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Real-World Comparative Effectiveness Of Tocilizumab Monotherapy Vs. Tumor Necrosis Factor Inhibitors With Methotrexate In Patients With Rheumatoid Arthritis, Leslie R. Harrold, George W. Reed, Jennie Best, Steve Zlotnick, Joel M. Kremer Dec 2018

Real-World Comparative Effectiveness Of Tocilizumab Monotherapy Vs. Tumor Necrosis Factor Inhibitors With Methotrexate In Patients With Rheumatoid Arthritis, Leslie R. Harrold, George W. Reed, Jennie Best, Steve Zlotnick, Joel M. Kremer

Open Access Articles

INTRODUCTION: Controlled clinical studies have shown that the efficacy of tocilizumab (TCZ) monotherapy is superior to that of tumor necrosis factor inhibitor (TNFi) monotherapy and comparable to that of TCZ plus methotrexate (MTX) for the treatment of rheumatoid arthritis (RA). This study compared the real-world effectiveness of TCZ monotherapy vs. TNFis plus MTX in US patients with RA.

METHODS: TCZ-naive patients from the Corrona RA registry with prior exposure to > /= 1 TNFi who initiated TCZ monotherapy or TNFi + MTX were included. Outcomes included mean change in Clinical Disease Activity Index (CDAI), achievement of low disease activity (LDA; CDAI < /= 10), achievement of modified American College of Rheumatology (mACR) 20/50 responses, and mean change in modified Health Assessment Questionnaire (mHAQ) at 6 months. Patients initiating TNFi + MTX were grouped by MTX dose ( < /= 10 mg; > 10 to ...


Magnitude And Impact Of Multiple Chronic Conditions With Advancing Age In Older Adults Hospitalized With Acute Myocardial Infarction, Mayra Tisminetzky, Hoa L. Nguyen, Jerry H. Gurwitz, David D. Mcmanus, Joel M. Gore, Sonal Singh, Jorge L. Yarzebski, Robert J. Goldberg Dec 2018

Magnitude And Impact Of Multiple Chronic Conditions With Advancing Age In Older Adults Hospitalized With Acute Myocardial Infarction, Mayra Tisminetzky, Hoa L. Nguyen, Jerry H. Gurwitz, David D. Mcmanus, Joel M. Gore, Sonal Singh, Jorge L. Yarzebski, Robert J. Goldberg

Open Access Articles

BACKGROUND: To examine age-specific differences in the frequency and impact of cardiac and non-cardiac conditions among patients aged 65years and older hospitalized with acute myocardial infarction (AMI).

METHODS: Study population consisted of 3863 adults hospitalized with AMI at 11 medical centers in central Massachusetts on a biennial basis between 2001 and 2011. The presence of 11 chronic conditions (five cardiac and six non-cardiac) was based on the review of hospital medical records.

RESULTS: Participants' median age was 79years, 49% were men, and had an average of three chronic conditions (average of cardiac conditions: 2.6 and average of non-cardiac conditions ...


Robust Genome Editing With Short Single-Stranded And Long, Partially Single-Stranded Dna Donors In Caenorhabditis Elegans, Gregoriy A. Dokshin, Krishna S. Ghanta, Katherine M. Piscopo, Craig C. Mello Nov 2018

Robust Genome Editing With Short Single-Stranded And Long, Partially Single-Stranded Dna Donors In Caenorhabditis Elegans, Gregoriy A. Dokshin, Krishna S. Ghanta, Katherine M. Piscopo, Craig C. Mello

Open Access Articles

CRISPR-based genome editing using ribonucleoprotein complexes and synthetic single-stranded oligodeoxynucleotide (ssODN) donors can be highly effective. However, reproducibility can vary, and precise, targeted integration of longer constructs-such as green fluorescent protein tags remains challenging in many systems. Here, we describe a streamlined and optimized editing protocol for the nematode Caenorhabditis elegans We demonstrate its efficacy, flexibility, and cost-effectiveness by affinity-tagging 14 Argonaute proteins in C. elegans using ssODN donors. In addition, we describe a novel PCR-based, partially single-stranded, "hybrid" donor design that yields high efficiency editing with large (kilobase-scale) constructs. We use these hybrid donors to introduce fluorescent protein tags ...


Deaf And Hard-Of-Hearing Learners In Emergency Medicine, Lisa M. Meeks, Alina Engelman, Alicia Booth, Michael Argenyi Nov 2018

Deaf And Hard-Of-Hearing Learners In Emergency Medicine, Lisa M. Meeks, Alina Engelman, Alicia Booth, Michael Argenyi

Open Access Articles

Approximately 23% of Americans over age 12 have some level of hearing loss.1 Emergency departments can reduce healthcare barriers for deaf and hard-of-hearing (DHoH) patients through improved patient-physician communication. DHoH students, once they become physicians, may provide one mechanism for reducing existing healthcare disparities and communication barriers for DHoH patients, and may be more adept with patients facing other communication barriers. A renewed interest in disability access and a commitment to social justice has increased efforts toward the inclusion of individuals with disabilities in medical education and training. Despite this increased interest and a growing number of DHoH students ...


Development And Validation Of A Weight Literacy Scale In English And Spanish, Monica L. Wang, Tariana V. Little, Christine F. Frisard, Amy Borg, Stephenie C. Lemon, Milagros C. Rosal Oct 2018

Development And Validation Of A Weight Literacy Scale In English And Spanish, Monica L. Wang, Tariana V. Little, Christine F. Frisard, Amy Borg, Stephenie C. Lemon, Milagros C. Rosal

Open Access Articles

OBJECTIVES: To develop and validate a Weight Literacy Scale in English and Spanish for adults.

METHODS: The two-phase study utilized quantitative and qualitative methods. Phase 1 of the study consisted of developing an initial survey (English and Spanish versions) assessing weight literacy based on a review of the literature; conducting semi-structured interviews with content experts (N = 9) to refine survey items; and conducting in-person cognitive interviews with 20 study participants (N = 10 English-speaking and N = 10 Spanish-speaking adults) for survey pre-testing. Survey items were modified based on Phase 1 findings. Phase 2 consisted of a psychometric study of the Weight ...


Comparison Of Prescribing Practices For Older Adults Treated By Female Versus Male Physicians: A Retrospective Cohort Study, Paula A. Rochon, Jerry H. Gurwitz Oct 2018

Comparison Of Prescribing Practices For Older Adults Treated By Female Versus Male Physicians: A Retrospective Cohort Study, Paula A. Rochon, Jerry H. Gurwitz

Open Access Articles

IMPORTANCE: Subtle but important differences have been described in the way that male and female physicians care for their patients, with some evidence suggesting women are more likely to adhere to best practice recommendations.

OBJECTIVE: To determine if male and female physicians differ in their prescribing practices as measured by the initiation of lower-than-recommended dose cholinesterase inhibitor (ChEI) drug therapy for dementia management.

DESIGN, SETTING, AND PARTICIPANTS: All community-dwelling Ontario residents aged 66 years and older with dementia and newly dispensed an oral ChEI drug (donepezil, galantamine, or rivastigmine) between April 1, 2010 and June 30, 2016 were included.

MAIN ...


Generation And Characterization Of Monoclonal Antibodies That Recognize Human And Murine Supervillin Protein Isoforms, Tara C. Smith, Richard G. Saul, Elisabeth R. Barton, Elizabeth J. Luna Oct 2018

Generation And Characterization Of Monoclonal Antibodies That Recognize Human And Murine Supervillin Protein Isoforms, Tara C. Smith, Richard G. Saul, Elisabeth R. Barton, Elizabeth J. Luna

Open Access Articles

Supervillin isoforms have been implicated in cell proliferation, actin filament-based motile processes, vesicle trafficking, and signal transduction. However, an understanding of the roles of these proteins in cancer metastasis and physiological processes has been limited by the difficulty of obtaining specific antibodies against these highly conserved membrane-associated proteins. To facilitate research into the biological functions of supervillin, monoclonal antibodies were generated against the bacterially expressed human supervillin N-terminus. Two chimeric monoclonal antibodies with rabbit Fc domains (clones 1E2/CPTC-SVIL-1; 4A8/CPTC-SVIL-2) and two mouse monoclonal antibodies (clones 5A8/CPTC-SVIL-3; 5G3/CPTC-SVIL-4) were characterized with respect to their binding sites, affinities ...


Substantial Increase In Compliance With Saturated Fatty Acid Intake Recommendations After One Year Following The American Heart Association Diet, Miaomiao Zhao, David E. Chiriboga, Barbara C. Olendzki, Bin Xie, Yawen Li, Lisa Jo Mcgonigal, Ana Maldonado-Contreras, Yunsheng Ma Oct 2018

Substantial Increase In Compliance With Saturated Fatty Acid Intake Recommendations After One Year Following The American Heart Association Diet, Miaomiao Zhao, David E. Chiriboga, Barbara C. Olendzki, Bin Xie, Yawen Li, Lisa Jo Mcgonigal, Ana Maldonado-Contreras, Yunsheng Ma

Open Access Articles

The American Heart Association (AHA) dietary guidelines recommend 30(-)35% of energy intake (%E) be from total fat, < 7%E from saturated fatty acids (SFA), and < 1%E from trans fatty acid (TFA). This study evaluates the effect of AHA dietary counselling on fat intake. Between 2009 and 2014, 119 obese adults with metabolic syndrome (MetS), (71% women, average 52.5 years of age, and 34.9 kg/m(2) of body mass index), received individual and group counselling on the AHA diet, over a one-year study period. Each participant attended 2 individual sessions (months 1 and 12) and 12 group sessions, at one-month intervals. At baseline and one-year, we collected three random 24-h diet recalls (two weekdays and one weekend day). Fat intake patterns over time were analyzed using paired-t test and linear mixed-effect models. There was significant variation on SFA and TFA intake per meal, being highest at dinner, in restaurants, and on weekends. Over the one-year study period, daily intake of total fat, SFA, and TFA decreased by 27%, 37% and 41%, respectively (p-value < 0.01, each). Correspondingly, the percentage of participants complying with AHA's recommendations, increased from 25.2% to 40.2% for total fat (p-value = 0.02); from 2.5% to 20.7% for SFA (p-value < 0.01); and from 45.4% to 62% for TFA (p-value = 0.02). Additionally, SFA intake for all meal types at home decreased significantly (p-value < 0.05, each). AHA dietary counselling significantly increased the compliance with AHA dietary guidelines, with an eightfold increase in compliance in SFA intake. Nonetheless, ~80% of our participants still exceeded the recommended SFA intake. Substantial efforts are needed to encourage low-SFA and low-TFA food preparation at home, with strong public health policies to decrease SFA and TFA in restaurants and prepared foods.


Tip55, A Splice Isoform Of The Kat5 Acetyltransferase, Is Essential For Developmental Gene Regulation And Organogenesis, Diwash Acharya, Bernadette Nera, Zachary J. Milstone, Lauren Bourke, Yeonsoo Yoon, Jaime A. Rivera-Pérez, Chinmay M. Trivedi, Thomas G. Fazzio Oct 2018

Tip55, A Splice Isoform Of The Kat5 Acetyltransferase, Is Essential For Developmental Gene Regulation And Organogenesis, Diwash Acharya, Bernadette Nera, Zachary J. Milstone, Lauren Bourke, Yeonsoo Yoon, Jaime A. Rivera-Pérez, Chinmay M. Trivedi, Thomas G. Fazzio

Open Access Articles

Regulation of chromatin structure is critical for cell type-specific gene expression. Many chromatin regulatory complexes exist in several different forms, due to alternative splicing and differential incorporation of accessory subunits. However, in vivo studies often utilize mutations that eliminate multiple forms of complexes, preventing assessment of the specific roles of each. Here we examined the developmental roles of the TIP55 isoform of the KAT5 histone acetyltransferase. In contrast to the pre-implantation lethal phenotype of mice lacking all four Kat5 transcripts, mice specifically deficient for Tip55 die around embryonic day 11.5 (E11.5). Prior to developmental arrest, defects in heart ...


Protection Induced By A Francisella Tularensis Subunit Vaccine Delivered By Glucan Particles, Adam O. Whelan, Helen C. Flick-Smith, Jane Homan, Zu T. Shen, Zoe Carpenter, Payam Khoshkenar, Ambily Abraham, Nicola J. Walker, Stuart M. Levitz, Gary R. Ostroff, Petra C. F. Oyston Oct 2018

Protection Induced By A Francisella Tularensis Subunit Vaccine Delivered By Glucan Particles, Adam O. Whelan, Helen C. Flick-Smith, Jane Homan, Zu T. Shen, Zoe Carpenter, Payam Khoshkenar, Ambily Abraham, Nicola J. Walker, Stuart M. Levitz, Gary R. Ostroff, Petra C. F. Oyston

Open Access Articles

Francisella tularensis is an intracellular pathogen causing the disease tularemia, and an organism of concern to biodefence. There is no licensed vaccine available. Subunit approaches have failed to induce protection, which requires both humoral and cellular immune memory responses, and have been hampered by a lack of understanding as to which antigens are immunoprotective. We undertook a preliminary in silico analysis to identify candidate protein antigens. These antigens were then recombinantly expressed and encapsulated into glucan particles (GPs), purified Saccharomyces cerevisiae cell walls composed primarily of beta-1,3-glucans. Immunological profiling in the mouse was used to down-selection to seven lead ...


Extracellular Vesicles In Oral Squamous Carcinoma Carry Oncogenic Mirna Profile And Reprogram Monocytes Via Nf-Kappab Pathway, Fatemeh Momen-Heravi, Shashi Bala Oct 2018

Extracellular Vesicles In Oral Squamous Carcinoma Carry Oncogenic Mirna Profile And Reprogram Monocytes Via Nf-Kappab Pathway, Fatemeh Momen-Heravi, Shashi Bala

Open Access Articles

Extracellular vesicles (EVs) are carriers of different biomacromolecules that participate in cellular signaling and disease pathogenesis. Although it has been shown that EVs can play an active role in cellular communication and different stages of cancer progression, the role of EVs in oral squamous cell carcinoma (OSCC) cancer pathogenesis, especially in the crosstalk of cancer cells with immune cells is unknown. Here, we present a detailed analysis of findings regarding the profile of EVs in OSCC and the role of EVs and associated miRNAs in the crosstalk of malignant cells with monocytes. We demonstrate that EVs are detectable in significantly ...


Adeno-Associated Virus Neutralizing Antibodies In Large Animals And Their Impact On Brain Intraparenchymal Gene Transfer, Dan Wang, Li Zhong, Mengxin Li, Jia Li, Karen Tran, Lingzhi Ren, Ran He, Jun Xie, Richard P. Moser, Cara Fraser, Tim Kuchel, Miguel Sena-Esteves, Terence R. Flotte, Neil Aronin, Guangping Gao Oct 2018

Adeno-Associated Virus Neutralizing Antibodies In Large Animals And Their Impact On Brain Intraparenchymal Gene Transfer, Dan Wang, Li Zhong, Mengxin Li, Jia Li, Karen Tran, Lingzhi Ren, Ran He, Jun Xie, Richard P. Moser, Cara Fraser, Tim Kuchel, Miguel Sena-Esteves, Terence R. Flotte, Neil Aronin, Guangping Gao

Open Access Articles

Pre-existing neutralizing antibody (NAb) against adeno-associated virus (AAV) commonly found in primates is a major host barrier that can severely compromise in vivo gene transfer by AAV vectors. To achieve proof-of-concept success in clinical development of recombinant AAV (rAAV)-based in vivo gene therapy, it is crucial to consider the potential interference of NAb and to enroll serologically compatible study subjects. In this study, we report a large AAV NAb dataset comprising multiple large animal species and AAV serotypes and compare two NAb assays based on in vitro or in vivo transduction inhibition, respectively. Together with previously published AAV seroepidemiology ...


Disrupted Asymmetry Of Inter- And Intra-Hemispheric Functional Connectivity In Patients With Drug-Naive, First-Episode Schizophrenia And Their Unaffected Siblings, Furong Zhu, Feng Liu, Wenbin Guo, Jindong Chen, Qinji Su, Zhikun Zhang, Huabing Li, Xiaoduo Fan, Jingping Zhao Oct 2018

Disrupted Asymmetry Of Inter- And Intra-Hemispheric Functional Connectivity In Patients With Drug-Naive, First-Episode Schizophrenia And Their Unaffected Siblings, Furong Zhu, Feng Liu, Wenbin Guo, Jindong Chen, Qinji Su, Zhikun Zhang, Huabing Li, Xiaoduo Fan, Jingping Zhao

Open Access Articles

BACKGROUND: Lack of normal asymmetry in the brain has been reported in patients with schizophrenia. However, it remains unclear whether disrupted asymmetry originates from inter-hemispheric functional connectivity (FC) and/or intra-hemispheric FC in this patient population.

METHODS: Forty-four patients with drug-naive, first-episode schizophrenia, 42 unaffected siblings, and 44 healthy controls underwent resting-state functional magnetic resonance imaging (fMRI) scan. The parameter of asymmetry (PAS) and support vector machine (SVM) were used to analyze the data. Patients were treated with olanzapine for 8 weeks.

FINDINGS: Compared with healthy controls, patients showed lower PAS scores in the left middle temporal gyrus (MTG)/inferior ...


Use Of Structural Equation Models To Predict Dengue Illness Phenotype, Sangshin Park, Anon Srikiatkhachorn, Siripen Kalayanarooj, Louis Macareo, Sharone Green, Jennifer F. Friedman, Alan L. Rothman Oct 2018

Use Of Structural Equation Models To Predict Dengue Illness Phenotype, Sangshin Park, Anon Srikiatkhachorn, Siripen Kalayanarooj, Louis Macareo, Sharone Green, Jennifer F. Friedman, Alan L. Rothman

Open Access Articles

BACKGROUND: Early recognition of dengue, particularly patients at risk for plasma leakage, is important to clinical management. The objective of this study was to build predictive models for dengue, dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS) using structural equation modelling (SEM), a statistical method that evaluates mechanistic pathways.

METHODS/FINDINGS: We performed SEM using data from 257 Thai children enrolled within 72 h of febrile illness onset, 156 with dengue and 101 with non-dengue febrile illnesses. Models for dengue, DHF, and DSS were developed based on data obtained three and one day(s) prior to fever resolution (fever ...


Interleukin-1 Receptor-Associated Kinase 4 (Irak4) Plays A Dual Role In Myddosome Formation And Toll-Like Receptor Signaling, Dominic De Nardo, Katherine R. Balka, Yamel Cardona Gloria, Vikram R. Rao, Eicke Latz, Seth L. Masters Sep 2018

Interleukin-1 Receptor-Associated Kinase 4 (Irak4) Plays A Dual Role In Myddosome Formation And Toll-Like Receptor Signaling, Dominic De Nardo, Katherine R. Balka, Yamel Cardona Gloria, Vikram R. Rao, Eicke Latz, Seth L. Masters

Open Access Articles

Toll-like receptors (TLRs) form part of the host innate immune system, in which they act as sensors of microbial and endogenous danger signals. Upon TLR activation, the intracellular Toll/interleukin-1 receptor domains of TLR dimers initiate oligomerization of a multiprotein signaling platform comprising myeloid differentiation primary response 88 (MyD88) and members of the interleukin-1 receptor-associated kinase (IRAK) family. Formation of this myddosome complex initiates signal transduction pathways, leading to the activation of transcription factors and the production of inflammatory cytokines. To date, little is known about the assembly and disassembly of the myddosome and about the mechanisms by which these ...


Angiomotins Stimulate Lats Kinase Autophosphorylation And Act As Scaffolds That Promote Hippo Signaling, Sebastian Mana-Capelli, Dannel Mccollum Sep 2018

Angiomotins Stimulate Lats Kinase Autophosphorylation And Act As Scaffolds That Promote Hippo Signaling, Sebastian Mana-Capelli, Dannel Mccollum

Open Access Articles

The Hippo pathway controls cell proliferation, differentiation, and survival by regulating the YAP transcriptional coactivator in response to various stimuli, including the mechanical environment. The major YAP regulators are the LATS1/2 kinases, which phosphorylate and inhibit YAP. LATS1/2 are activated by phosphorylation on a hydrophobic motif (HM) outside the kinase domain by MST1/2 and other kinases. Phosphorylation of the HM motif then triggers autophosphorylation of the kinase in the activation loop (AL) to fully activate the kinase, a process facilitated by MOB1. The angiomotin family of proteins (AMOT, AMOTL1, and AMOTL2) bind LATS1/2 and promote its ...


Modulation Of Cav1.3b L-Type Calcium Channels By M1 Muscarinic Receptors Varies With Cavbeta Subunit Expression, Mandy L. Roberts-Crowley, Ann R. Rittenhouse Sep 2018

Modulation Of Cav1.3b L-Type Calcium Channels By M1 Muscarinic Receptors Varies With Cavbeta Subunit Expression, Mandy L. Roberts-Crowley, Ann R. Rittenhouse

Open Access Articles

OBJECTIVES: We examined whether two G protein-coupled receptors (GPCRs), muscarinic M1 receptors (M1Rs) and dopaminergic D2 receptors (D2Rs), utilize endogenously released fatty acid to inhibit L-type Ca(2+) channels, CaV1.3. HEK-293 cells, stably transfected with M1Rs, were used to transiently transfect D2Rs and CaV1.3b with different CaVbeta-subunits, allowing for whole-cell current measurement from a pure channel population.

RESULTS: M1R activation with Oxotremorine-M inhibited currents from CaV1.3b coexpressed with alpha2delta-1 and a beta1b, beta2a, beta3, or beta4-subunit. Surprisingly, the magnitude of inhibition was less with beta2a than with other CaVbeta-subunits. Normalizing currents revealed kinetic changes after modulation with ...


Co-Dependent Assembly Of Drosophila Pirna Precursor Complexes And Pirna Cluster Heterochromatin, Gen Zhang, Shikui Tu, Tianxiong Yu, Xiao-Ou Zhang, Swapnil S. Parhad, Zhiping Weng, William E. Theurkauf Sep 2018

Co-Dependent Assembly Of Drosophila Pirna Precursor Complexes And Pirna Cluster Heterochromatin, Gen Zhang, Shikui Tu, Tianxiong Yu, Xiao-Ou Zhang, Swapnil S. Parhad, Zhiping Weng, William E. Theurkauf

Open Access Articles

In Drosophila, the piRNAs that guide germline transposon silencing are produced from heterochromatic clusters marked by the HP1 homolog Rhino. We show that Rhino promotes cluster transcript association with UAP56 and the THO complex, forming RNA-protein assemblies that are unique to piRNA precursors. UAP56 and THO are ubiquitous RNA-processing factors, and null alleles of uap56 and the THO subunit gene tho2 are lethal. However, uap56(sz15) and mutations in the THO subunit genes thoc5 and thoc7 are viable but sterile and disrupt piRNA biogenesis. The uap56(sz15) allele reduces UAP56 binding to THO, and the thoc5 and thoc7 mutations disrupt ...


Upregulation Of Hla-E By Dengue And Not Zika Viruses, Elena Drews, Awadalkareem Adam, Phone Htoo, Elizabeth Townsley, Anuja Mathew Sep 2018

Upregulation Of Hla-E By Dengue And Not Zika Viruses, Elena Drews, Awadalkareem Adam, Phone Htoo, Elizabeth Townsley, Anuja Mathew

Open Access Articles

Introduction: The most severe form of dengue virus (DENV) illness, dengue haemorrhagic fever, is characterised by plasma leakage and increased vascular permeability.

Objectives: Given the critical role that endothelial cells play in the pathogenesis of DENV, we wanted to determine whether infection with DENV altered the expression of MHC class I related genes including HLA-E.

Results: In this study, we provide evidence that HLA-E but not MICA/B or HLA-G is upregulated by all four serotypes of DENV in an endothelial cell line human microvascular endothelial cells (HMEC)-1. In contrast, Zika virus (ZIKV), a related flavivirus, where plasma leakage ...


Optical Temperature Sensing With Infrared Excited Upconversion Nanoparticles, Kory Green, Kai Huang, Hai Pan, Gang Han, Shuang Fang Lim Sep 2018

Optical Temperature Sensing With Infrared Excited Upconversion Nanoparticles, Kory Green, Kai Huang, Hai Pan, Gang Han, Shuang Fang Lim

Open Access Articles

Upconversion Nanoparticles (UCNPs) enable direct measurement of the local temperature with high temporal and thermal resolution and sensitivity. Current studies focusing on small animals and cellular systems, based on continuous wave (CW) infrared excitation sources, typically lead to localized thermal heating. However, the effects of upconversion bioimaging at the molecular scale, where higher infrared intensities under a tightly focused excitation beam, coupled with pulsed excitation to provide higher peak powers, is not well understood. We report on the feasibility of 800 and 980 nm excited UCNPs in thermal sensing under pulsed excitation. The UCNPs report temperature ratiometrically with sensitivities in ...


Reduced Incidence And Better Liver Disease Outcomes Among Chronic Hcv Infected Patients Who Consume Cannabis, Adeyinka Adejumo, Oluwole Muyiwa Adegbala, Kelechi Lauretta Adejumo, Terence N. Bukong Sep 2018

Reduced Incidence And Better Liver Disease Outcomes Among Chronic Hcv Infected Patients Who Consume Cannabis, Adeyinka Adejumo, Oluwole Muyiwa Adegbala, Kelechi Lauretta Adejumo, Terence N. Bukong

Open Access Articles

Background and Aim: The effect of cannabis use on chronic liver disease (CLD) from Hepatitis C Virus (HCV) infection, the most common cause of CLD, has been controversial. Here, we investigated the impact of cannabis use on the prevalence of CLD among HCV infected individuals.

Methods: We analyzed hospital discharge records of adults (age > /= 18 years) with a positive HCV diagnosis. We evaluated records from 2007 to 2014 of the Nationwide Inpatient Sample (NIS). We excluded records with other causes of chronic liver diseases (alcohol, hemochromatosis, NAFLD, PBC, HBV, etc.). Of the 188,333 records, we matched cannabis users to ...


The Impact Of Joint Commission International Accreditation On Time Periods In The Operating Room: A Retrospective Observational Study, Takenori Inomata, Ju Mizuno, Masao Iwagami, Shiori Kawasaki, Akie Shimada, Eiichi Inada, Tina Shiang, Atsushi Amano Sep 2018

The Impact Of Joint Commission International Accreditation On Time Periods In The Operating Room: A Retrospective Observational Study, Takenori Inomata, Ju Mizuno, Masao Iwagami, Shiori Kawasaki, Akie Shimada, Eiichi Inada, Tina Shiang, Atsushi Amano

Open Access Articles

The Joint Commission International (JCI) is responsible for upholding standards in healthcare and organizations in compliance receive accreditation. JCI requires quality improvement on patient safety goals, but requirements may prolong the total procedure/surgery time and reduce efficiency. Here, we evaluate the impact of JCI requirements on time periods in the operating room. We included patients who received elective and emergency surgeries under general anesthesia at Juntendo University Hospital between December 2014 and June 2016. Patients were classified as before and after JCI accreditation on December 12, 2015. The primary outcome was total procedure/surgery time. Secondary outcomes include five ...


Yap Drives Cutaneous Squamous Cell Carcinoma Formation And Progression, Zoe Vincent-Mistiaen, Ahmed Elbediwy, Hannah Vanyai, Jennifer L. Cotton, Gordon Stamp, Emma Nye, Bradley Spencer-Dene, Gareth J. Thomas, Junhao Mao, Barry Thompson Sep 2018

Yap Drives Cutaneous Squamous Cell Carcinoma Formation And Progression, Zoe Vincent-Mistiaen, Ahmed Elbediwy, Hannah Vanyai, Jennifer L. Cotton, Gordon Stamp, Emma Nye, Bradley Spencer-Dene, Gareth J. Thomas, Junhao Mao, Barry Thompson

Open Access Articles

Squamous cell carcinoma (SCC) can progress to malignant metastatic cancer, including an aggressive subtype known as spindle cell carcinoma (spSCC). spSCC formation involves epithelial-to-mesenchymal transition (EMT), yet the molecular basis of this event remains unknown. The transcriptional co-activator YAP undergoes recurrent amplification in human SCC and overexpression of YAP drives SCC formation in mice. Here, we show that human spSCC tumours also feature strong nuclear localisation of YAP and overexpression of activated YAP (NLS-YAP-5SA) with Keratin-5 (K5-CreERt) is sufficient to induce rapid formation of both SCC and spSCC in mice. spSCC tumours arise at sites of epithelial scratch wounding, where ...


Defective Cortex Glia Plasma Membrane Structure Underlies Light-Induced Epilepsy In Cpes Mutants, Govind Kunduri, Daniel Turner-Evans, Yutaka Konya, Yoshihiro Izumi, Kunio Nagashima, Stephen Lockett, Joost Holthuis, Takeshi Bamba, Usha Acharya, Jairaj K. Acharya Sep 2018

Defective Cortex Glia Plasma Membrane Structure Underlies Light-Induced Epilepsy In Cpes Mutants, Govind Kunduri, Daniel Turner-Evans, Yutaka Konya, Yoshihiro Izumi, Kunio Nagashima, Stephen Lockett, Joost Holthuis, Takeshi Bamba, Usha Acharya, Jairaj K. Acharya

Open Access Articles

Seizures induced by visual stimulation (photosensitive epilepsy; PSE) represent a common type of epilepsy in humans, but the molecular mechanisms and genetic drivers underlying PSE remain unknown, and no good genetic animal models have been identified as yet. Here, we show an animal model of PSE, in Drosophila, owing to defective cortex glia. The cortex glial membranes are severely compromised in ceramide phosphoethanolamine synthase (cpes)-null mutants and fail to encapsulate the neuronal cell bodies in the Drosophila neuronal cortex. Expression of human sphingomyelin synthase 1, which synthesizes the closely related ceramide phosphocholine (sphingomyelin), rescues the cortex glial abnormalities and ...


Sumo-Targeted Ubiquitin Ligases (Stubls) Reduce The Toxicity And Abnormal Transcriptional Activity Associated With A Mutant, Aggregation-Prone Fragment Of Huntingtin, Kentaro Ohkuni, Nagesh Pasupala, Jennifer Peek, Grace Lauren Holloway, Gloria D. Sclar, Reuben Levy-Myers, Richard E. Baker, Munira A. Basrai, Oliver Kerscher Sep 2018

Sumo-Targeted Ubiquitin Ligases (Stubls) Reduce The Toxicity And Abnormal Transcriptional Activity Associated With A Mutant, Aggregation-Prone Fragment Of Huntingtin, Kentaro Ohkuni, Nagesh Pasupala, Jennifer Peek, Grace Lauren Holloway, Gloria D. Sclar, Reuben Levy-Myers, Richard E. Baker, Munira A. Basrai, Oliver Kerscher

Open Access Articles

Cell viability and gene expression profiles are altered in cellular models of neurodegenerative disorders such as Huntington's Disease (HD). Using the yeast model system, we show that the SUMO-targeted ubiquitin ligase (STUbL) Slx5 reduces the toxicity and abnormal transcriptional activity associated with a mutant, aggregation-prone fragment of huntingtin (Htt), the causative agent of HD. We demonstrate that expression of an aggregation-prone Htt construct with 103 glutamine residues (103Q), but not the non-expanded form (25Q), results in severe growth defects in slx5Delta and slx8Delta cells. Since Slx5 is a nuclear protein and because Htt expression affects gene transcription, we assessed ...


Opposing Roles Of Fancj And Hltf Protect Forks And Restrain Replication During Stress, Min Peng, Ke Cong, Nicholas J. Panzarino, Sumeet Nayak, Jennifer Calvo, Bin Deng, Lihua Julie Zhu, Monika Morocz, Lili Hegedus, Lajos Haracska, Sharon B. Cantor Sep 2018

Opposing Roles Of Fancj And Hltf Protect Forks And Restrain Replication During Stress, Min Peng, Ke Cong, Nicholas J. Panzarino, Sumeet Nayak, Jennifer Calvo, Bin Deng, Lihua Julie Zhu, Monika Morocz, Lili Hegedus, Lajos Haracska, Sharon B. Cantor

Open Access Articles

The DNA helicase FANCJ is mutated in hereditary breast and ovarian cancer and Fanconi anemia (FA). Nevertheless, how loss of FANCJ translates to disease pathogenesis remains unclear. We addressed this question by analyzing proteins associated with replication forks in cells with or without FANCJ. We demonstrate that FANCJ-knockout (FANCJ-KO) cells have alterations in the replisome that are consistent with enhanced replication stress, including an aberrant accumulation of the fork remodeling factor helicase-like transcription factor (HLTF). Correspondingly, HLTF contributes to fork degradation in FANCJ-KO cells. Unexpectedly, the unrestrained DNA synthesis that characterizes HLTF-deficient cells is FANCJ dependent and correlates with S1 ...


Macular Phototoxicity After Corneal Cross-Linking, Paulo Rodolfo Barbisan Tagliari, Marina Goncalves Viturino Monteiro, Fernanda Maria Souto Silveira, Bo Tian, Roberto Damian Pacheco Pinto, Lucas Barasnevicius Quagliato, Mauricio Abujamra Nascimento, Rosane Silvestre De Castro, Carlos Eduardo Arieta Leite Sep 2018

Macular Phototoxicity After Corneal Cross-Linking, Paulo Rodolfo Barbisan Tagliari, Marina Goncalves Viturino Monteiro, Fernanda Maria Souto Silveira, Bo Tian, Roberto Damian Pacheco Pinto, Lucas Barasnevicius Quagliato, Mauricio Abujamra Nascimento, Rosane Silvestre De Castro, Carlos Eduardo Arieta Leite

Open Access Articles

Purpose: To assess potential vascular, structural, and functional changes to the macula in patients with keratoconus that underwent ultraviolet A (UVA)-riboflavin-mediated corneal collagen cross-linking (CXL) therapy.

Patients and methods: Seventeen eyes from 17 patients of age 16 years or older with keratoconus undergoing CXL treatment were studied. The same eye served as its own control (before CXL vs after CXL). Eyes were evaluated in terms of best-corrected visual acuity (BCVA), refractive error, intraocular pressure, Amsler grid, retinography, fluorescein angiography, autofluorescence, and spectral domain optical coherence tomography (SD-OCT) prior to CXL and 7 and 30 days after treatment. Multifocal electroretinography ...


Treatment Of Triple-Negative Breast Cancer Cells With The Canady Cold Plasma Conversion System: Preliminary Results, Xiaoqian Cheng, Warren Rowe, Lawan Ly, Alexey Shashurin, Taisen Zhuang, Shruti Wigh, Giacomo Basadonna, Barry Trink, Michael Keidar, Jerome Canady Sep 2018

Treatment Of Triple-Negative Breast Cancer Cells With The Canady Cold Plasma Conversion System: Preliminary Results, Xiaoqian Cheng, Warren Rowe, Lawan Ly, Alexey Shashurin, Taisen Zhuang, Shruti Wigh, Giacomo Basadonna, Barry Trink, Michael Keidar, Jerome Canady

Open Access Articles

Triple-negative breast cancer is a phenotype of breast cancer where the expression level of estrogen, progesterone and human epidermal growth factor receptor 2 (HER2) receptors are low or absent. It is more frequently diagnosed in younger and premenopausal women, among which African and Hispanic have a higher rate. Cold atmospheric plasma has revealed its promising ant-cancer capacity over the past two decades. In this study, we report the first cold plasma jet delivered by the Canady Cold Plasma Conversion Unit and characterization of its electric and thermal parameters. The unit effectively reduced the viability of triple-negative breast cancer up to ...


Prevalence And Management Of Iron Overload In Pyruvate Kinase Deficiency: Report From The Pyruvate Kinase Deficiency Natural History Study, Eduard J. Van Beers, Peter E. Newburger, Rachael F. Grace Sep 2018

Prevalence And Management Of Iron Overload In Pyruvate Kinase Deficiency: Report From The Pyruvate Kinase Deficiency Natural History Study, Eduard J. Van Beers, Peter E. Newburger, Rachael F. Grace

Open Access Articles

Pyruvate kinase (PK) deficiency is the most common red cell glycolytic enzyme defect causing hereditary non-spherocytic hemolytic anemia. Current treatments are mainly supportive and include red cell transfusions and splenectomy.11 Regular red cell transfusions are known to result in iron overload; however, the prevalence and spectrum of transfusion-independent iron overload in the overall PK deficient population has not been well defined. This analysis describes the prevalence and clinical characteristics of iron overload in patients enrolled in the PK Deficiency Natural History Study (NHS) with a focus on those patients who are not regularly transfused.2


Tolerating The Unwelcome Guest; How The Host Withstands Persistent Mycobacterium Tuberculosis, Andrew J. Olive, Christopher M. Sassetti Sep 2018

Tolerating The Unwelcome Guest; How The Host Withstands Persistent Mycobacterium Tuberculosis, Andrew J. Olive, Christopher M. Sassetti

Open Access Articles

Our understanding of the host response to infections has historically focused on "resistance" mechanisms that directly control pathogen replication. However, both pathogen effectors and antimicrobial immune pathways have the capacity to damage host tissue, and the ability to tolerate these insults can also be critical for host survival. These "tolerance" mechanisms may be equally as important as resistance to prevent disease in the context of a persistent infection, such as tuberculosis, when resistance mechanisms are ineffective and the pathogen persists in the tissue for long periods. Host tolerance encompasses a wide range of strategies, many of which involve regulation of ...