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https://www.readbyqxmd.com/read/28350802/impact-of-lopinavir-ritonavir-exposure-in-hiv-1-infected-children-and-adolescents-in-madrid-spain-during-2000-2014
#1
Patricia Rojas Sánchez, Luis Prieto, Santiago Jiménez De Ory, Elisa Fernández Cooke, Maria Luisa Navarro, José Tomas Ramos, África Holguín
BACKGROUND: The most-used protease-inhibitor in children is Lopinavir-ritonavir (LPV/r), which provides durable suppression of viral load and increases CD4+T-counts. This study describes the virological outcome of the HIV-1-infected paediatric population exposed to LPV/r during 15 years in Spain. METHODOLOGY: Patients from the Madrid Cohort of HIV-1-infected-children and adolescents exposed to LPV/r as different line therapy during 2000-2014 were selected. The baseline epidemiological-clinical features, viral suppression, changes in CD4+T-CD8+T cell counts and drug susceptibility were recorded before and during LPV/r exposure...
2017: PloS One
https://www.readbyqxmd.com/read/28345623/liposomes-loaded-with-bioactive-lipids-enhance-antibacterial-innate-immunity-irrespective-of-drug-resistance
#2
Noemi Poerio, Francesca Bugli, Francesco Taus, Marilina B Santucci, Carlo Rodolfo, Francesco Cecconi, Riccardo Torelli, Francesco Varone, Riccardo Inchingolo, Fabio Majo, Vincenzina Lucidi, Sabrina Mariotti, Roberto Nisini, Maurizio Sanguinetti, Maurizio Fraziano
Phagocytosis is a key mechanism of innate immunity, and promotion of phagosome maturation may represent a therapeutic target to enhance antibacterial host response. Phagosome maturation is favored by the timely and coordinated intervention of lipids and may be altered in infections. Here we used apoptotic body-like liposomes (ABL) to selectively deliver bioactive lipids to innate cells, and then tested their function in models of pathogen-inhibited and host-impaired phagosome maturation. Stimulation of macrophages with ABLs carrying phosphatidic acid (PA), phosphatidylinositol 3-phosphate (PI3P) or PI5P increased intracellular killing of BCG, by inducing phagosome acidification and ROS generation...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28344893/integrated-analysis-of-somatic-mutations-and-immune-microenvironment-in-malignant-pleural-mesothelioma
#3
Kazuma Kiyotani, Jae-Hyun Park, Hiroyuki Inoue, Aliya Husain, Sope Olugbile, Makda Zewde, Yusuke Nakamura, Wickii T Vigneswaran
To investigate the link between the genomic landscape of cancer cells and immune microenvironment in tumor tissues, we characterized somatic mutations and tumor-infiltrating lymphocytes (TILs) in malignant pleural mesothelioma (MPM), including mutation/neoantigen load, spatial heterogeneity of somatic mutations of cancer cells and TILs (T-cell receptor β (TCRβ) repertoire), and expression profiles of immune-related genes using specimens of three different tumor sites (anterior, posterior, and diaphragm) obtained from six MPM patients...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344881/immunosurveillance-and-immunoediting-in-mmtv-pymt-induced-mammary-oncogenesis
#4
Emilie T E Gross, Semi Han, Prasantha Vemu, Carlos D Peinado, Martin Marsala, Lesley G Ellies, Jack D Bui
Evidence of cancer immunosurveillance and immunoediting processes has been primarily demonstrated in mouse models of chemically induced oncogenesis. Although these models are very tractable, they are characterized by high mutational loads that represent a minority of human cancers. In this study, we sought to determine whether cancer immunosurveillance and immunoediting could be demonstrated in a more clinically relevant oncogene-induced model of carcinogenesis, the MMTV-PyMT (PyMT) mammary carcinoma model...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344865/identification-of-genetic-determinants-of-breast-cancer-immune-phenotypes-by-integrative-genome-scale-analysis
#5
Wouter Hendrickx, Ines Simeone, Samreen Anjum, Younes Mokrab, François Bertucci, Pascal Finetti, Giuseppe Curigliano, Barbara Seliger, Luigi Cerulo, Sara Tomei, Lucia Gemma Delogu, Cristina Maccalli, Ena Wang, Lance D Miller, Francesco M Marincola, Michele Ceccarelli, Davide Bedognetti
Cancer immunotherapy is revolutionizing the clinical management of several tumors, but has demonstrated limited activity in breast cancer. The development of more effective treatments is hindered by incomplete knowledge of the genetic determinant of immune responsiveness. To fill this gap, we mined copy number alteration, somatic mutation, and expression data from The Cancer Genome Atlas (TCGA). By using RNA-sequencing data from 1,004 breast cancers, we defined distinct immune phenotypes characterized by progressive expression of transcripts previously associated with immune-mediated rejection...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28342241/overt-and-occult-hepatitis-b-virus-infection-among-community-children-in-northwest-china
#6
Haixia Su, Zhongjun Shao, Zhongshu Pu, Yang Wang, Lei Zhang, Weilu Zhang, Bo Wang, Anhui Wang, Zhaohua Ji, Yongping Yan, Yuhai Zhang
Although a universal newborn hepatitis B (HB) immunization program has been implemented in China, hepatitis B virus (HBV) breakthrough infection, including HB surface antigen (HBsAg)-positive infection and occult HBV infection (OBI), still occurs during infancy or childhood. Obtaining the actual prevalence of HBV infection in general children is important for preventing and controlling the spread of HB. Accordingly, we investigated the prevalence of overt infection and OBI in community children and compared the serological and virological characteristics of OBI and HBsAg-carrier children to clarify the mechanisms related to OBI...
March 25, 2017: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/28331993/molecular-characterization-and-phylogenetic-analysis-of-human-influenza-a-viruses-isolated-in-iran-during-the-2014-2015-season
#7
Elham Moasser, Farida Behzadian, Afagh Moattari, Fatemeh Fotouhi, Amir Rahimi, Hassan Zaraket, Seyed Younes Hosseini
Influenza A viruses are an important cause of severe infectious diseases in humans and are characterized by their fast evolution rate. Global monitoring of these viruses is critical to detect newly emerging variants during annual epidemics. Here, we sought to genetically characterize influenza A/H1N1pdm09 and A/H3N2 viruses collected in Iran during the 2014-2015 influenza season. A total of 200 nasopharyngeal swabs were collected from patients with influenza-like illnesses. Swabs were screened for influenza A and B using real-time PCR...
March 22, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28327559/quasispecies-of-hepatitis-c-virus-participate-in-cell-specific-infectivity
#8
Takasuke Fukuhara, Satomi Yamamoto, Chikako Ono, Shota Nakamura, Daisuke Motooka, Hiroyuki Mori, Takeshi Kurihara, Asuka Sato, Tomokazu Tamura, Takashi Motomura, Toru Okamoto, Michio Imamura, Toru Ikegami, Tomoharu Yoshizumi, Yuji Soejima, Yoshihiko Maehara, Kazuaki Chayama, Yoshiharu Matsuura
It is well documented that a variety of viral quasispecies are found in the patients with chronic infection of hepatitis C virus (HCV). However, the significance of quasispecies in the specific infectivity to individual cell types remains unknown. In the present study, we analyzed the role of quasispecies of the genotype 2a clone, JFH1 (HCVcc), in specific infectivity to the hepatic cell lines, Huh7.5.1 and Hep3B. HCV RNA was electroporated into Huh7.5.1 cells and Hep3B/miR-122 cells expressing miR-122 at a high level...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28325300/one-step-biallelic-and-scarless-correction-of-a-%C3%AE-thalassemia-mutation-in-patient-specific-ipscs-without-drug-selection
#9
Yali Liu, Yi Yang, Xiangjin Kang, Bin Lin, Qian Yu, Bing Song, Ge Gao, Yaoyong Chen, Xiaofang Sun, Xiaoping Li, Lei Bu, Yong Fan
Monogenic disorders (MGDs), which are caused by single gene mutations, have a serious effect on human health. Among these, β-thalassemia (β-thal) represents one of the most common hereditary hematological diseases caused by mutations in the human hemoglobin β (HBB) gene. The technologies of induced pluripotent stem cells (iPSCs) and genetic correction provide insights into the treatments for MGDs, including β-thal. However, traditional approaches for correcting mutations have a low efficiency and leave a residual footprint, which leads to some safety concerns in clinical applications...
March 17, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28323753/budget-impact-of-antiretroviral-therapy-in-a-french-clinic-cohort-anrs-gota
#10
Emmanuelle Papot, Roland Landman, Françoise Louni, Charlotte Charpentier, Gilles Peytavin, Agnès Certain, Clémence Fradet, Daniela Rojas Castro, Marie Preau, Cécile Goujard, Patrick Yeni, Yazdan Yazdanpanah
OBJECTIVES: In this study, we first assessed costs associated with the use of ART in an infectious diseases University Hospital Clinic, we secondly evaluated characteristics associated with these costs, and finally simulated the impact on the overall ART budget of switching 1- and 2-line regimens to less costly regimens (as effective and well-tolerated). DESIGN: Cohort analysis including PLHIV ≥ 18 years on ART to estimate ART costs during 2014. METHODS: This study was conducted in the Bichat-Claude Bernard University Hospital Clinic in Paris, France, where 4,501 PLHIV consulted in 2014...
March 18, 2017: AIDS
https://www.readbyqxmd.com/read/28323493/microparticles-containing-erlotinib-loaded-solid-lipid-nanoparticles-for-treatment-of-non-small-cell-lung-cancer
#11
Zahra Bakhtiary, Jaleh Barar, Ayuob Aghanejad, Amir Ata Saei, Elhameh Nemati, Jafar Ezzati Nazhad Dolatabadi, Yadollah Omidi
Non-small cell lung cancer (NSCLC) patients with sensitizing mutations in the exons 18-21 of the epithelial growth factor receptor (EGFR) geneshowincreased kinase activity of EGFR. Hence, tyrosine kinase inhibitors (TKIs) such as erlotinib (ETB) havecommonly been used as the second line therapeutic option in metastatic NSCLC. While the ETB is available as an oral dosage form, the local delivery of this TKI to the diseased cells of the lung may ameliorate its therapeutic impacts. In the current study, we report on the development of ETB-loaded solid lipid nanoparticle (SLN) based formulation of dry powder inhaler (ETB-SLN DPI)...
March 21, 2017: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/28323327/an-explicit-model-for-the-inbreeding-load-in-the-evolutionary-analysis-of-selfing
#12
Aurora García-Dorado
I present analytical predictions for the equilibrium inbreeding load expected in a population under mutation, selection and a regular mating system, for any population size and for any magnitude and recessivity of the deleterious effects. Using this prediction, I deduce the relative fitness of mutant alleles with small effect on selfing, to explore the situations where selfing or outcrossing are expected to evolve. The results obtained are in agreement with previous literature, showing that natural selection is expected to lead to stable equilibria where populations show either complete outcrossing or complete selfing, and that selfing is promoted by large deleterious mutation rates...
March 21, 2017: Evolution; International Journal of Organic Evolution
https://www.readbyqxmd.com/read/28320919/pan-cancer-analysis-distinguishes-transcriptional-changes-of-aneuploidy-from-proliferation
#13
Christopher Buccitelli, Lorena Salgueiro, Konstantina Rowald, Rocio Sotillo, Balca R Mardin, Jan O Korbel
Patterns of gene expression in tumors can arise as a consequence of or result in genomic instability, characterized by the accumulation of somatic copy number alterations (SCNAs) and point mutations (PMs). Expression signatures have been widely used as markers for genomic instability, and both SCNAs and PMs could be thought to associate with distinct signatures given their different formation mechanisms. Here we test this notion by systematically investigating SCNA, PM, and transcriptome data from 2660 cancer patients representing 11 tumor types...
March 20, 2017: Genome Research
https://www.readbyqxmd.com/read/28314751/identification-of-glycopeptides-as-post-translationally-modified-neoantigens-in-leukemia
#14
Stacy A Malaker, Sarah A Penny, Lora G Steadman, Paisley T Myers, Justin Loke, Manoj Raghavan, Dina L Bai, Jeffery Shabanowitz, Donald Hunt, Mark Cobbold
Leukemias are highly immunogenic but have a low mutational load, providing few mutated peptide targets. Thus, the identification of alternative neoantigens is a pressing need. Here, we identify 36 MHC class I-associated peptide antigens with O-linked β-N-acetylglucosamine (O-GlcNAc) modifications as candidate neoantigens, using three experimental approaches. Thirteen of these peptides were also detected with disaccharide units on the same residues and two contain either mono- and/or di-methylated arginine residues...
March 17, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28306559/immunotherapy-a-new-treatment-paradigm-in-bladder-cancer
#15
Nicole N Davarpanah, Akira Yuno, Jane B Trepel, Andrea B Apolo
PURPOSE OF REVIEW: T-cell checkpoint blockade has become a dynamic immunotherapy for bladder cancer. In 2016, atezolizumab, an immune checkpoint inhibitor, became the first new drug approved in metastatic urothelial carcinoma (mUC) in over 30 years. In 2017, nivolumab was also approved for the same indication. This overview of checkpoint inhibitors in clinical trials focuses on novel immunotherapy combinations, predictive biomarkers including mutational load and neoantigen identification, and an evaluation of the future of bladder cancer immunotherapy...
March 16, 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/28303897/synergistic-efficacy-of-bisbenzimidazole-and-carbonyl-cyanide-3-chlorophenylhydrazone-combination-against-mdr-bacterial-strains
#16
Devapriya Sinha, Stuti Pandey, Raja Singh, Vinod Tiwari, Kirti Sad, Vibha Tandon
Activation of efflux systems and the formation of biofilm are majorly adapted by microbes to resist antimicrobial agents. PPEF (bisbenzimidazole) targeting topoisomerase IA is observed to be an effective bactericidal agent against both Gram-positive and Gram-negative bacterial strains and thus can be developed as potent broad-spectrum antibiotic against MDR strains. PPEF treatment did not cause target specific mutation instead it leads to up-regulation of efflux gene in E. coli K12 as a mechanism of resistance...
March 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28303490/immune-checkpoint-inhibitors-in-gliomas
#17
REVIEW
Aaron C Tan, Amy B Heimberger, Mustafa Khasraw
PURPOSE OF REVIEW: Malignant gliomas result in disproportionately high morbidity and mortality compared with other primary tumors, and progression of disease is inevitable. Novel therapies to improve outcomes are needed and immune checkpoint inhibitors hold significant promise. RECENT FINDINGS: A limited body of preclinical evidence suggests that checkpoint inhibitors may be effective treatment for gliomas. Biomarkers to identify characteristics of gliomas responsive to these therapies will be essential...
April 2017: Current Oncology Reports
https://www.readbyqxmd.com/read/28302372/experiences-during-newborn-screening-for-glutaric-aciduria-type-1-diagnosis-treatment-genotype-phenotype-and-outcomes
#18
Fang-Chih Tsai, Han-Jui Lee, An-Guor Wang, Shu-Chen Hsieh, Yung-Hsiu Lu, Ming-Che Lee, Ju-Shan Pai, Tzu-Hung Chu, Chia-Feng Yang, Ting-Rong Hsu, Chih-Jou Lai, Ming-Tzu Tsai, Ping-Hsun Ho, Min-Chieh Lin, Ling-Yee Cheng, Ya-Chin Chuang, Dau-Ming Niu
BACKGROUND: Glutaric aciduria type 1 (GA-1) is an organic acidemia with potentially severe neurological sequelae. In Taiwan, newborn screening (NBS) for GA-1 began in 2001, but large-scale reporting is lacking. This study describes Taiwan's largest newborn screening population to date. METHODS: Between 2001 and 2015, 1,490,636 newborns were screened for GA-1. Confirmatory examinations included the carnitine loading test. Confirmed patients were treated with a low lysine diet, carnitine, and high-energy intake during illness...
March 13, 2017: Journal of the Chinese Medical Association: JCMA
https://www.readbyqxmd.com/read/28301548/hiv-1-genetic-diversity-and-antiretroviral-drug-resistance-among-individuals-from-roraima-state-northern-brazil
#19
André de Lima Guerra Corado, Gonzalo Bello, Renato Augusto Carvalho Leão, Fabiana Granja, Felipe Gomes Naveca
The HIV-1 epidemic in Brazil has spread towards the Northern country region, but little is known about HIV-1 subtypes and prevalence of HIV strains with resistance mutations to antiretrovirals in some of the Northern states. HIV-1 protease (PR) and reverse transcriptase (RT) sequences were obtained from 73 treatment-naive and -experienced subjects followed between 2013 and 2014 at a public health reference unit from Roraima, the northernmost Brazilian state. The most prevalent HIV-1 clade observed in the study population was the subtype B (91%), followed by subtype C (9%)...
2017: PloS One
https://www.readbyqxmd.com/read/28298901/unveiling-another-missing-piece-in-ebv-driven-lymphomagenesis-ebv-encoded-micrornas-expression-in-eber-negative-burkitt-lymphoma-cases
#20
Lucia Mundo, Maria R Ambrosio, Matteo Picciolini, Giuseppe Lo Bello, Sara Gazaneo, Leonardo Del Porro, Stefano Lazzi, Mohsen Navari, Noel Onyango, Massimo Granai, Cristiana Bellan, Giulia De Falco, Davide Gibellini, Pier P Piccaluga, Lorenzo Leoncini
Epstein-Barr virus (EBV) is a gammaherpesvirus linked to a number of lymphoid and epithelial malignancies, including Burkitt lymphoma (BL) in which its frequency ranges from 30% in sporadic cases to 100% in the endemic ones. The possible contribution of EBV to BL pathogenesis is largely unknown. It has been suggested that EBV may be associated with all of the cases, including those diagnosed as EBV negative by a mechanism of hit-and-run. Early during oncogenesis, viral genes are essential for initiating disease...
2017: Frontiers in Microbiology
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