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https://www.readbyqxmd.com/read/29352723/which-hiv-infected-adults-with-high-cd4-t-cell-counts-benefit-most-from-immediate-initiation-of-antiretroviral-therapy-a-post-hoc-subgroup-analysis-of-the-start-trial
#1
Jean-Michel Molina, Birgit Grund, Fred Gordin, Ian Williams, Mauro Schechter, Marcello Losso, Matthew Law, Ernest Ekong, Noluthando Mwelase, Athanasios Skoutelis, Martin J Wiselka, Linos Vandekerckhove, Thomas Benfield, David Munroe, Jens D Lundgren, James D Neaton
BACKGROUND: Immediate initiation of antiretroviral therapy (ART) in asymptomatic adults with CD4 counts higher than 500 cells per μL, as recommended, might not always be possible in resource-limited settings. We aimed to identify subgroups of individuals who would benefit most from immediate treatment. METHODS: The START trial was a randomised controlled trial in asymptomatic, HIV-positive adults previously untreated with ART. Participants with CD4 counts higher than 500 cells per μL were randomly assigned to receive immediate ART or to defer ART until CD4 counts were lower than 350 cells per μL...
January 15, 2018: Lancet HIV
https://www.readbyqxmd.com/read/29352292/rna-seq-of-kaposi-s-sarcoma-reveals-alterations-in-glucose-and-lipid-metabolism
#2
For Yue Tso, Andrew V Kossenkov, Salum J Lidenge, Owen Ngalamika, John R Ngowi, Julius Mwaiselage, Jayamanna Wickramasinghe, Eun Hee Kwon, John T West, Paul M Lieberman, Charles Wood
Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent of Kaposi's sarcoma (KS). It is endemic in a number of sub-Saharan African countries with infection rate of >50%. The high prevalence of HIV-1 coupled with late presentation of advanced cancer staging make KS the leading cancer in the region with poor prognosis and high mortality. Disease markers and cellular functions associated with KS tumorigenesis remain ill-defined. Several studies have attempted to investigate changes of the gene profile with in vitro infection of monoculture models, which are not likely to reflect the cellular complexity of the in vivo lesion environment...
January 19, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29352052/estrogen-receptor-positive-breast-cancer-exploiting-signaling-pathways-implicated-in-endocrine-resistance
#3
REVIEW
Adam M Brufsky, Maura N Dickler
Advancements in molecular profiling and endocrine therapy (ET) have led to more focused clinical attention on precision medicine. These advances have expanded our understanding of breast cancer (BC) pathogenesis and hold promising implications for the future of therapy. The estrogen receptor-α is a predominant endocrine regulatory protein in the breast and in estrogen-induced BC. Successful targeting of proteins and genes within estrogen receptor (ER) nuclear and nonnuclear pathways remains a clinical goal...
January 19, 2018: Oncologist
https://www.readbyqxmd.com/read/29351936/intravitreal-bevacizumab-for-postviral-fever-retinitis-a-novel-approach-for-early-resolution-of-macular-oedema
#4
Rohan Chawla, Dheepak M Sundar, Prasad Gupta, Kanhaiya Mittal
Severe macular oedema causing marked loss of vision is seen in cases of retinitis developing postviral fever. The use of antivascular endothelial growth factor agents for macular oedema and submacular fluid secondary to viral retinitis has not been studied or well established in the past. We report a case series of two patients of postviral retinitis with severe macular oedema resistant to steroid therapy, treated with intravitreal bevacizumab. The patients showed significant symptomatic improvement in the visual acuity...
January 18, 2018: BMJ Case Reports
https://www.readbyqxmd.com/read/29351333/simultaneous-quantification-of-four-antiretroviral-drugs-in-breast-milk-samples-from-hiv-positive-women-by-an-ultra-high-performance-liquid-chromatography-tandem-mass-spectrometry-uplc-ms-ms-method
#5
Alicia Ramírez-Ramírez, Elías Sánchez-Serrano, Giselle Loaiza-Flores, Noemí Plazola-Camacho, Rosa Georgina Rodríguez-Delgado, Ricardo Figueroa-Damián, Mauricio Domínguez-Castro, Margarita López-Martínez, Zayra Flores-García, Jessica Hernández-Pineda
The primary strategy to avoid mother-to-child transmission of human immunodeficiency virus (HIV) through breastfeeding is administration of highly active antiretroviral therapy (HAART) to HIV-positive pregnant women. Because significant changes in the pharmacokinetics of antiretroviral (ARV) drugs occur during pregnancy, quantifying HAART and the viral load in breast milk in this population is essential. Here, we developed an analytical assay for the simultaneous quantification of four ARV drugs in breast milk using ultra-performance liquid chromatography coupled to tandem mass spectrometry...
2018: PloS One
https://www.readbyqxmd.com/read/29350173/membranoproliferative-glomerulonephritis-and-interstitial-nephritis-in-the-setting-of-epstein-barr-virus-related-hemophagocytic-syndrome%C3%A2
#6
Iolanda Godinho, Estela Nogueira, Sofia Jorge, António Teixeira Alves, António Gomes da Costa
BACKGROUND: Hemophagocytic syndrome (HPS) is a rare, aggressive disorder characterized by dysregulation of lymphocyte and macrophage activity, which culminates in tissue infiltration with hemophagocytosis and ultimately organ failure. Renal involvement frequently ensues and usually results in acute tubular necrosis with associated interstitial inflammation. Less frequently, glomerulopathy can also be found. CASE: We report a case of a 24-year-old Caucasian woman with previous asymptomatic hematuria, mild proteinuria, and normal renal function who presented to us with fever...
January 19, 2018: Clinical Nephrology
https://www.readbyqxmd.com/read/29350111/sustained-viral-suppression-with-co-administration-of-oxcarbazepine-and-dolutegravir
#7
Manar M Kandil, Melissa E Badowski, Christopher A Schriever
Co-administration of dolutegravir and oxcarbazepine has been reported to reduce levels of dolutegravir and therefore is contraindicated due to insufficient data to make dosing recommendations. We present eight cases in which patients with human immunodeficiency virus (HIV) inadvertently received oxcarbazepine while concurrently receiving 50 mg of dolutegravir daily as part of their antiretroviral therapy. Upon further evaluation, lab results revealed that despite the risk of decreased levels of dolutegravir due to possible oxcarbazepine enzyme induction, patients maintained at or near virologic suppression (viral load <20 copies/ml)...
January 1, 2018: International Journal of STD & AIDS
https://www.readbyqxmd.com/read/29346443/exposure-to-previous-cart-is-associated-with-significant-liver-fibrosis-and-cirrhosis-in-human-immunodeficiency-virus-infected-patients
#8
Evrim Anadol, Kristina Lust, Christoph Boesecke, Carolynne Schwarze-Zander, Raphael Mohr, Jan-Christian Wasmuth, Jürgen Kurt Rockstroh, Jonel Trebicka
INTRODUCTION: Combined antiretroviral therapy (cART) has improved survival in HIV-patients. While the first antiretrovirals, which became available in particular D-drugs (especially didanosine and stavudine) and unboosted protease inhibitors, may impair liver function, the modern cART seems to decrease liver fibrosis. This study assessed the influence of exposure to previous antiretrovirals on liver fibrosis in HIV-infected patients. METHODS: This observational cross-sectional single-center study recruited 333 HIV patients and assessed liver fibrosis using transient elastography (TE)...
2018: PloS One
https://www.readbyqxmd.com/read/29346270/resistance-to-hiv-integrase-inhibitors-about-r263k-and-e157q-mutations
#9
REVIEW
Charlotte Charpentier, Diane Descamps
The use of integrase inhibitors (INI) is increasing in antiretroviral therapies (ART) and INI are not all equal regarding genetic barrier to resistance. The aim of this manuscript was to review main in vivo and in vitro knowledge about two particular integrase resistance-associated mutations: R263K and E157Q. The R263K mutation was the first mutation rarely found selected at time of virological failure in patients failing a first-line dolutegravir-based treatment. Further in vitro studies on R263K mutants showed a moderate increase in phenotypic resistance level and a drastic reduction in viral replicative capacity...
January 18, 2018: Viruses
https://www.readbyqxmd.com/read/29346185/higher-art-adherence-is-associated-with-lower-systemic-inflammation-in-treatment-na%C3%A3-ve-ugandans-who-achieve-virologic-suppression
#10
Jose R Castillo-Mancilla, Mary Morrow, Yap Boum, Helen Byakwaga, Jessica E Haberer, Jeffrey N Martin, David Bangsberg, Samantha Mawhinney, Nicholas Musinguzi, Yong Huang, Russell P Tracy, Tricia H Burdo, Kenneth Williams, Conrad Muzoora, Peter W Hunt, Mark J Siedner
BACKGROUND: Residual systemic inflammation persists despite suppressive antiretroviral therapy (ART) and is associated with non-AIDS clinical outcomes. We aimed to evaluate the association between ART adherence and inflammation in Ugandans living with HIV who were predominantly receiving nevirapine-based ART with a thymidine analog backbone and were virologically suppressed by conventional assays. METHODS: Plasma concentrations of interleukin-6 (IL-6), D-dimer, soluble (s)CD14, sCD163, the kynurenine/tryptophan (K/T) ratio, in addition to CD8 T-cell activation, were measured at baseline and 6 months after ART initiation in treatment-naïve adults who achieved an undetectable plasma HIV RNA (<400 copies/mL) at their 6-month visit...
January 16, 2018: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/29345515/safety-of-biologic-agents-for-psoriasis-in-patients-with-viral-hepatitis
#11
Nawaf AlMutairi, Hesham Alaadin Abouzaid
INTRODUCTION: Biologics are highly effective, important treatment options for moderate-to-severe psoriasis. Biologics are well tolerated and have few side effects. However, the use of biologics in patients with concomitant chronic viral hepatitis is debatable. Recent reports have suggested a very low associated risk of reactivation of chronic hepatitis B (HBV) and C (HCB). OBJECTIVE: To evaluate the safety and effectiveness of biologics for moderate to severe psoriasis patients with concomitant chronic viral hepatitis...
January 18, 2018: Journal of Dermatological Treatment
https://www.readbyqxmd.com/read/29345394/viruses-as-key-modulators-of-the-tgf-%C3%AE-pathway-a-double-edged-sword-involved-in-cancer
#12
REVIEW
Habibollah Mirzaei, Ebrahim Faghihloo
Transforming growth factor-β (TGF-β) signaling pathway is a key network in cell signaling that controls vital processes such as proliferation, differentiation, apoptosis, epithelial-mesenchymal transition, and migration, thus acting as a double-edged sword in normal development and diseases, in particular organ fibrosis, vascular disorders, and cancer. Early in tumorigenesis, the pathway exerts anti-tumor effects through suppressing cell cycle and inducing apoptosis, while during late stages, it functions as a tumor promoter by enhancing tumor invasiveness and metastasis...
January 18, 2018: Reviews in Medical Virology
https://www.readbyqxmd.com/read/29345371/therapeutic-manipulation-of-host-cell-death-pathways-to-facilitate-clearance-of-persistent-viral-infections
#13
REVIEW
James Cooney, Cody Allison, Simon Preston, Marc Pellegrini
Most persistent viral infections can be controlled, but not cured, by current therapies. Abrogated antiviral immunity and stable latently infected cells represent major barriers to cure. This necessitates life-long suppressive antiviral therapy. Achieving a cure for HIV, hepatitis B virus, Epstein Barr-virus, and others, requires novel approaches to facilitate the clearance of infected cells from the host. One such approach is to target host cell death pathways, rather than the virus itself. Here, we summarize recent findings from studies that have utilized therapeutics to manipulate host cell death pathways as a means to treat and cure persistent viral infections...
January 9, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29344849/a-simple-protocol-for-transfecting-human-mesenchymal-stem-cells
#14
Talita Giacomet de Carvalho, Felipe Matheus Pellenz, Alvaro Laureano, Lucia Mariano da Rocha Silla, Roberto Giugliani, Guilherme Baldo, Ursula Matte
OBJECTIVES AND RESULTS: Mesenchymal stromal cells (MSCs) are potential targets for cell and gene therapy-based approaches against a variety of different diseases. The MSCs from bone marrow are a promising target population as they are capable of differentiating along multiple lineages and have significant expansion capability. These characteristics make them strong candidates for delivering genes and restoring organ systems function. However, as other primary cells, MSCs are difficult to transfect...
January 17, 2018: Biotechnology Letters
https://www.readbyqxmd.com/read/29344772/safety-and-efficacy-of-lamivudine-or-telbivudine-started-in-early-pregnancy-for-mothers-with-active-chronic-hepatitis-b
#15
Tianyu He, Yuqing Bai, Haodong Cai, Xiaojuan Ou, Min Liu, Wei Yi, Jidong Jia
BACKGROUND: Few data exist regarding use of nucleos(t)ide analogs started in early pregnancy for mothers with active chronic hepatitis B (CHB). We assessed the safety and efficacy of lamivudine/telbivudine initiated in the first trimester versus no treatment in mothers with active CHB. METHODS: We retrospectively enrolled 94 mothers newly diagnosed with active CHB in the first trimester of pregnancy. Patients with or without antiviral therapy were followed until postpartum week 28...
January 17, 2018: Hepatology International
https://www.readbyqxmd.com/read/29344726/the-safety-and-efficacy-of-elbasvir-and-grazoprevir-in-participants-with-hepatitis-c-virus-genotype-1b-infection
#16
Stefan Zeuzem, Lawrence Serfaty, John Vierling, Wendy Cheng, Jacob George, Jan Sperl, Simone Strasser, Hiromitsu Kumada, Peggy Hwang, Michael Robertson, Janice Wahl, Eliav Barr, Rohit Talwani, Heather Platt
BACKGROUND: Genotype 1b (GT1b) is the most common subtype of the hepatitis C virus (HCV). We present an integrated analysis of 1070 participants with HCV GT1b infection from 30 countries who received elbasvir/grazoprevir for 12 weeks. METHODS: This is a retrospective analysis of data from participants with chronic HCV GT1b infection enrolled in 11 phase II/III clinical trials. All participants received elbasvir 50 mg plus grazoprevir 100 mg once daily for 12 weeks...
January 17, 2018: Journal of Gastroenterology
https://www.readbyqxmd.com/read/29343578/a-new-quinoline-brd4-inhibitor-targets-a-distinct-latent-hiv-1-reservoir-for-re-activation-from-other-shock-drugs
#17
Erik Abner, Mateusz Stoszko, Lei Zeng, Heng-Chang Chen, Andrea Izquierdo-Bouldstridge, Tsuyoshi Konuma, Eduard Zorita, Elisa Fanunza, Qiang Zhang, Tokameh Mahmoudi, Ming-Ming Zhou, Guillaume J Filion, Albert Jordan
Upon HIV-1 infection, a reservoir of latently infected resting T cells prevents the eradication of the virus from patients. To achieve complete depletion, the existing virus-suppressing antiretroviral therapy must be combined with drugs that reactivate the dormant viruses. We previously described a novel chemical scaffold compound, MMQO (8-methoxy-6-methylquinolin-4-ol) that is able to reactivate viral transcription in several models of HIV latency including J-Lat cells through an unknown mechanism. MMQO potentiates the activity of known latency-reversing agents (LRAs) or 'shock' drugs such as PKC agonists or HDAC inhibitors...
January 17, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29343568/an-alternate-route-for-adeno-associated-virus-entry-independent-of-aavr
#18
Amanda M Dudek, Sirika Pillay, Andreas S Puschnik, Claude M Nagamine, Fang Cheng, Jianming Qiu, Jan E Carette, Luk H Vandenberghe
Determinants and mechanisms of cell attachment and entry steer the Adeno-Associated Virus (AAV) in its utility as a gene therapy vector. Thus far a systematic assessment of how diverse AAV serotypes engage their proteinaceous receptor AAVR (KIAA0319L) to establish transduction has been lacking, despite potential implications for cell and tissue tropism. Here, a large set of human and simian AAVs as well as in silico reconstructed ancestral AAV capsids were interrogated for AAVR usage. We identified a distinct AAV capsid lineage comprised of AAV4 and AAVrh32...
January 17, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29343567/parainfluenza-virus-infection-sensitizes-cancer-cells-to-dna-damaging-agents-implications-for-oncolytic-virus-therapy
#19
Candace R Fox, Griffith D Parks
We have previously shown that the Parainfluenza virus 5 (PIV5) mutant P/V-CPI- is restricted for spread in normal cells but not in cancer cells in vitro and is effective at reducing tumor burden in mouse model systems. Here we show that P/V-CPI- infection of human laryngeal cancer HEp-2 cells results in the majority of the cells dying, but unexpectedly, over time there is an emergence of a population of cells which survive as P/V-CPI- persistently infected (PI) cells. P/V-CPI- PI cells had elevated levels of basal caspase activation, and viability was highly dependent on activity of cellular inhibitors of apoptosis (IAPs) such as Survivin and XIAP...
January 17, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29343463/the-impact-of-mhealth-interventions-systematic-review-of-systematic-reviews
#20
REVIEW
Milena Soriano Marcolino, João Antonio Queiroz Oliveira, Marcelo D'Agostino, Antonio Luiz Ribeiro, Maria Beatriz Moreira Alkmim, David Novillo-Ortiz
BACKGROUND: Mobile phone usage has been rapidly increasing worldwide. mHealth could efficiently deliver high-quality health care, but the evidence supporting its current effectiveness is still mixed. OBJECTIVE: We performed a systematic review of systematic reviews to assess the impact or effectiveness of mobile health (mHealth) interventions in different health conditions and in the processes of health care service delivery. METHODS: We used a common search strategy of five major scientific databases, restricting the search by publication date, language, and parameters in methodology and content...
January 17, 2018: JMIR MHealth and UHealth
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