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Caroline Furtado Noble, Fernanda Malta, Gaspar Lisboa-Neto, Michele Soares Gomes-Gouvêa, Andrea Gurgel Batista Leite, Vanessa Fusco Duarte de Castro, Rubia Anita Ferraz Santana, Flair José Carrilho, Maria Cássia Mendes-Correa, João Renato Rebello Pinho
Resistance-associated variants (RAVs) represent a challenge to the success of new HCV therapies. The aim of this study was to describe the prevalence of naturally occurring NS5B RAVs in Brazilian direct acting antivirals (DAA)-naïve patients infected with HCV genotype 1, or co-infected with HIV. Patient enrollment and sample collection were performed between 2011 and 2013. Using Sanger-based sequencing, 244 sequences were obtained. RAVs detected in HCV-1a sequences were V321A (1.6 %), M414V (1.3 %), A421V (21...
October 4, 2016: Archives of Virology
Sayuri Nitta, Yasuhiro Asahina, Mami Matsuda, Norie Yamada, Ryuichi Sugiyama, Takahiro Masaki, Ryosuke Suzuki, Nobuyuki Kato, Mamoru Watanabe, Takaji Wakita, Takanobu Kato
Direct-acting antivirals (DAAs) for hepatitis C virus (HCV) have potent anti-HCV effects but may provoke resistance-associated variants (RAVs). In this study, we assessed the characteristics of these RAVs and explored efficacious anti-HCV reagents using recombinant HCV with NS5A from a genotype 1b strain. We replaced the NS5A of JFH1 with that of Con1 (JFH1/5ACon1) and introduced known NS5A inhibitor resistance mutations (L31M, L31V, L31I and Y93H) individually or in combination. Susceptibilities against anti-HCV reagents were also investigated...
October 5, 2016: Scientific Reports
Kalie Kebed, Eric Kruse, Karima Addetia, Boguslawa Ciszek, Minnie Thykattil, Brittney Guile, Roberto M Lang, Victor Mor-Avi
Current guidelines recommend that the atria be measured in 2D echocardiographic (2DE) apical views using the method-of-disks (MOD) or area-length (AL) technique as an alternative, although no definitive data exists that these are interchangeable. However, standard apical views maximize the long-axis of the left ventricle, rather than the dimensions of the atria, resulting in atrial foreshortening. We hypothesized that the increase in normal values of atrial volumes in the recent guidelines update was driven by data obtained using either the AL technique or dedicated atrial-focused views, which maximize the longitudinal dimension of the atria and thus provide larger volumes than the MOD measurements in standard apical views...
October 1, 2016: International Journal of Cardiovascular Imaging
María Ángeles Jimenez-Sousa, Mónica Gutiérrez-Rivas, Alejandro Álvaro-Meca, Mónica García-Álvarez, P Richard Harrigan, Cesare Giovanni Fedele, Verónica Briz, Sonia Vázquez-Morón, Salvador Resino
BACKGROUND: Resistance-associated variants have been related to treatment failure of hepatitis C virus (HCV) therapy with direct-acting antiviral drugs. The aim of our study was to analyze the prevalence of clinically relevant resistance-associated variants within NS3 in patients infected with HCV genotype 1a (GT1a) in Spain. METHODS: We performed a cross-sectional study on 2568 patients from 115 hospitals throughout Spain (2014-2015). The viral NS3 protease gene was amplified by nested polymerase chain reaction and sequenced by Sanger sequencing using an ABI PRISM 377 DNA sequencer...
2016: PloS One
Astrid M Newsum, Cynthia K Y Ho, Faydra I Lieveld, Thijs J W Van De Laar, Sylvie M Koekkoek, Sjoerd P Rebers, Jan T M Van Der Meer, Anne M J Wensing, Greet J Boland, Joop E Arends, Karel J Van Erpecum, Maria Prins, Richard Molenkamp, Janke Schinkel
OBJECTIVES: The Q80K polymorphism is a naturally occurring resistance-associated variant (RAV) in the hepatitis C virus (HCV) NS3 region and is likely transmissible between hosts. This study describes the Q80K origin and prevalence among HCV risk groups in the Netherlands and examines whether Q80K is linked to specific transmission networks. DESIGN AND METHODS: Stored blood samples from HCV genotype 1a infected patients were used for PCR and sequencing to reconstruct the NS3 maximum likelihood phylogeny...
September 20, 2016: AIDS
Takuji Araki, Hiroki Okada, Hiroshi Onishi
PURPOSE: To evaluate the importance of selecting an appropriate catheter shape for the right adrenal vein (RAV) anatomy on CT to the success of right adrenal venous sampling (RAVS) by elucidating the interactions of anatomical factors with catheter shape. MATERIALS AND METHODS: 130 patients with enhanced CT underwent RAVS using two catheters: catheter 1 was planar and catheter 2 was a three-dimensional shape. The following anatomical factors on CT were evaluated in each patient: presence of a right adrenal tumor, presence of a common trunk with an accessory right hepatic vein, diameter of the RAV, short and long diameters of the IVC, ratio of the long to the short diameter of IVC, and the transverse, modified transverse, and vertical angles of the RAV...
September 20, 2016: Japanese Journal of Radiology
Zhen-Yong Keck, Yong Wang, Patrick Lau, Garry Lund, Sneha Rangarajan, Catherine Fauvelle, Grant C Liao, Frederick W Holtsberg, Kelly L Warfield, M Javad Aman, Brian G Pierce, Thomas R Fuerst, Justin R Bailey, Thomas F Baumert, Roy A Mariuzza, Norman M Kneteman, Steven K H Foung
: Direct acting antivirals (DAAs) have led to a high cure rate in treated patients with chronic hepatitis C virus (HCV) infection but this still leaves a large number of treatment failures secondary to the emergence of resistance-associated variants (RAVs). To increase the barrier to resistance, a complementary strategy is to employ neutralizing human monoclonal antibodies (HMAbs) to prevent acute infection. However, earlier efforts with the selected antibodies led to RAVs in animal and clinical studies...
September 19, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Reona Morio, Michio Imamura, Yoshiiku Kawakami, Kei Morio, Tomoki Kobayashi, Satoe Yokoyama, Yuki Kimura, Yuko Nagaoki, Tomokazu Kawaoka, Masataka Tsuge, Akira Hiramatsu, C Nelson Hayes, Hiroshi Aikata, Shoichi Takahashi, Daiki Miki, Hidenori Ochi, Nami Mori, Shintaro Takaki, Keiji Tsuji, Kazuaki Chayama
BACKGROUND: Daclatasvir and asunaprevir combination therapy has shown a high virological response for chronic genotype 1 hepatitis C virus (HCV)-infected patients. However, the safety and efficacy of the therapy for older patients are unknown. METHODS: One hundred seventy patients younger than 75 years and 139 patients aged 75 years or older with genotype 1 HCV infection were treated for 24 weeks with daclatasvir plus asunaprevir. Pretreatment drug-resistance-associated variants at NS5A-L31 and NS5A-Y93 were determined by the Invader assay...
September 8, 2016: Journal of Gastroenterology
Baojian Guo, Yafeng Wei, Ruibin Xu, Shen Lin, Haiye Luan, Chao Lv, Xinzhong Zhang, Xiyun Song, Rugen Xu
APETALA2/Ethylene-Responsive Factor (AP2/ERF) gene family is plant specific transcription factor. It plays critical roles in development process, tolerance to biotic and abiotic stresses, and responses to plant hormones. However, limited data are available on the contributions of AP2/ERF gene family in barley (Hordeum vulgare L.). In the present study, 121 HvAP2/ERF genes in barley were identified by using bioinformatics methods. A total of 118 HvAP2/ERF (97.5%) genes were located on seven chromosomes. According to phylogenetic classification of AP2/ERF family in Arabidopsis, HvAP2/ERF proteins were divided into AP2 (APETALA2), RAV (Related to ABI3/VP), DREB (dehydration responsive element binding), ERF (ethylene responsive factors) and soloist sub families...
2016: PloS One
Hui-Lian Wang, Xi Lu, Xudong Yang, Nan Xu
BACKGROUND & AIMS: Daclatasvir plus asunaprevir (DCV + ASV) has demonstrated potent antiviral activity in patients with hepatitis C virus (HCV) genotype 1b infection. A definite conclusion about efficacy and safety of DCV + ASV in patients with HCV genotype 1b is not available. A meta-analysis was conducted to evaluate outcomes of all-oral treatment with DCV + ASV in terms of sustained virological response at 12 (SVR12 ) , 24 (SVR24 ) weeks and adverse effects (AEs) after the end of treatment...
September 6, 2016: Journal of Gastroenterology and Hepatology
Andrew J Tanentzap, William G Lee
Abiotic filters have been found either to increase or reduce evolutionary relatedness in plant communities, making it difficult to generalize responses of this major feature of biodiversity to future environmental change. Here, we hypothesized that the responses of phylogenetic structure to environmental change ultimately depend on how species have evolved traits for tolerating the resulting abiotic changes. Working within ephemeral wetlands, we tested whether species were increasingly related as flooding duration intensified...
September 6, 2016: New Phytologist
Naoki Morishita, Naoki Hiramatsu, Tsugiko Oze, Ayako Urabe, Yuki Tahata, Ryoko Yamada, Takayuki Yakushijin, Atsushi Hosui, Sadaharu Iio, Akira Yamada, Hideki Hagiwara, Eiji Mita, Yukinori Yamada, Toshifumi Ito, Masami Inada, Kazuhiro Katayama, Iwao Yabuuchi, Yasuharu Imai, Hayato Hikita, Ryotaro Sakamori, Yuichi Yoshida, Tomohide Tatsumi, Norio Hayashi, Tetsuo Takehara
AIM: Simeprevir (SMV)-based triple therapy is an effective retreatment option following failure of telaprevir (TVR)-based triple therapy. However, it is unclear whether the persistence of resistance-associated variants (RAVs) induced by TVR-based therapy may reduce the treatment effect of SMV-based therapy. METHODS: The factors associated with the treatment effect, including RAVs in the NS3 region, were examined in 21 patients with genotype 1b HCV infection who were treated with SMV-based therapy after failure of TVR-based therapy...
September 4, 2016: Hepatology Research: the Official Journal of the Japan Society of Hepatology
Xiaoming Song, Jinpeng Wang, Xiao Ma, Yuxian Li, Tianyu Lei, Li Wang, Weina Ge, Di Guo, Zhenyi Wang, Chunjin Li, Jianjun Zhao, Xiyin Wang
The AP2/ERF superfamily, one of the most important transcription factor families, plays crucial roles in response to biotic and abiotic stresses. So far, a comprehensive evolutionary inference of its origination and expansion has not been available. Here, we identified 515 AP2/ERF genes in B. napus, a neo-tetraploid forming ~7500 years ago, and found that 82.14% of them were duplicated in the tetraploidization. A prominent subgenome bias was revealed in gene expression, tissue-specific, and gene conversion...
2016: Frontiers in Plant Science
Davina Gorton, Suchandan Sikder, Natasha L Williams, Lisa Chilton, Catherine M Rush, Brenda L Govan, Madeleine W Cunningham, Natkunam Ketheesan
Rheumatic fever and rheumatic heart disease (RF/RHD) develop following repeated infection with group A streptococci (GAS). We used the Rat Autoimmune Valvulitis (RAV) model of RF/RHD to demonstrate that repetitive booster immunization with GAS-derived recombinant M protein (rM5) resulted in an enhanced anti-cardiac myosin antibody response that may contribute to the breaking of immune tolerance leading to RF/RHD and increased infiltration of heart valves by mononuclear cells. With each boost, more inflammatory cells were observed infiltrating heart tissue which could lead to severe cardiac damage...
August 25, 2016: Autoimmunity
Miguel Jiménez-Pérez, Rocío González-Grande, Pilar España Contreras, Isabel Pinazo Martínez, Jesús de la Cruz Lombardo, Raúl Olmedo Martín
The use of direct-acting antivirals (DAAs) to treat chronic hepatitis C has resulted in a significant increase in rates of sustained viral response (around 90%-95%) as compared with the standard treatment of peginterferon/ribavirin. Despite this, however, the rates of therapeutic failure in daily clinical practice range from 10%-15%. Most of these cases are due to the presence of resistant viral variants, resulting from mutations produced by substitutions of amino acids in the viral target protein that reduce viral sensitivity to DAAs, thus limiting the efficacy of these drugs...
August 7, 2016: World Journal of Gastroenterology: WJG
Licao Cui, Kewei Feng, Mengxing Wang, Meng Wang, Pingchuan Deng, Weining Song, Xiaojun Nie
BACKGROUND: The AP2/ERF transcription factor is one of the most important gene families in plants, which plays the vital role in regulating plant growth and development as well as in response to diverse stresses. Although AP2/ERFs have been thoroughly characterized in many plant species, little is known about this family in the model plant Brachypodium distachyon, especially those involved in the regulatory network of stress processes. RESULTS: In this study, a comprehensive genome-wide search was performed to identify AP2/ERF gene family in Brachypodium and a total of 141 BdAP2/ERFs were obtained...
2016: BMC Genomics
T Ruggiero, E Burdino, A Calcagno, S Bonora, L Boglione, G Di Perri, V Ghisetti
PURPOSE: Data on the frequency of HCV naturally occurring drug-resistant variants (RAVs) at baseline in HIV/HCV coinfected patients are scarce. METHODS: NS3-HCV RAVs were studied by full-population direct sequencing from plasma specimens of 345 DAA-naïve patients with HCV chronic hepatitis (159 of them with HIV/HCV-coinfection). RESULTS: NS3 RAVs were identified in 31.5 % of patients, with a significant proportion of HIV/HCV coinfected DAA-naïve patients compared to those with HCV monoinfection (38 vs...
August 13, 2016: Infection
Moshe Rav-Acha, Chee Yuan Ng, E Kevin Heist, Guy Rozen, Fadi Chalhoub, William J Kostis, Jeremy Ruskin, Moussa Mansour
INTRODUCTION: The treatment of atrial tachycardia (AT) occurring after ablation for atrial fibrillation (AF) is challenging. The most common ablation strategy relies on entrainment, and electroanatomic activation mapping (EAM) using a conventional window of interest (WOI), centered on the easily detectable atrial signal on the coronary sinus catheter. We describe a novel EAM annotation technique that uses a WOI starting 40 ms prior to the P wave in order to detect the reentrant AT exit site...
August 10, 2016: Journal of Cardiovascular Electrophysiology
Dong Zhang, Qing-fu Wang, Xin-chao Shi, Huan Wang, Jun Zhao, Li-li Yang, Wei-li Wang, Hao-bin Ding, Qing Chang
OBJECTIVE: To analyze and compare the characteristics of musculoskeletal ultrasonography and X-ray of knee osteoarthritis, and to investigate the advantages of them. METHODS: According to the inclusion and exclusion criteria, 57 cases (66 knees) were collected from February 2015 to May 2015. Among them, there were 48 females and 9 males with an average age of (58.9 +/- 9.8) years old (ranged, 41 to 78 years old). The main symptoms included unilateral or bilateral knee pain and locked joints explicit areas of tender points...
May 2016: Zhongguo Gu Shang, China Journal of Orthopaedics and Traumatology
Christopher M Owens, Bradley B Brasher, Alex Polemeropoulos, Michael H J Rhodin, Nicole McAllister, Kelly A Wong, Christopher T Jones, Lijuan Jiang, Kai Lin, Yat Sun Or
EDP-239, a potent and selective hepatitis C virus (HCV) nonstructural protein 5A (NS5A) inhibitor developed for the treatment of HCV infection, has been investigated in vitro and in vivo This study sought to characterize genotypic changes in the HCV NS5A sequence of genotype 1 (GT1) replicons and to compare those changes to GT1 viral RNA mutations isolated from clinical trial patients. Resistance selection experiments in vitro using a subgenomic replicon identified resistance-associated mutations (RAMs) at GT1a NS5A amino acid positions 24, 28, 30, 31, and 93 that confer various degrees of resistance to EDP-239...
October 2016: Antimicrobial Agents and Chemotherapy
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