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https://www.readbyqxmd.com/read/28346597/association-of-risk-of-viremia-immunosuppression-serious-clinical-events-and-mortality-with-increasing-age-in-perinatally-human-immunodeficiency-virus-infected-youth
#1
Anne M Neilan, Brad Karalius, Kunjal Patel, Russell B Van Dyke, Mark J Abzug, Allison L Agwu, Paige L Williams, Murli Purswani, Deborah Kacanek, James M Oleske, Sandra K Burchett, Andrew Wiznia, Miriam Chernoff, George R Seage, Andrea L Ciaranello
Importance: As perinatally human immunodeficiency virus-infected youth (PHIVY) in the United States grow older and more treatment experienced, clinicians need updated information about the association of age, CD4 cell count, viral load (VL), and antiretroviral (ARV) drug use with risk of opportunistic infections, key clinical events, and mortality to understand patient risks and improve care. Objective: To examine the incidence or first occurrence during follow-up of key clinical events (including Centers for Disease Control and Prevention stage B [CDC-B] and stage C [CDC-C] events) and mortality among PHIVY stratified by age, CD4 cell count, and VL and ARV status...
March 27, 2017: JAMA Pediatrics
https://www.readbyqxmd.com/read/28346504/diagnostic-accuracy-of-two-multiplex-real-time-polymerase-chain-reaction-assays-for-the-diagnosis-of-meningitis-in-children-in-a-resource-limited-setting
#2
Jermaine Khumalo, Mark Nicol, Diana Hardie, Rudzani Muloiwa, Phindile Mteshana, Colleen Bamford
INTRODUCTION: Accurate etiological diagnosis of meningitis is important, but difficult in resource-limited settings due to prior administration of antibiotics and lack of viral diagnostics. We aimed to develop and validate 2 real-time multiplex PCR (RT-PCR) assays for the detection of common causes of community-acquired bacterial and viral meningitis in South African children. METHODS: We developed 2 multiplex RT- PCRs for detection of S. pneumoniae, N. meningitidis, H...
2017: PloS One
https://www.readbyqxmd.com/read/28346436/detailed-comparison-of-retroviral-vectors-and-promoter-configurations-for-stable-and-high-transgene-expression-in-human-induced-pluripotent-stem-cells
#3
D Hoffmann, J W Schott, F K Geis, L Lange, F-J Müller, D Lenz, D Zychlinski, D Steinemann, M Morgan, T Moritz, A Schambach
Correction of patient-specific induced pluripotent stem cells (iPSC) upon gene delivery through retroviral vectors offers new treatment perspectives for monogenetic diseases. Gene-modified iPSC clones can be screened for safe integration sites and differentiated into transplantable cells of interest. However, the current bottleneck is epigenetic vector silencing. In order to identify the most suitable retroviral expression system in iPSC, we systematically compared vectors from different retroviral genera, different promoters and their combination with ubiquitous chromatin opening elements (UCOE), and several envelope pseudotypes...
March 27, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28346077/effects-of-brief-messages-about-antiretroviral-therapy-and-condom-use-benefits-among-black-and-latino-msm-in-three-us-cities
#4
Jeffrey H Herbst, Gordon Mansergh, Nicole Pitts, Damian Denson, Matthew J Mimiaga, Jeremy Holman
This pilot study examined effects of HIV prevention messages about self and partner benefits of antiretroviral therapy (ART) and condom effectiveness on increased intentions for behavior change. Data were from Messages4Men, a study examining prevention messages among 320 HIV-positive and 605 HIV-negative black and Latino MSM. Men completed a computer-based assessment after message exposure, and multivariable models controlled for risky sex and demographics. A majority of HIV-positive men reported increased intentions for ART use; 22% reported partner benefit information was new...
March 27, 2017: Journal of Homosexuality
https://www.readbyqxmd.com/read/28345163/pharmacokinetics-and-safety-of-letermovir-a-novel-anti-human-cytomegalovirus-drug-in-patients-with-renal-impairment
#5
D Kropeit, J Scheuenpflug, K Erb-Zohar, A Halabi, H-P Stobernack, E G J Hulskotte, A van Schanke, H Zimmermann, H Rübsamen-Schaeff
AIMS: Human cytomegalovirus remains a significant issue for immunocompromised patients and existing viral polymerase targeting therapies are associated with significant toxicity. Accordingly, the viral terminase complex inhibitor, letermovir, is in development. We assessed letermovir pharmacokinetics in renal impairment. METHODS: This was a Phase 1, open-label, non-randomised trial. Estimated glomerular filtration rate (eGFR) based on the Modification of Diet Renal Disease equation was used to create 3 groups of 8 subjects: healthy function (eGFR ≥90 mL/min/1...
March 26, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28344998/low-dose-liver-targeted-gene-therapy-for-pompe-disease-enhances-therapeutic-efficacy-of-ert-via-immune-tolerance-induction
#6
Sang-Oh Han, Giuseppe Ronzitti, Benjamin Arnson, Christian Leborgne, Songtao Li, Federico Mingozzi, Dwight Koeberl
Pompe disease results from acid α-glucosidase (GAA) deficiency, and enzyme replacement therapy (ERT) with recombinant human (rh) GAA has clinical benefits, although its limitations include the short half-life of GAA and the formation of antibody responses. The present study compared the efficacy of ERT against gene transfer with an adeno-associated viral (AAV) vector containing a liver-specific promoter. GAA knockout (KO) mice were administered either a weekly injection of rhGAA (20 mg/kg) or a single injection of AAV2/8-LSPhGAA (8 × 10(11) vector genomes [vg]/kg)...
March 17, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28344987/safe-and-effective-gene-therapy-for-murine-wiskott-aldrich-syndrome-using-an-insulated-lentiviral-vector
#7
Swati Singh, Iram Khan, Socheath Khim, Brenda Seymour, Karen Sommer, Matthew Wielgosz, Zachary Norgaard, Hans-Peter Kiem, Jennifer Adair, Denny Liggitt, Arthur Nienhuis, David J Rawlings
Wiskott-Aldrich syndrome (WAS) is a life-threatening immunodeficiency caused by mutations within the WAS gene. Viral gene therapy to restore WAS protein (WASp) expression in hematopoietic cells of patients with WAS has the potential to improve outcomes relative to the current standard of care, allogeneic bone marrow transplantation. However, the development of viral vectors that are both safe and effective has been problematic. While use of viral transcriptional promoters may increase the risk of insertional mutagenesis, cellular promoters may not achieve WASp expression levels necessary for optimal therapeutic effect...
March 17, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28344872/intravenously-usable-fully-serotype-3-oncolytic-adenovirus-coding-for-cd40l-as-an-enabler-of-dendritic-cell-therapy
#8
Sadia Zafar, Suvi Parviainen, Mikko Siurala, Otto Hemminki, Riikka Havunen, Siri Tähtinen, Simona Bramante, Lotta Vassilev, Hongjie Wang, Andre Lieber, Silvio Hemmi, Tanja de Gruijl, Anna Kanerva, Akseli Hemminki
Vaccination with dendritic cells (DCs), the most potent professional antigen-presenting cells in the body, is a promising approach in cancer immunotherapy. However, tumors induce immunosuppression in their microenvironment that suppresses and impairs the function of DCs. Therefore, human clinical trials with DC therapy have often been disappointing. To improve the therapeutic efficacy and to overcome the major obstacles of DC therapy, we generated a novel adenovirus, Ad3-hTERT-CMV-hCD40L, which is fully serotype 3 and expresses hCD40L for induction of antitumor immune response...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344151/enhancing-oligodendrocyte-differentiation-by-transient-transcription-activation-via-dna-nanoparticle-mediated-transfection
#9
Xiaowei Li, Stephany Y Tzeng, Camila Gadens Zamboni, Vassilis E Koliatsos, Guo-Li Ming, Jordan J Green, Hai-Quan Mao
Current approaches to derive oligodendrocytes from human pluripotent stem cells (hPSCs) need extended exposure of hPSCs to growth factors and small molecules, which limits their clinical application because of the lengthy culture time required and low generation efficiency of myelinating oligodendrocytes. Compared to extrinsic growth factors and molecules, oligodendrocyte differentiation and maturation can be more effectively modulated by regulation of the cell transcription network. In the developing central nervous system (CNS), two basic helix-loop-helix transcription factors, Olig1 and Olig2, are decisive in oligodendrocyte differentiation and maturation...
March 23, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28343935/blood-derived-products-in-pediatrics-new-laboratory-tools-for-optimizing-potency-assignment-and-reducing-side-effects
#10
REVIEW
Jean Amiral, Jerard Seghatchian
Neonates and children can develop rare bleeding disorders due to congenital/acquired coagulation Factor deficiencies, or allo-immune/autoimmune complications, or can undergo surgeries at high haemorrhagic risk. They then need specialized transfusion of blood components/products, or purified blood extracted products or recombinant proteins. Blood-derived therapies conventionally used for management of affected infants with genetic/acquired deficiencies, bleeding problems (coagulation Factor reduced or missing) or thrombotic disorders (reduced or missing anticoagulant proteins) pose some additional risks...
March 15, 2017: Transfusion and Apheresis Science
https://www.readbyqxmd.com/read/28343759/incidence-of-postsuppression-virologic-rebound-in-perinatally-hiv-infected-asian-adolescents-on-stable-combination-antiretroviral-therapy
#11
Tavitiya Sudjaritruk, Linda Aurpibul, Penh Sun Ly, Thoa Phan Kim Le, Torsak Bunupuradah, Rawiwan Hansudewechakul, Pagakrong Lumbiganon, Kulkanya Chokephaibulkit, Nik Khairulddin Nik Yusoff, Lam Van Nguyen, Kamarul Azahar Mohd Razali, Moy Siew Fong, Revathy A Nallusamy, Nia Kurniati, Viet Chau Do, David C Boettiger, Annette H Sohn, Azar Kariminia
PURPOSE: To assess the incidence and predictors of postsuppression virologic rebound (VR) among adolescents on stable combination antiretroviral therapy in Asia. METHODS: Perinatally HIV-infected Asian adolescents (10-19 years) with documented virologic suppression (two consecutive viral loads [VLs] <400 copies/mL ≥6 months apart) were included. Baseline was the date of the first VL <400 copies/mL at age ≥10 years or the 10th birthday for those with prior suppression...
March 23, 2017: Journal of Adolescent Health: Official Publication of the Society for Adolescent Medicine
https://www.readbyqxmd.com/read/28342989/patient-engagement-and-study-design-of-prop-up-a-multi-site-patient-centered-prospective-observational-study-of-patients-undergoing-hepatitis-c-treatment
#12
Donna M Evon, Carol E Golin, Paul Stewart, Michael W Fried, Shani Alston, Bryce Reeve, Anna S Lok, Richard K Sterling, Joseph K Lim, Nancy Reau, Souvik Sarkar, David R Nelson, K Rajender Reddy, Adrian M Di Bisceglie
BACKGROUND: New highly efficacious direct-acting antiviral (DAA) therapies are available to treat chronic hepatitis C viral (HCV) infection. Real-world, patient-centered data on harms and benefits associated with these therapies are needed. METHODS: PROP UP is a multi-center prospective observational study that plans to enroll 1600 patients starting treatment with recently-approved DAA regimens. Informed by extensive input from a HCV patient engagement group who prioritized outcomes most important to them, patient-reported outcomes will be characterized using surveys at five time points: Baseline (T1), treatment week 4 (T2), end of treatment (T3), 12weeks post-treatment (T4), 12months post-treatment (T5)...
March 22, 2017: Contemporary Clinical Trials
https://www.readbyqxmd.com/read/28342861/microrna-548j-inhibits-type-i-interferon-production-by-targeting-zbtb11-in-patients-with-chronic-hepatitis-b
#13
Kangkang Yu, Qian Li, Qi Cheng, Chong Huang, Jianming Zheng, Shengsen Chen, Qingxia Ling, Mengqi Zhu, Mingquan Chen, Guangfeng Shi, Ning Li
Type I IFNs play crucial roles in antiviral immune responses. By inducing cellular resistance to viral infection and apoptosis of virus-infected cells, they impair virus replication and eliminate the invading pathogens. However, in CHB patients, generation of type I IFN was significantly impaired and the underlying mechanisms have not been fully understood. MicroRNA-548 family has been implicated in regulating antiviral response upon various infections. Here we explored the potential role of miR-548j in modulating type I IFN production in CHB...
March 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28342803/antigen-specific-ctls-to-produce-autologous-cells-product-for-adoptive-cellular-therapy
#14
Sai Liu, Yi Shao, Jie Xu, Na Jiang, Yanchao Dai, Yu Wang, Huanqin 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 anti-AIDS field. OBJECTIVE: This study is to established a HLA-A02 specific CTL cell culture method with comparison of the effects of different cytokines used in CTLs 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 CTLs production...
March 22, 2017: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/28341877/short-courses-of-daily-prednisolone-during-upper-respiratory-tract-infections-reduce-relapse-frequency-in-childhood-nephrotic-syndrome
#15
Asiri S Abeyagunawardena, R S Thalgahagoda, Pathum V Dissanayake, Shamali Abeyagunawardena, Y A Illangasekera, Umeshi I Karunadasa, Richard S Trompeter
BACKGROUND: Relapses of childhood nephrotic syndrome (NS) are frequently precipitated by viral upper respiratory tract infections (URTIs). A review of the literature reveals that in patients with steroid-dependent NS on alternate day corticosteroids, a short course of daily corticosteroid therapy during the course of an URTI may reduce relapse frequency. OBJECTIVE: To assess the effect of a short course of low-dose corticosteroid therapy during the course of an URTI on relapse frequency in patients with steroid-sensitive NS who have not been taking any treatment for a minimum period of 3 months...
March 24, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28341860/high-plasma-lipid-levels-reduce-efficacy-of-adenovirus-mediated-gene-therapy
#16
A M Kivelä, J Huusko, E Gurzeler, A Laine, M H Dijkstra, G Dragneva, C B F Andersen, S K Moestrup, S Ylä-Herttuala
Adenoviruses are very efficient vectors for delivering therapeutic genes in preclinical and clinical trials. However, randomized controlled human trials have often been lacking clear clinically relevant results. We hypothesized that high lipid levels and specific lipoproteins could significantly decrease adenoviral transduction efficiency in vivo. Here we demonstrate that mice on a high fat diet have lower transgene expression compared to mice on a regular chow. In addition, on a high fat diet, ApoE(-/-) mice have much higher plasma transgene levels compared to LDLR-deficient mice...
March 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28341749/suppression-of-interferon-mediated-anti-hbv-response-by-single-cpg-methylation-in-the-5-utr-of-trim22
#17
Keo-Heun Lim, Eun-Sook Park, Doo Hyun Kim, Kyung Cho Cho, Kwang Pyo Kim, Yong Kwang Park, Sung Hyun Ahn, Seung Hwa Park, Kee-Hwan Kim, Chang Wook Kim, Hong Seok Kang, Ah Ram Lee, Soree Park, Heewoo Sim, Juhee Won, Kieun Seok, Jueng Soo You, Jeong-Hoon Lee, Nam-Joon Yi, Kwang-Woong Lee, Kyung-Suk Suh, Baik L Seong, Kyun-Hwan Kim
OBJECTIVE: Interferons (IFNs) mediate direct antiviral activity. They play a crucial role in the early host immune response against viral infections. However, IFN therapy for HBV infection is less effective than for other viral infections. DESIGN: We explored the cellular targets of HBV in response to IFNs using proteome-wide screening. RESULTS: Using LC-MS/MS, we identified proteins downregulated and upregulated by IFN treatment in HBV X protein (HBx)-stable and control cells...
March 23, 2017: Gut
https://www.readbyqxmd.com/read/28340951/epstein-barr-virus-hemophagocytic-lymphohistiocytosis-related-to-rituximab-use-and-immunopathogenetic-insights
#18
Sotirios G Papageorgiou, Sotirios Tsiodras, Georgios Siakallis, Efthimia Bazani, Aris Spathis, Garyfalia Poulakou, Penelope Korkolopoulou, Ioannis Panayiotides, Vasiliki Pappa
Anti-CD20-based chemo-immunotherapeutic regimens have been suggested to assist in the management of Epstein-Barr virus (EBV)-induced hemophagocytic lymphohistiocytosis (HLH) and EBV-associated post-transplant lymphoproliferative disorders (EBV-PTLD), by reducing EBV viral load and EBV-induced inflammation. Herein we report a fatal EBV-related HLH in the context of Hodgkin lymphoma (HL)-like Richter's transformation of B chronic lymphocytic leukemia (B-CLL), two months after rituximab treatment. The complex balance between EBV driven T-cell stimulation and immunosuppressive therapy in the context of multiple immune deficits is discussed...
December 2016: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28339647/detection-of-human-immunodeficiency-virus-1-ribonucleic-acid-in-the-peritoneal-effluent-of-renal-failure-patients-on-highly-active-antiretroviral-therapy
#19
Kwazi C Z Ndlovu, Wilbert Sibanda, Alain Assounga
Background.: We evaluated the shedding of human immunodeficiency virus (HIV)-1 particles into continuous ambulatory peritoneal dialysis (CAPD) effluents of HIV-positive patients with end-stage renal disease (ESRD). Methods.: A total of 58 HIV-positive patients with ESRD on highly active antiretroviral therapy (HAART) who had Tenckhoff catheters inserted between September 2012 and February 2015 were prospectively reviewed and followed for 18 months. Peritoneal dialysis (PD) effluent samples from functioning CAPD catheters and plasma samples were obtained at three points during regular clinic visits on days 45 ± 37, 200 ± 19 and 377 ± 13 after catheter insertion...
February 20, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28339162/sofosbuvir-based-treatment-is-safe-and-effective-in-indian-hepatitis-c-patients-on-maintenance-haemodialysis-a-retrospective-study
#20
Mohammed Shujauddin Akhil, Balaji Kirushnan, Melvin Martin, Kanakaraj Arumugam, N K Ganesh Prasad, Rajan Ravichandran
AIM: This study evaluates the safety and efficacy of direct-acting antivirals (DAAs) including sofosbuvir, ledipasvir and daclatasvir in patients with hepatitis C viraemia who were on maintenance haemodialysis METHODS: Data on patients who received sofosbuvir and ribavirin were analysed. Patients who experienced treatment failure with the above regimen received sofosbuvir and ledipasvir for infection with HCV genotype 1. Those having HCV genotype 3 infection received sofosbuvir and daclatasvir...
March 24, 2017: Nephrology
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