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https://www.readbyqxmd.com/read/28709498/targeting-fyn-kinase-in-alzheimer-s-disease
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
https://www.readbyqxmd.com/read/28489389/stabilization-of-foam-lamella-using-novel-surface-grafted-nanocellulose-based-nanofluids
#8
Bing Wei, Hao Li, Qinzhi Li, Yangbing Wen, Lin Sun, Peng Wei, Wanfen Pu, Yibo Li
To solve the potential risk of present oilfield chemistries to subterranean environment, our group contributes to the development of "green" petroleum production processes. This proof-of-concept research studied the well-defined nanocellulose-based nanofluids, i.e., original (NC), AMPS grafted (NC-KY), and AMPS and hydrophobic chains grafted (NC-KYSS), in stabilizing foam lamella for potential use in enhanced oil recovery (EOR). The data showed that the collaboration of the surface-functional nanocellulose considerately improved the foam stability particularly in the presence of hydrocarbons due to the thickened foam film coupled with the molecular interactions at interior lamella...
May 16, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28441355/-188-re-liposome-can-induce-mitochondrial-autophagy-and-reverse-drug-resistance-for-ovarian-cancer-from-bench-evidence-to-preliminary-clinical-proof-of-concept
#9
Chia-Ming Chang, Keng-Li Lan, Wen-Sheng Huang, Yi-Jang Lee, Te-Wei Lee, Chih-Hsien Chang, Chi-Mu Chuang
Despite standard treatment, about 70% of ovarian cancer will recur. Cancer stem cells (CSCs) have been implicated in the drug-resistance mechanism. Several drug resistance mechanisms have been proposed, and among these, autophagy plays a crucial role for the maintenance and tumorigenicity of CSCs. Compared to their differentiated counterparts, CSCs have been demonstrated to display a significantly higher level of autophagy flux. Moreover, mitophagy, a specific type of autophagy that selectively degrades excessive or damaged mitochondria, is shown to contribute to cancer progression and recurrence in several types of tumors...
April 25, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28371251/surface-engineering-of-spherical-metal-nanoparticles-with-polymers-toward-selective-asymmetric-synthesis-of-nanobowls-and-janus-type-dimers
#10
Ben Liu, Srinivas Thanneeru, Aaron Lopes, Lei Jin, Meghan McCabe, Jie He
New synthetic methods capable of controlling structural and compositional complexities of asymmetric nanoparticles (NPs) are very challenging but highly desired. A simple and general synthetic approach to designing sophisticated asymmetric NPs by anisotropically patterning the surface of isotropic metallic NPs with amphiphilic block copolymers (BCPs) is reported. The selective galvanic replacement and seed-mediated growth of a second metal can be achieved on the exposed surface of metal NPs, resulting in the formation of nanobowls and Janus-type metal-metal dimers, respectively...
April 3, 2017: Small
https://www.readbyqxmd.com/read/28369516/comprehensive-chromosome-screening-and-gene-expression-analysis-from-the-same-biopsy-in-human-preimplantation-embryos
#11
Diego Marin, Yujue Wang, Xin Tao, Richard T Scott, Nathan R Treff
STUDY QUESTION: Can simultaneous comprehensive chromosome screening (CCS) and gene expression analysis be performed on the same biopsy of preimplantation human embryos? SUMMARY ANSWER: For the first time, CCS and reliable gene expression analysis have been performed on the same human preimplantation embryo biopsy. WHAT IS KNOWN ALREADY: A single trophectoderm (TE) biopsy is routinely used for many IVF programs offering CCS for selection of only chromosomally normal embryos for transfer...
May 1, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/28272644/croconamides-a-new-dual-hydrogen-bond-donating-motif-for-anion-recognition-and-organocatalysis
#12
Anne Jeppesen, Bjarne E Nielsen, Dennis Larsen, Olivia M Akselsen, Theis I Sølling, Theis Brock-Nannestad, Michael Pittelkow
We introduce bis-aryl croconamides as a new member in the family of dual hydrogen bonding anion receptors. In this study a series of croconamides are synthesised, and the selectivity for anion binding is investigated (Cl(-) > Br(-) > I(-) in CH2Cl2). The croconamides exhibit different structures in the crystal phase depending on the substituents on the aromatic rings, and furthermore, the crystal structure revealed the presence of tautomers. DFT calculations elucidated the complex structures formed upon addition of anion to the croconamides, confirming the order of association constants towards the halogen anions...
March 8, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28245243/serelaxin-as-a-potential-treatment-for-renal-dysfunction-in-cirrhosis-preclinical-evaluation-and-results-of-a-randomized-phase-2-trial
#13
Victoria K Snowdon, Neil J Lachlan, Anna M Hoy, Patrick W F Hadoke, Scott I Semple, Dilip Patel, Will Mungall, Timothy J Kendall, Adrian Thomson, Ross J Lennen, Maurits A Jansen, Carmel M Moran, Antonella Pellicoro, Prakash Ramachandran, Isaac Shaw, Rebecca L Aucott, Thomas Severin, Rajnish Saini, Judy Pak, Denise Yates, Neelesh Dongre, Jeremy S Duffield, David J Webb, John P Iredale, Peter C Hayes, Jonathan A Fallowfield
BACKGROUND: Chronic liver scarring from any cause leads to cirrhosis, portal hypertension, and a progressive decline in renal blood flow and renal function. Extreme renal vasoconstriction characterizes hepatorenal syndrome, a functional and potentially reversible form of acute kidney injury in patients with advanced cirrhosis, but current therapy with systemic vasoconstrictors is ineffective in a substantial proportion of patients and is limited by ischemic adverse events. Serelaxin (recombinant human relaxin-2) is a peptide molecule with anti-fibrotic and vasoprotective properties that binds to relaxin family peptide receptor-1 (RXFP1) and has been shown to increase renal perfusion in healthy human volunteers...
February 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28220124/in-vivo-efficacy-of-umbilical-cord-blood-stem-cell-derived-nk-cells-in-the-treatment-of-metastatic-colorectal-cancer
#14
John P Veluchamy, Silvia Lopez-Lastra, Jan Spanholtz, Fenna Bohme, Nina Kok, Daniëlle A M Heideman, Henk M W Verheul, James P Di Santo, Tanja D de Gruijl, Hans J van der Vliet
Therapeutic monoclonal antibodies against the epidermal growth factor receptor (EGFR) act by inhibiting EGFR downstream signaling and by eliciting a natural killer (NK) cell-mediated antitumor response. The IgG1 mAb cetuximab has been used for treatment of RAS(wt) metastatic colorectal cancer (mCRC) patients, showing limited efficacy. In the present study, we address the potential of adoptive NK cell therapy to overcome these limitations investigating two allogeneic NK cell products, i.e., allogeneic activated peripheral blood NK cells (A-PBNK) and umbilical cord blood stem cell-derived NK cells (UCB-NK)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28153778/accelerating-the-clinical-development-of-protein-based-vaccines-for-malaria-by-efficient-purification-using-a-four-amino-acid-c-terminal-c-tag
#15
Jing Jin, Kathryn A Hjerrild, Sarah E Silk, Rebecca E Brown, Geneviève M Labbé, Jennifer M Marshall, Katherine E Wright, Sandra Bezemer, Stine B Clemmensen, Sumi Biswas, Yuanyuan Li, Aadil El-Turabi, Alexander D Douglas, Pim Hermans, Frank J Detmers, Willem A de Jongh, Matthew K Higgins, Rebecca Ashfield, Simon J Draper
Development of bespoke biomanufacturing processes remains a critical bottleneck for translational studies, in particular when modest quantities of a novel product are required for proof-of-concept Phase I/II clinical trials. In these instances the ability to develop a biomanufacturing process quickly and relatively cheaply, without risk to product quality or safety, provides a great advantage by allowing new antigens or concepts in immunogen design to more rapidly enter human testing. These challenges with production and purification are particularly apparent when developing recombinant protein-based vaccines for difficult parasitic diseases, with Plasmodium falciparum malaria being a prime example...
June 2017: International Journal for Parasitology
https://www.readbyqxmd.com/read/28125304/omalizumab-for-treating-chronic-spontaneous-urticaria-an-expert-review-on-efficacy-and-safety
#16
Ana M Giménez-Arnau
Chronic spontaneous urticaria (CSU) is characterized by the recurrence of itchy hives and/or angioedema for greater than six weeks, with no known external trigger. Omalizumab, a humanized, recombinant, monoclonal anti-IgE antibody, is the only approved add-on therapy for H1-antihistamine refractory CSU patients. Areas covered: The objective of this article is to discuss the mechanism of action, pharmacokinetics and pharmacodynamics of omalizumab for the treatment of CSU. The review also summarizes efficacy and safety data from proof-of-concept, phase II (X-CUISITE, MYSTIQUE), and pivotal phase III omalizumab studies (ASTERIA I, ASTERIA II, and GLACIAL)...
March 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28062705/novel-p21-activated-kinase-4-pak4-allosteric-modulators-overcome-drug-resistance-and-stemness-in-pancreatic-ductal-adenocarcinoma
#17
Amro Aboukameel, Irfana Muqbil, William Senapedis, Erkan Baloglu, Yosef Landesman, Sharon Shacham, Michael Kauffman, Philip A Philip, Ramzi M Mohammad, Asfar S Azmi
The p21-activated kinase 4 (PAK4) is a key downstream effector of the Rho family GTPases and is found to be overexpressed in pancreatic ductal adenocarcinoma (PDAC) cells but not in normal human pancreatic ductal epithelia (HPDE). Gene copy number amplification studies in PDAC patient cohorts confirmed PAK4 amplification making it an attractive therapeutic target in PDAC. We investigated the antitumor activity of novel PAK4 allosteric modulators (PAM) on a panel of PDAC cell lines and chemotherapy-resistant flow-sorted PDAC cancer stem cells (CSC)...
January 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28032501/single-particle-ratiometric-pressure-sensing-based-on-double-sensor-colloidal-nanocrystals
#18
Monica Lorenzon, Valerio Pinchetti, Francesco Bruni, Wan Ki Bae, Francesco Meinardi, Victor I Klimov, Sergio Brovelli
Ratiometric pressure sensitive paints (r-PSPs) are all-optical probes for monitoring oxygen flows in the vicinity of complex or miniaturized surfaces. They typically consist of a porous binder embedding mixtures of a reference and a sensor chromophore exhibiting oxygen-insensitive and oxygen-responsive luminescence, respectively. Here, we demonstrate the first example of an r-PSP based on a single two-color emitter that removes limitations of r-PSPs based on chromophore mixtures such as different temperature dependencies of the two chromophores, cross-readout between the reference and sensor signals and phase segregation...
January 10, 2017: Nano Letters
https://www.readbyqxmd.com/read/27913075/the-photosensitivity-model-is-not-a-model-for-partial-focal-seizures-rebuttal
#19
Roger J Porter
No abstract text is available yet for this article.
November 22, 2016: Epilepsy Research
https://www.readbyqxmd.com/read/27908525/the-photosensitivity-model-is-not-a-model-for-partial-focal-seizures
#20
Roger J Porter
New, more effective and less toxic medications are desperately needed for patients with partial (focal) epilepsy. Many hurdles prevent the appropriate study of promising compounds. One of these hurdles is the difficult gap between Phase I and Phase II-the expensive proof of concept to suggest that human trials in partial seizure patients will be successful. A short-cut, the photoparoxysmal response (PPR) model has recently been used to increase confidence in moving a compound into Phase II and III (K-N Trenite et al...
November 22, 2016: Epilepsy Research
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