovski, Rémi Salomon, Laurence Heidet, Wassila Carpentier, Dominique Gaillard, Alba Carrea, Loreto Gesualdo, Daniele Cusi, Claudia Izzi, Francesco Scolari, Joanna A E Van Wijk, Adela Arapovic, Mirna Saraga-Babic, Marijan Saraga, Nenad Kunac, Ali Samii, Donna M. Mcdonald-Mcginn, Terrence B. Crowley, Elaine H. Zackai, Dorota Drozdz, Monika Miklaszewska, Marcin Tkaczyk, Przemyslaw Sikora, Maria Szczepanska, Malgorzata Mizerska-Wasiak, Grazyna Krzemien, Agnieszka Szmigielska, Marcin Zaniew, John M. Darlow, Prem Puri, David Barton, Emilio Casolari, Susan L. Furth, Bradley A. Warady, Zoran Gucev, Hakon Hakonarson, Hana Flogelova, Velibor Tasic, Anna Latos-Bielenska, Anna Materna-Kiryluk, Landino Allegri, Craig S. Wong, Iain A Drummond, Vivette D'Agati, Akira Imamoto, Jonathan M. Barasch, Friedhelm Hildebrandt, Krzysztof Kiryluk, Richard P. Lifton, Bernice E. Morrow, Cecile Jeanpierre, Virginia E. Papaioannou, Gian Marco Ghiggeri, Ali G. Gharavi, Nicholas Katsanis, Simone Sanna-Cherchi

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: The DiGeorge syndrome, the most common of the microdeletion syndromes, affects multiple organs, including the heart, the nervous system, and the kidney. It is caused by deletions on chromosome 22q11.2; the genetic driver of the kidney defects is unknown.

METHODS: We conducted a genomewide search for structural variants in two cohorts: 2080 patients with congenital kidney and urinary tract anomalies and 22,094 controls. We performed exome and targeted resequencing in samples obtained from 586 additional patients with congenital kidney anomalies. We also carried out functional studies using zebrafish and mice.

RESULTS: We identified heterozygous deletions of 22q11.2 in 1.1% …

Mechanisms Of Therapeutic Resistance In Prostate Cancer, Mary Nakazawa, Channing Paller, Natasha Kyprianou

Urology Faculty Publications

Prostate cancer is the second leading cause of cancer deaths in the USA. The challenge in managing castration-resistant prostate cancer (CRPC) stems not from the lack of therapeutic options but from the limited duration of clinical and survival benefit offered by treatments in this setting due to primary and acquired resistance. The remarkable molecular heterogeneity and tumor adaptability in advanced prostate cancer necessitate optimization of such treatment strategies. While the future of CRPC management will involve newer targeted therapies in deliberately biomarker-selected patients, interventions using current approaches may exhibit improved clinical benefit if employed in the context of optimal sequencing …

Topical Anaesthetics For Pain Control During Repair Of Dermal Laceration., Baraa O. Tayeb, Anthony Eidelman, Cristy L. Eidelman, Ewan D. Mcnicol, Daniel B. Carr

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Topical local anaesthetics provide effective analgesia for patients undergoing numerous superficial procedures, including repair of dermal lacerations. The need for cocaine in topical anaesthetic formulations has been questioned because of concern about adverse effects, thus novel preparations of cocaine-free anaesthetics have been developed. This review was originally published in 2011 and has been updated in 2017.

OBJECTIVES: To assess whether benefits of non-invasive topical anaesthetic application occur at the expense of decreased analgesic efficacy. To compare the efficacy of various single-component or multi-component topical anaesthetic agents for repair of dermal lacerations. To determine the clinical necessity for topical application …

Inhibition Of Cdk8 Mediator Kinase Suppresses Estrogen Dependent Transcription And The Growth Of Estrogen Receptor Positive Breast Cancer, Martina S. Mcdermott, Alexander A. Chumanevich, Chang-Uk Lim, Jiaxin Liang, Mengqian Chen, Serena Altilia, David Oliver, James M. Rae, Michael Shtutman, Hippokratis Kiaris, Balázs Győrffy, Igor Roninson, Eugenia Broude

Faculty Publications

Hormone therapy targeting estrogen receptor (ER) is the principal treatment for ER-positive breast cancers. However, many cancers develop resistance to hormone therapy while retaining ER expression. Identifying new druggable mediators of ER function can help to increase the efficacy of ER-targeting drugs. Cyclin-dependent kinase 8 (CDK8) is a Mediator complex-associated transcriptional regulator with oncogenic activities. Expression of CDK8, its paralog CDK19 and their binding partner Cyclin C are negative prognostic markers in breast cancer. Meta-analysis of transcriptome databases revealed an inverse correlation between CDK8 and ERα expression, suggesting that CDK8 could be functionally associated with ER. We have found that …

Calcium's Role As Nuanced Modulator Of Cellular Physiology In The Brain, Hilaree N. Frazier, Shaniya Maimaiti, Katie L. Anderson, Lawrence D. Brewer, John C. Gant, Nada M. Porter, Olivier Thibault

Pharmacology and Nutritional Sciences Faculty Publications

Neuroscientists studying normal brain aging, spinal cord injury, Alzheimer’s disease (AD) and other neurodegenerative diseases have focused considerable effort on carefully characterizing intracellular perturbations in calcium dynamics or levels. At the cellular level, calcium is known for controlling life and death and orchestrating most events in between. For many years, intracellular calcium has been recognized as an essential ion associated with nearly all cellular functions from cell growth to degeneration. Often the emphasis is on the negative impact of calcium dysregulation and the typical worse-case-scenario leading inevitably to cell death. However, even high amplitude calcium transients, when executed acutely can …

Mechanisms Of Modulation Of Brain Microvascular Endothelial Cells Function By Thrombin., Eugen Brailoiu, Megan M. Shipsky, Guang Yan, Mary E. Abood, G. Cristina Brailoiu

College of Pharmacy Faculty Papers

Brain microvascular endothelial cells are a critical component of the blood-brain barrier. They form a tight monolayer which is essential for maintaining the brain homeostasis. Blood-derived proteases such as thrombin may enter the brain during pathological conditions like trauma, stroke, and inflammation and further disrupts the permeability of the blood-brain barrier, via incompletely characterized mechanisms. We examined the underlying mechanisms evoked by thrombin in rat brain microvascular endothelial cells (RBMVEC). Our results indicate that thrombin, acting on protease-activated receptor 1 (PAR1) increases cytosolic Ca

Quantitative Assessment Of White Matter Injury In Preterm Neonates: Association With Outcomes., Ting Guo, Emma G Duerden, Elysia Adams, Vann Chau, Helen M Branson, M Mallar Chakravarty, Kenneth J Poskitt, Anne Synnes, Ruth E Grunau, Steven P Miller

Brain and Mind Institute Researchers' Publications

OBJECTIVE: To quantitatively assess white matter injury (WMI) volume and location in very preterm neonates, and to examine the association of lesion volume and location with 18-month neurodevelopmental outcomes.

METHODS: Volume and location of WMI was quantified on MRI in 216 neonates (median gestational age 27.9 weeks) who had motor, cognitive, and language assessments at 18 months corrected age (CA). Neonates were scanned at 32.1 postmenstrual weeks (median) and 68 (31.5%) had WMI; of 66 survivors, 58 (87.9%) had MRI and 18-month outcomes. WMI was manually segmented and transformed into a common image space, accounting for intersubject anatomical variability. Probability …

Evaluation Of Treatment-Related Mortality Among Paediatric Cancer Deaths: A Population Based Analysis., Jason D Pole, Paul Gibson, Marie-Chantal Ethier, Tanya Lazor, Donna L Johnston, Carol Portwine, Mariana Silva, Sarah Alexander, Lillian Sung

Paediatrics Publications

BACKGROUND: Objectives were to describe the proportion of deaths due to treatment-related mortality (TRM) and to identify risk factors and probable causes of TRM among paediatric cancer deaths in a population-based cohort.

METHODS: We included children with cancer ⩽18 years diagnosed and treated in Ontario who died between January 2003 and December 2012. Deaths were identified using a provincial registry, the Pediatric Oncology Group of Ontario Networked Information System. Probable causes of TRM were described.

RESULTS: Among the 964 deaths identified, 821 were included. The median age at diagnosis was 6.6 years (range 0-18.8) and 51.8% had at least one …