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https://www.readbyqxmd.com/read/28520967/in-vivo-models-of-human-immunodeficiency-virus-persistence-and-cure-strategies
#1
Christopher C Nixon, Maud Mavigner, Guido Silvestri, J Victor Garcia
Current HIV therapy is not curative regardless of how soon after infection it is initiated or how long it is administered, and therapy interruption almost invariably results in robust viral rebound. Human immunodeficiency virus persistence is therefore the major obstacle to a cure for AIDS. The testing and implementation of novel yet unproven approaches to HIV eradication that could compromise the health status of HIV-infected individuals might not be ethically warranted. Therefore, adequate in vitro and in vivo evidence of efficacy is needed to facilitate the clinical implementation of promising strategies for an HIV cure...
March 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28491286/unwinding-focal-segmental-glomerulosclerosis
#2
REVIEW
Vasil Peev, Eunsil Hahm, Jochen Reiser
Focal segmental glomerulosclerosis (FSGS) represents the most common primary glomerular disease responsible for the development of end-stage renal disease (ESRD) in the United States (US). The disease progresses from podocyte injury to chronic kidney disease (CKD), ultimately leading to total nephron degeneration. Extensive basic science research has been conducted to unwind the mechanisms of FSGS and, with those insights, understand major contributors of CKD in general. As a result, several putative molecules and pathways have been studied, all implicated in the disease; some serve, in addition, as early biomarkers...
2017: F1000Research
https://www.readbyqxmd.com/read/28482505/sirna-nanoparticle-conjugate-in-gene-silencing-a-future-cure-to-deadly-diseases
#3
REVIEW
Rituparna Acharya, Suman Saha, Sayantan Ray, Sugata Hazra, Manoj K Mitra, Jui Chakraborty
Alzheimers, cancer, acquired immune deficiency syndrome (AIDS) are considered to be some of the most deadly diseases of the 21st century on account of their severity and rapid increase in the number of affected population and with scarce cases of recovery, they still remain a troubling paradox. Specifically, with millions of cancer patients worldwide and lack of proper cure for the same, understanding the deadly disease at the molecular level and planning a therapeutic strategy in the same line is the need of the hour...
July 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28473734/long-term-survival-of-aids-patients-treated-with-only-traditional-chinese-medicine
#4
Yifei Wang, Fujun Jin, Qiaoli Wang, Zucai Suo
Traditional Chinese herbal medicine (TCM) has been used in Chinese society for more than 5,000 years to treat diseases from inflammation to cancer. Here, we report the case of nine living AIDS patients in the age range of 51 to 67 who were treated with either a unique formula of TCM alone from 2001 to 2009 or the TCM from 2001 to 2006 and then switched to occasional antiretroviral therapy. Surprisingly, the viral loads of eight patients were at undetectable levels on June 28, 2016, while the remaining patient had a low viral load of 29 copies/ml...
April 1, 2017: Alternative & Complementary Therapies: a New Bimonthly Publication for Health Care Practitioners
https://www.readbyqxmd.com/read/28471431/current-application-of-crispr-cas9-gene-editing-technique-to-eradication-of-hiv-aids
#5
REVIEW
Z Huang, A Tomitaka, A Raymond, M Nair
Human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) remains a major health hazard despite significant advances in prevention and treatment of HIV infection. The major reason for the persistence of HIV/AIDS is the inability of existing treatments to clear or eradicate the multiple HIV reservoirs that exist in the human body. To suppress the virus replication and rebound, HIV/AIDS patients must take life-long antiviral medications. The clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated nuclease 9 (Cas9) system is an emerging gene-editing technique with the potential to eliminate or disrupt HIV-integrated genomes or HIV-infected cells from multiple HIV reservoirs, which could result in the complete cure of HIV/AIDS...
May 4, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28465838/a-critical-review-of-the-evidence-concerning-the-hiv-latency-reversing-effect-of-disulfiram-the-possible-explanations-for-its-inability-to-reduce-the-size-of-the-latent-reservoir-in-vivo-and-the-caveats-associated-with-its-use-in-practice
#6
REVIEW
Harry D J Knights
Combination antiretroviral therapy (cART) effectively suppresses the replication of human immunodeficiency virus type 1 (HIV-1), improves immune function, and decreases the morbidity of acquired immune deficiency syndrome (AIDS). However, it is unable to eradicate the virus because it does not eliminate latently infected cells. The latent reservoir poses the major barrier to an HIV-1 cure. The "shock and kill" strategy aims to reactivate the virus and destroy latently infected cells. Many latency reversing agents (LRAs) reactivate HIV in vitro, but the absence of damaging side-effects and efficacy in vivo make disulfiram particularly promising...
2017: AIDS Research and Treatment
https://www.readbyqxmd.com/read/28464317/joint-analysis-of-longitudinal-and-survival-aids-data-with-a-spatial-fraction-of-long-term-survivors-a-bayesian-approach
#7
Rui Martins, Giovani L Silva, Valeska Andreozzi
A typical survival analysis with time-dependent covariates usually does not take into account the possible random fluctuations or the contamination by measurement errors of the variables. Ignoring these sources of randomness may cause bias in the estimates of the model parameters. One possible way for overcoming that limitation is to consider a longitudinal model for the time-varying covariates jointly with a survival model for the time to the event of interest, thereby taking advantage of the complementary information flowing between these two-model outcomes...
May 2, 2017: Biometrical Journal. Biometrische Zeitschrift
https://www.readbyqxmd.com/read/28432928/a-humanized-mouse-based-hiv-1-viral-outgrowth-assay-with-higher-sensitivity-than-in-vitro-qvoa-in-detecting-latently-infected-cells-from-individuals-on-art-with-undetectable-viral-loads
#8
Paige Charlins, Kimberly Schmitt, Leila Remling-Mulder, Louise E Hogan, Emily Hanhauser, Kristen S Hobbs, Frederick Hecht, Steven G Deeks, Timothy J Henrich, Ramesh Akkina
Assays that can verify full viral eradication are essential in the context of achieving a cure for HIV/AIDS. In vitro quantitative viral out growth assays (qVOA) are currently the gold standard for measuring latent HIV-1 but these assays often fail to detect very low levels of replication-competent virus. Here we investigated an alternative in vivo approach for sensitive viral detection using humanized mice (hmVOA). Peripheral blood CD4+ T cell samples from HIV subjects on stable ART with undetectable viral loads by RT-PCR were first assayed by in vitro qVOA...
April 19, 2017: Virology
https://www.readbyqxmd.com/read/28432094/the-use-of-synthetic-hybrid-strains-to-determine-the-role-of-replicon-3-in-virulence-of-the-burkholderia-cepacia-complex
#9
Kirsty Agnoli, Roman Freitag, Margarida C Gomes, Christian Jenul, Angela Suppiger, Olga Mannweiler, Carmen Frauenknecht, Daniel Janser, Annette C Vergunst, Leo Eberl
The Burkholderia cepacia complex (Bcc) displays a wealth of metabolic diversity with great biotechnological potential, but the utilisation of these bacteria is limited by their opportunistic pathogenicity to humans. The third replicon of the Bcc, megaplasmid pC3 (0.5 to 1.4 Mb, previously chromosome 3), is important for various phenotypes, including virulence, antifungal and proteolytic activities, and the utilization of certain substrates. Approximately half of plasmid pC3 is well-conserved throughout sequenced Bcc members, while the other half is not...
April 21, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28429679/mycobacterium-avium-complex-disease
#10
Charles L Daley
Despite the ubiqitous nature of Mycobacterium avium complex (MAC) organisms in the environment, relatively few of those who are infected develop disease. Thus, some degree of susceptibility due to either underlying lung disease or immunosuppression is required. The frequency of pulmonary MAC disease is increasing in many areas, and the exact reasons are unknown. Isolation of MAC from a respiratory specimen does not necessarily mean that treatment is required, as the decision to treatment requires the synthesis of clinical, radiographic, and microbiologic information as well as a weighing of the risks and benefits for the individual patient...
April 2017: Microbiology Spectrum
https://www.readbyqxmd.com/read/28418987/the-roles-of-behavioral-and-social-science-research-in-the-fight-against-hiv-aids-a-functional-framework
#11
Paul Gaist, Michael J Stirratt
Landmark advances have been made in HIV/AIDS prevention and treatment. These include proof-of-concept and public health implementation of pre-exposure prophylaxis (PrEP) and "treatment as prevention" (TasP) to reduce HIV transmission as well as definitive evidence of the clinical gain from early antiretroviral treatment (ART) initiation. Significant progress has been made in understanding and addressing the social contexts and behavioral factors that impact HIV prevention, care, and treatment interventions...
April 7, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28417477/a-flexible-family-of-transformation-cure-rate-models
#12
M V Koutras, F S Milienos
In this paper, we introduce a flexible family of cure rate models, mainly motivated by the biological derivation of the classical promotion time cure rate model and assuming that a metastasis-competent tumor cell produces a detectable-tumor mass only when a specific number of distinct biological factors affect the cell. Special cases of the new model are, among others, the promotion time (proportional hazards), the geometric (proportional odds), and the negative binomial cure rate model. In addition, our model generalizes specific families of transformation cure rate models and some well-studied destructive cure rate models...
April 17, 2017: Statistics in Medicine
https://www.readbyqxmd.com/read/28413739/genetic-modulation-therapy-through-stem-cell-transplantation-for-human-immunodeficiency-virus-1-infection
#13
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/28406033/the-impact-of-hiv-antiretroviral-treatment-perception-on-risky-sexual-behaviour-in-botswana-a-short-report
#14
Gobopamang Letamo, Mpho Keetile, Kannan Navaneetham
The aim of this article is to investigate the impact of ART perception on risky sexual behaviours in Botswana. Using binary logistic regression analysis controlling for individual characteristics, the results tend to support the hypothesis that ART misconceptions do not necessarily increase risky sexual behaviours. In particular, the study findings suggest the belief that ARVs cure HIV and AIDS and that people on ARVs should not always use condoms do not necessarily lead to increased risky sexual behaviours, particularly among women...
April 13, 2017: AIDS Care
https://www.readbyqxmd.com/read/28404854/autologous-stem-cell-transplantation-disrupts-adaptive-immune-responses-during-rebound-shiv-viremia
#15
Daniel B Reeves, Christopher W Peterson, Hans-Peter Kiem, Joshua T Schiffer
Primary HIV-1 infection induces a virus-specific adaptive/cytolytic immune response that impacts plasma viral load setpoint and rate of progression to AIDS. Combination antiretroviral therapy (cART) suppresses plasma viremia to undetectable levels that rebound upon cART treatment interruption. Following cART withdrawal, the memory component of the virus-specific adaptive immune response may improve viral control compared to primary infection. Here, using primary infection and treatment interruption data from macaques infected with simian/human immunodeficiency virus (SHIV), we observe lower peak viral load but unchanged viral setpoint during viral rebound...
April 12, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28392467/predicted-coreceptor-usage-at-end-stage-hiv-disease-in-tissues-derived-from-subjects-on-antiretroviral-therapy-with-an-undetectable-plasma-viral-load
#16
S L Lamers, G B Fogel, E S Liu, D J Nolan, M Salemi, A E Barbier, R Rose, E J Singer, M S McGrath
HIV cure research is increasingly focused on anatomical tissues as sites for residual HIV replication during combined antiretroviral therapy (cART). Tissue-based HIV could contribute to low-level immune activation and viral rebound over the course of infection and could also influence the development of diseases, such as atherosclerosis, neurological disorders and cancers. cART-treated subjects have a decreased and irregular presence of HIV among tissues, which has resulted in a paucity of actual evidence concerning how or if HIV persists, replicates and evolves in various anatomical sites during therapy...
April 6, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28380207/tuberculosis-control-program-in-the-municipal-context-performance-evaluation
#17
Tiemi Arakawa, Gabriela Tavares Magnabosco, Rubia Laine de Paula Andrade, Maria Eugenia Firmino Brunello, Aline Aparecida Monroe, Antonio Ruffino-Netto, Lucia Marina Scatena, Tereza Cristina Scatena Villa
OBJECTIVE: The objective of this study is to evaluate the performance of the Tuberculosis Control Program in municipalities of the State of São Paulo. METHODS: This is a program evaluation research, with ecological design, which uses three non-hierarchical groups of the municipalities of the State of São Paulo according to their performance in relation to operational indicators. We have selected 195 municipalities with at least five new cases of tuberculosis notified in the Notification System of the State of São Paulo and with 20,000 inhabitants or more in 2010...
March 30, 2017: Revista de Saúde Pública
https://www.readbyqxmd.com/read/28366764/in%C3%A2-vivo-excision-of-hiv-1-provirus-by-sacas9-and-multiplex-single-guide-rnas-in-animal-models
#18
Chaoran Yin, Ting Zhang, Xiying Qu, Yonggang Zhang, Raj Putatunda, Xiao Xiao, Fang Li, Weidong Xiao, Huaqing Zhao, Shen Dai, Xuebin Qin, Xianming Mo, Won-Bin Young, Kamel Khalili, Wenhui Hu
CRISPR-associated protein 9 (Cas9)-mediated genome editing provides a promising cure for HIV-1/AIDS; however, gene delivery efficiency in vivo remains an obstacle to overcome. Here, we demonstrate the feasibility and efficiency of excising the HIV-1 provirus in three different animal models using an all-in-one adeno-associated virus (AAV) vector to deliver multiplex single-guide RNAs (sgRNAs) plus Staphylococcus aureus Cas9 (saCas9). The quadruplex sgRNAs/saCas9 vector outperformed the duplex vector in excising the integrated HIV-1 genome in cultured neural stem/progenitor cells from HIV-1 Tg26 transgenic mice...
May 3, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28361837/early-squamous-neoplasia-of-the-esophagus-the-endoscopic-approach-to-diagnosis-and-management
#19
REVIEW
Kesavan Kandiah, Fergus J Q Chedgy, Sharmila Subramaniam, Sreedhari Thayalasekaran, Arun Kurup, Pradeep Bhandari
Considerable focus has been placed on esophageal adenocarcinoma in the last 10 years because of its rising incidence in the West. However, squamous cell cancer (SCC) continues to be the most common type of esophageal cancer in the rest of the world. The detection of esophageal SCC (ESCC) in its early stages can lead to early endoscopic resection and cure. The increased incidence of ESCC in high-risk groups, such as patients with head and neck squamous cancers, highlights the need for screening programs. Lugol's iodine chromoendoscopy remains the gold standard technique in detecting early ESCC, however, safer techniques such as electronic enhancement or virtual chromoendoscopy would be ideal...
March 2017: Saudi Journal of Gastroenterology: Official Journal of the Saudi Gastroenterology Association
https://www.readbyqxmd.com/read/28342803/antigen-specific-ctls-to-produce-autologous-cells-product-for-adoptive-cellular-therapy
#20
Sai Liu, Yi Shao, Jie Xu, Na Jiang, Yanchao Dai, Yu Wang, Huanqing Sun, Jianping Sun, Yonghong Zhang
As antiretroviral therapy provides long term viral suppression but no cure, alternative therapies such as adoptive cellular therapy have thus been investigated in the anti-AIDS field. OBJECTIVE: This study sought to establish a HLA-A02 specific CTL cell culture method with comparison of the effects of different cytokines used in CTL cultivation to decide the best cultivation environment. In order to produce CTLs with targeted HLA-A02 restricted antigen specificity for adoptive cellular therapy, we evaluated autologous PBMC cultivation in different cytokine environment to select a better expansion condition to produce qualified CTL production...
March 22, 2017: International Journal of Infectious Diseases: IJID
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