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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Alexandrov, T.; Golyandina, N.; Spirov, A.;

    We present investigation of gene expression profiles by means of singular spectrum analysis (SSA). The biological problem under investigation is the decomposition of bicoid protein profiles of Drosophila melanogaster into the sum of a signal and noise, where the former consists of an exponential-in-distance pattern and is close to constant nonspecific component, or “background.” The signal processing problems addressed are (i) trend extraction from a noisy signal, (ii) batch processing of similar data, and (iii) analytical approximation of the signal components by the sum of exponential and constant-like functions. The proposed methods are evaluated on the given 17 series.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Research Letters in ...arrow_drop_down
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Research Letters in ...arrow_drop_down
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Spangenburg, Espen E.(Department of Kinesiology, University of Maryland, School of Public Health) Pratt, Stephen J. P.(Department of Orthopaedics, University of Maryland, School of Medicine) Wohlers, Lindsay M.(Department of Kinesiology, University of Maryland, School of Public Health) Lovering, Richard M.(Department of Orthopaedics, University of Maryland, School of Medicine);

    Triglyceride storage is altered across various chronic health conditions necessitating various techniques to visualize and quantify lipid droplets (LDs). Here, we describe the utilization of the BODIPY (493/503) dye in skeletal muscle as a means to analyze LDs. We found that the dye was a convenient and simple approach to visualize LDs in both sectioned skeletal muscle and cultured adult single fibers. Furthermore, the dye was effective in both fixed and nonfixed cells, and the staining seemed unaffected by permeabilization. We believe that the use of the BODIPY (493/503) dye is an acceptable alternative and, under certain conditions, a simpler method for visualizing LDs stored within skeletal muscle.

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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Hindawi Publishing C...arrow_drop_down
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Ybe, Joel A.; Clegg, Mary E.; Illingworth, Melissa; Gonzalez, Claire; +1 Authors

    The interaction between HIP family proteins (HIP1 and HIP12/1R) and clathrin is fundamental to endocytosis. We used circular dichroism (CD) to study the stability of an HIP1 subfragment (aa468-530) that is splayed open. CD thermal melts show HIP1 468-530 is only stable at low temperatures, but this HIP1 fragment contains a structural unit that does not melt out even at 83C∘. We then created HIP1 mutants to probe our hypothesis that a short hydrophobic path in the opened region is the binding site for clathrin light chain. We found that the binding of hub/LCb was sensitive to mutating two distantly separated basic residues (K474 and K494). The basic patches marked by K474 and K494 are conserved in HIP12/1R. The lack of conservation in sla2p (S. cerevisiae), HIP1 from D. melanogaster, and HIP1 homolog ZK370.3 from C. elegans implies the binding of HIP1 and HIP1 homologs to clathrin light chain may be different in these organisms.

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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Shirley, Lawrence A.; Aguilar, Laura K.; Aguilar-Cordova, Estuardo; Bloomston, Mark; +1 Authors

    Pancreatic adenocarcinoma is an aggressive disease that has poor outcomes despite maximal traditional therapies. Thus, treatment of this cancer demands innovative strategies to be used in addition to standing therapies in order to provide new avenues of care. Here, we describe the technique of using endoscopic ultrasound in order to directly inject both novel and conventional therapies into pancreatic tumors. We detail the rationale behind this strategy and the many benefits it provides. We then describe our technique in detail, including our experience injecting the AdV-tk adenoviral vector to create an in situ vaccine effect.

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    Authors: Gao, Peisong(Department of Medicine, Johns Hopkins Asthma and Allergy Center, Johns Hopkins University School of Medicine);
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Hindawi Publishing C...arrow_drop_down
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Hindawi Publishing C...arrow_drop_down
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Zhang, Haojian; Li, Shaoguang;

    Chronic myeloid leukemia (CML) is a myeloproliferative disease derived from an abnormal hematopoietic stem cell (HSC) and is consistently associated with the formation of Philadelphia (Ph) chromosome. Tyrosine kinase inhibitors (TKIs) are highly effective in treating chronic phase CML but do not eliminate leukemia stem cells (LSCs), which are believed to be related to disease relapse. Therefore, one major challenge in the current CML research is to understand the biology of LSCs and to identify the molecular difference between LSCs and its normal stem cell counterparts. Comparing the gene expression profiles between LSCs and normal HSCs by DNA microarray assay is a systematic and unbiased approach to address this issue. In this paper, we present a DNA microarray dataset for CML LSCs and normal HSCs to show that the microarray assay will benefit the current and future studies of the biology of CML stem cells.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Hindawi Publishing C...arrow_drop_down
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Hindawi Publishing C...arrow_drop_down
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    Authors: Simons, Laura E; Sieberg, Christine B; Claar, Robyn Lewis;

    BACKGROUND: Anxiety is the most common psychiatric condition in children and adolescents, and is linked to significant disruptions across domains of function. Due to the avoidant nature of anxiety and pain-related disability, studying anxiety symptoms in children with chronic and recurrent pain conditions is important.OBJECTIVES: To examine anxiety symptoms in a large cohort of children and adolescents evaluated for complex chronic and recurrent pain conditions.METHODS: Through retrospective chart review, data on anxiety, pain and functional disability were collected from 655 children evaluated at a multidisciplinary pain clinic over a three-year period.RESULTS: Approximately 11% of children and adolescents reported clinically elevated anxiety symptoms, with elevated levels across dimensions of anxiety ranging from 14% (social anxiety, worry) to 27% (physiological). In addition, a notable 31% of the sample potentially minimized their anxiety by responding in a socially desirable manner. Anxiety was linearly associated with greater pain-related functional disability, but was not directly correlated with pain. Moderation analyses revealed that at low levels of worry, higher levels of pain were associated with greater functional disability, whereas at high levels of worry, pain no longer predicted the level of functional disability.CONCLUSIONS: These findings document the prevalence of anxiety in children and adolescents with chronic pain, and also extend recent studies examining the complex relationships among pain, anxiety and pain-related disability.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Pain Research and Ma...arrow_drop_down
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Pain Research and Ma...arrow_drop_down
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    Authors: Choi, Young-Seok; Jia, Xiaofeng;
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Hindawi Publishing C...arrow_drop_down
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    Authors: Robison, Patrick(Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine) Hernández-Ochoa, Erick O.(Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine) Schneider, Martin F.(Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine);

    Primary culture models of single adult skeletal muscle fibers dissociated from locomotor muscles adhered to glass coverslips are routine and allow monitoring of functional processes in living cultured fibers. To date, such isolated fiber cultures have not been established for respiratory muscles, despite the fact that dysfunction of core respiratory muscles leading to respiratory arrest is the most common cause of death in many muscular diseases. Here we present the first description of an adherent culture system for single adult intercostal muscle fibers from the adult mouse. This system allows for monitoring functional properties of these living muscle fibers in culture with or without electrical field stimulation to drive muscle fiber contraction at physiological or pathological respiratory firing patterns. We also provide initial characterization of these fibers, demonstrating several common techniques in this new model system in the context of the established Flexor Digitorum Brevis muscle primary culture model.

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    Authors: Hull, Mark; Shafran, Stephen; Wong, Alex; Tseng, Alice; +6 Authors

    Background. Hepatitis C virus (HCV) coinfection occurs in 20–30% of Canadians living with HIV and is responsible for a heavy burden of morbidity and mortality. Purpose. To update national standards for management of HCV-HIV coinfected adults in the Canadian context with evolving evidence for and accessibility of effective and tolerable DAA therapies. The document addresses patient workup and treatment preparation, antiviral recommendations overall and in specific populations, and drug-drug interactions. Methods. A standing working group with HIV-HCV expertise was convened by The Canadian Institute of Health Research HIV Trials Network to review recently published HCV antiviral data and update Canadian HIV-HCV Coinfection Guidelines. Results. The gap in sustained virologic response between HCV monoinfection and HIV-HCV coinfection has been eliminated with newer HCV antiviral regimens. All coinfected individuals should be assessed for interferon-free, Direct Acting Antiviral HCV therapy. Regimens vary in content, duration, and success based largely on genotype. Reimbursement restrictions forcing the use of pegylated interferon is not acceptable if optimal patient care is to be provided. Discussion. Recommendations may not supersede individual clinical judgement. Treatment advances published since December 2015 are not considered in this document.

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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Alexandrov, T.; Golyandina, N.; Spirov, A.;

    We present investigation of gene expression profiles by means of singular spectrum analysis (SSA). The biological problem under investigation is the decomposition of bicoid protein profiles of Drosophila melanogaster into the sum of a signal and noise, where the former consists of an exponential-in-distance pattern and is close to constant nonspecific component, or “background.” The signal processing problems addressed are (i) trend extraction from a noisy signal, (ii) batch processing of similar data, and (iii) analytical approximation of the signal components by the sum of exponential and constant-like functions. The proposed methods are evaluated on the given 17 series.

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    Authors: Spangenburg, Espen E.(Department of Kinesiology, University of Maryland, School of Public Health) Pratt, Stephen J. P.(Department of Orthopaedics, University of Maryland, School of Medicine) Wohlers, Lindsay M.(Department of Kinesiology, University of Maryland, School of Public Health) Lovering, Richard M.(Department of Orthopaedics, University of Maryland, School of Medicine);

    Triglyceride storage is altered across various chronic health conditions necessitating various techniques to visualize and quantify lipid droplets (LDs). Here, we describe the utilization of the BODIPY (493/503) dye in skeletal muscle as a means to analyze LDs. We found that the dye was a convenient and simple approach to visualize LDs in both sectioned skeletal muscle and cultured adult single fibers. Furthermore, the dye was effective in both fixed and nonfixed cells, and the staining seemed unaffected by permeabilization. We believe that the use of the BODIPY (493/503) dye is an acceptable alternative and, under certain conditions, a simpler method for visualizing LDs stored within skeletal muscle.

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    Authors: Ybe, Joel A.; Clegg, Mary E.; Illingworth, Melissa; Gonzalez, Claire; +1 Authors

    The interaction between HIP family proteins (HIP1 and HIP12/1R) and clathrin is fundamental to endocytosis. We used circular dichroism (CD) to study the stability of an HIP1 subfragment (aa468-530) that is splayed open. CD thermal melts show HIP1 468-530 is only stable at low temperatures, but this HIP1 fragment contains a structural unit that does not melt out even at 83C∘. We then created HIP1 mutants to probe our hypothesis that a short hydrophobic path in the opened region is the binding site for clathrin light chain. We found that the binding of hub/LCb was sensitive to mutating two distantly separated basic residues (K474 and K494). The basic patches marked by K474 and K494 are conserved in HIP12/1R. The lack of conservation in sla2p (S. cerevisiae), HIP1 from D. melanogaster, and HIP1 homolog ZK370.3 from C. elegans implies the binding of HIP1 and HIP1 homologs to clathrin light chain may be different in these organisms.

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    Authors: Shirley, Lawrence A.; Aguilar, Laura K.; Aguilar-Cordova, Estuardo; Bloomston, Mark; +1 Authors

    Pancreatic adenocarcinoma is an aggressive disease that has poor outcomes despite maximal traditional therapies. Thus, treatment of this cancer demands innovative strategies to be used in addition to standing therapies in order to provide new avenues of care. Here, we describe the technique of using endoscopic ultrasound in order to directly inject both novel and conventional therapies into pancreatic tumors. We detail the rationale behind this strategy and the many benefits it provides. We then describe our technique in detail, including our experience injecting the AdV-tk adenoviral vector to create an in situ vaccine effect.

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    Authors: Gao, Peisong(Department of Medicine, Johns Hopkins Asthma and Allergy Center, Johns Hopkins University School of Medicine);
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    Authors: Zhang, Haojian; Li, Shaoguang;

    Chronic myeloid leukemia (CML) is a myeloproliferative disease derived from an abnormal hematopoietic stem cell (HSC) and is consistently associated with the formation of Philadelphia (Ph) chromosome. Tyrosine kinase inhibitors (TKIs) are highly effective in treating chronic phase CML but do not eliminate leukemia stem cells (LSCs), which are believed to be related to disease relapse. Therefore, one major challenge in the current CML research is to understand the biology of LSCs and to identify the molecular difference between LSCs and its normal stem cell counterparts. Comparing the gene expression profiles between LSCs and normal HSCs by DNA microarray assay is a systematic and unbiased approach to address this issue. In this paper, we present a DNA microarray dataset for CML LSCs and normal HSCs to show that the microarray assay will benefit the current and future studies of the biology of CML stem cells.

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    Authors: Simons, Laura E; Sieberg, Christine B; Claar, Robyn Lewis;

    BACKGROUND: Anxiety is the most common psychiatric condition in children and adolescents, and is linked to significant disruptions across domains of function. Due to the avoidant nature of anxiety and pain-related disability, studying anxiety symptoms in children with chronic and recurrent pain conditions is important.OBJECTIVES: To examine anxiety symptoms in a large cohort of children and adolescents evaluated for complex chronic and recurrent pain conditions.METHODS: Through retrospective chart review, data on anxiety, pain and functional disability were collected from 655 children evaluated at a multidisciplinary pain clinic over a three-year period.RESULTS: Approximately 11% of children and adolescents reported clinically elevated anxiety symptoms, with elevated levels across dimensions of anxiety ranging from 14% (social anxiety, worry) to 27% (physiological). In addition, a notable 31% of the sample potentially minimized their anxiety by responding in a socially desirable manner. Anxiety was linearly associated with greater pain-related functional disability, but was not directly correlated with pain. Moderation analyses revealed that at low levels of worry, higher levels of pain were associated with greater functional disability, whereas at high levels of worry, pain no longer predicted the level of functional disability.CONCLUSIONS: These findings document the prevalence of anxiety in children and adolescents with chronic pain, and also extend recent studies examining the complex relationships among pain, anxiety and pain-related disability.

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    Authors: Choi, Young-Seok; Jia, Xiaofeng;
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    Authors: Robison, Patrick(Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine) Hernández-Ochoa, Erick O.(Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine) Schneider, Martin F.(Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine);

    Primary culture models of single adult skeletal muscle fibers dissociated from locomotor muscles adhered to glass coverslips are routine and allow monitoring of functional processes in living cultured fibers. To date, such isolated fiber cultures have not been established for respiratory muscles, despite the fact that dysfunction of core respiratory muscles leading to respiratory arrest is the most common cause of death in many muscular diseases. Here we present the first description of an adherent culture system for single adult intercostal muscle fibers from the adult mouse. This system allows for monitoring functional properties of these living muscle fibers in culture with or without electrical field stimulation to drive muscle fiber contraction at physiological or pathological respiratory firing patterns. We also provide initial characterization of these fibers, demonstrating several common techniques in this new model system in the context of the established Flexor Digitorum Brevis muscle primary culture model.

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    Authors: Hull, Mark; Shafran, Stephen; Wong, Alex; Tseng, Alice; +6 Authors

    Background. Hepatitis C virus (HCV) coinfection occurs in 20–30% of Canadians living with HIV and is responsible for a heavy burden of morbidity and mortality. Purpose. To update national standards for management of HCV-HIV coinfected adults in the Canadian context with evolving evidence for and accessibility of effective and tolerable DAA therapies. The document addresses patient workup and treatment preparation, antiviral recommendations overall and in specific populations, and drug-drug interactions. Methods. A standing working group with HIV-HCV expertise was convened by The Canadian Institute of Health Research HIV Trials Network to review recently published HCV antiviral data and update Canadian HIV-HCV Coinfection Guidelines. Results. The gap in sustained virologic response between HCV monoinfection and HIV-HCV coinfection has been eliminated with newer HCV antiviral regimens. All coinfected individuals should be assessed for interferon-free, Direct Acting Antiviral HCV therapy. Regimens vary in content, duration, and success based largely on genotype. Reimbursement restrictions forcing the use of pegylated interferon is not acceptable if optimal patient care is to be provided. Discussion. Recommendations may not supersede individual clinical judgement. Treatment advances published since December 2015 are not considered in this document.

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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Hindawi Publishing C...arrow_drop_down
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/