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https://www.readbyqxmd.com/read/28106981/controlling-multi-cycle-replication-of-live-attenuated-hiv-1-using-an-unnatural-genetic-switch
#1
Zhe Yuan, Nanxi Wang, Guobin Kang, Wei Niu, Qingsheng Li, Jiantao Guo
A safe and effective human immunodeficiency virus type 1 (HIV-1) vaccine is urgently needed, but remains elusive. While HIV-1 live-attenuated vaccine can provide potent protection as demonstrated in rhesus macaque-simian immunodeficiency virus model, the potential pathogenic consequences associated with the uncontrolled virus replication preclude such vaccine from clinical applications. We investigated a novel approach to address this problem by controlling live-attenuated HIV-1 replication through an unnatural genetic switch that was based on the amber suppression strategy...
January 20, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28100259/antitumor-activity-of-mir-34a-in-peritoneal-mesothelioma-relies-on-c-met-and-axl-inhibition-persistent-activation-of-erk-and-akt-signaling-as-a-possible-cytoprotective-mechanism
#2
Rihan El Bezawy, Michelandrea De Cesare, Marzia Pennati, Marcello Deraco, Paolo Gandellini, Valentina Zuco, Nadia Zaffaroni
BACKGROUND: The value of microRNAs (miRNAs) as novel targets for cancer therapy is now widely recognized. However, no information is currently available on the expression/functional role of miRNAs in diffuse malignant peritoneal mesothelioma (DMPM), a rapidly lethal disease, poorly responsive to conventional treatments, for which the development of new therapeutic strategies is urgently needed. Here, we evaluated the expression and biological effects of miR-34a-one of the most widely deregulated miRNAs in cancer and for which a lipid-formulated mimic is already clinically available-in a large cohort of DMPM clinical samples and a unique collection of in house-developed preclinical models, with the aim to assess the potential of a miR-34a-based approach for disease treatment...
January 18, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28099189/productive-infection-of-human-neural-progenitor-cells-by-r5-tropic-hiv-1-opiate-co-exposure-heightens-infectivity-and-functional-vulnerability
#3
Joyce M Balinang, Ruturaj R Masvekar, Kurt F Hauser, Pamela E Knapp
OBJECTIVE: Human immunodeficiency virus type-1 (HIV-1) causes a spectrum of CNS complications; many are worsened by opiate co-exposure. Human neural progenitor cells (hNPCs) give rise to all CNS neurons and macroglia. We tested the hypothesis that hNPC maturation and fate are altered by HIV and opiates, contributing to HIV-1-related neuropathology. Since reports that hNPCs are infectable remain controversial, we rigorously examined hNPC infection and ability to propagate infection, and determined whether HIV effects on hNPC function required infection...
January 17, 2017: AIDS
https://www.readbyqxmd.com/read/28093967/anchored-lentiviral-vector-episomes-for-stem-cell-gene-therapy-in-fanconi-anemia
#4
Santhosh Chakkaramakkil Verghese, Peter Kurre
Fanconi anemia (FA) is an autosomal recessive¬, multisystem DNA repair disorder with prominent defects in hematopoietic stem cell maintenance that result in their progressive attrition and failure in early school age. Allogeneic stem cell transplantation has proved curative for patients with suitable donors. This, along with the characteristic survival advantage of phenotypically normal over non-corrected FA stem cells underscores the compelling rationale for stem cell gene therapy in FA. While integrating lentiviral vectors (LV) have become the preferred platform for genetic correction in several hematologic and immunodeficiency disorders, the residual oncogenic potential by these vectors raises concerns in FA stem cells with potentially preexisting genetic lesions...
January 13, 2017: Current Gene Therapy
https://www.readbyqxmd.com/read/28091735/comprehensive-assessment-of-peripheral-blood-tcr%C3%AE-repertoire-in-infectious-mononucleosis-and-chronic-active-ebv-infection-patients
#5
Shenglin Liu, Qian Zhang, Dongli Huang, Wenli Zhang, Fengluan Zhong, Jia Feng, Xueru Chen, Qingxiang Meng, Xiaofan Chen, Wei Zhang, Hongyu Zhang
Epstein-Barr virus (EBV) primary infection is usually asymptomatic, but it sometimes progresses to infectious mononucleosis (IM). Occasionally, some people develop chronic active EBV infection (CAEBV) with underlying immunodeficiency, which belongs to a continuous spectrum of EBV-associated lymphoproliferative disorders (EBV(+) LPD) with heterogeneous clinical presentations and high mortality. It has been well established that T cell-mediated immune response plays a critical role in the disease evolution of EBV infection...
January 14, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28089909/immunosuppression-via-loss-of-il2r%C3%AE-enhances-long-term-functional-integration-of-hesc-derived-photoreceptors-in-the-mouse-retina
#6
Jie Zhu, Helen Cifuentes, Joseph Reynolds, Deepak A Lamba
Loss of photoreceptors is a common endpoint in degenerative retinal diseases. Human pluripotent stem cells provide a potential source for photoreceptor replacement, but, even in mouse models, the efficiency and efficacy of transplantation-based repair remains poor. In this study, we examined the degree to which immune rejection contributes to these disappointing outcomes using an immunodeficient IL2 receptor γ (IL2rγ)-null mouse model. Our results show that prevention of cell rejection in the normal and degenerating retinal environment significantly improves long-term survival and integration of hESC-derived donor retinal cells...
December 29, 2016: Cell Stem Cell
https://www.readbyqxmd.com/read/28088790/intraperitoneal-immunotherapy-with-t-cells-stably-and-transiently-expressing-anti-epcam-car-in-xenograft-models-of-peritoneal-carcinomatosis
#7
Wei Xia Ang, Zhendong Li, Zhixia Chi, Shou-Hui Du, Can Chen, Johan C K Tay, Han Chong Toh, John E Connolly, Xue Hu Xu, Shu Wang
The epithelial cell adhesion molecule (EpCAM) is overexpressed in a wide variety of tumor types, including peritoneal carcinomatosis (PC) from gastrointestinal and gynecological malignancies. To develop a chimeric antigen receptor T (CART) cell therapy approach to treat patients with end-stage PC, we constructed third generation CARs specific to EpCAM using the 4D5MOC-B single chain variable fragment. CART cells were generated with lentiviral transduction and exhibited specific in vitro killing activity against EpCAM-positive human ovarian and colorectal cancer cells...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28073767/analyses-of-sensitivity-to-the-missing-at-random-assumption-using-multiple-imputation-with-delta-adjustment-application-to-a-tuberculosis-hiv-prevalence-survey-with-incomplete-hiv-status-data
#8
Finbarr P Leacy, Sian Floyd, Tom A Yates, Ian R White
Multiple imputation with delta adjustment provides a flexible and transparent means to impute univariate missing data under general missing-not-at-random mechanisms. This facilitates the conduct of analyses assessing sensitivity to the missing-at-random (MAR) assumption. We review the delta-adjustment procedure and demonstrate how it can be used to assess sensitivity to departures from MAR, both when estimating the prevalence of a partially observed outcome and when performing parametric causal mediation analyses with a partially observed mediator...
January 10, 2017: American Journal of Epidemiology
https://www.readbyqxmd.com/read/28068935/qualitative-insights-into-implementation-processes-and-outcomes-of-a-randomized-trial-on-peer-support-and-hiv-care-engagement-in-rakai-uganda
#9
April Monroe, Gertrude Nakigozi, William Ddaaki, Jeremiah Mulamba Bazaale, Ronald H Gray, Maria J Wawer, Steven J Reynolds, Caitlin E Kennedy, Larry W Chang
BACKGROUND: People living with human immunodeficiency virus (HIV) who have not yet initiated antiretroviral therapy (ART) can benefit from being engaged in care and utilizing preventive interventions. Community-based peer support may be an effective approach to promote these important HIV services. METHODS: After conducting a randomized trial of the impact of peer support on pre-ART outcomes, we conducted a qualitative evaluation to better understand trial implementation, processes, and results...
January 10, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28068510/current-knowledge-and-priorities-for-future-research-in-late-effects-after-hematopoietic-stem-cell-transplantation-hct-for-severe-combined-immunodeficiency-patients-a-consensus-statement-from-the-second-pediatric-blood-and-marrow-transplant-consortium-international
#10
REVIEW
Jennifer Heimall, Jennifer Puck, Rebecca Buckley, Thomas A Fleisher, Andrew R Gennery, Benedicte Neven, Mary Slatter, Elie Haddad, Luigi D Notarangelo, K Scott Baker, Andrew C Dietz, Christine Duncan, Michael A Pulsipher, Mort J Cowan
Severe combined immunodeficiency (SCID) is 1 of the most common indications for pediatric hematopoietic cell transplantation (HCT) in patients with primary immunodeficiency. Historically, SCID was diagnosed in infants who presented with opportunistic infections within the first year of life. With newborn screening (NBS) for SCID in most of the United States, the majority of infants with SCID are now diagnosed and treated in the first 3.5 months of life; however, in the rest of the world, the lack of NBS means that most infants with SCID still present with infections...
January 6, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28067666/versatile-humanized-niche-model-enables-study-of-normal-and-malignant-human-hematopoiesis
#11
Ander Abarrategi, Katie Foster, Ashley Hamilton, Syed A Mian, Diana Passaro, John Gribben, Ghulam Mufti, Dominique Bonnet
The BM niche comprises a tightly controlled microenvironment formed by specific tissue and cells that regulates the behavior of hematopoietic stem cells (HSCs). Here, we have provided a 3D model that is tunable in different BM niche components and useful, both in vitro and in vivo, for studying the maintenance of normal and malignant hematopoiesis. Using scaffolds, we tested the capacity of different stromal cell types to support human HSCs. Scaffolds coated with human mesenchymal stromal cells (hMSCs) proved to be superior in terms of HSC engraftment and long-term maintenance when implanted in vivo...
January 9, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28063260/prevalence-of-communication-between-mothers-and-daughters-on-sexuality-and-associated-factors-in-sagamu-southwest-nigeria
#12
Oluwadamilola A Opawale, Victor J Animasahun, Helena J Chapman
BACKGROUND: As adolescents transition from childhood to adulthood, effective mother-daughter communication on sexuality plays a role in reducing high-risk behaviours linked to human immunodeficiency virus (HIV) infection and early pregnancy and childbirth. The objective of the study was to examine the prevalence of mother-daughter communication on sexuality and associated factors in Sagamu, southwest Nigeria. METHODS: Using multistage sampling, surveys were conducted using 234 female youth enrolled at a secondary school...
January 7, 2017: International Journal of Adolescent Medicine and Health
https://www.readbyqxmd.com/read/28062389/internet-based-hiv-prevention-with-at-home-sexually-transmitted-infection-testing-for-young-men-having-sex-with-men-study-protocol-of-a-randomized-controlled-trial-of-keep-it-up-2-0
#13
Brian Mustanski, Krystal Madkins, George J Greene, Jeffrey T Parsons, Brent A Johnson, Patrick Sullivan, Michael Bass, Rebekah Abel
BACKGROUND: Human immunodeficiency virus (HIV) infections are increasing among young men who have sex with men (YMSM), yet few HIV prevention programs have studied this population. Keep It Up! (KIU!), an online HIV prevention program tailored to diverse YMSM, was developed to fill this gap. The KIU! 2.0 randomized controlled trial (RCT) was launched to establish intervention efficacy. OBJECTIVE: The objective of the KIU! study is to advance scientific knowledge of technology-based behavioral HIV prevention, as well as improve public health by establishing the efficacy of an innovative electronic health (eHealth) prevention program for ethnically and racially diverse YMSM...
January 7, 2017: JMIR Research Protocols
https://www.readbyqxmd.com/read/28053365/integrated-biological-behavioural-surveillance-in-pandemic-threat-warning-systems
#14
Maureen Miller, Emily Hagan
Economically and politically disruptive disease outbreaks are a hallmark of the 21st century. Although pandemics are driven by human behaviours, current surveillance systems for identifying pandemic threats are largely reliant on the monitoring of disease outcomes in clinical settings. Standardized integrated biological-behavioural surveillance could, and should, be used in community settings to complement such clinical monitoring. The usefulness of such an approach has already been demonstrated in studies on human immunodeficiency virus, where integrated surveillance contributed to a biologically based and quantifiable understanding of the behavioural risk factors associated with the transmission dynamics of the virus...
January 1, 2017: Bulletin of the World Health Organization
https://www.readbyqxmd.com/read/28051925/a-social-work-plan-to-promote-hiv-testing-a-social-marketing-approach
#15
J P Morgan-Siebe
Many people living with human immunodeficiency virus (HIV) do not know that they are infected. It is important for infected persons to get tested for HIV in order to be diagnosed and medically treated. HIV has no known cure, but it can be controlled and sometimes prevented with proper medical care. The social work profession has ideal positioning to be extraordinarily helpful in work that promotes HIV testing, leading to reducing then eliminating new HIV diagnoses. Social marketing interventions, along with audience segmenting are explained...
January 4, 2017: Social Work in Health Care
https://www.readbyqxmd.com/read/28050264/therapy-of-hiv-infection-current-approaches-and-prospects
#16
M M Prokofjeva, S N Kochetkov, V S Prassolov
The human immunodeficiency virus type 1 (HIV-1) is the causative agent of one of the most dangerous human diseases - the acquired immune deficiency syndrome (AIDS). Over the past 30 years since the discovery of HIV-1, a number of antiviral drugs have been developed to suppress various stages of the HIV-1 life cycle. This approach has enables the suppression of virus replication in the body, which significantly prolongs the life of HIV patients. The main downside of the method is the development of viral resistance to many anti-HIV drugs, which requires the creation of new drugs effective against drug-resistant viral forms...
October 2016: Acta Naturae
https://www.readbyqxmd.com/read/28048423/we-fg-bra-08-potential-role-of-the-glycolytic-oscillator-in-acute-hypoxia-in-tumors
#17
L Che Fru, E Adamson, D Campos, S Fain, S Jacques, A van der Kogel, K Nickel, C Song, R Kimple, M Kissick
PURPOSE: Oscillatory dynamics in acute hypoxia have been observed, but poorly understood. They have mostly been attributed to vascular perturbations, but no link has yet been made to metabolic causes. We set out to determine the fundamental frequencies and test for coherence in tumor oxygen dynamics and spatial properties. METHODS: Severe combined immunodeficient (SCID) mice were inoculated onto bilateral flanks with human derived head and neck carcinoma (UW-SCC22) cell line xenografts...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28043619/identifying-patients-at-high-risk-of-tuberculosis-recurrence
#18
Ruxana T Sadikot
Several studies have been done in relation to recurrence of tuberculosis (TB) following completion of treatment. However, recurrence of TB is still a major problem from a public health perspective in high-burden countries, where no special attention is being given to this issue. Disease recurrence is an important indicator of the efficacy of antituberculosis treatment. The rate of recurrence is highly variable and has been estimated to range from 4.9% to 25%. This variability is not only a reflection of regional epidemiology of recurrence but differences in the definitions used by the TB control programs...
December 2016: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/28043600/benefits-and-challenges-of-molecular-diagnostics-for-childhood-tuberculosis
#19
Cristina Gutierrez
Expanding tuberculosis (TB)-diagnostic services, including access to rapid tests, is a World Health Organization (WHO) strategy to accelerate progress toward ending TB. Faster and more sensitive molecular tests capable of diagnosing TB and drug-resistant TB have the technical capacity to address limitations associated with smears and cultures by increasing accuracy and shortening turnaround times as compared with those of these conventional laboratory methods. Nucleic acid amplification assays used to detect and analyze Mycobacterium tuberculosis (MTB)-complex nucleic acids can be used directly on specimens from patients suspected of having TB...
December 2016: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/28043518/tuberculosis-in-vulnerable-populations-in-eastern-mediterranean-region-implications-for-control
#20
Sadia Shakoor, Rumina Hasan
AIMS & OBJECTIVES: Socially and economically disadvantaged or "vulnerable" people are at high risk of tuberculosis (TB) and also contribute to active chains of TB transmission. Included in such vulnerable populations are children, women, prisoners, people living with human immunodeficiency virus, the homeless, and displaced people. The ongoing active transmission of TB among such populations is made more difficult to assess and control by difficult access, health inequities, poverty, and other chronic and debilitating health conditions at individual, domestic, and community levels...
December 2016: International Journal of Mycobacteriology
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