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https://www.readbyqxmd.com/read/28923897/controlled-human-malaria-infection-applications-advances-and-challenges
#1
Danielle I Stanisic, James S McCarthy, Michael F Good
Controlled Human Malaria Infection (CHMI) entails deliberate infection with malaria parasites either by mosquito bite or direct injection of sporozoites or parasitised erythrocytes. When required, the resulting blood-stage infection is curtailed by the administration of anti-malarial drugs. Inducing a malaria infection via inoculation with infected blood was first used as a treatment (malariotherapy) for neurosyphilis in Europe and the United States in the early 1900s. More recently, CHMI has been applied to the fields of malaria vaccine and drug development where it is used to evaluate products in well-controlled early phase proof-of-concept clinical studies thus facilitating progression of only the most promising candidates for further evaluation in malaria-endemic areas...
September 18, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28891786/a-framework-and-case-studies-for-evaluation-of-enzyme-ontogeny-in-children-s-health-risk-evaluation
#2
Gary Ginsberg, Suryanarayana V Vulimiri, Yu-Sheng Lin, Jayaram Kancherla, Brenda Foos, Babasaheb Sonawane
Knowledge of the ontogeny of Phase I and Phase II metabolizing enzymes may be used to inform children's vulnerability based upon likely differences in internal dose from xenobiotic exposure. This might provide a qualitative assessment of toxicokinetic (TK) variability and uncertainty pertinent to early lifestages and help scope a more quantitative physiologically based toxicokinetic (PBTK) assessment. Although much is known regarding the ontogeny of metabolizing systems, this is not commonly utilized in scoping and problem formulation stage of human health risk evaluation...
September 11, 2017: Journal of Toxicology and Environmental Health. Part A
https://www.readbyqxmd.com/read/28881315/double-track-electrochemical-green-approach-for-simultaneous-dissolution-profiling-of-naproxen-sodium-and-diphenhydramine-hydrochloride
#3
Mostafa A Shehata, Esraa M Fawaz, Mohamed K Abd El-Rahman, Ezzat M Abdel-Moety
Acquisition of the dissolution profiles of more than single active ingredient in a multi-analyte pharmaceutical formulation is a mandatory manufacturing practice that is dominated by utilization of the off-line separation-based chromatographic methods. This contribution adopts a new "Double-Track" approach with the ultimate goal of advancing the in-line potentiometric sensors to their most effective applicability for simultaneous acquisition of the dissolution profiles of two active ingredients in a binary pharmaceutical formulation...
August 31, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28851316/a-non-controlled-single-arm-open-label-phase-ii-study-of-intravenous-and-intratumoral-administration-of-parvoryx-in-patients-with-metastatic-inoperable-pancreatic-cancer-parvoryx02-protocol
#4
Jacek Hajda, Monika Lehmann, Ottheinz Krebs, Meinhard Kieser, Karsten Geletneky, Dirk Jäger, Michael Dahm, Bernard Huber, Tilman Schöning, Oliver Sedlaczek, Albrecht Stenzinger, Niels Halama, Volker Daniel, Barbara Leuchs, Assia Angelova, Jean Rommelaere, Christine E Engeland, Christoph Springfeld, Guy Ungerechts
BACKGROUND: Metastatic pancreatic cancer has a dismal prognosis, with a mean six-month progression-free survival of approximately 50% and a median survival of about 11 months. Despite intensive research, only slight improvements of clinical outcome could be achieved over the last decades. Hence, new and innovative therapeutic strategies are urgently required. ParvOryx is a drug product containing native parvovirus H-1 (H-1PV). Since H-1PV was shown to exert pronounced anti-neoplastic effects in pre-clinical models of pancreatic cancer, the drug appears to be a promising candidate for treatment of this malignancy...
August 29, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28837082/rna-interference-and-bmp-2-stimulation-allows-equine-chondrocytes-redifferentiation-in-3d-hypoxia-cell-culture-model-application-for-matrix-induced-autologous-chondrocyte-implantation
#5
Rodolphe Rakic, Bastien Bourdon, Magalie Hervieu, Thomas Branly, Florence Legendre, Nathalie Saulnier, Fabrice Audigié, Stéphane Maddens, Magali Demoor, Philippe Galera
As in humans, osteoarthritis (OA) causes considerable economic loss to the equine industry. New hopes for cartilage repair have emerged with the matrix-associated autologous chondrocyte implantation (MACI). Nevertheless, its limitation is due to the dedifferentiation occurring during the chondrocyte amplification phase, leading to the loss of its capacity to produce a hyaline extracellular matrix (ECM). To enhance the MACI therapy efficiency, we have developed a strategy for chondrocyte redifferentiation, and demonstrated its feasibility in the equine model...
August 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28827709/electrochemical-hydroxylation-of-c3-c12-n-alkanes-by-recombinant-alkane-hydroxylase-alkb-and-rubredoxin-2-alkg-from-pseudomonas-putida-gpo1
#6
Yi-Fang Tsai, Wen-I Luo, Jen-Lin Chang, Chun-Wei Chang, Huai-Chun Chuang, Ravirala Ramu, Guor-Tzo Wei, Jyh-Myng Zen, Steve S-F Yu
An unprecedented method for the efficient conversion of C3-C12 linear alkanes to their corresponding primary alcohols mediated by the membrane-bound alkane hydroxylase (AlkB) from Pseudomonas putida GPo1 is demonstrated. The X-ray absorption spectroscopy (XAS) studies support that electrons can be transferred from the reduced AlkG (rubredoxin-2, the redox partner of AlkB) to AlkB in a two-phase manner. Based on this observation, an approach for the electrocatalytic conversion from alkanes to alcohols mediated by AlkB using an AlkG immobilized screen-printed carbon electrode (SPCE) is developed...
August 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28815281/quantitative-characterization-of-colloidal-assembly-of-graphene-oxide-silver-nanoparticle-hybrids-using-aerosol-differential-mobility-coupled-mass-analyses
#7
Thai Phuong Nguyen, Wei-Chang Chang, Yen-Chih Lai, Ta-Chih Hsiao, De-Hao Tsai
In this work, we develop an aerosol-based, time-resolved ion mobility-coupled mass characterization method to investigate colloidal assembly of graphene oxide (GO)-silver nanoparticle (AgNP) hybrid nanostructure on a quantitative basis. Transmission electron microscopy (TEM) and zeta potential (ZP) analysis were used to provide visual information and elemental-based particle size distributions, respectively. Results clearly show a successful controlled assembly of GO-AgNP by electrostatic-directed heterogeneous aggregation between GO and bovine serum albumin (BSA)-functionalized AgNP under an acidic environment...
August 16, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28806064/conditional-displacement-hybridization-assay-for-multiple-snp-phasing
#8
Tsz Wing Fan, Henson L Lee Yu, I-Ming Hsing
The two chromosomal copies of the human genome are highly polymorphic, and the allelic content on each strand can dictate a person's biological outcomes. While many of the current diagnostic tools are able to detect the presence of multiple mutations at the same time, most cannot determine the phase of these mutations unless long-range PCR or sequencing techniques are used or if templates are compartmentalized into single copies prior to amplification. Here, an enzyme-coupled hybridization assay, named conditional displacement hybridization assay (CDHA), is described for the concurrent and rapid determination of the presence and phase of SNP variants...
August 25, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28782145/manometric-evaluation-of-the-motilin-receptor-agonist-camicinal-gsk962040-in-humans
#9
E Deloose, I Depoortere, J de Hoon, A Van Hecken, O E Dewit, L S Vasist Johnson, M E Barton, G E Dukes, J Tack
BACKGROUND: The gut hormone motilin stimulates gastrointestinal motility by inducing gastric phase III of the migrating motor complex (MMC) and enhancing the rate of gastric emptying. Camicinal (GSK962040), a small molecule motilin receptor agonist, has been shown to increase gastrointestinal motility. METHODS: In this proof of concept study the effects of camicinal on MMC activity, esophageal and gastric pH was evaluated in eight healthy volunteers as a secondary endpoint...
August 6, 2017: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/28767654/cancer-stem-cell-related-gene-expression-as-a-potential-biomarker-of-response-for-first-in-class-imipridone-onc201-in-solid-tumors
#10
Varun V Prabhu, Amriti R Lulla, Neel S Madhukar, Marie D Ralff, Dan Zhao, Christina Leah B Kline, A Pieter J Van den Heuvel, Avital Lev, Mathew J Garnett, Ultan McDermott, Cyril H Benes, Tracy T Batchelor, Andrew S Chi, Olivier Elemento, Joshua E Allen, Wafik S El-Deiry
Cancer stem cells (CSCs) correlate with recurrence, metastasis and poor survival in clinical studies. Encouraging results from clinical trials of CSC inhibitors have further validated CSCs as therapeutic targets. ONC201 is a first-in-class small molecule imipridone in Phase I/II clinical trials for advanced cancer. We have previously shown that ONC201 targets self-renewing, chemotherapy-resistant colorectal CSCs via Akt/ERK inhibition and DR5/TRAIL induction. In this study, we demonstrate that the anti-CSC effects of ONC201 involve early changes in stem cell-related gene expression prior to tumor cell death induction...
2017: PloS One
https://www.readbyqxmd.com/read/28760486/a-novel-brain-computer-interface-for-classification-of-social-joint-attention-in-autism-and-comparison-of-3-experimental-setups-a-feasibility-study
#11
Carlos P Amaral, Marco A Simões, Susana Mouga, João Andrade, Miguel Castelo-Branco
BACKGROUND: We present a novel virtual-reality P300-based Brain Computer Interface (BCI) paradigm using social cues to direct the focus of attention. We combined interactive immersive virtual-reality (VR) technology with the properties of P300 signals in a training tool which can be used in social attention disorders such as autism spectrum disorder (ASD). NEW METHOD: We tested the novel social attention training paradigm (P300-based BCI paradigm for rehabilitation of joint-attention skills) in 13 healthy participants, in 3 EEG systems...
July 29, 2017: Journal of Neuroscience Methods
https://www.readbyqxmd.com/read/28753067/a-randomized-placebo-controlled-phase-2-trial-of-cnto-6785-in-chronic-obstructive-pulmonary-disease
#12
Andreas Eich, Veronika Urban, Marek Jutel, Jiri Vlcek, Jae Jeong Shim, Vasiliy I Trofimov, Chong-Kin Liam, Ping-Hung Kuo, Yanyan Hou, Jun Xiao, Patrick Branigan, Christopher D O'Brien
Interleukin (IL)-17A may be an underlying factor in the pathophysiology of chronic obstructive pulmonary disease (COPD). Anti-IL-17 monoclonal antibodies have been used successfully in treating several immune-mediated inflammatory diseases. This phase 2, randomized, placebo-controlled, double-blind, parallel-group, proof-of-concept study is the first clinical study evaluating the efficacy and safety of the anti-IL-17A monoclonal antibody CNTO 6785 in patients with symptomatic moderate-to-severe COPD. Patients were treated with CNTO 6785 (n = 93) or placebo (n = 94) intravenously at Weeks 0, 2, and 4 (induction), then Weeks 8 and 12, and followed till Week 24...
July 28, 2017: COPD
https://www.readbyqxmd.com/read/28737272/dynamic-coupling-between-fmri-local-connectivity-and-interictal-eeg-in-focal-epilepsy-a-wavelet-analysis-approach
#13
Amir Omidvarnia, Mangor Pedersen, David N Vaughan, Jennifer M Walz, David F Abbott, Andrew Zalesky, Graeme D Jackson
Simultaneous scalp EEG-fMRI recording is a noninvasive neuroimaging technique for combining electrophysiological and hemodynamic aspects of brain function. Despite the time-varying nature of both measurements, their relationship is usually considered as time-invariant. The aim of this study was to detect direct associations between scalp-recorded EEG and regional changes of hemodynamic brain connectivity in focal epilepsy through a time-frequency paradigm. To do so, we developed a voxel-wise framework that analyses wavelet coherence between dynamic regional phase synchrony (DRePS, calculated from fMRI) and band amplitude fluctuation (BAF) of a target EEG electrode with dominant interictal epileptiform discharges (IEDs)...
July 24, 2017: Human Brain Mapping
https://www.readbyqxmd.com/read/28709498/targeting-fyn-kinase-in-alzheimer-s-disease
#14
REVIEW
Haakon B Nygaard
The past decade has brought tremendous progress in unraveling the pathophysiology of Alzheimer's disease (AD). While increasingly sophisticated immunotherapy targeting soluble and aggregated brain amyloid-beta (Aβ) continues to dominate clinical research in AD, a deeper understanding of Aβ physiology has led to the recognition of distinct neuronal signaling pathways linking Aβ to synaptotoxicity and neurodegeneration and to new targets for therapeutic intervention. Identifying specific signaling pathways involving Aβ has allowed for the development of more precise therapeutic interventions targeting the most relevant molecular mechanisms leading to AD...
June 13, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/28603846/decoupling-of-a-tight-fit-transceiver-phased-array-for-human-brain-imaging-at-9-4t-loop-overlapping-rediscovered
#15
Nikolai I Avdievich, Ioannis-Angelos Giapitzakis, Andreas Pfrommer, Anke Henning
PURPOSE: To improve the decoupling of a transceiver human head phased array at ultra-high fields (UHF, ≥ 7T) and to optimize its transmit (Tx) and receive (Rx) performance, a single-row eight-element (1 × 8) tight-fit transceiver overlapped loop array was developed and constructed. Overlapping the loops increases the RF field penetration depth but can compromise decoupling by generating substantial mutual resistance. METHODS: Based on analytical modeling, we optimized the loop geometry and relative positioning to simultaneously minimize the resistive and inductive coupling and constructed a 9...
June 11, 2017: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
https://www.readbyqxmd.com/read/28603208/ultra-early-phase-pathologies-of-alzheimer-s-disease-and-other-neurodegenerative-diseases
#16
REVIEW
Hitoshi Okazawa
The concept of neurodegenerative diseases and the therapeutics targeting these intractable diseases are changing rapidly. Protein aggregation as the top of pathological cascade is now challenged, and many alternative ideas are proposed. Early molecular pathologies before microscopic detection of diseases protein aggregates, which I propose to call "Ultra-Early Phase pathologies or phase 0 pathologies", are the focus of research that might explain the failures of clinical trials with anti-Aβ antibodies against Alzheimer's disease...
2017: Proceedings of the Japan Academy. Series B, Physical and Biological Sciences
https://www.readbyqxmd.com/read/28579415/elagolix-for-the-management-of-heavy-menstrual-bleeding-associated-with-uterine-fibroids-results-from-a-phase-2a-proof-of-concept-study
#17
RANDOMIZED CONTROLLED TRIAL
David F Archer, Elizabeth A Stewart, Rita I Jain, Robert A Feldman, Andrea S Lukes, Janine D North, Ahmed M Soliman, Jingjing Gao, Juki W Ng, Kristof Chwalisz
OBJECTIVE: To evaluate the safety and efficacy of elagolix vs. placebo and elagolix with low-dose E2/progestogen add-back therapy. DESIGN: Proof-of-concept, dose-ranging, multiple-cohort study. SETTING: Clinics. PATIENT(S): Premenopausal women with fibroids and heavy menstrual bleeding (menstrual blood loss [MBL] >80 mL per cycle). INTERVENTION(S): Three months' treatment with elagolix alone: 100 mg twice daily (BID), 200 mg BID, 300 mg BID, 400 mg once daily (QD), or 600 mg QD (all but the 600 mg QD arm were placebo controlled); or elagolix plus add-back therapy: 200 mg BID plus continuous low-dose E2 0...
July 2017: Fertility and Sterility
https://www.readbyqxmd.com/read/28547320/real-time-noninvasive-monitoring-of-intracranial-fluid-shifts-during-dialysis-using-volumetric-integral-phase-shift-spectroscopy-vips-a-proof-of-concept-study
#18
Chethan P Venkatasubba Rao, Eric M Bershad, Eusebia Calvillo, Nelson Maldonado, Rahul Damani, Sreedhar Mandayam, Jose I Suarez
BACKGROUND: Cerebral edema, which is associated with increased intracranial fluid, is often a complication of many acute neurological conditions. There is currently no accepted method for real-time monitoring of intracranial fluid volume at the bedside. We evaluated a novel noninvasive technique called "Volumetric Integral Phase-shift Spectroscopy (VIPS)" for detecting intracranial fluid shifts during hemodialysis. METHODS: Subjects receiving scheduled hemodialysis for end-stage renal disease and without a history of major neurological conditions were enrolled...
May 25, 2017: Neurocritical Care
https://www.readbyqxmd.com/read/28535880/development-and-validation-of-a-novel-quantification-approach-for-gradient-elution-reversed-phase-high-performance-liquid-chromatography-coupled-to-tandem-icp-mass-spectrometry-rp-hplc-icp-ms-ms-and-its-application-to-diclofenac-and-its-related-compounds
#19
Balázs Klencsár, Lieve Balcaen, Filip Cuyckens, Frédéric Lynen, Frank Vanhaecke
A novel quantification approach, compensating for the effect of gradient elution on the instrumental response during reversed phase high-performance liquid chromatography - inductively coupled plasma - tandem mass spectrometry analysis, has been developed and validated. As a proof of concept, diclofenac and its related compounds, including its major metabolite i.e. 4'-hydroxy-diclofenac, have been quantitatively determined in human plasma matrix. An inductively coupled plasma - tandem mass spectrometer has been applied for the interference-free determination of Cl as (35)ClH2(+) using H2 as a reaction gas in the collision/reaction cell...
June 29, 2017: Analytica Chimica Acta
https://www.readbyqxmd.com/read/28522444/harmonization-of-serum-thyroid-stimulating-hormone-measurements-paves-the-way-for-the-adoption-of-a-more-uniform-reference-interval
#20
Linda M Thienpont, Katleen Van Uytfanghe, Linde A C De Grande, Dries Reynders, Barnali Das, James D Faix, Finlay MacKenzie, Brigitte Decallonne, Akira Hishinuma, Bruno Lapauw, Paul Taelman, Paul Van Crombrugge, Annick Van den Bruel, Brigitte Velkeniers, Paul Williams
BACKGROUND: The IFCC Committee for Standardization of Thyroid Function Tests developed a global harmonization approach for thyroid-stimulating hormone measurements. It is based on a multiassay method comparison study with clinical serum samples and target setting with a robust factor analysis method. Here we describe the Phase IV method comparison and reference interval (RI) studies conducted with the objective to recalibrate the participating assays and demonstrate the proof-of-concept...
July 2017: Clinical Chemistry
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