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https://www.readbyqxmd.com/read/28231247/favipiravir-pharmacokinetics-in-ebola-infected-patients-of-the-jiki-trial-reveals-concentrations-lower-than-targeted
#1
Thi Huyen Tram Nguyen, Jérémie Guedj, Xavier Anglaret, Cédric Laouénan, Vincent Madelain, Anne-Marie Taburet, Sylvain Baize, Daouda Sissoko, Boris Pastorino, Anne Rodallec, Géraldine Piorkowski, Sara Carazo, Mamoudou N Conde, Jean-Luc Gala, Joseph Akoi Bore, Caroline Carbonnelle, Frédéric Jacquot, Hervé Raoul, Denis Malvy, Xavier de Lamballerie, France Mentré
BACKGROUND: In 2014-2015, we assessed favipiravir tolerance and efficacy in patients with Ebola virus (EBOV) disease (EVD) in Guinea (JIKI trial). Because the drug had never been used before for this indication and that high concentrations of the drugs were needed to achieve antiviral efficacy against EBOV, a pharmacokinetic model had been used to propose relevant dosing regimen. Here we report the favipiravir plasma concentrations that were achieved in participants in the JIKI trial and put them in perspective with the model-based targeted concentrations...
February 23, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28229458/life-course-health-development-of-individuals-with-neurodevelopmental-conditions
#2
REVIEW
Robert J Palisano, Briano Di Rezze, Debra Stewart, Peter L Rosenbaum, Oksana Hlyva, Matthew Freeman, Tram Nguyen, Jan Willem Gorter
The life course health development (LCHD) model by Halfon et al. conceptualizes health development occurring through person-environment transactions that enable well-being and participation in desired social roles throughout life, areas that have not received adequate attention in healthcare. The aim of this 'perspectives' paper is to apply the six core tenets of the LCHD model and the concept of health development trajectories to individuals with lifelong neurodevelopmental conditions. We share the perspective that modifiable aspects of the environment often restrict health development; we then advocate that children, beginning at a young age, should engage in 'real-world' experiences that prepare them for current and future social roles...
February 23, 2017: Developmental Medicine and Child Neurology
https://www.readbyqxmd.com/read/28220340/preventing-youth-from-falling-through-the-cracks-between-child-adolescent-and-adult-mental-health-services-a-systematic-review-of-models-of-care
#3
Tram Nguyen, Mark G Embrett, Neil G Barr, Gillian M Mulvale, Diana K Vania, Glen E Randall, Briano DiRezze
Optimizing the transition between child and adolescent mental health services (CAMHS) and adult mental health services (AMHS) is a priority for healthcare systems. The purpose of this systematic review is to: (1) identify and compare models of care that may be used to facilitate the transition from CAMHS to AMHS; and (2) discuss trends and implications to inform future research and practice. Results identified three models of care which move beyond healthcare services and incorporate a broader range of services that better meet the dynamic needs of transition-aged youth...
February 20, 2017: Community Mental Health Journal
https://www.readbyqxmd.com/read/28219898/sk4-k-channels-are-therapeutic-targets-for-the-treatment-of-cardiac-arrhythmias
#4
Shiraz Haron-Khun, David Weisbrod, Hanna Bueno, Dor Yadin, Joachim Behar, Asher Peretz, Ofer Binah, Edith Hochhauser, Michael Eldar, Yael Yaniv, Michael Arad, Bernard Attali
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a stress-provoked ventricular arrhythmia, which also manifests sinoatrial node (SAN) dysfunction. We recently showed that SK4 calcium-activated potassium channels are important for automaticity of cardiomyocytes derived from human embryonic stem cells. Here SK4 channels were identified in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from healthy and CPVT2 patients bearing a mutation in calsequestrin 2 (CASQ2-D307H) and in SAN cells from WT and CASQ2-D307H knock-in (KI) mice...
February 20, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28219792/conjugative-type-iv-secretion-in-gram-positive-pathogens-trag-a-lytic-transglycosylase-and-endopeptidase-interacts-with-translocation-channel-protein-tram
#5
Verena Kohler, Ines Probst, Andreas Aufschnaiter, Sabrina Büttner, Lisa Schaden, Gerald Rechberger, Günther Koraimann, Elisabeth Grohmann, Walter Keller
Conjugative transfer plays a major role in the transmission of antibiotic resistance in bacteria. pIP501 is a Gram-positive conjugative model plasmid with the broadest transfer host-range known so far and is frequently found in Enterococcus faecalis and Enterococcus faecium clinical isolates. The pIP501 type IV secretion system is encoded by 15 transfer genes. In this work, we focus on the VirB1-like protein TraG, a modular peptidoglycan metabolizing enzyme, and the VirB8-homolog TraM, a potential member of the translocation channel...
February 17, 2017: Plasmid
https://www.readbyqxmd.com/read/28217134/proteasome-activity-profiling-uncovers-alteration-of-catalytic-%C3%AE-2-and-%C3%AE-5-subunits-of-the-stress-induced-proteasome-during-salinity-stress-in-tomato-roots
#6
Judit Kovács, Péter Poór, Farnusch Kaschani, Balakumaran Chandrasekar, Tram N Hong, Johana C Misas-Villamil, Bo T Xin, Markus Kaiser, Herman S Overkleeft, Irma Tari, Renier A L van der Hoorn
The stress proteasome in the animal kingdom facilitates faster conversion of oxidized proteins during stress conditions by incorporating different catalytic β subunits. Plants deal with similar kind of stresses and also carry multiple paralogous genes encoding for each of the three catalytic β subunits. Here, we investigated the existence of stress proteasomes upon abiotic stress (salt stress) in tomato roots. In contrast to Arabidopsis thaliana, tomato has a simplified proteasome gene set with single genes encoding each β subunit except for two genes encoding β2...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28215851/a-novel-neoadjuvant-therapy-for-operable-locally-invasive-non-small-cell-lung-cancer-phase-i-study-of-neoadjuvant-stereotactic-body-radiotherapy-linnearre-i-nct02433574
#7
Nhu-Tram A Nguyen, Naghmeh Isfahanian, Gregory Pond, Wael Hanna, Jean-Claude Cutz, James Wright, Anand Swaminath, Yaron Shargall, Tom Chow, Marcin Wierzbicki, Gordon Okawara, Kimmen Quan, Christian Finley, Rosalyn Juergens, Theodoros Tsakiridis
BACKGROUND: Despite improved staging and surgical techniques, the rate of incomplete resection (R1) of non-small-cell lung cancer (NSCLC) has not significantly decreased. Patients with R1 resection have worse survival compared with those with complete resection (R0). Stereotactic body radiotherapy (SBRT) is a rapid and convenient radiotherapy treatment that delivers high-dose radiotherapy to tumors with high precision while sparing normal organs. Although its efficacy in treating small lung tumors is documented, its use as neoadjuvant therapy for locally advanced (LA) NSCLC has not been examined...
January 31, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28210557/desmoid-tumor-following-abdominally-based-free-flap-breast-reconstruction
#8
Christine Oh, Ziyad S Hammoudeh, Brian T Carlsen
Desmoid tumors are fibroblastic connective tissue tumors that most commonly develop within the anterior abdominal wall. The etiology of desmoid tumors has not been well defined; however, hereditary, hormonal, traumatic, and surgery-related causes have been implicated. Desmoid tumors are believed to arise from musculoaponeurotic structures. Development in the breast is very rare. Several reports of desmoid tumors arising in the vicinity of the fibrous capsule of a breast implant have been described, but to date, the authors are not aware of any published cases following autologous breast reconstruction...
February 2017: Gland Surgery
https://www.readbyqxmd.com/read/28203559/fulminant-course-in-a-case-of-malignant-phyllodes-tumor
#9
Young Woo Chang, Hwan Soo Kim, Deok Woo Kim, Gil Soo Son
We present the case of a 31-year-old woman with an inflammatory and ulcerative malignant phyllodes tumor in her right breast. A right modified radical mastectomy and transverse rectus abdominis myocutaneous (TRAM) flap were performed. A month after the initial operation, several masses recurred at the superior margin and deep margin of the TRAM flap. Wide excision was performed, but masses recurred at the inferior margin and in both lung fields 2 weeks after the second operation. Six weeks after the second operation, the patient died due to progression of dyspnea and respiratory failure...
February 2017: Annals of Surgical Treatment and Research
https://www.readbyqxmd.com/read/28198179/breast-reconstruction-after-mastectomy-for-breast-cancer-comparative-analysis-of-early-and-delayed-reconstruction
#10
William Seidel, Jorge Bins Ely, Daniel Ongaratto Barazzetti, Renata Della Giustina, Gustavo P Walter, Thiago A Ferri, Rosemeri Maurici, Janaína L Narciso-Schiavon
BACKGROUND: Early reconstruction after mastectomy for breast cancer with definitive implants has been widely used, especially with the evolution of conservative surgical breast cancer treatments. We aimed to identify different characteristics associated with plastic surgery, based on immediate or delayed reconstruction time and evaluate quality of life in patients undergoing mastectomy for cancer. METHODS: This is a cross-sectional analytical study that evaluated adult patients undergoing mastectomy for breast cancer and breast reconstruction in Plastic Surgery Service at a tertiary hospital...
February 14, 2017: Minerva Chirurgica
https://www.readbyqxmd.com/read/28197106/inhibition-of-intermediate-conductance-calcium-activated-k-channel-kca3-1-and-fibroblast-mitogenesis-by-%C3%AE-linolenic-acid-and-alterations-of-channel-expression-in-the-lysosomal-storage-disorders-fabry-disease-and-niemann-pick-c
#11
Aida Oliván-Viguera, Javier Lozano-Gerona, Laura López de Frutos, Jorge J Cebolla, Pilar Irún, Edgar Abarca-Lachen, Ana J García-Malinis, Ángel Luis García-Otín, Yolanda Gilaberte, Pilar Giraldo, Ralf Köhler
The calcium/calmodulin-gated KCa3.1 channel regulates normal and abnormal mitogenesis by controlling K(+)-efflux, cell volume, and membrane hyperpolarization-driven calcium-entry. Recent studies suggest modulation of KCa3.1 by omega-3 fatty acids as negative modulators and impaired KCa3.1 functions in the inherited lysosomal storage disorder (LSD), Fabry disease (FD). In the first part of present study, we characterize KCa3.1 in murine and human fibroblasts and test the impact of omega-3 fatty acids on fibroblast proliferation...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28193090/estimating-false-recent-classification-for-the-limiting-antigen-avidity-eia-and-bed-capture-enzyme-immunoassay-in-vietnam-implications-for-hiv-1-incidence-estimates
#12
Neha S Shah, Yen T Duong, Linh-Vi Le, Nguyen Anh Tuan, Bharat Parekh, Hoang Thi Thanh Ha, Quang Duy Pham, Cao Thi Thu Cuc, Trudy Dobbs, Tran Hong Tram, Truong Tx Lien, Nick Wagar, Chunfu Yang, Amy Martin, Mitchell I Wolfe, Hien Tran Nguyen, Andrea A Kim
BACKGROUND: Laboratory tests that can distinguish recent from long-term HIV infection are used to estimate HIV incidence in a population but can potentially misclassify a proportion of long-term HIV infections as recent. Correct application of an assay requires determination of the proportion false recents (PFR) as part of the assay characterization and for calculating HIV incidence in a local population using a HIV incidence assay. METHODS: From April 2009 to December 2010, blood specimens were collected from HIV-infected individuals attending 9 outpatient clinics (OPCs) in Vietnam (4 from northern and 5 from southern Vietnam)...
February 14, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28176817/structural-insights-into-human-angiogenin-variants-implicated-in-parkinson-s-disease-and-amyotrophic-lateral-sclerosis
#13
William J Bradshaw, Saima Rehman, Tram T K Pham, Nethaji Thiyagarajan, Rebecca L Lee, Vasanta Subramanian, K Ravi Acharya
Mutations in Angiogenin (ANG), a member of the Ribonuclease A superfamily (also known as RNase 5) are known to be associated with Amyotrophic Lateral Sclerosis (ALS, motor neurone disease) (sporadic and familial) and Parkinson's Disease (PD). In our previous studies we have shown that ANG is expressed in neurons during neuro-ectodermal differentiation, and that it has both neurotrophic and neuroprotective functions. In addition, in an extensive study on selective ANG-ALS variants we correlated the structural changes to the effects on neuronal survival and the ability to induce stress granules in neuronal cell lines...
February 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28155011/photobiomodulation-laser-and-pulsed-electrical-field-increase-the-viability-of-the-musculocutaneous-flap-in-diabetic-rats
#14
Gabriella de Paula Marcondes Ferreira Leite, Lais Mara Siqueira das Neves, Carlos Alberto Silva, Rinaldo Roberto de Jesus Guirro, Thamires Rodrigues de Souza, Ana Karina de Souza, Sérgio Britto Garcia, Elaine Caldeira de Oliveira Guirro
The purpose of this study is to investigate the effect of pulsed electrical field (PEF) and photobiomodulation laser (PBM) on the viability of the TRAM flap in diabetic rats. Fifty Wistar rats were divided into five homogeneous groups: Group 1-control; Group 2-diabetics; Group 3-diabetics + PEF; Group 4-diabetic + laser 660 nm, 10 J/cm(2), 0.27 J; Group 5-diabetic + laser 660 nm, 140 J/cm(2), 3.9 J. The percentage of necrotic area was evaluated using software Image J®. The peripheral circulation of the flap was evaluated by infrared thermography FLIR T450sc (FLIR® Systems-Oregon USA)...
February 2, 2017: Lasers in Medical Science
https://www.readbyqxmd.com/read/28151482/critical-role-of-reactive-oxygen-species-ros-for-synergistic-enhancement-of-apoptosis-by-vemurafenib-and-the-potassium-channel-inhibitor-tram-34-in-melanoma-cells
#15
Daniel Bauer, Felix Werth, Ha An Nguyen, Felix Kiecker, Jürgen Eberle
Inhibition of MAP kinase pathways by selective BRAF inhibitors, such as vemurafenib and dabrafenib, have evolved as key therapies of BRAF-mutated melanoma. However, tumor relapse and therapy resistance have remained as major problems, which may be addressed by combination with other pathway inhibitors. Here we identified the potassium channel inhibitor TRAM-34 as highly effective in combination with vemurafenib. Thus apoptosis was significantly enhanced and cell viability was decreased. The combination vemurafenib/TRAM-34 was also effective in vemurafenib-resistant cells, suggesting that acquired resistance may be overcome...
February 2, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28148794/hiv-1-vpu-downmodulates-icam-1-expression-resulting-in-decreased-killing-of-infected-cd4-t-cells-by-nk-cells
#16
Scott M Sugden, Tram N Q Pham, Éric A Cohen
: HIV-1 Vpu is known to alter the expression of numerous cell surface molecules. Given the ever-increasing list of Vpu targets identified to date, we undertook a proteomic screen to discover novel cell membrane proteins modulated by this viral protein. Plasma membrane proteome isolates from Vpu-inducible T cells were subjected to SILAC-based mass spectrometry analysis and putative targets were validated by infection of primary CD4(+) T cells. We report here that while Intercellular Adhesion Molecule (ICAM)-1 and ICAM-3 are upregulated by HIV-1 infection, expression of Vpu offsets this increase by downregulating these molecules from the cell surface...
February 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28134560/chloroquine-attenuates-lipopolysaccharide-induced-inflammatory-responses-through-upregulation-of-usp25
#17
Changyu Ding, Fangfang Li, Yupeng Long, Jiang Zheng
Lipopolysaccharide (LPS) is a key pathogenic factor in sepsis, and its recognition by toll-like receptor 4 (TLR4) can activate two district signaling pathways, leading to activation of transcription factors including NF-κB and interferon regulatory factor 3 (IRF3). Chloroquine (CQ) has been shown to affect LPS-TLR4 colocalization and inhibit both MyD88-dependent and TRAM/TRIF-dependent pathways, though the mechanism involved is still poorly understood. Here, we found that the ubiquitin-proteasome system might be involved in this process...
November 30, 2016: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28132836/heme-oxygenase-2-binds-myristate-to-regulate-retrovirus-assembly-and-tlr4-signaling
#18
Yiping Zhu, Shukun Luo, Yosef Sabo, Cheng Wang, Liang Tong, Stephen P Goff
N-myristoylation is the covalent attachment of myristic acid to the N terminus of proteins in eukaryotic cells. The matrix domain (MA) of HIV-1 Gag protein is N-myristoylated and plays an important role in virus budding. In screening for host factors that interact with HIV-1 MA, we found that heme oxygenase (HO-2) specifically binds the myristate moiety of Gag. HO-2 was also found to bind TRAM, an adaptor protein for Toll-like receptor 4 (TLR4), and thereby impact both virus replication and cellular inflammatory responses...
February 8, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28126850/structural-insights-into-the-atomistic-mechanisms-of-action-of-small-molecule-inhibitors-targeting-the-kca3-1-channel-pore
#19
Hai M Nguyen, Vikrant Singh, Brandon Pressly, David Paul Jenkins, Heike Wulff, Vladimir Yarov-Yarovoy
The calcium-activated potassium channel KCa3.1 constitutes an attractive pharmacological target for immunosuppression, fibroproliferative disorders, atherosclerosis and stroke. However, there currently is no available crystal structure of this medically relevant channel that could be used for structure-assisted drug design. Using the Rosetta molecular modeling suite we generated a molecular model of the KCa3.1 pore and tested the model by first confirming previously mapped binding sites and visualizing the mechanism of TRAM-34, senicapoc and NS6180 inhibition at the atomistic level...
January 26, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28119159/hindbrain-dpp-iv-inhibition-improves-glycemic-control-and-promotes-negative-energy-balance
#20
Elizabeth G Mietlicki-Baase, Lauren E McGrath, Kieran Koch-Laskowski, Joanna Krawczyk, Tram Pham, Rinzin Lhamo, David J Reiner, Matthew R Hayes
The beneficial glycemic and food intake-suppressive effects of glucagon-like peptide-1 (GLP-1) have made this neuroendocrine system a leading target for pharmacological approaches to the treatment of diabetes and obesity. One strategy to increase the activity of endogenous GLP-1 is to prevent the rapid degradation of the hormone by the enzyme dipeptidyl peptidase-IV (DPP-IV). However, despite the expression of both DPP-IV and GLP-1 in the brain, and the clear importance of central GLP-1 receptor (GLP-1R) signaling for glycemic and energy balance control, the metabolic effects of central inhibition of DPP-IV activity are unclear...
January 22, 2017: Physiology & Behavior
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