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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/29352704/treatment-of-adult-chronic-indeterminate-chagas-disease-with-benznidazole-and-three-e1224-dosing-regimens-a-proof-of-concept-randomised-placebo-controlled-trial
#2
Faustino Torrico, Joaquim Gascon, Lourdes Ortiz, Cristina Alonso-Vega, María-Jesús Pinazo, Alejandro Schijman, Igor C Almeida, Fabiana Alves, Nathalie Strub-Wourgaft, Isabela Ribeiro
BACKGROUND: Chagas disease is a major neglected vector-borne disease. In this study, we investigated the safety and efficacy of three oral E1224 (a water-soluble ravuconazole prodrug) regimens and benznidazole versus placebo in adult chronic indeterminate Chagas disease. METHOD: In this proof-of-concept, double-blind, randomised phase 2 clinical trial, we recruited adults (18-50 years) with confirmed diagnosis of Trypanosoma cruzi infection from two outpatient units in Bolivia...
January 15, 2018: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/29352703/inotuzumab-ozogamicin-in-combination-with-low-intensity-chemotherapy-for-older-patients-with-philadelphia-chromosome-negative-acute-lymphoblastic-leukaemia-a-single-arm-phase-2-study
#3
Hagop Kantarjian, Farhad Ravandi, Nicholas J Short, Xuelin Huang, Nitin Jain, Koji Sasaki, Naval Daver, Naveen Pemmaraju, Joseph D Khoury, Jeffrey Jorgensen, Yesid Alvarado, Marina Konopleva, Guillermo Garcia-Manero, Tapan Kadia, Musa Yilmaz, Gautam Bortakhur, Jan Burger, Steven Kornblau, William Wierda, Courtney DiNardo, Alessandra Ferrajoli, Jovitta Jacob, Rebecca Garris, Susan O'Brien, Elias Jabbour
BACKGROUND: Inotuzumab ozogamicin, an anti-CD22 monoclonal antibody bound to a toxin, calicheamicin, has shown single-agent activity in relapsed or refractory acute lymphoblastic leukaemia. We aimed to assess the activity and safety of inotuzumab ozogamicin in combination with low-intensity chemotherapy in older patients with acute lymphoblastic leukaemia. METHODS: We did a single-arm, phase 2 study at the MD Anderson Cancer Center (Houston, TX, USA). Eligible patients were aged 60 years or older and had newly diagnosed, Philadelphia chromosome-negative, acute lymphoblastic leukaemia, and an Eastern Cooperative Oncology Group performance status of 3 or lower...
January 15, 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29352633/current-concerns-and-perspectives-on-zika-virus-co-infection-with-arboviruses-and-hiv
#4
REVIEW
Hussin A Rothan, Mehdi R M Bidokhti, Siddappa N Byrareddy
Dissemination of vector-borne viruses, such as Zika virus (ZIKV), in tropical and sub-tropical regions has a complicated impact on the immunopathogenesis of other endemic viruses such as dengue virus (DENV), chikungunya virus (CHIKV) and human immunodeficiency virus (HIV). The consequences of the possible co-infections with these viruses have specifically shown significant impact on the treatment and vaccination strategies. ZIKV is a mosquito-borne flavivirus from African and Asian lineages that causes neurological complications in infected humans...
January 16, 2018: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29352598/who-consultation-on-etec-and-shigella-burden-of-disease-geneva-6-7th-april-2017-meeting-report
#5
Divya Hosangadi, Peter G Smith, David C Kaslow, Birgitte K Giersing
According to the 2015 Global Burden of Disease Study, diarrhea ranked ninth among causes of death for all ages, and fourth among children under 5 years old, accounting for an estimated 499,000 deaths in this young age group. It was also the second most common cause of years lived with disability (2.39 billion YLDs). The goal of the WHO/UNICEF Integrated Global Action Plan for the Prevention and Control of Pneumonia and Diarrhea (GAPPD) is to reduce deaths from diarrhea in children under 5 years of age to less than 1 per 1000 live births, by 2025...
January 15, 2018: Vaccine
https://www.readbyqxmd.com/read/29352500/characterization-of-skin-blister-fluids-from-children-with-epstein-barr-virus-associated-lymphoproliferative-disease
#6
Taizo Wada, Tomoko Toma, Hanae Miyazawa, Eiko Koizumi, Tetsujiro Shirahashi, Yusuke Matsuda, Akihiro Yachie
Epstein-Barr virus (EBV)-associated T- or natural killer (NK)-cell lymphoproliferative disease (LPD) is a heterogeneous group of disorders characterized by chronic proliferation of EBV-infected lymphocytes. Patients may present with severe skin manifestations, including hypersensitivity to mosquito bites (HMB) and hydroa vacciniforme (HV)-like eruption, which are characterized by blister formation and necrotic ulceration. Skin biopsy specimens show inflammatory reactions comprising EBV-infected lymphocytes...
January 20, 2018: Journal of Dermatology
https://www.readbyqxmd.com/read/29352427/preserved-in-vitro-immunoreactivity-in-children-receiving-long-term-immunosuppressive-therapy-due-to-inflammatory-bowel-disease-or-autoimmune-hepatitis
#7
Teresa Schleker, Eva-Maria Jacobsen, Benjamin Mayer, Gudrun Strauss, Klaus-Michael Debatin, Carsten Posovszky
BACKGROUND: Children with inflammatory bowel disease (IBD) or autoimmune hepatitis (AIH) are at risk for severe infections. This is partially a result of their chronic disease condition but, moreover, a side effect of their immunosuppressive therapy. Currently, vaccinations with live vaccines are regarded as contraindicated under immunosuppressive therapy, mainly because of concerns about side effects and a lack of data showing an adequate immune reaction. As there is no systematic study on the individual immunoreactivity under immunosuppressive therapy in this patient group, we analyzed the lymphocyte subgroups and immunoreactivity of lymphocytes in children with IBD or AIH with and without immunosuppressive therapy in vitro...
January 19, 2018: Molecular and Cellular Pediatrics
https://www.readbyqxmd.com/read/29352420/diagnosis-and-management-of-hepatitis-c-infection-in-primary-care-settings
#8
Debra Guss, Jagannath Sherigar, Paul Rosen, Smruti R Mohanty
Hepatitis C virus (HCV) infection is a significant health problem worldwide, and is the leading cause of cirrhosis, hepatocellular carcinoma, and liver transplantation in the United States. The management of HCV has changed significantly over the last 5 years, as treatments have become simpler and more efficacious. Medication efficacy is now greater than 90%, with a high barrier to resistance and few side effects. This review is a collaboration between primary care and hepatology providers to explore all aspects of HCV management: acute versus chronic HCV infection, transmission and testing, and diagnosis and treatment...
January 19, 2018: Journal of General Internal Medicine
https://www.readbyqxmd.com/read/29352409/recent-perspectives-on-the-molecular-basis-of-biofilm-formation-by-pseudomonas-aeruginosa-and-approaches-for-treatment-and-biofilm-dispersal
#9
REVIEW
Sinosh Skariyachan, Vaishnavi Sneha Sridhar, Swathi Packirisamy, Supreetha Toplar Kumargowda, Sneha Basavaraj Challapilli
Pseudomonas aeruginosa, a Gram-negative, rod-shaped bacterium causes widespread diseases in humans. This bacterium is frequently related to nosocomial infections such as pneumonia, urinary tract infections (UTIs) and bacteriaemia especially in immunocompromised patients. The current review focuses on the recent perspectives on biofilms formation by these bacteria. Biofilms are communities of microorganisms in which cells stick to each other and often adhere to a surface. These adherent cells are usually embedded within a self-produced matrix of extracellular polymeric substance (EPS)...
January 19, 2018: Folia Microbiologica
https://www.readbyqxmd.com/read/29352388/cutaneous-granulomatosis-a-comprehensive-review
#10
REVIEW
Benedetta Terziroli Beretta-Piccoli, Carlo Mainetti, Marie-Astrid Peeters, Emmanuel Laffitte
Cutaneous granulomatosis is a heterogeneous group of diseases, characterized by a skin inflammatory reaction triggered by a wide variety of stimuli, including infections, foreign bodies, malignancy, metabolites, and chemicals. From a pathogenic point of view, they are divided into non-infectious and infectious granulomas. Pathophysiological mechanisms are still poorly understood. Non-infectious granulomatous skin diseases include granuloma annulare, necrobiosis lipoidica, rheumatic nodules, foreign body granulomas, cutaneous sarcoidosis, and interstitial granulomatous dermatitis...
January 19, 2018: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/29352371/innate-and-adaptive-t-cells-in-influenza-disease
#11
REVIEW
Simone Nüssing, Sneha Sant, Marios Koutsakos, Kanta Subbarao, Thi H O Nguyen, Katherine Kedzierska
Influenza is a major global health problem, causing infections of the respiratory tract, often leading to acute pneumonia, life-threatening complications and even deaths. Over the last seven decades, vaccination strategies have been utilized to protect people from complications of influenza, especially groups at high risk of severe disease. While current vaccination regimens elicit strain-specific antibody responses, they fail to generate cross-protection against seasonal, pandemic and avian viruses. Moreover, vaccines designed to generate influenza-specific T-cell responses are yet to be optimized...
January 20, 2018: Frontiers of Medicine
https://www.readbyqxmd.com/read/29352337/impact-of-hepatitis-b-carrier-status-on-the-outcomes-of-surgical-treatment-of-colorectal-liver-metastases
#12
Kin Pan Au, Kenneth Siu Ho Chok, Albert Chi Yan Chan, Wing Chiu Dai, Tan To Cheung, Chung Mau Lo
BACKGROUND: Chronic hepatitis B virus (HBV) infection is associated with a lower incidence of colorectal liver metastases. We explored the impact of HBV carrier status on outcomes of surgical treatment of colorectal liver metastases. METHODS: A retrospective analysis was conducted for consecutive patients undergoing liver resection for colorectal liver metastases from 2000 to 2016. HBV carriers were matched with controls by propensity scoring. RESULTS: 304 patients with known HBV carrier status who underwent resection of colorectal liver metastases were studied...
January 19, 2018: World Journal of Surgery
https://www.readbyqxmd.com/read/29352299/bunyavirus-requirement-for-endosomal-k-reveals-new-roles-of-cellular-ion-channels-during-infection
#13
Samantha Hover, Becky Foster, Juan Fontana, Alain Kohl, Steve A N Goldstein, John N Barr, Jamel Mankouri
In order to multiply and cause disease a virus must transport its genome from outside the cell into the cytosol, most commonly achieved through the endocytic network. Endosomes transport virus particles to specific cellular destinations and viruses exploit the changing environment of maturing endocytic vesicles as triggers to mediate genome release. Previously we demonstrated that several bunyaviruses, which comprise the largest family of negative sense RNA viruses, require the activity of cellular potassium (K+) channels to cause productive infection...
January 19, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29352298/hexokinase-ii-may-be-dispensable-for-cd4-t-cell-responses-against-a-virus-infection
#14
Siva Karthik Varanasi, Ujjaldeep Jaggi, Nissim Hay, Barry T Rouse
Activation of CD4 T cells leads to their metabolic reprogramming which includes enhanced glycolysis, catalyzed through hexokinase enzymes. Studies in some systems indicate that the HK2 isoform is the most up regulated isoform in activated T cells and in this report the relevance of this finding is evaluated in an infectious disease model. Genetic ablation of HK2 was achieved in only T cells and the outcome was evaluated by measures of T cell function. Our results show that CD4 T cells from both HK2 depleted and WT animals displayed similar responses to in vitro stimulation and yielded similar levels of Th1, Treg or Th17 subsets when differentiated in vitro...
2018: PloS One
https://www.readbyqxmd.com/read/29352292/rna-seq-of-kaposi-s-sarcoma-reveals-alterations-in-glucose-and-lipid-metabolism
#15
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/29352265/type-i-ifn-operates-pyroptosis-and-necroptosis-during-multidrug-resistant-a-baumannii-infection
#16
Yang Li, Xiaomin Guo, Chunmiao Hu, Yan Du, Chuansheng Guo, Di Wang, Weiheng Zhao, Gonghua Huang, Chunliang Li, Qiumin Lu, Ren Lai, Tao Xu, Xiaopeng Qi
Multidrug-resistant Acinetobacter baumannii, a common pathogen responsible for nosocomial infections, is the main cause for outbreaks of infectious diseases, such as pneumonia, meningitis, and bacteremia, especially among critically ill patients. Epidemic A. baumannii is a growing public health concern as it is resistant to all existing antimicrobial agents, thereby necessitating the development of new therapeutic approaches to mount an effective immune response against this bacterial pathogen. In this study, we identified a critical role for type I interferon (IFN) in epigenetic regulation during A...
January 19, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29352240/transcriptome-analysis-in-spleen-reveals-differential-regulation-of-response-to-newcastle-disease-virus-in-two-chicken-lines
#17
Jibin Zhang, Michael G Kaiser, Melissa S Deist, Rodrigo A Gallardo, David A Bunn, Terra R Kelly, Jack C M Dekkers, Huaijun Zhou, Susan J Lamont
Enhancing genetic resistance of chickens to Newcastle Disease Virus (NDV) provides a promising way to improve poultry health, and to alleviate poverty and food insecurity in developing countries. In this study, two inbred chicken lines with different responses to NDV, Fayoumi and Leghorn, were challenged with LaSota NDV strain at 21 days of age. Through transcriptome analysis, gene expression in spleen at 2 and 6 days post-inoculation was compared between NDV-infected and control groups, as well as between chicken lines...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29352230/histology-immunohistochemistry-and-in-situ-hybridization-reveal-overlooked-ebola-virus-target-tissues-in-the-ebola-virus-disease-guinea-pig-model
#18
Timothy K Cooper, Louis Huzella, Joshua C Johnson, Oscar Rojas, Sri Yellayi, Mei G Sun, Sina Bavari, Amanda Bonilla, Randy Hart, Peter B Jahrling, Jens H Kuhn, Xiankun Zeng
Survivors of Ebola virus infection may become subclinically infected, but whether animal models recapitulate this complication is unclear. Using histology in combination with immunohistochemistry and in situ hybridization in a retrospective review of a guinea pig confirmation-of-virulence study, we demonstrate for the first time Ebola virus infection in hepatic oval cells, the endocardium and stroma of the atrioventricular valves and chordae tendinae, satellite cells of peripheral ganglia, neurofibroblasts and Schwann cells of peripheral nerves and ganglia, smooth muscle cells of the uterine myometrium and vaginal wall, acini of the parotid salivary glands, thyroid follicular cells, adrenal medullary cells, pancreatic islet cells, endometrial glandular and surface epithelium, and the epithelium of the vagina, penis and, prepuce...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29352171/a-urine-dependent-human-urothelial-organoid-offers-a-potential-alternative-to-rodent-models-of-infection
#19
Harry Horsley, Dhanuson Dharmasena, James Malone-Lee, Jennifer L Rohn
Murine models describe a defined host/pathogen interaction for urinary tract infection, but human cell studies are scant. Although recent human urothelial organoid models are promising, none demonstrate long-term tolerance to urine, the natural substrate of the tissue and of the uropathogens that live there. We developed a novel human organoid from progenitor cells which demonstrates key structural hallmarks and biomarkers of the urothelium. After three weeks of transwell culture with 100% urine at the apical interface, the organoid stratified into multiple layers...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29351986/phase-ii-study-of-oral-jak1-jak2-inhibitor-ruxolitinib-in-advanced-relapsed-refractory-hodgkin-lymphoma
#20
Eric Van den Neste, Marc André, Thomas Gastinne, Aspasia Stamatoullas, Corinne Haioun, Amine Belhabri, Oumedaly Reman, Olivier Casasnovas, Hervé Guesquieres, Gregor Verhoef, Marie-José Claessen, Hélène A Poirel, Marie-Christine Copin, Romain Dubois, Peter Vandenberghe, Ioanna-Andrea Stoian, Anne S Cottereau, Sarah Bailly, Laurent Knoops, Franck Morschhauser
JAK2 constitutive activation/overexpression is common in classical Hodgkin lymphoma, and several cytokines stimulate Hodgkin lymphoma cells by recognizing JAK1-/JAK2-bound receptors. JAK blockade may thus be therapeutically beneficial in HL. This Phase II study assessed the safety and efficacy of ruxolitinib, an oral JAK1/2 inhibitor, in relapsed/refractory Hodgkin lymphoma patients. The primary objective was overall response rate according to IHP 2007 criteria. Thirty-three advanced patients (median prior lines: 5; refractory: 82%) were included; nine (27...
January 19, 2018: Haematologica
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