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https://www.readbyqxmd.com/read/28982375/pkr-involvement-in-alzheimer-s-disease
#1
REVIEW
Jacques Hugon, François Mouton-Liger, Julien Dumurgier, Claire Paquet
BACKGROUND: Brain lesions in Alzheimer's disease (AD) are characterized by Aβ accumulation, neurofibrillary tangles, and synaptic and neuronal vanishing. According to the amyloid cascade hypothesis, Aβ1-42 oligomers could trigger a neurotoxic cascade with kinase activation that leads to tau phosphorylation and neurodegeneration. Detrimental pathways that are associated with kinase activation could also be linked to the triggering of direct neuronal death, the production of free radicals, and neuroinflammation...
October 5, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28956672/proxy-reported-quality-of-life-and-family-impact-for-children-followed-longitudinally-by-a-pediatric-palliative-care-team
#2
Meaghann Weaver, Christopher Wichman, Cheryl Darnall, Sue Bace, Catherine Vail, Andrew MacFadyen
BACKGROUND: One goal of pediatric palliative care is to maintain quality of life for children and their families. Quality-of-life investigations may be enhanced by considering clinically important metrics in addition to statistical significance. OBJECTIVE: The purpose of this study was to longitudinally evaluate the effect of time on quality of life and family impact for pediatric palliative care patients across all diagnoses and ages. DESIGN: This prospective quality-of-life study included administration of a 23-item PedsQL™ Measurement Model to evaluate for physical, emotional, social, and cognitive dimensions of the child's quality of life and a 36-item PedsQL Family Impact Module to assess for the familial impact at time of initial palliative care consultation, Month 6, and Month 12...
September 28, 2017: Journal of Palliative Medicine
https://www.readbyqxmd.com/read/28950235/a-physicochemical-descriptor-based-method-for-effective-and-rapid-screening-of-dual-inhibitors-against-bace-1-and-gsk-3%C3%AE-as-targets-for-alzheimer-s-disease
#3
Akhil Kumar, Gaurava Srivastava, Ashok Sharma
Due to multifactorial nature of Alzheimer's disease one target-one ligand hypothesis often looks insufficient. BACE-1 and GSK-3β are well established therapeutic drug targets and interaction between BACE-1 and GSK-3β pathways has also been established. Thus, designing of dual inhibitor for these two targets seems rational and may provide effective therapeutic strategies against AD. Recent studies revealed that only two scaffolds i.e. triazinone and curcumin act as a dual inhibitor against BACE-1 and GSK-3β...
September 8, 2017: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/28944861/panax-notoginseng-saponins-attenuates-sevoflurane%C3%A2-induced-nerve-cell-injury-by-modulating-akt-signaling-pathway
#4
Xu Yang, Sun Yang, Chen Hong, Wang Yu, Wang Guonian
General anesthesia in patients with or at risk for neuronal injury remains challenging due to the neurotoxic effects of volatile anesthetics. One inhalation anesthetic, sevoflurane, induces neuronal damage, including neuroapoptosis, and learning and memory impairment. Panax Notoginseng Saponins (PNS) is the active ingredient of Sanqui and has been reported to exert neuroprotective effects. In the current study, the protective effect of PNS on sevoflurane‑induced nerve cell injury was explored. Cell proliferation was significantly reduced in a dose‑dependent manner following stimulation with sevoflurane...
November 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28930140/identification-of-phlogacantholide-c-as-a-novel-adam10-enhancer-from-traditional-chinese-medicinal-plants
#5
Myriam Meineck, Florian Schuck, Sara Abdelfatah, Thomas Efferth, Kristina Endres
Background: Alzheimer's disease is one of the most prevalent dementias in the elderly population with increasing numbers of patients. One pivotal hallmark of this disorder is the deposition of protein aggregates stemming from neurotoxic amyloid-beta peptides. Synthesis of those peptides has been efficiently prevented in AD model mice by activation of an enzyme called alpha-secretase. Therefore, drugs with the capability to increase the expression of this enzyme, named ADAM10, have been suggested as a valuable therapeutic medication...
December 5, 2016: Medicines (Basel, Switzerland)
https://www.readbyqxmd.com/read/28923680/potent-and-selective-bace-1-peptide-inhibitors-lower-brain-a%C3%AE-levels-mediated-by-brain-shuttle-transport
#6
Nadine Ruderisch, Daniel Schlatter, Andreas Kuglstatter, Wolfgang Guba, Sylwia Huber, Carlo Cusulin, Jörg Benz, Arne Christian Rufer, Joerg Hoernschemeyer, Christophe Schweitzer, Tina Bülau, Achim Gärtner, Eike Hoffmann, Jens Niewoehner, Christoph Patsch, Karlheinz Baumann, Hansruedi Loetscher, Eric Kitas, Per-Ola Freskgård
Therapeutic approaches to fight Alzheimer's disease include anti-Amyloidβ (Aβ) antibodies and secretase inhibitors. However, the blood-brain barrier (BBB) limits the brain exposure of biologics and the chemical space for small molecules to be BBB permeable. The Brain Shuttle (BS) technology is capable of shuttling large molecules into the brain. This allows for new types of therapeutic modalities engineered for optimal efficacy on the molecular target in the brain independent of brain penetrating properties...
September 7, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28923172/handgrip-strength-is-associated-with-but-poorly-predicts-disability-in-older-women-with-acute-low-back-pain-a-12-month-follow-up-study
#7
Diogo Carvalho Felício, Juliano Bergamaschine Mata Diz, Daniele Sirineu Pereira, Bárbara Zille de Queiroz, Juscélio Pereira de Silva, Bruno de Souza Moreira, Vinícius Cunha Oliveira, Leani Souza Máximo Pereira
BACKGROUND: Older women with low back pain (LBP) constitute a special subpopulation at risk of severe and permanent disability. It is important to identify factors limiting functionality in this population in order to reduce costs and improve both prevention and intervention. Handgrip strength (HGS) is a biomarker of aging associated with several adverse health outcomes, but long-term associations with disability in older patients with LBP are not known. OBJECTIVE: To examine whether HGS predicts disability in older women with acute low back pain (LBP)...
October 2017: Maturitas
https://www.readbyqxmd.com/read/28915693/the-application-of-is6110-baced-loop-mediated-isothermal-amplification-lamp-in-the-early-diagnosis-of-tuberculous-meningitis
#8
Wen-Wen Sun, Qin Sun, Li-Ping Yan, Qing Zhang
Here, we evaluated the potential activity of rapid Mycobacterium tuberculosis detection with loop-mediated isothermal amplification (LAMP), for the early diagnosis of tuberculous meningitis (TBM). Patients with suspected TBM from January 2014 to December 2015 were reviewed retrospectively. The cerebrospinalfluid(CSF) was collected. Acid-fast bacillus (AFB) staining, MGIT 960 culture, real-time fluorescent quantitative polymerase chain reaction (RTFQ PCR) and LAMP were performed. A total of 200 patients were included in the study...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28901306/bronchial-artery-chemoembolization-combined-with-radioactive-iodine-125-seed-implantation-in-the-treatment-of-advanced-nonsmall-cell-lung-cancer
#9
Yaoyong Chen, Yuwei Li, Yuming Jia, Kaijian Lei, Xinfeng Zhang, Yueyong Cao, Jun Zhu
OBJECTIVE: The aim of this study was to investigate the short-term efficacy and safety of bronchial artery chemoembolization (BACE) combined with radioactive iodine-125 seed implantation in the treatment of nonsmall cell lung cancer (NSCLC). MATERIALS AND METHODS: Sixty-two Stage III-IV NSCLC patients were divided into Groups A and B. Thirty cases were treated with BACE combined with radioactive iodine-125 seed implantation in the Group A and 32 cases were treated with BACE alone in the Group B until disease progression...
2017: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/28877031/genetic-associations-with-gestational-duration-and-spontaneous-preterm-birth
#10
Ge Zhang, Bjarke Feenstra, Jonas Bacelis, Xueping Liu, Lisa M Muglia, Julius Juodakis, Daniel E Miller, Nadia Litterman, Pan-Pan Jiang, Laura Russell, David A Hinds, Youna Hu, Matthew T Weirauch, Xiaoting Chen, Arun R Chavan, Günter P Wagner, Mihaela Pavličev, Mauris C Nnamani, Jamie Maziarz, Minna K Karjalainen, Mika Rämet, Verena Sengpiel, Frank Geller, Heather A Boyd, Aarno Palotie, Allison Momany, Bruce Bedell, Kelli K Ryckman, Johanna M Huusko, Carmy R Forney, Leah C Kottyan, Mikko Hallman, Kari Teramo, Ellen A Nohr, George Davey Smith, Mads Melbye, Bo Jacobsson, Louis J Muglia
BACKGROUND: Despite evidence that genetic factors contribute to the duration of gestation and the risk of preterm birth, robust associations with genetic variants have not been identified. We used large data sets that included the gestational duration to determine possible genetic associations. METHODS: We performed a genomewide association study in a discovery set of samples obtained from 43,568 women of European ancestry using gestational duration as a continuous trait and term or preterm (<37 weeks) birth as a dichotomous outcome...
September 21, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28872858/fast-and-reliable-thermodynamic-approach-for-determining-the-protonation-state-of-the-asp-dyad
#11
Jinfeng Huang, Bin Sun, Yuan Yao, Junjun Liu
The protonation state of the asp dyad is significantly important in revealing enzymatic mechanisms and developing drugs. However, it is hard to determine by calculating free energy changes between possible protonation states, because the free energy changes due to protein conformational flexibility are usually much larger than those originating from different locations of protons. Sophisticated and computationally expensive methods such as free energy perturbation, thermodynamic integration (TI), and quantum mechanics/molecular mechanics are therefore usually used for this purpose...
September 25, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28870602/the-brazilian-back-complaints-in-the-elders-brazilian-bace-study-characteristics-of-brazilian-older-adults-with-a-new-episode-of-low-back-pain
#12
Fabianna Resende De Jesus-Moraleida, Paulo Henrique Ferreira, Manuela Loureiro Ferreira, Juscelio Pereira Da Silva, Marcella Guimarães Assis, Leani Souza Máximo Pereira
OBJECTIVE: Low back pain (LBP) is little explored in the aging population especially when considering age-relevant and culturally dependent outcomes. We aimed to describe socio-demographic and clinical characteristics of Brazilian older people with a new episode of LBP presenting to primary care. METHODS: We sourced baseline information on socio-demographic, pain-related and clinical characteristics from 602 older adults from the Brazilian Back Complaints in the Elders (Brazilian BACE) study...
August 10, 2017: Brazilian Journal of Physical Therapy
https://www.readbyqxmd.com/read/28867212/mir-124-downregulates-bace-1-and-alters-autophagy-in-app-ps1-transgenic-mice
#13
Xiaoxue Du, Xue Huo, Yang Yang, Zhiying Hu, Benson O A Botchway, Yuting Jiang, Marong Fang
One role of BACE 1 (Beta-site amyloid precursor protein cleaving enzyme 1) is to cleave the sequential amyloid precursor protein (APP) into β-Amyloid (Aβ), the accumulation of which is an important participant in the formation of the amyloid plaques and neurofibrillary tangles of Alzheimer's disease (AD). Our previous study showed BACE 1, the potential functional downstream target of miR-124, to be connected to cell death in AD cell models. Recent studies have shown that autophagy is altered in AD, however, as to whether miR-124 is involved in this alteration is not clear...
October 5, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28860676/the-historical-disturbance-regime-of-mountain-norway-spruce-forests-in-the-western-carpathians-and-its-influence-on-current-forest-structure-and-composition
#14
Pavel Janda, Volodymyr Trotsiuk, Martin Mikoláš, Radek Bače, Thomas A Nagel, Rupert Seidl, Meelis Seedre, Robert C Morrissey, Stanislav Kucbel, Peter Jaloviar, Marián Jasík, Juraj Vysoký, Pavel Šamonil, Vojtěch Čada, Hana Mrhalová, Jana Lábusová, Markéta H Nováková, Miloš Rydval, Lenka Matějů, Miroslav Svoboda
In order to gauge ongoing and future changes to disturbance regimes, it is necessary to establish a solid baseline of historic disturbance patterns against which to evaluate these changes. Further, understanding how forest structure and composition respond to variation in past disturbances may provide insight into future resilience to climate-driven alterations of disturbance regimes. We established 184 plots (mostly 1000 m(2)) in 14 primary mountain Norway spruce forests in the Western Carpathians. On each plot we surveyed live and dead trees and regeneration, and cored around 25 canopy trees...
March 15, 2017: Forest Ecology and Management
https://www.readbyqxmd.com/read/28836062/chronic-cerebral-hypoperfusion-promotes-amyloid-beta-pathogenesis-via-activating-%C3%AE-%C3%AE-secretases
#15
Zhiyou Cai, Zhou Liu, Ming Xiao, Chuanling Wang, Fuming Tian
Chronic cerebral hypoperfusion (CCH) contributes to the Alzheimer's-like pathogenesis, but the relationship between CCH and the occurrence of Alzheimer's disease (AD) remains obscure. The aim is to elucidate the potential pathophysiological mechanism in the field of amyloid-beta (Aβ) pathology induced by CCH. A rat model of CCH has been developed with permanent bilateral occlusion of common carotid arteries (BCCAO). The cognitive function of rats was tested by the Morris water maze. The levels of Aβ (Aβ40 and Aβ42) and soluble amyloid precursor protein (sAPP: sAPPα and sAPPβ) were determined by enzyme linked immunosorbent assay...
August 24, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28835787/c5-c6-carbocyclic-fused-iminothiadiazine-dioxides-as-bace-inhibitors-their-compositions-and-their-use
#16
EDITORIAL
Benjamin Blass
No abstract text is available yet for this article.
August 10, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28828994/computational-chemistry-study-of-natural-alkaloids-and-homemade-databank-to-predict-inhibitory-potential-against-key-enzymes-in-neurodegenerative-disease
#17
Vitor Prates Lorenzo, Mateus Feitosa Alves, Luciana Scotti, Sócrates Golzio Dos Santos, Margareth de Fátima Formiga Melo Diniz, Marcus Tullius Scotti
Cissampelos sympodialis Eichl is used in folk medicine for the treatment of various inflammatory diseases; several alkaloids were isolated from this species and some of them have anti-allergic activity, immunomodulatory and spasmolytic. Treatment of rats with the total tertiary alkaloid fraction showed an antidepressant effect. One of the depression causes can be the deficiency of monoamines, which is a factor displayed in patients with Alzheimer's disease. Theoretical studies using in silico methods have aided in the process of drug discovery...
August 21, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28821627/angiographic-and-clinical-outcomes-of-balloon-remodeling-versus-unassisted-coil-embolization-in-the-ruptured-aneurysm-cohort-of-the-gel-the-nec-study
#18
Guilherme Dabus, Waleed Brinjikji, Arun P Amar, Josser E Delgado Almandoz, Orlando M Diaz, Pascal Jabbour, Ricardo Hanel, Ferdinand Hui, Michael Kelly, Kennith F Layton, Jeffrey W Miller, Elad I Levy, Christopher J Moran, Dae Chul Suh, Henry Woo, Robbin Sellar, Brian Hoh, Avery Evans, David F Kallmes
BACKGROUND AND PURPOSE: GEL THE NEC (GTN) was a multicenter prospective registry developed to assess the safety and efficacy of HydroSoft coils in treating intracranial aneurysms. We compared the angiographic and clinical outcomes of aneurysms treated with balloon assisted coil embolization (BACE) versus unassisted coil embolization (CE) in the ruptured aneurysm cohort. MATERIALS AND METHODS: GTN was performed at 27 centers in five countries. Patients aged 21-90 years with a ruptured aneurysm 3-15 mm in size were eligible for enrollment...
August 18, 2017: Journal of Neurointerventional Surgery
https://www.readbyqxmd.com/read/28817734/treatment-gap-and-barriers-for-mental-health-care-a-cross-sectional-community-survey-in-nepal
#19
Nagendra P Luitel, Mark J D Jordans, Brandon A Kohrt, Sujit D Rathod, Ivan H Komproe
CONTEXT: There is limited research on the gap between the burden of mental disorders and treatment use in low- and middle-income countries. OBJECTIVES: The aim of this study was to assess the treatment gap among adults with depressive disorder (DD) and alcohol use disorder (AUD) and to examine possible barriers to initiation and continuation of mental health treatment in Nepal. METHODS: A three-stage sampling technique was used in the study to select 1,983 adults from 10 Village Development Committees (VDCs) of Chitwan district...
2017: PloS One
https://www.readbyqxmd.com/read/28817311/beta-secretase-inhibitors-in-phase-i-and-phase-ii-clinical-trials-for-alzheimer-s-disease
#20
REVIEW
Charbel E-H Moussa
BACE 1 is a protease that cleaves the transmembrane amyloid precursor protein and generates amyloid-β peptides that accumulate in AD brains. No known mutations are identified in the gene encoding BACE1 in AD. However, enzyme levels are elevated in AD and a single residue mutation in amyloid precursor protein protects against protein cleavage by BACE1, suggesting BACE involvement in disease pathogenesis. Drugs that can inhibit BACE1 would theoretically prevent Aβ accumulation and halt AD onset and progression...
October 2017: Expert Opinion on Investigational Drugs
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