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https://www.readbyqxmd.com/read/28527892/outbreak-of-zika-virus-infection-in-singapore-an-epidemiological-entomological-virological-and-clinical-analysis
#1
(no author information available yet)
BACKGROUND: An outbreak of Zika virus infection was detected in Singapore in August, 2016. We report the first comprehensive analysis of a national response to an outbreak of Zika virus infection in Asia. METHODS: In the first phase of the outbreak, patients with suspected Zika virus infection were isolated in two national referral hospitals until their serum tested negative for the virus. Enhanced vector control and community engagement measures were deployed in disease clusters, including stepped-up mosquito larvicide and adulticide use, community participation in source reduction (destruction of mosquito breeding sites), and work with the local media to promote awareness of the outbreak...
May 17, 2017: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/28527420/factors-predictive-of-locoregional-recurrence-following-neoadjuvant-chemotherapy-in-patients-with-large-operable-or-locally-advanced-breast-cancer-an-analysis-of-the-eortc-10994-big-1-00-study
#2
Pauline Gillon, Nathan Touati, Christel Breton-Callu, Leen Slaets, David Cameron, Hervé Bonnefoi
PURPOSE: Identification of clinicopathological factors predicting for a locoregional recurrence (LRR) after neoadjuvant chemotherapy (NAC) could help to decide on the optimal locoregional radiotherapy. The objective of this trial is to identify those factors in the context of a phase III trial (European Organisation for Research and Treatment of Cancer 10994). METHODS: Patients received NAC followed by surgery with or without radiotherapy. Radiotherapy was administered according to pre-specified guidelines...
May 17, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28522589/identification-of-cancer-targeted-tropomyosin-inhibitors-and-their-synergy-with-microtubule-drugs
#3
Mark A Currier, Justine R Stehn, Ashleigh Swain, Duo Chen, Jeff Hook, Eleanor Eiffe, Andrew Heaton, David Brown, Brooke Nartker, David W Eaves, Nina Kloss, Herbert Treutlein, Jun Zeng, Irina B Alieva, Vera B Dugina, Edna C Hardeman, Peter W Gunning, Timothy P Cripe
Actin filaments, with their associated tropomyosin polymers, and microtubules are dynamic cytoskeletal systems regulating numerous cell functions. While anti-microtubule drugs are well-established, anti-actin drugs have been more elusive. We previously targeted actin in cancer cells by inhibiting the function of a tropomyosin isoform enriched in cancer cells, Tpm3.1, using a first-in-class compound, TR100. Here, we screened over 200 other anti-tropomyosin analogues for anti-cancer and on-target activity using a series of in vitro cell-based and biochemical assays...
May 18, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28518408/s-adenosylmethionine-mediated-apoptosis-is-potentiated-by-autophagy-inhibition-induced-by-chloroquine-in-human-breast-cancer-cells
#4
Donatella Delle Cave, Vincenzo Desiderio, Laura Mosca, Concetta Paola Ilisso, Luigi Mele, Michele Caraglia, Giovanna Cacciapuoti, Marina Porcelli
The naturally-occurring sulfonium compound S-adenosyl-L-methionine (AdoMet) is an ubiquitous sulfur-nucleoside that represents the main methyl donor in numerous methylation reactions. In recent years, it has been shown that AdoMet possesses antiproliferative properties in various cancer cells, but the molecular mechanisms at the basis of the effect induced by AdoMet have been only in part investigated. In the present study, we found that AdoMet strongly inhibited the proliferation of breast cancer cells MCF-7 by inducing both autophagy and apoptosis...
May 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28512001/low-dose-inflammatory-potential-of-silica-particles-in-human-derived-thp-1-macrophage-cell-culture-studies-mechanism-and-effects-of-particle-size-and-iron
#5
Premshekharan Gayatri, Hongqiao Zhang, Kennedy Nguyen, Henry Jay Forman, Valerie Jean Leppert
Silica and iron are major constituents in ambient particulate matter, and iron is a common impurity in many engineered nanomaterials. The purpose of this work was to determine the pro-inflammatory and other biological effects and mechanism of particle size and iron presence under low dose, non-cytotoxic conditions that are likely to approximate actual exposure levels, in contrast with higher dose studies in which cytotoxicity occurs. Specifically, human-derived THP-1 macrophages were exposed to 1 μg/ml of pristine and iron-coated 50 nm and 2 μm engineered silica nanoparticles...
May 13, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28511118/simultaneous-determination-of-selective-serotonin-reuptake-inhibitors-and-their-main-metabolites-in-human-breast-milk-by-liquid-chromatography-electrospray-mass-spectrometry
#6
Etienne Weisskopf, Alice Panchaud, Kim An Nguyen, Delphine Grosjean, Jean-Michel Hascoët, Chantal Csajka, Chin B Eap, Nicolas Ansermot
A bioanalytical method by high performance liquid chromatography coupled to electrospray mass spectrometry (HPLC-ESI-MS), adapted from a previously published method in plasma, was validated in breast milk for the simultaneous quantification of all antidepressants belonging to the class of selective serotonin reuptake inhibitors (citalopram, fluoxetine, fluvoxamine, paroxetine and sertraline) and their major metabolites (desmethylcitalopram and norfluoxetine). Milk samples (250μl) first underwent protein precipitation followed by solid-phase extraction on a reversed phase/cation exchange sorbent...
July 1, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28507171/first-in-man-demonstration-of-direct-endothelin-mediated-natriuresis-and-diuresis
#7
Robert W Hunter, Rebecca Moorhouse, Tariq E Farrah, Iain M MacIntyre, Takae Asai, Peter J Gallacher, Debbie Kerr, Vanessa Melville, Alicja Czopek, Emma E Morrison, Jess R Ivy, James W Dear, Matthew A Bailey, Jane Goddard, David J Webb, Neeraj Dhaun
Endothelin (ET) receptor antagonists are potentially novel therapeutic agents in chronic kidney disease and resistant hypertension, but their use is complicated by sodium and water retention. In animal studies, this side effect arises from ETB receptor blockade in the renal tubule. Previous attempts to determine whether this mechanism operates in humans have been confounded by the hemodynamic consequences of ET receptor stimulation/blockade. We aimed to determine the effects of ET signaling on salt transport in the human nephron by administering subpressor doses of the ET-1 precursor, big ET-1...
May 15, 2017: Hypertension
https://www.readbyqxmd.com/read/28497176/five-weekly-s-1-plus-cisplatin-therapy-combined-with-trastuzumab-therapy-in-her2-positive-gastric-cancer-a-phase-ii-trial-and-biomarker-study-wjog7212g
#8
Yuji Miura, Yasutaka Sukawa, Shuichi Hironaka, Misuzu Mori, Kazuhiro Nishikawa, Shinya Tokunaga, Hiroyuki Okuda, Takeshi Sakamoto, Keisei Taku, Kazuo Nishikawa, Toshikazu Moriwaki, Yuji Negoro, Yutaka Kimura, Keita Uchino, Katsunori Shinozaki, Hiroharu Shinozaki, Nobuyuki Musha, Hirotsugu Yoshiyama, Takashi Tsuda, Yoshinori Miyata, Naotoshi Sugimoto, Tsuyoshi Shirakawa, Miki Ito, Kimio Yonesaka, Kenichi Yoshimura, Narikazu Boku, Katsuhiko Nosho, Toshimi Takano, Ichinosuke Hyodo
BACKGROUND: Five-weekly S-1 plus cisplatin (SP) therapy is the standard care for advanced gastric or esophagogastric junction cancer (GC/EGJC) in East Asia. However, its efficacy and safety when combined with trastuzumab therapy for human epidermal growth factor receptor 2 (HER2)-positive advanced GC/EGJC remains unclear. METHODS: Patients received 5-weekly SP therapy (S-1 at 40-60 mg twice daily for 21 days plus cisplatin at 60 mg/m(2) on day 8, every 5 weeks) plus trastuzumab therapy (first dose of 8 mg/kg, then 6 mg/kg every 3 weeks)...
May 11, 2017: Gastric Cancer
https://www.readbyqxmd.com/read/28496485/phytochemicals-antioxidant-and-antiproliferative-properties-of-rosmarinus-officinalis-l-on-u937-and-caco-2-cells
#9
Yacine Amar, Boumediene Meddah, Irene Bonacorsi, Gregorio Costa, Gaetana Pezzino, Antonina Saija, Mariateresa Cristani, Soulef Boussahel, Guido Ferlazzo, Aicha Tirtouil Meddah
Rosmarinus officinalis L., a medicinal herb from the labiates family, has been reported to have potential benefit in the treatment and prevention of several diseases. In particular its phenolics have demonstrated protective effects on various types of cancer through several mechanisms. The present study aimed to determine the effects of rosemary phenolic extracts on human cell functions, with particular regard to their anti-proliferative properties in three cell types U937, CaCo-2 and the peripheral blood mononuclear cells (PBMCs)...
2017: Iranian Journal of Pharmaceutical Research: IJPR
https://www.readbyqxmd.com/read/28495400/rapid-breakthrough-of-131-i-in-an-in-vitro-human-epidermis-model
#10
U Nygren, A Hedman, T Nylén, L Thors
Skin contamination with radionuclides may cause local radiation damage, but also systemic distribution if the nuclides penetrate the epidermal membrane. Detailed information of the skin absorption of radionuclides is of importance for e.g. dose estimations and development of decontamination strategies. In the present study, penetration of (131)I through human epidermis was studied using an in vitro flow through diffusion chamber. Epidermis was exposed to a Na(131)I-solution, used in nuclear medicine, and the potential concentration-dependency of skin penetration was examined by including two concentrations of non-radioactive NaI...
May 8, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28490463/a-first-in-human-phase-i-dose-escalation-study-of-tak-117-a-selective-pi3k-alpha-isoform-inhibitor-in-patients-with-advanced-solid-malignancies
#11
Dejan Juric, Johann S de Bono, Patricia M LoRusso, John Nemunaitis, Elisabeth I Heath, Eunice L Kwak, Teresa Macarulla Mercadé, Elena Geuna, Maria Jose de Miguel-Luken, Chirag Patel, Keisuke Kuida, Serap Sankoh, Eric H Westin, Fabian Zohren, Yaping Shou, Josep Tabernero
Purpose: To evaluate the safety, maximum tolerated dose (MTD), pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of TAK-117 (MLN1117/INK1117), an investigational PI3Kα-selective inhibitor, in patients with advanced solid tumors. <p>Experimental Design: Seventy-one patients received oral TAK-117 once daily (QD, 100-300 mg [n = 24]), or 3 days per week (Mon-Wed-Fri [MWF], 200-1200 mg [n = 27]; Mon-Tue-Wed [MTuW], 200-900 mg [n = 20]), in 21-day cycles. Dose escalation proceeded via a 3+3 design...
May 10, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28489678/safety-and-efficacy-of-the-antiganglioside-gd3-antibody-ecromeximab-kw2871-combined-with-high-dose-interferon-%C3%AE-2b-in-patients-with-metastatic-melanoma
#12
Ahmad A Tarhini, Stergios J Moschos, Yan Lin, Hui-Min Lin, Cindy Sander, Yan Yin, Ralph Venhaus, Thomas F Gajewski, John M Kirkwood
This study evaluated the safety and clinical benefit of ecromeximab (KW2871) combined with high-dose interferon-α2b (HDI) in patients with metastatic melanoma. We also carried out pharmacokinetic and immune monitoring studies of this combination. This was an open-label, phase 1/2 study of ecromeximab plus HDI in patients with measurable metastatic melanoma. Eligible patients received ecromeximab-HDI combination therapy: ecromeximab administered intravenously once every 2 weeks and HDI at a dose of 20 million units (MU)/m administered intravenously for 5 consecutive days per week for the first 4 weeks (induction phase) and then at 10 MU/m subcutaneously thrice weekly through week 14 (maintenance phase)...
April 7, 2017: Melanoma Research
https://www.readbyqxmd.com/read/28488894/development-of-a-uhplc-ms-ms-srm-method-for-the-quantitation-of-endogenous-glucagon-and-dosed-glp-1-from-human-plasma
#13
James W Howard, Richard G Kay, Ben Jones, Jaimini Cegla, Tricia Tan, Steve Bloom, Colin S Creaser
AIM: The performance of glucagon and GLP-1 immunoassays is often poor, but few sensitive LC-MS/MS methods exist as alternatives. EXPERIMENTAL: A multiplexed LC-MS/MS method using a 2D extraction technique was developed. RESULTS: The method was established for the quantitation of endogenous glucagon (LLOQ: 15 pg/ml) and dosed GLP-1 (LLOQ: 25 pg/ml) in human plasma, and is the first such method avoiding immunoenrichment. Specificity of endogenous glucagon quantitation was assured using a novel approach with a supercharging mobile phase additive to access a sensitive qualifier SRM...
May 10, 2017: Bioanalysis
https://www.readbyqxmd.com/read/28488350/cranial-reconstruction-using-allogeneic-mesenchymal-stromal-cells-a-phase-1-first-in-human-trial
#14
David Anthony Morrison, Alan Matthew Kop, Anastasia Nilasaroya, Marian Sturm, Kathryn Shaw, Stephen Honeybul
Cranioplasty is necessary for patients that have undergone craniectomy following trauma, stroke or other causes of elevated intracranial pressure. This study assessed the effectiveness of treating cranial defects with a combination of allogeneic mesenchymal stromal cells (MSC) on a ceramic carrier and polymer scaffold, to produce viable bone and healing of a cranial void. Patients underwent a baseline CT scan for construct design. Two sets of interlocking moulds were 3D-printed to enable shaping of two polymer meshes which formed the boundaries of the construct corresponding to restoration of the skull interna and externa...
May 9, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28485775/determination-of-phloroglucinol-by-hplc-ms-ms-and-its-application-to-a-bioequivalence-study-in-healthy-volunteers
#15
X-Q Li, R-T Wang, Q-H Wang, X-L Tang, C-T Lu, H-G Gong, A-D Wen
OBJECTIVE: The aim of this study was to compare the pharmacokinetic characteristics of phloroglucinol between an orally disintegrating tablet and an orally lyophilized tablet of phloroglucinol in healthy volunteers under fasting condition. PATIENTS AND METHODS: A rapid and simple method based on high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method has been developed and validated for the determination of phloroglucinol in human plasma...
April 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28483710/current-nonclinical-testing-paradigms-in-support-of-safe-clinical-trials-an-iq-consortium-drusafe-perspective
#16
Lynne D Butler, Peggy Guzzie-Peck, James Hartke, Matthew S Bogdanffy, Yvonne Will, Dolores Diaz, Elisabeth Mortimer-Cassen, Mazin Derzi, Nigel Greene, Joseph J DeGeorge
The transition from nonclinical to First-in-Human (FIH) testing is one of the most challenging steps in drug development. In response to serious outcomes in a recent Phase 1 trial (sponsored by Bial), IQ Consortium/DruSafe member companies reviewed their nonclinical approach to progress small molecules safely to FIH trials. As a common practice, safety evaluation begins with target selection and continues through iterative in silico and in vitro screening to identify molecules with increased probability of acceptable in vivo safety profiles...
May 5, 2017: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/28481726/rotavirus-shedding-following-administration-of-rv3-bb-human-neonatal-rotavirus-vaccine
#17
Daniel Cowley, Karen Boniface, Nada Bogdanovic-Sakran, Carl D Kirkwood, Julie E Bines
The RV3-BB human neonatal rotavirus vaccine aims to provide protection from severe rotavirus disease from birth. A phase IIa safety and immunogenicity trial was undertaken in Dunedin, New Zealand between January 2012 and April 2014. Healthy, full-term (≥36 weeks gestation) babies, who were 0-5 days old were randomly assigned (1:1:1) to receive three doses of oral RV3-BB vaccine with the first dose given at 0-5 days after birth (neonatal schedule), or the first dose given at about 8 weeks after birth (infant schedule), or to receive placebo (placebo schedule)...
May 8, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28478943/feasibility-safety-and-tolerance-of-subcutaneous-synthetic-canine-b-type-natriuretic-peptide-syncbnp-in-healthy-dogs-and-dogs-with-stage-b1-mitral-valve-disease
#18
M A Oyama, P F Solter, C L Thorn, J A Stern
INTRODUCTION: An important aspect of heart failure is the progressive ineffectiveness of the salutary natriuretic peptide system and its secondary messenger, 3',5'-cyclic guanosine monophosphate (cGMP). In humans with acute heart failure, administration of exogenous natriuretic peptide is associated with improvement in clinical signs and reduction of cardiac filling pressures. This study aimed to determine the feasibility, tolerance, and safety of subcutaneous (SC) synthetic canine B-type natriuretic peptide (syncBNP) administration in dogs...
May 3, 2017: Journal of Veterinary Cardiology: the Official Journal of the European Society of Veterinary Cardiology
https://www.readbyqxmd.com/read/28472535/learning-from-human-cadaveric-prosections-examining-anxiety-in-speech-therapy-students
#19
Juan Jose Criado-Álvarez, Jaime González González, Carmen Romo Barrientos, Isabel Ubeda-Bañon, Daniel Saiz-Sanchez, Alicia Flores-Cuadrado, Juan Carlos Albertos-Marco, Alino Martinez-Marcos, Alicia Mohedano-Moriano
Human anatomy education often utilizes the essential practices of cadaver dissection and examination of prosected specimens. However, these exposures to human cadavers and confronting death can be stressful and anxiety-inducing for students. This study aims to understand the attitudes, reactions, fears, and states of anxiety that speech therapy students experience in the dissection room. To that end, a before-and-after cross-sectional analysis was conducted with speech therapy students undertaking a dissection course for the first time...
May 4, 2017: Anatomical Sciences Education
https://www.readbyqxmd.com/read/28468667/dynamics-of-freshwater-snails-and-schistosoma-infection-prevalence-in-schoolchildren-during-the-construction-and-operation-of-a-multipurpose-dam-in-central-c%C3%A3-te-d-ivoire
#20
Nana R Diakité, Mirko S Winkler, Jean T Coulibaly, Négnorogo Guindo-Coulibaly, Jürg Utzinger, Eliézer K N'Goran
BACKGROUND: The construction and operation of small multipurpose dams in Africa have a history of altering the transmission of water-based diseases, including schistosomiasis. The current study was designed to investigate the abundance and dynamics of schistosomiasis intermediate host snails and Schistosoma infections in humans during the construction and the first years of operation of a small multipurpose dam in Côte d'Ivoire. METHODS: The study was carried out in Raffierkro and four neighbouring villages in central Côte d'Ivoire between 2007 and 2012...
May 4, 2017: Infectious Diseases of Poverty
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