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https://www.readbyqxmd.com/read/28442262/an-integrated-chemical-biology-approach-reveals-the-mechanism-of-action-of-hiv-replication-inhibitors
#1
Nicholas Pagano, Peter Teriete, Margrith E Mattmann, Li Yang, Beth A Snyder, Zhaohui Cai, Marintha L Heil, Nicholas D P Cosford
Continuous flow (microfluidic) chemistry was employed to prepare a small focused library of dihydropyrimidinone (DHPM) derivatives. Compounds in this class have been reported to exhibit activity against the human immunodeficiency virus (HIV), but their molecular target had not been identified. We tested the initial set of DHPMs in phenotypic assays providing a hit (1i) that inhibited the replication of the human immunodeficiency virus HIV in cells. Flow chemistry-driven optimization of 1i led to the identification of HIV replication inhibitors such as 1l with cellular potency comparable with the clinical drug nevirapine (NVP)...
April 8, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28439755/what-do-key-stakeholders-think-about-hiv-self-testing-in-canada-results-from-a-cross-sectional-survey
#2
N Pant Pai, M Smallwood, D Gulati, N Lapczak, A Musten, C Gaydos, C Johnston, M Steben, T Wong, N Engel, J Kim
Human immunodeficiency virus (HIV) self-testing presents an empowering alternative to facility-based testing for reaching undiagnosed HIV infected individuals, but is not currently available in Canada. We surveyed stakeholders (clinical providers, public health professionals, researchers) engaged in HIV testing initiatives nationwide to identify the concerns, opportunities and challenges to implementing HIV self-testing in Canada. An online cross-sectional survey was disseminated by the Canadian Institutes of Health Research Centre for REACH 2...
April 24, 2017: AIDS and Behavior
https://www.readbyqxmd.com/read/28439684/impact-of-altered-endogenous-igg-on-unspecific-mab-clearance
#3
Saskia Fuhrmann, Charlotte Kloft, Wilhelm Huisinga
Immunodeficient mice are crucial models to evaluate the efficacy of monoclonal antibodies (mAbs). When studying mAb pharmacokinetics (PK), protection from elimination by binding to the neonatal Fc receptor (FcRn) is known to be a major process influencing the unspecific clearance of endogenous and therapeutic IgG. The concentration of endogenous IgG in immunodeficient mice, however is reduced, and this effect on the FcRn protection mechanism and subsequently on unspecific mAb clearance is unknown, yet of great importance for the interpretation of mAb PK data...
April 24, 2017: Journal of Pharmacokinetics and Pharmacodynamics
https://www.readbyqxmd.com/read/28433855/the-electrophysiology-of-neurohiv-a-systematic-review-of-eeg-and-meg-studies-in-people-with-hiv-infection-since-the-advent-of-highly-active-antiretroviral-therapy
#4
Ana Lucia Fernández-Cruz, Lesley K Fellows
OBJECTIVE: The Human Immunodeficiency Virus (HIV) has an impact on the brain, even when the infection is well-controlled with modern highly-active antiretroviral therapy (HAART). While dementia is rare in those on HAART, milder cognitive impairment is common. The causes, patterns, and evolution of brain dysfunction in people living with HIV remain uncertain. We evaluate whether electrophysiological methods provide informative measures of brain dysfunction in this population. METHODS: A systematic literature search identified studies that used EEG or MEG to evaluate persons living with HIV published between 1996 (when HAART became available) and 2016...
March 31, 2017: Clinical Neurophysiology: Official Journal of the International Federation of Clinical Neurophysiology
https://www.readbyqxmd.com/read/28433605/stability-of-patient-specific-features-of-altered-dna-replication-timing-in-xenografts-of-primary-human-acute-lymphoblastic-leukemia
#5
Takayo Sasaki, Juan Carlos Rivera-Mulia, Daniel Vera, Jared Zimmerman, Sunny Das, Michelle Padget, Naoto Nakamichi, Bill H Chang, Jeff Tyner, Brian J Druker, Andrew P Weng, Curt I Civin, Connie J Eaves, David M Gilbert
Genome-wide DNA replication timing (RT) profiles reflect the global 3D chromosome architecture of cells. They also provide a comprehensive and unique megabase-scale picture of the cellular epigenetic state. Thus normal differentiation involves reproducible changes in RT and transformation generally perturbs these, although the potential effects of altered RT on the properties of transformed cells remain largely unknown. A major challenge to interrogating these issues in human acute lymphoid leukemia (ALL) is the low proliferative activity of most of the cells, which may be further reduced in cryopreserved samples and difficult to overcome in vitro...
April 19, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28428162/the-use-of-intervention-mapping-to-develop-a-tailored-web-based-intervention-condom-him
#6
Joyal Miranda, José Côté
BACKGROUND: Many HIV (human immunodeficiency virus) prevention interventions are currently being implemented and evaluated, with little information published on their development. A framework highlighting the method of development of an intervention can be used by others wanting to replicate interventions or develop similar interventions to suit other contexts and settings. It provides researchers with a comprehensive development process of the intervention. OBJECTIVE: The objective of this paper was to describe how a systematic approach, intervention mapping, was used to develop a tailored Web-based intervention to increase condom use among HIV-positive men who have sex with men...
April 19, 2017: JMIR Public Health and Surveillance
https://www.readbyqxmd.com/read/28424699/patient-s-experience-in-pediatric-primary-immunodeficiency-disorders-computerized-classification-of-questionnaires
#7
Urs Mücke, Christian Klemann, Ulrich Baumann, Almut Meyer-Bahlburg, Xiaowei Kortum, Frank Klawonn, Werner M Lechner, Lorenz Grigull
INTRODUCTION: Primary immunodeficiency disorders (PIDs) are a heterogeneous group of more than 200 rare diseases. Timely diagnosis is of uttermost importance. Therefore, we aimed to develop a diagnostic questionnaire with computerized pattern-recognition in order to support physicians to identify suspicious patient histories. MATERIALS AND METHODS: Standardized interviews were conducted with guardians of children with PID. The questionnaire based on parental observations was developed using Colaizzis' framework for content analysis...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28423509/histone-lysine-methyltransferase-g9a-is-a-novel-epigenetic-target-for-the-treatment-of-hepatocellular-carcinoma
#8
Masayuki Yokoyama, Tetsuhiro Chiba, Yoh Zen, Motohiko Oshima, Yuko Kusakabe, Yoshiko Noguchi, Kaori Yuki, Shuhei Koide, Shiro Tara, Atsunori Saraya, Kazumasa Aoyama, Naoya Mimura, Satoru Miyagi, Masanori Inoue, Toru Wakamatsu, Tomoko Saito, Sadahisa Ogasawara, Eiichiro Suzuki, Yoshihiko Ooka, Akinobu Tawada, Masayuki Otsuka, Masaru Miyazaki, Osamu Yokosuka, Atsushi Iwama
Histone H3 lysine 9 dimethylation (H3K9me2) is mainly regulated by the histone lysine methyltransferase G9a and is associated with the repression of transcription. However, both the role of G9a and the significance of H3K9me2 in hepatocellular carcinoma (HCC) cells remain unclear. In this study, we conducted loss-of-function assay of G9a using short-hairpin RNA and pharmacological interference. Knockdown of G9a reduced H3K9me2 levels and impaired both HCC cell growth and sphere formation. However, transforming growth factor β1-induced epithelial mesenchymal transition (EMT) was not suppressed by G9a knockdown...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28418524/evaluating-testing-strategies-for-identifying-youths-with-hiv-infection-and-linking-youths-to-biomedical-and-other-prevention-services
#9
Robin Lin Miller, Cherrie B Boyer, Danielle Chiaramonte, Peter Lindeman, Kate Chutuape, Bendu Cooper-Walker, Bill G Kapogiannis, Craig M Wilson, J Dennis Fortenberry
Importance: Most human immunodeficiency virus (HIV)-infected youths are unaware of their serostatus (approximately 60%) and therefore not linked to HIV medical or prevention services. The need to identify promising and scalable approaches to promote uptake of HIV testing among youths at risk is critical. Objective: To evaluate a multisite HIV testing program designed to encourage localized HIV testing programs focused on self-identified sexual minority males and to link youths to appropriate prevention services after receipt of their test results...
April 17, 2017: JAMA Pediatrics
https://www.readbyqxmd.com/read/28415580/the-n-terminal-polypeptide-derived-from-viral-macrophage-inflammatory-protein-ii-reverses-breast-cancer-epithelial-tomesenchymal-transition-via-a-pdgfra-dependent-mechanism
#10
Qing-Ling Yang, Ling-Yu Zhang, Hai-Feng Wang, Yu Li, Yue-Yue Wang, Tian-Tian Chen, Meng-Fen Dai, Hai-Hua Wu, Su-Lian Chen, Wen-Rui Wang, Qiong Wu, Chang-Jie Chen, Cong-Zhao Zhou
NT21MP, a 21-residue peptide derived from the viral macrophage inflammatory protein II, competed effectively with the natural ligand of CXC chemokine receptor 4 (CXCR4), stromal cell-derived factor 1-alpha, to induce apoptosis and inhibit growth in breast cancer. Its role in tumor epithelial-to-mesenchymal transition (EMT) regulation remains unknown. In this study, we evaluated the reversal of EMT upon NT21MP treatment and examined its role in the inhibition of EMT in breast cancer. The parental cells of breast cancer (SKBR-3 and MCF-7) and paclitaxel-resistant (SKBR-3 PR and MCF-7 PR) cells were studied in vitro and in combined immunodeficient mice...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28413739/genetic-modulation-therapy-through-stem-cell-transplantation-for-human-immunodeficiency-virus-1-infection
#11
REVIEW
Varshil Mehta, Divya Chandramohan, Shivika Agarwal
Highly active anti-retroviral treatment has changed the dimensions of the outcomes for patients suffering from human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS). However, HIV infection is still an ailment which is spreading throughout the world extensively. Given the confinements of the present restorative methodologies and the non-availability of any strategic vaccination against HIV, there is a squeezing need to build a therapeutic treatment. Viral tropism for HIV includes CD4+ cells, macrophages, and microglial cells, and it is through binding with co-receptors C-C chemokine receptor type 5 (CCR5) and C-X-C chemokine receptor type 4 (CXCR4)...
March 13, 2017: Curēus
https://www.readbyqxmd.com/read/28413361/cost-effectiveness-analysis-of-the-national-decentralization-policy-of-antiretroviral-treatment-programme-in-zambia
#12
Shinsuke Miyano, Gardner Syakantu, Kenichi Komada, Hiroyoshi Endo, Tomohiko Sugishita
BACKGROUND: In resource-limited settings with a high prevalence of human immunodeficiency virus (HIV) infection such as Zambia, decentralization of HIV/acquired immunodeficiency syndrome (HIV/AIDS) treatment and care with effective use of resources is a cornerstone of universal treatment and care. OBJECTIVES: This research aims to analyse the cost effectiveness of the National Mobile Antiretroviral Therapy (ART) Services Programme in Zambia as a means of decentralizing ART services...
2017: Cost Effectiveness and Resource Allocation: C/E
https://www.readbyqxmd.com/read/28412396/systems-approach-to-uncover-signaling-networks-in-primary-immunodeficiency-diseases
#13
Jeff Choi, Rosemary Fernandez, Holden T Maecker, Manish J Butte
This broad, unbiased approach of studying signaling across all circulating immune cells in healthy subjects allowed identification of disrupted signaling networks in patients with primary immunodeficiencies.
April 12, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28409656/condomless-sex-and-hiv-transmission-among-serodifferent-couples-current-evidence-and-recommendations
#14
Alan Koff, Carole Goldberg, Onyema Ogbuagu
Human immunodeficiency virus (HIV) infection remains a global pandemic. The primary driver of HIV incidence is sexual transmission between serodifferent individuals. Condoms, when used consistently and correctly, are effective at preventing sexually-transmitted HIV infections, and are considered an integral component of a comprehensive approach to HIV prevention. However, the demonstrated effectiveness of antiretroviral therapy (ART) to prevent HIV transmission, known as treatment as prevention, and of pre-exposure prophylaxis, have raised an intriguing dilemma on the necessity and additive preventive benefit of condom use among individuals in serodifferent relationships utilizing these prevention strategies...
April 14, 2017: Annals of Medicine
https://www.readbyqxmd.com/read/28408360/technology-use-and-preferences-for-mobile-phone-based-hiv-prevention-and-treatment-among-black-young-men-who-have-sex-with-men-exploratory-research
#15
Ian W Holloway, Terrell Ja Winder, Charles Herbert Lea, Diane Tan, Donte Boyd, David Novak
BACKGROUND: Black young men who have sex with men (BYMSM) experience higher human immunodeficiency virus (HIV) incidence than their white and Latino counterparts. OBJECTIVE: The aim of our study was to understand BYMSM's preferences for mobile phone-based HIV prevention and treatment in order to inform culturally tailored interventions to reduce the spread of HIV and improve HIV treatment outcomes in this population. METHODS: Qualitative focus groups (N=6) with BYMSM aged 18-29 years (N=41; 46%, 19/41 HIV-positive) were conducted to elucidate their preferences for the design and delivery of mobile phone-based HIV prevention and treatment interventions...
April 13, 2017: JMIR MHealth and UHealth
https://www.readbyqxmd.com/read/28407645/designing-human-immunodeficiency-virus-counselling-and-testing-services-to-maximize-uptake-among-high-school-learners-in-south-africa-what-matters
#16
Michael Strauss, Gavin George, Bruce Rhodes
BACKGROUND: Increasing human immunodeficiency virus (HIV) testing in South Africa is vital for the HIV response. Targeting young people is important as they become sexually active and because HIV risk rapidly increases as youth enter their 20s. This study aims to increase the understanding of high school learners' preferences regarding the characteristics of HIV testing service delivery models and to inform policy makers and implementers regarding potential barriers to and facilitators of HIV testing...
May 2017: Sexually Transmitted Diseases
https://www.readbyqxmd.com/read/28402933/pdk1-inhibitor-gsk2334470-exerts-antitumor-activity-in-multiple-myeloma-and-forms-a-novel-multitargeted-combination-with-dual-mtorc1-c2-inhibitor-pp242
#17
Chunmei Yang, Xianbo Huang, Hui Liu, Feng Xiao, Jueying Wei, Liangshun You, Wenbin Qian
A deeper understanding of the complex pathogenesis of multiple myeloma (MM) continues to lead to novel therapeutic approaches. Prior studies suggest that 3-phosphoinositide-dependent kinase 1 (PDK1) is expressed and active, acting as a crucial regulator of molecules that are essential for myelomagenesis. In the present study, we show that GSK2334470 (GSK-470), a novel and highly specific inhibitor of PDK1, induces potent cytotoxicity in MM cell lines including Dexamethasone-resistant cell line, but not in human normal cells...
March 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28399860/the-chinese-medicine-jc-001-enhances-the-chemosensitivity-of-lewis-lung-tumors-to-cisplatin-by-modulating-the-immune-response
#18
Meng-Hsien Chuang, Ming-Shiou Jan, Jinghua Tsai Chang, Fung-Jou Lu
BACKGROUND: JC-001 is a Chinese medicine that can modulate the immunity in Hepa 1-6 tumor-bearing mice, and we questioned whether JC-001 can serve as efficient adjuvant chemotherapy. We aimed to identify a novel approach for enhancing cis-diamminedichloroplatinum (II) (CDDP)-based chemotherapy by immunomodulation. METHODS: The anti-tumor activity in vitro was determined based on foci formation and a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay...
April 11, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28399797/a-machine-learning-approach-for-viral-genome-classification
#19
Mohamed Amine Remita, Ahmed Halioui, Abou Abdallah Malick Diouara, Bruno Daigle, Golrokh Kiani, Abdoulaye Baniré Diallo
BACKGROUND: Advances in cloning and sequencing technology are yielding a massive number of viral genomes. The classification and annotation of these genomes constitute important assets in the discovery of genomic variability, taxonomic characteristics and disease mechanisms. Existing classification methods are often designed for specific well-studied family of viruses. Thus, the viral comparative genomic studies could benefit from more generic, fast and accurate tools for classifying and typing newly sequenced strains of diverse virus families...
April 11, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28394918/a-novel-technique-of-serial-biopsy-in-mouse-brain-tumour-models
#20
Sasha Rogers, Hilary Hii, Joel Huang, Mathew Ancliffe, Nick G Gottardo, Peter Dallas, Sharon Lee, Raelene Endersby
Biopsy is often used to investigate brain tumour-specific abnormalities so that treatments can be appropriately tailored. Dacomitinib (PF-00299804) is a tyrosine kinase inhibitor (TKI), which is predicted to only be effective in cancers where the targets of this drug (EGFR, ERBB2, ERBB4) are abnormally active. Here we describe a method by which serial biopsy can be used to validate response to dacomitinib treatment in vivo using a mouse glioblastoma model. In order to determine the feasibility of conducting serial brain biopsies in mouse models with minimal morbidity, and if successful, investigate whether this can facilitate evaluation of chemotherapeutic response, an orthotopic model of glioblastoma was used...
2017: PloS One
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