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Levels And Patterns Of Self-Reported And Objectively-Measured Free-Living Physical Activity Among Prostate Cancer Survivors: A Prospective Cohort Study, Lee Smith, Jung Ae Lee, Junbae Mun, Ratna Pakpahan, Kellie R Imm, Sonya Izadi, Adam S Kibel, Graham A Colditz, Robert L Grubb Iii, Kathleen Y Wolin, Siobhan Sutcliffe, Lin Yang Mar 2019

Levels And Patterns Of Self-Reported And Objectively-Measured Free-Living Physical Activity Among Prostate Cancer Survivors: A Prospective Cohort Study, Lee Smith, Jung Ae Lee, Junbae Mun, Ratna Pakpahan, Kellie R Imm, Sonya Izadi, Adam S Kibel, Graham A Colditz, Robert L Grubb Iii, Kathleen Y Wolin, Siobhan Sutcliffe, Lin Yang

Open Access Publications

BACKGROUND: No prior study has measured or compared self-reported and objectively measured physical activity trajectories in prostate cancer survivors before and after treatment.

METHODS: Clinically localized prostate cancer patients treated with radical prostatectomy were recruited between 2011 and 2014. Of the 350 participants enrolled at the main site, 310 provided self-reported physical activity at baseline before radical prostatectomy, and 5 weeks, 6 months, and 12 months after radical prostatectomy. A subset of participants (n = 81) provided objectively measured physical activity at all study time points by wearing an accelerometer for 7 days each. Changes in activity over time were …


Association Of Blood Concentrations Of Complement Split Product Ic3b And Serum C3 With Systemic Lupus Erythematosus Disease Activity, Alfred H J Kim, Vibeke Strand, Deepali P Sen, Qiang Fu, Nancy L Mathis, Martin J Schmidt, Robin R Bruchas, Nick R Staten, Paul K Olson, Chad M Stiening, John P Atkinson Mar 2019

Association Of Blood Concentrations Of Complement Split Product Ic3b And Serum C3 With Systemic Lupus Erythematosus Disease Activity, Alfred H J Kim, Vibeke Strand, Deepali P Sen, Qiang Fu, Nancy L Mathis, Martin J Schmidt, Robin R Bruchas, Nick R Staten, Paul K Olson, Chad M Stiening, John P Atkinson

Open Access Publications

OBJECTIVE: To examine correlations between blood levels of complement split product iC3b and serum component C3 with clinically meaningful changes in disease activity in patients with systemic lupus erythematosus (SLE).

METHODS: A total of 159 consecutive patients with SLE, diagnosed according to the American College of Rheumatology or Systemic Lupus International Collaborating Clinics classification criteria, were enrolled in CASTLE (Complement Activation Signatures in Systemic Lupus Erythematosus), a prospective observational study. Patients with 1-7 study visits were included in this longitudinal analysis. In addition, 48 healthy volunteers were enrolled to establish a normal reference value for the ratio of blood iC3b …


Genetics Of Group A Streptococci, Kyu Hong Cho, Gary C Port, Michael Caparon Mar 2019

Genetics Of Group A Streptococci, Kyu Hong Cho, Gary C Port, Michael Caparon

Open Access Publications

No abstract provided.


Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, And Exploratory Efficacy Of The Novel Enzyme Replacement Therapy Avalglucosidase Alfa (Neogaa) In Treatment-Naïve And Alglucosidase Alfa-Treated Patients With Late-Onset Pompe Disease: A Phase 1, Open-Label, Multicenter, Multinational, Ascending Dose Study, Loren D M Pena, Alan Pestronk, Et Al Mar 2019

Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, And Exploratory Efficacy Of The Novel Enzyme Replacement Therapy Avalglucosidase Alfa (Neogaa) In Treatment-Naïve And Alglucosidase Alfa-Treated Patients With Late-Onset Pompe Disease: A Phase 1, Open-Label, Multicenter, Multinational, Ascending Dose Study, Loren D M Pena, Alan Pestronk, Et Al

Open Access Publications

This multicenter/multinational, open-label, ascending-dose study (NCT01898364) evaluated safety, tolerability, pharmacokinetics, pharmacodynamics, and exploratory efficacy of repeat-dose avalglucosidase alfa (neoGAA), a second-generation, recombinant acid α-glucosidase replacement therapy, in late-onset Pompe disease (LOPD). Patients ≥18 years, alglucosidase alfa naïve (Naïve) or previously receiving alglucosidase alfa for ≥9 months (Switch), with baseline FVC ≥50% predicted and independently ambulatory, received every-other-week avalglucosidase alfa 5, 10, or 20 mg/kg over 24 weeks. 9/10 Naïve and 12/14 Switch patients completed the study. Avalglucosidase alfa was well-tolerated; no deaths/life-threatening serious adverse events (SAEs). One Naïve patient withdrew for study drug-related SAEs (respiratory distress/chest discomfort). Infusion-associated reactions (IARs) …


Genetic Susceptibility To Alopecia., Jouni Uitto Feb 2019

Genetic Susceptibility To Alopecia., Jouni Uitto

Department of Dermatology and Cutaneous Biology Faculty Papers

No abstract provided.


Saturated Fatty Acid Activates T Cell Inflammation Through A Nicotinamide Nucleotide Transhydrogenase (Nnt)-Dependent Mechanism, Grace Mccambridge, Madhur Agrawal, Alanna Keady, Philip A. Kern, Hatice Hasturk, Barbara S. Nikolajczyk, Leena P. Bharath Feb 2019

Saturated Fatty Acid Activates T Cell Inflammation Through A Nicotinamide Nucleotide Transhydrogenase (Nnt)-Dependent Mechanism, Grace Mccambridge, Madhur Agrawal, Alanna Keady, Philip A. Kern, Hatice Hasturk, Barbara S. Nikolajczyk, Leena P. Bharath

Pharmacology and Nutritional Sciences Faculty Publications

Circulating fatty acids (FAs) increase with obesity and can drive mitochondrial damage and inflammation. Nicotinamide nucleotide transhydrogenase (NNT) is a mitochondrial protein that positively regulates nicotinamide adenine dinucleotide phosphate (NADPH), a key mediator of energy transduction and redox homeostasis. The role that NNT-regulated bioenergetics play in the inflammatory response of immune cells in obesity is untested. Our objective was to determine how free fatty acids (FFAs) regulate inflammation through impacts on mitochondria and redox homeostasis of peripheral blood mononuclear cells (PBMCs). PBMCs from lean subjects were activated with a T cell-specific stimulus in the presence or absence of generally pro-inflammatory …


Transcranial Direct Current Stimulation Of Motor Cortex Enhances Running Performance., Seung-Bo Park, Dong Jun Sung, Bokyung Kim, Sojung Kim, Joung-Kyue Han Feb 2019

Transcranial Direct Current Stimulation Of Motor Cortex Enhances Running Performance., Seung-Bo Park, Dong Jun Sung, Bokyung Kim, Sojung Kim, Joung-Kyue Han

College of Science & Mathematics Departmental Research

Transcranial direct current stimulation (tDCS) is a technique used to modulate neuronal excitability through non-invasive brain stimulation that can enhance exercise performance. We hypothesize that tDCS would improve submaximal running time to exhaustion (TTE) and delay the increase in the rating of perceived exertion (RPE) over time. We also hypothesize that tDCS would not lead to difference in cardiorespiratory responses. We employed a randomized, single-blinded, and counterbalanced design in which 10 trained men participated. After receiving either 20 min of 1.98 mA anodal tDCS applied over the primary motor cortex (M1) or sham-operated control on separate days, participants completed a …


Insulin Resistance And Chronic Kidney Disease Progression, Cardiovascular Events, And Death: Findings From The Chronic Renal Insufficiency Cohort Study, Sarah J Schrauben, Patricia Kao, Et Al Feb 2019

Insulin Resistance And Chronic Kidney Disease Progression, Cardiovascular Events, And Death: Findings From The Chronic Renal Insufficiency Cohort Study, Sarah J Schrauben, Patricia Kao, Et Al

Open Access Publications

BACKGROUND: Insulin resistance contributes to the metabolic syndrome, which is associated with the development of kidney disease. However, it is unclear if insulin resistance independently contributes to an increased risk of chronic kidney disease (CKD) progression or CKD complications. Additionally, predisposing factors responsible for insulin resistance in the absence of diabetes in CKD are not well described. This study aimed to describe factors associated with insulin resistance and characterize the relationship of insulin resistance to CKD progression, cardiovascular events and death among a cohort of non-diabetics with CKD.

METHODS: Data was utilized from Chronic Renal Insufficiency Cohort Study participants without …


A Parent-Led Intervention To Promote Recovery Following Pediatric Injury: Study Protocol For A Randomized Controlled Trial, Meghan L. Marsac, Ginny Sprang, Leila Guller, Kristen L. Kohser, John M. Draus Jr., Nancy Kassam-Adams Feb 2019

A Parent-Led Intervention To Promote Recovery Following Pediatric Injury: Study Protocol For A Randomized Controlled Trial, Meghan L. Marsac, Ginny Sprang, Leila Guller, Kristen L. Kohser, John M. Draus Jr., Nancy Kassam-Adams

Pediatrics Faculty Publications

Background: Injury is one of the most prevalent potentially emotionally traumatic events that children experience and can lead to persistent impaired physical and emotional health. There is a need for interventions that promote full physical and emotional recovery and that can be easily accessed by all injured children. Based on research evidence regarding post-injury recovery, we created the Cellie Coping Kit for Children with Injury intervention to target key mechanisms of action and refined the intervention based on feedback from children, families, and experts in the field. The Cellie Coping Kit intervention is parent-guided and includes a toy (for engagement), …


Plaidoh: A Novel Method For Functional Prediction Of Long Non-Coding Rnas Identifies Cancer-Specific Lncrna Activities, Sarah C Pyfrom, Hong Luo, Jacqueline E Payton Feb 2019

Plaidoh: A Novel Method For Functional Prediction Of Long Non-Coding Rnas Identifies Cancer-Specific Lncrna Activities, Sarah C Pyfrom, Hong Luo, Jacqueline E Payton

Open Access Publications

BACKGROUND: Long non-coding RNAs (lncRNAs) exhibit remarkable cell-type specificity and disease association. LncRNA's functional versatility includes epigenetic modification, nuclear domain organization, transcriptional control, regulation of RNA splicing and translation, and modulation of protein activity. However, most lncRNAs remain uncharacterized due to a shortage of predictive tools available to guide functional experiments.

RESULTS: To address this gap for lymphoma-associated lncRNAs identified in our studies, we developed a new computational method, Predicting LncRNA Activity through Integrative Data-driven 'Omics and Heuristics (PLAIDOH), which has several unique features not found in other methods. PLAIDOH integrates transcriptome, subcellular localization, enhancer landscape, genome architecture, chromatin interaction, …


A Visual Interactive Analytic Tool For Filtering And Summarizing Large Health Data Sets Coded With Hierarchical Terminologies (Viads)., Xia Jing, Matthew Emerson, David Masters, Matthew Brooks, Jacob Buskirk, Nasseef Abukamail, Chang Liu, James J. Cimino, Jay H. Shubrook, Sonsoles De Lacalle, Yuchun Zhou, Vimla L. Patel Feb 2019

A Visual Interactive Analytic Tool For Filtering And Summarizing Large Health Data Sets Coded With Hierarchical Terminologies (Viads)., Xia Jing, Matthew Emerson, David Masters, Matthew Brooks, Jacob Buskirk, Nasseef Abukamail, Chang Liu, James J. Cimino, Jay H. Shubrook, Sonsoles De Lacalle, Yuchun Zhou, Vimla L. Patel

Faculty Publications & Research of the TUC College of Osteopathic Medicine

BACKGROUND: Vast volumes of data, coded through hierarchical terminologies (e.g., International Classification of Diseases, Tenth Revision-Clinical Modification [ICD10-CM], Medical Subject Headings [MeSH]), are generated routinely in electronic health record systems and medical literature databases. Although graphic representations can help to augment human understanding of such data sets, a graph with hundreds or thousands of nodes challenges human comprehension. To improve comprehension, new tools are needed to extract the overviews of such data sets. We aim to develop a visual interactive analytic tool for filtering and summarizing large health data sets coded with hierarchical terminologies (VIADS) as an online, and publicly …


Discovery Of Selective Toxoplasma Gondii Dihydrofolate Reductase Inhibitors For The Treatment Of Toxoplasmosis, Allen T Hopper, Adam Brockman, Andy Wise, Julie Gould, Jennifer Barks, Joshua B Radke, L. David Sibley, Yongmao Zou, Stephen Thomas Feb 2019

Discovery Of Selective Toxoplasma Gondii Dihydrofolate Reductase Inhibitors For The Treatment Of Toxoplasmosis, Allen T Hopper, Adam Brockman, Andy Wise, Julie Gould, Jennifer Barks, Joshua B Radke, L. David Sibley, Yongmao Zou, Stephen Thomas

2010-2019 OA Pubs

A safer treatment for toxoplasmosis would be achieved by improving the selectivity and potency of dihydrofolate reductase (DHFR) inhibitors, such as pyrimethamine (1), for Toxoplasma gondii DHFR ( TgDHFR) relative to human DHFR ( hDHFR). We previously reported on the identification of meta-biphenyl analog 2, designed by in silico modeling of key differences in the binding pocket between TgDHFR and hDHFR. Compound 2 improves TgDHFR selectivity 6.6-fold and potency 16-fold relative to 1. Here, we report on the optimization and structure-activity relationships of this arylpiperazine series leading to the discovery of 5-(4-(3-(2-methoxypyrimidin-5-yl)phenyl)piperazin-1-yl)pyrimidine-2,4-diamine 3. Compound 3 has a TgDHFR IC


Timely Linkage Of Individuals To Substance Use Disorder Treatment: Development, Implementation, And Evaluation Of Findhelpnowky.Org, Terry Lee Bunn, Dana Quesinberry, Tyler Jennings, Amber Kizewski, Heather Jackson, Sarah Mckee, Sarah Eustice Feb 2019

Timely Linkage Of Individuals To Substance Use Disorder Treatment: Development, Implementation, And Evaluation Of Findhelpnowky.Org, Terry Lee Bunn, Dana Quesinberry, Tyler Jennings, Amber Kizewski, Heather Jackson, Sarah Mckee, Sarah Eustice

Kentucky Injury Prevention and Research Center Faculty Publications

Background: Substance use disorders (SUD) have steadily increased over the last two decades. Seeking SUD treatment involves searching SUD treatment facility types (inpatient, outpatient and intensive outpatient, residential and family residential, and detoxification facilities) that offer specialized SUD treatment depending on individual needs and preferences. Referrals to SUD treatment require innovative strategies that rapidly link individuals to SUD treatment when they are at the critical stage of readiness. The aim of this study was to develop, implement, and evaluate a user-friendly SUD treatment facility opening availability website called FindHelpNowKY.org. The objectives of the study were to 1) recruit SUD treatment …


A Comparison Of The Diagnosis Of Gastroparesis In 4 H Pediatric Gastric Emptying Studies Versus 2 H Studies., Sarah T. Edwards, Jose Cocjin, Stephanie B. Theut, Douglas C. Rivard, Ashley K. Sherman, Craig A. Friesen Feb 2019

A Comparison Of The Diagnosis Of Gastroparesis In 4 H Pediatric Gastric Emptying Studies Versus 2 H Studies., Sarah T. Edwards, Jose Cocjin, Stephanie B. Theut, Douglas C. Rivard, Ashley K. Sherman, Craig A. Friesen

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: In adults, there is a consensus for standards to diagnose gastroparesis utilizing a gastric emptying study as the key diagnostic modality but there is no consensus for a standard in pediatrics. Additionally, some cost savings might be achieved if symptoms could be utilized to predict patients with gastroparesis. The aims of the current study were to confirm the sensitivity of a 4 h study in the pediatric population and to assess whether the severity of symptoms were predictive of delayed gastric emptying.

STUDY: This was a single site, two part study. In the first part, results were reviewed for …


Reinterpretation Of The Substrate Specificity Of The Voltage-Sensing Phosphatase During Dimerization., Martin Kruse, Susy C Kohout, Bertil Hille Feb 2019

Reinterpretation Of The Substrate Specificity Of The Voltage-Sensing Phosphatase During Dimerization., Martin Kruse, Susy C Kohout, Bertil Hille

Cooper Medical School of Rowan University Departmental Research

Voltage-sensing phosphatases (VSPs) cleave both 3- and 5-phosphates from inositol phospholipids in response to membrane depolarization. When low concentrations of Ciona intestinalis VSP are expressed in Xenopus laevis oocytes, the 5-phosphatase reaction can be observed during large membrane depolarizations. When higher concentrations are expressed, the 5-phosphatase activity is observed with smaller depolarizations, and the 3-phosphatase activity is revealed with strong depolarization. Here we ask whether this apparent induction of 3-phosphatase activity is attributable to the dimerization that has been reported when VSP is expressed at higher concentrations. Using a simple kinetic model, we show that these enzymatic phenomena can be …


Identification Of Novel Regulatory Genes In Apap Induced Hepatocyte Toxicity By A Genome-Wide Crispr-Cas9 Screen., Katherine Shortt, Daniel P. Heruth, Nini Zhang, Weibin Wu, Shipra Singh, Ding-You Li, Li Qin Zhang, Gerald J. Wyckoff, Lei S Qi, Craig A. Friesen, Shui Qing Ye Feb 2019

Identification Of Novel Regulatory Genes In Apap Induced Hepatocyte Toxicity By A Genome-Wide Crispr-Cas9 Screen., Katherine Shortt, Daniel P. Heruth, Nini Zhang, Weibin Wu, Shipra Singh, Ding-You Li, Li Qin Zhang, Gerald J. Wyckoff, Lei S Qi, Craig A. Friesen, Shui Qing Ye

Manuscripts, Articles, Book Chapters and Other Papers

Acetaminophen (APAP) is a commonly used analgesic responsible for more than half of acute liver failure cases. Identification of previously unknown genetic risk factors would provide mechanistic insights and novel therapeutic targets for APAP-induced liver injury. This study used a genome-wide CRISPR-Cas9 screen to evaluate genes that are protective against, or cause susceptibility to, APAP-induced liver injury. HuH7 human hepatocellular carcinoma cells containing CRISPR-Cas9 gene knockouts were treated with 15 mM APAP for 30 minutes to 4 days. A gene expression profile was developed based on the 1) top screening hits, 2) overlap of expression data from APAP overdose studies, …


Virus-Specific Memory T Cells Populate Tumors And Can Be Repurposed For Tumor Immunotherapy, Pamela C. Rosato, Sathi Wijeyesinghe, J Michael Stolley, Christine E. Nelson, Rachel Davis, Luke S. Manlove, Christopher A. Pennell, Bruce R. Blazar, Clark C. Chen, Melissa A. Geller, Vaiva Vezys, David Masopust Feb 2019

Virus-Specific Memory T Cells Populate Tumors And Can Be Repurposed For Tumor Immunotherapy, Pamela C. Rosato, Sathi Wijeyesinghe, J Michael Stolley, Christine E. Nelson, Rachel Davis, Luke S. Manlove, Christopher A. Pennell, Bruce R. Blazar, Clark C. Chen, Melissa A. Geller, Vaiva Vezys, David Masopust

Faculty Publications

The immunosuppressive tumor microenvironment limits the success of current immunotherapies. The host retains memory T cells specific for previous infections throughout the entire body that are capable of executing potent and immediate immunostimulatory functions. Here we show that virus-specific memory T cells extend their surveillance to mouse and human tumors. Reactivating these antiviral T cells can arrest growth of checkpoint blockade-resistant and poorly immunogenic tumors in mice after injecting adjuvant-free non-replicating viral peptides into tumors. Peptide mimics a viral reinfection event to memory CD8+ T cells, triggering antigen presentation and cytotoxic pathways within the tumor, activating dendritic cells and natural …


Gene Therapy Targeting Sarm1 Blocks Pathological Axon Degeneration In Mice, Stefanie Geisler, Shay X. Huang, Amy Strickland, Ryan A. Doan, Daniel W. Summers, Xianrong Mao, Jiwoong Park, Aaron Diantonio, Jeffrey Milbrandt Feb 2019

Gene Therapy Targeting Sarm1 Blocks Pathological Axon Degeneration In Mice, Stefanie Geisler, Shay X. Huang, Amy Strickland, Ryan A. Doan, Daniel W. Summers, Xianrong Mao, Jiwoong Park, Aaron Diantonio, Jeffrey Milbrandt

Open Access Publications

Axonal degeneration (AxD) following nerve injury, chemotherapy, and in several neurological disorders is an active process driven by SARM1, an injury-activated NADase. Axons of SARM1-null mice exhibit greatly delayed AxD after transection and in models of neurological disease, suggesting that inhibiting SARM1 is a promising strategy to reduce pathological AxD. Unfortunately, no drugs exist to target SARM1. We, therefore, developed SARM1 dominant-negatives that potently block AxD in cellular models of axotomy and neuropathy. To assess efficacy in vivo, we used adeno-associated virus-mediated expression of the most potent SARM1 dominant-negative and nerve transection as a model of severe AxD. While axons …


Assessing The Effect Of Patient To Provider Language Discordance On Depression Screening Utilizing The Patient Health Questionnaire: An Epidemiology Study., Luis A. Murillo, Georgi Alex Grekoff, John C. Sheffield Feb 2019

Assessing The Effect Of Patient To Provider Language Discordance On Depression Screening Utilizing The Patient Health Questionnaire: An Epidemiology Study., Luis A. Murillo, Georgi Alex Grekoff, John C. Sheffield

Reading Hospital Family Medicine Residency

Background: As depression screening becomes a standard in primary care, the question remains of how effective and equitable screening can be implemented to avoid cultural and language-related disparities.

Methods: In this retrospective cohort study, rates of depression screening were compared for 3626 adult patients at a family medicine residency-based health centre in Pennsylvania, USA. The PHQ-2/PHQ-9 modality was verbally administered by nursing staff at the time of patient intake as part of a universal screening initiative. Chi-square analysis was used to determine the univariate associations of performed depression screening with variables of language, ethnicity, gender and number of office visits. …


Gen-1 Immunotherapy For The Treatment Of Ovarian Cancer, Premal H Thaker, Nicholas Borys, Jason Fewell, Khursheed Anwer Feb 2019

Gen-1 Immunotherapy For The Treatment Of Ovarian Cancer, Premal H Thaker, Nicholas Borys, Jason Fewell, Khursheed Anwer

2010-2019 OA Pubs

GEN-1 is a gene-based immunotherapy, comprising a human IL-12 gene expression plasmid and a synthetic plasmid delivery system, delivered intraperitoneally (ip.) to produce local and persistent levels of a pleiotropic immunocytokine, IL-12, at the tumor site in patients with advanced ovarian cancer. The goal of local and persistent IL-12 delivery is to remodel the highly immunosuppressive tumor microenvironment to favor immune stimulation while avoiding serious systemic toxicities, a major limitation of recombinant IL-12 therapy. Safe and sustained local production of IL-12 and related immunocytokines at the tumor site could produce potentially more favorable immunological changes in the tumor microenvironment and …


The History And Future Of Digital Health In The Field Of Behavioral Medicine., Danielle Arigo, Danielle E Jake-Schoffman, Kathleen Wolin, Ellen Beckjord, Eric B Hekler, Sherry L Pagoto Feb 2019

The History And Future Of Digital Health In The Field Of Behavioral Medicine., Danielle Arigo, Danielle E Jake-Schoffman, Kathleen Wolin, Ellen Beckjord, Eric B Hekler, Sherry L Pagoto

College of Science & Mathematics Departmental Research

Since its earliest days, the field of behavioral medicine has leveraged technology to increase the reach and effectiveness of its interventions. Here, we highlight key areas of opportunity and recommend next steps to further advance intervention development, evaluation, and commercialization with a focus on three technologies: mobile applications (apps), social media, and wearable devices. Ultimately, we argue that future of digital health behavioral science research lies in finding ways to advance more robust academic-industry partnerships. These include academics consciously working towards preparing and training the work force of the twenty first century for digital health, actively working towards advancing methods …


Multicentre, Randomised Clinical Trial Of Paediatric Concussion Assessment Of Rest And Exertion (Pedcare): A Study To Determine When To Resume Physical Activities Following Concussion In Children., Andrée-Anne Ledoux, Nicholas J Barrowman, Kathy Boutis, Adrienne Davis, Sarah Reid, Gurinder Sangha, Ken J Farion, Kevin Belanger, Mark S Tremblay, Keith Owen Yeates, Carol Dematteo, Nick Reed, Roger Zemek Feb 2019

Multicentre, Randomised Clinical Trial Of Paediatric Concussion Assessment Of Rest And Exertion (Pedcare): A Study To Determine When To Resume Physical Activities Following Concussion In Children., Andrée-Anne Ledoux, Nicholas J Barrowman, Kathy Boutis, Adrienne Davis, Sarah Reid, Gurinder Sangha, Ken J Farion, Kevin Belanger, Mark S Tremblay, Keith Owen Yeates, Carol Dematteo, Nick Reed, Roger Zemek

Paediatrics Publications

INTRODUCTION:
Rest until symptom-free, followed by a progressive stepwise return to activities, is often prescribed in the management of paediatric concussions. Recent evidence suggests prolonged rest may hinder recovery, and early resumption of physical activity may be associated with more rapid recovery postconcussion. The primary objective is to determine whether the early reintroduction of non-contact physical activity beginning 72 hours postinjury reduces postconcussive symptoms at 2 weeks in children following an acute concussion as compared with a rest until asymptomatic protocol.

METHODS AND ANALYSIS:
This study is a randomised clinical trial across three Canadian academic paediatric emergency departments. A total …


Patterns Of Joint Involvement In Juvenile Idiopathic Arthritis And Prediction Of Disease Course: A Prospective Study With Multilayer Non-Negative Matrix Factorization., Simon W M Eng, Florence A Aeschlimann, Mira Van Veenendaal, Roberta A Berard, Alan M Rosenberg, Quaid Morris, Rae S M Yeung Feb 2019

Patterns Of Joint Involvement In Juvenile Idiopathic Arthritis And Prediction Of Disease Course: A Prospective Study With Multilayer Non-Negative Matrix Factorization., Simon W M Eng, Florence A Aeschlimann, Mira Van Veenendaal, Roberta A Berard, Alan M Rosenberg, Quaid Morris, Rae S M Yeung

Paediatrics Publications

BACKGROUND:
Joint inflammation is the common feature underlying juvenile idiopathic arthritis (JIA). Clinicians recognize patterns of joint involvement currently not part of the International League of Associations for Rheumatology (ILAR) classification. Using unsupervised machine learning, we sought to uncover data-driven joint patterns that predict clinical phenotype and disease trajectories.

METHODS AND FINDINGS:
We analyzed prospectively collected clinical data, including joint involvement using a standard 71-joint homunculus, for 640 discovery patients with newly diagnosed JIA enrolled in a Canada-wide study who were followed serially for five years, treatment-naïve except for nonsteroidal anti-inflammatory drugs (NSAIDs) and diagnosed within one year of symptom …


Dynamic Light Scattering Optical Coherence Tomography To Probe Motion Of Subcellular Scatterers., Nico J J Arezza, Marjan Razani, Michael C Kolios Feb 2019

Dynamic Light Scattering Optical Coherence Tomography To Probe Motion Of Subcellular Scatterers., Nico J J Arezza, Marjan Razani, Michael C Kolios

Medical Biophysics Publications

Optical coherence tomography (OCT) is used to provide anatomical information of biological systems but can also provide functional information by characterizing the motion of intracellular structures. Dynamic light scattering OCT was performed on intact, control MCF-7 breast cancer cells and cells either treated with paclitaxel to induce apoptosis or deprived of nutrients to induce oncosis. Autocorrelations (ACs) of the temporal fluctuations of OCT intensity signals demonstrate a significant decrease in decorrelation time after 24 h in both the paclitaxel-treated and nutrient-deprived cell groups but no significant differences between the two groups. The acquired ACs were then used as input for …


Napoli-1 Phase 3 Study Of Liposomal Irinotecan In Metastatic Pancreatic Cancer: Final Overall Survival Analysis And Characteristics Of Long-Term Survivors, Andrea Wang-Gillam, Richard A Hubner, Jens T Siveke, Daniel D Von Hoff, Bruce Belanger, Floris A De Jong, Beloo Mirakhur, Li-Tzong Chen Feb 2019

Napoli-1 Phase 3 Study Of Liposomal Irinotecan In Metastatic Pancreatic Cancer: Final Overall Survival Analysis And Characteristics Of Long-Term Survivors, Andrea Wang-Gillam, Richard A Hubner, Jens T Siveke, Daniel D Von Hoff, Bruce Belanger, Floris A De Jong, Beloo Mirakhur, Li-Tzong Chen

Open Access Publications

BACKGROUND: Liposomal irinotecan (nal-IRI) plus 5-fluorouracil and leucovorin (5-FU/LV) is approved for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) previously treated with gemcitabine-based therapy. This approval was based on significantly improved median overall survival compared with 5-FU/LV alone (6.1 vs 4.2 months; hazard ratio [HR], 0.67) in the global phase 3 NAPOLI-1 trial. Here, we report the final survival analysis and baseline characteristics associated with long-term survivors (survival of ≥1 year) in the NAPOLI-1 trial.

PATIENTS AND METHODS: Patients with mPDAC were randomised to receive nal-IRI + 5-FU/LV (n = 117), nal-IRI (n = 151), or 5-FU/LV (n = 149) …


White Matter Damage, Neuroinflammation, And Neuronal Integrity In Hand, Aljoharah Alakkas, David B Clifford, Et Al. Feb 2019

White Matter Damage, Neuroinflammation, And Neuronal Integrity In Hand, Aljoharah Alakkas, David B Clifford, Et Al.

2010-2019 OA Pubs

HIV-associated neurocognitive disorders (HANDs) persist even with virologic suppression on combination antiretroviral therapy (cART), and the underlying pathophysiological mechanisms are not well understood. We performed structural magnetic resonance imaging and MR spectroscopy (MRS) in HIV+ individuals without major neurocognitive comorbidities. Study participants were classified as neurocognitively unimpaired (NU), asymptomatic (ANI), mild neurocognitive disorder (MND), or HIV-associated dementia (HAD). Using structural MRI, we measured volumes of cortical and subcortical gray matter and total and abnormal white matter (aWM). Using single-voxel MRS, we estimated metabolites in frontal gray matter (FGM) and frontal white matter (FWM) and basal ganglia (BG) regions. Adjusted odds …


Association Between Reductions Of Number Of Cigarettes Smoked Per Day And Mortality Among Older Adults In The United States, Maki Inoue-Choi, Patricia Hartge, Yikyung Park, Christian C Abnet, Neal D Freedman Feb 2019

Association Between Reductions Of Number Of Cigarettes Smoked Per Day And Mortality Among Older Adults In The United States, Maki Inoue-Choi, Patricia Hartge, Yikyung Park, Christian C Abnet, Neal D Freedman

2010-2019 OA Pubs

Many smokers do not quit but instead reduce the number of cigarettes they smoke per day (CPD) over their lifetime. Yet the associations of such changes in CPD with health risks are unclear. We examined the association of changes in CPD with subsequent death in the period 2004-2011 among 253,947 participants of the National Institutes of Health-AARP Diet and Health Study. Using a questionnaire assessing responders' history of smoking cigarettes, we identified cigarette smokers who quit, decreased, maintained, or increased their CPD between ages 25-29 and 50-59 years. Hazard ratios and 95% confidence intervals were obtained from multivariable adjusted Cox …


Clinical Genome Sequencing In An Unbiased Pediatric Cohort., Isabelle Thiffault, Emily G. Farrow, Lee Zellmer, Courtney D. Berrios, Neil Miller, Margaret Gibson, Raymond Caylor, Janda L. Jenkins, Deb Faller, Sarah E. Soden, Carol J. Saunders Feb 2019

Clinical Genome Sequencing In An Unbiased Pediatric Cohort., Isabelle Thiffault, Emily G. Farrow, Lee Zellmer, Courtney D. Berrios, Neil Miller, Margaret Gibson, Raymond Caylor, Janda L. Jenkins, Deb Faller, Sarah E. Soden, Carol J. Saunders

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE: We report for the first time, the use of clinical genome sequencing (GS) in an unbiased pediatric cohort. We describe the clinical validation, patient metrics, ordering patterns, results, reimbursement, and physician retrieval of results for the first consecutive 80 cases.

METHODS: Clinical GS was performed for both inpatients and outpatients undergoing etiologic evaluations. Results were reported in the electronic medical record. Evidence of report retrieval by clinicians and whether interpretation was concordant with laboratory report was obtained through retrospective chart review.

RESULTS: Twenty definitive diagnoses were made in 19 patients (24%; n = 80). Except for two partial gene …


Characteristics Of Late Fatal Infections After Allogeneic Hematopoietic Cell Transplantation., Maxim Norkin, Bronwen E. Shaw, Ruta Brazauskas, Heather R. Tecca, Helen L. Leather, Juan Gea-Banacloche, Rammurti T. Kamble, Zachariah Defilipp, David A. Jacobsohn, Olle Ringden, Yoshihiro Inamoto, Kimberly A. Kasow, David Buchbinder, Peter Shaw, Peiman Hematti, Raquel Schears, Sherif M. Badawy, Hillard M. Lazarus, Neel Bhatt, Biljana Horn, Saurabh Chhabra, Kristin M. Page, Betty Hamilton, Gerhard C. Hildebrandt, Jean A. Yared, Vaibhav Agrawal, Amer M. Beitinjaneh, Navneet Majhail, Tamila Kindwall-Keller, Richard F. Olsson, Helene Schoemans, Robert Peter Gale, Siddhartha Ganguly, Ibrahim A. Ahmed, Harry C. Schouten, Jane L. Liesveld, Nandita Khera, Amir Steinberg, Ami J. Shah, Melhem Solh, David I. Marks, Witold Rybka, Mahmoud Aljurf, Andrew C. Dietz, Usama Gergis, Biju George, Sachiko Seo, Mary E D Flowers, Minoo Battiwalla, Bipin N. Savani, Marcie L. Riches, John R. Wingard Feb 2019

Characteristics Of Late Fatal Infections After Allogeneic Hematopoietic Cell Transplantation., Maxim Norkin, Bronwen E. Shaw, Ruta Brazauskas, Heather R. Tecca, Helen L. Leather, Juan Gea-Banacloche, Rammurti T. Kamble, Zachariah Defilipp, David A. Jacobsohn, Olle Ringden, Yoshihiro Inamoto, Kimberly A. Kasow, David Buchbinder, Peter Shaw, Peiman Hematti, Raquel Schears, Sherif M. Badawy, Hillard M. Lazarus, Neel Bhatt, Biljana Horn, Saurabh Chhabra, Kristin M. Page, Betty Hamilton, Gerhard C. Hildebrandt, Jean A. Yared, Vaibhav Agrawal, Amer M. Beitinjaneh, Navneet Majhail, Tamila Kindwall-Keller, Richard F. Olsson, Helene Schoemans, Robert Peter Gale, Siddhartha Ganguly, Ibrahim A. Ahmed, Harry C. Schouten, Jane L. Liesveld, Nandita Khera, Amir Steinberg, Ami J. Shah, Melhem Solh, David I. Marks, Witold Rybka, Mahmoud Aljurf, Andrew C. Dietz, Usama Gergis, Biju George, Sachiko Seo, Mary E D Flowers, Minoo Battiwalla, Bipin N. Savani, Marcie L. Riches, John R. Wingard

Manuscripts, Articles, Book Chapters and Other Papers

We analyzed late fatal infections (LFIs) in allogeneic stem cell transplantation (HCT) recipients reported to the Center for International Blood and Marrow Transplant Research. We analyzed the incidence, infection types, and risk factors contributing to LFI in 10,336 adult and 5088 pediatric subjects surviving for ≥2 years after first HCT without relapse. Among 2245 adult and 377 pediatric patients who died, infections were a primary or contributory cause of death in 687 (31%) and 110 (29%), respectively. At 12 years post-HCT, the cumulative incidence of LFIs was 6.4% (95% confidence interval [CI], 5.8% to 7.0%) in adults, compared with 1.8% …


Handoffs From The Operating Room To The Intensive Care Unit After Cardiothoracic Surgery: From The Society Of Thoracic Surgeons Workforce On Critical Care, Subhasis Chatterjee, Jay G Shake, Rakesh C Arora, Daniel T Engelman, Michael S Firstenberg, Charles M Geller, Hitoshi Hirose, Vassyl A Lonchyna, Francis T Lytle, Rita K C Milewski, Rainer G H Moosdorf, Joseph Rabin, Rohan Sanjanwala, Marianne Galati, Glenn J Whitman Feb 2019

Handoffs From The Operating Room To The Intensive Care Unit After Cardiothoracic Surgery: From The Society Of Thoracic Surgeons Workforce On Critical Care, Subhasis Chatterjee, Jay G Shake, Rakesh C Arora, Daniel T Engelman, Michael S Firstenberg, Charles M Geller, Hitoshi Hirose, Vassyl A Lonchyna, Francis T Lytle, Rita K C Milewski, Rainer G H Moosdorf, Joseph Rabin, Rohan Sanjanwala, Marianne Galati, Glenn J Whitman

Library Staff Publications

No abstract provided.