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https://www.readbyqxmd.com/read/28340352/human-epistatic-interaction-controls-il7r-splicing-and-increases-multiple-sclerosis-risk
#1
Gaddiel Galarza-Muñoz, Farren B S Briggs, Irina Evsyukova, Geraldine Schott-Lerner, Edward M Kennedy, Tinashe Nyanhete, Liuyang Wang, Laura Bergamaschi, Steven G Widen, Georgia D Tomaras, Dennis C Ko, Shelton S Bradrick, Lisa F Barcellos, Simon G Gregory, Mariano A Garcia-Blanco
Multiple sclerosis (MS) is an autoimmune disorder where T cells attack neurons in the central nervous system (CNS) leading to demyelination and neurological deficits. A driver of increased MS risk is the soluble form of the interleukin-7 receptor alpha chain gene (sIL7R) produced by alternative splicing of IL7R exon 6. Here, we identified the RNA helicase DDX39B as a potent activator of this exon and consequently a repressor of sIL7R, and we found strong genetic association of DDX39B with MS risk. Indeed, we showed that a genetic variant in the 5' UTR of DDX39B reduces translation of DDX39B mRNAs and increases MS risk...
March 23, 2017: Cell
https://www.readbyqxmd.com/read/28340158/maintenance-therapy-is-associated-with-better-long-term-outcomes-in-adult-patients-with-primary-angiitis-of-the-central-nervous-system
#2
Hubert de Boysson, Jean-Jacques Parienti, Caroline Arquizan, Grégoire Boulouis, Nicolas Gaillard, Alexis Régent, Antoine Néel, Olivier Detante, Emanuel Touzé, Achille Aouba, Boris Bienvenu, Loïc Guillevin, Olivier Naggara, Mathieu Zuber, Christian Pagnoux
Objective.: We aimed to analyse the effect of maintenance therapy after induction on the outcomes of adult patients with primary angiitis of the CNS (PACNS). Methods.: We analysed long-term outcomes (relapse, survival and functional status) of patients enrolled in the French multicentre PACNS cohort who achieved remission after induction treatment and with ⩾12 months' follow-up, according to whether or not they received maintenance therapy. Good outcome was defined as relapse-free survival and good functional status (modified Rankin scale ⩽ 2) at last follow-up...
March 17, 2017: Rheumatology
https://www.readbyqxmd.com/read/28340145/human-abuse-potential-of-the-new-opioid-analgesic-molecule-nktr-181-compared-with-oxycodone
#3
Lynn Webster, Jack Henningfield, August R Buchhalter, Suresh Siddhanti, Lin Lu, Aleksandrs Odinecs, Carlo J Di Fonzo, Michael A Eldon
Objective.:  Evaluate the human abuse potential, pharmacokinetics, pharmacodynamics, and safety of NKTR-181, a novel mu-opioid agonist molecule, relative to oxycodone. Design.:  This randomized, single-center, double-blind, active- and placebo-controlled five-period crossover study enrolled healthy, adult, non-physically dependent recreational opioid users. Setting.:  Inpatient clinical research site. Subjects. : Forty-two randomized subjects (73...
March 10, 2017: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
https://www.readbyqxmd.com/read/28340102/impact-of-unrestricted-access-to-pregabalin-on-the-use-of-opioids-and-other-cns-active-medications-a-cross-sectional-time-series-analysis
#4
Herman Kwok, Wayne Khuu, Kimberly Fernandes, Diana Martins, Mina Tadrous, Samantha Singh, David N Juurlink, Tara Gomes
Objective. : Access to pregabalin via Ontario's public drug insurance program was expanded to an unrestricted model on April 1, 2013, from a prior authorization model. This study aims to identify the effect of expanded access on the rate of pregabalin use by publicly insured persons and to assess the characteristics of new patients initiating pregabalin following this expanded access. Methods. : We conducted a cross-sectional time series analysis using the linked health administrative records of residents of Ontario, Canada, with public drug coverage who were dispensed a prescription for pregabalin between April 1, 2006, and December 31, 2014...
March 6, 2017: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
https://www.readbyqxmd.com/read/28339401/is-huntingtin-dispensable-in-the-adult-brain
#5
Jeh-Ping Liu, Scott O Zeitlin
Huntingtin (HTT) is an essential protein during early embryogenesis and the development of the central nervous system (CNS). Conditional knock-out of mouse Huntingtin (Htt) expression in the CNS beginning during neural development, as well as reducing Htt expression only during embryonic and early postnatal stages, results in neurodegeneration in the adult brain. These findings suggest that HTT is important for the development and/or maintenance of the CNS, but they do not address the question of whether HTT is required specifically in the adult CNS for its normal functions and/or homeostasis...
March 21, 2017: Journal of Huntington's Disease
https://www.readbyqxmd.com/read/28339349/is-triclosan-a-neurotoxic-agent
#6
Joanna A Ruszkiewicz, Shaojun Li, Maliya B Rodriguez, Michael Aschner
Triclosan (TCS) is an antibacterial agent that has been used in many products since 1960s. Given its broad usage as an antiseptic TCS is present ubiquitously in the environment. Trace levels of TCS continue to be detected in many organisms, and it has been shown to be particularly toxic to aquatic species. The mechanisms underlying TCS-mediated toxicity include hormone dyshomeostasis, induction of oxidative stress, apoptosis and inflammation. Although TCS has been considered to be non-toxic to mammals, the adverse effects of continuous, long-term and low concentration exposure remain unknown...
2017: Journal of Toxicology and Environmental Health. Part B, Critical Reviews
https://www.readbyqxmd.com/read/28339319/intrathecal-magnetic-drug-targeting-for-localized-delivery-of-therapeutics-in-the-cns
#7
Indu Venugopal, Nazia Habib, Andreas Linninger
AIM: The challenge in treating neurological diseases is not lack of drug potency, but ineffective targeting techniques. We propose a technique called intrathecal magnetic drug targeting (IT-MDT), in which intrathecally injected magnetic nanoparticles (MNPs) are targeted to specific sites using external magnets. MATERIALS & METHODS: MRI and histology confirmed localization of MNPs via IT-MDT at target sites along the spine of Sprague-Dawley rats. RESULTS: MRI results confirmed greater MNP localization when the duration of magnet application was extended...
March 24, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28339315/identification-of-asymptomatic-prosthetic-joint-infection-microbiologic-and-operative-treatment-outcomes
#8
Przemysław L Bereza, Alicja Ekiel, Aleksandra Auguściak-Duma, Małgorzata Aptekorz, Iwona Wilk, Piotr Wojciechowski, Damian J Kusz, Gayane Martirosian
BACKGROUND: This prospective study investigated the role of mechanical and biological factors in aseptic implant loosening or presumed silent prosthetic joint infection (PJI). METHODS: Thirty-seven patients were investigated. Microbiologic and molecular methods were used to detect bacteria on the surface of the failed implants removed during revision arthroplasty. Histopathologic analysis was performed. The influence of body mass index (BMI) and various co-morbidities on implant failure also was determined...
March 24, 2017: Surgical Infections
https://www.readbyqxmd.com/read/28338622/phosphodiesterase-inhibitors-as-a-therapeutic-approach-to-neuroprotection-and-repair
#9
REVIEW
Eric P Knott, Mazen Assi, Sudheendra N R Rao, Mousumi Ghosh, Damien D Pearse
A wide diversity of perturbations of the central nervous system (CNS) result in structural damage to the neuroarchitecture and cellular defects, which in turn are accompanied by neurological dysfunction and abortive endogenous neurorepair. Altering intracellular signaling pathways involved in inflammation and immune regulation, neural cell death, axon plasticity and remyelination has shown therapeutic benefit in experimental models of neurological disease and trauma. The second messengers, cyclic adenosine monophosphate (cyclic AMP) and cyclic guanosine monophosphate (cyclic GMP), are two such intracellular signaling targets, the elevation of which has produced beneficial cellular effects within a range of CNS pathologies...
March 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28338451/superficial-siderosis-of-the-central-nervous-system-associated-with-intraspinal-hemorrhage-from-ventral-thoracic-epidural-veins-and-a-ventral-spinal-csf-leak-case-report
#10
Keisuke Takai, Takashi Komori, Manabu Niimura, Makoto Taniguchi
In most patients with superficial siderosis of the CNS, the exact source of bleeding remains unknown because of a lack of objective surgical data. The authors herein describe the case of a 58-year-old man with superficial siderosis of the CNS. The patient also had spinal CSF leakage due to a spinal dural defect. Repair surgery for the dural defect was performed using posterior laminoplasty with a transdural approach without spinal fixation. During repair surgery, the bleeding source was found to be the epidural vein around the defect...
March 24, 2017: Journal of Neurosurgery. Spine
https://www.readbyqxmd.com/read/28338398/dexamethasone-suppresses-jmjd3-gene-activation-via-a-putative-negative-glucocorticoid-response-element-and-maintains-integrity-of-tight-junctions-in-brain-microvascular-endothelial-cells
#11
Wonho Na, Jee Y Shin, Jee Y Lee, Sangyun Jeong, Won-Sun Kim, Tae Y Yune, Bong-Gun Ju
The blood-brain barrier (BBB) exhibits a highly selective permeability to support the homeostasis of the central nervous system (CNS). The tight junctions in the BBB microvascular endothelial cells seal the paracellular space to prevent diffusion. Thus, disruption of tight junctions results in harmful effects in CNS diseases and injuries. It has recently been demonstrated that glucocorticoids have beneficial effects on maintaining tight junctions in both in vitro cell and in vivo animal models. In the present study, we found that dexamethasone suppresses the expression of JMJD3, a histone H3K27 demethylase, via the recruitment of glucocorticoid receptor α (GRα) and nuclear receptor co-repressor (N-CoR) to the negative glucocorticoid response element (nGRE) in the upstream region of JMJD3 gene in brain microvascular endothelial cells subjected to TNFα treatment...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28338324/studies-to-examine-potential-tolerability-differences-between-the-5-ht2c-receptor-selective-agonists-lorcaserin-and-cp-809101
#12
Guy A Higgins, Leonardo B Silenieks, Amy Patrick, Ines A M De Lannoy, Paul J Fletcher, Linda A Parker, Neil J MacLusky, Laura C Sullivan, Teresa A Chavera, Kelly A Berg
Lorcaserin (LOR) is a selective 5-HT2C receptor agonist that has been FDA approved as a treatment for obesity. The most frequently reported side-effects of LOR include nausea and headache, which can be dose limiting. We have previously reported that in the rat, while LOR produced unconditioned signs characteristic of nausea/malaise, the highly selective 5-HT2C agonist CP-809101 (CP) produced fewer equivalent signs. Because this may indicate a subclass of 5-HT2C agonists having better tolerability, the present studies were designed to further investigate this apparent difference...
March 24, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28338245/infective-capacity-of-cryptococcus-neoformans-and-cryptococcus-gattii-in-a-human-astrocytoma-cell-line
#13
M C Olave, J C Vargas-Zambrano, A M Celis, E Castañeda, J M González
Pathogenesis of cryptococcosis in the central nervous system (CNS) is a topic of ongoing research, including the mechanisms by which this fungus invades and infects the brain. Astrocytes, the most common CNS cells, play a fundamental role in the local immune response. Astrocytes might participate in cryptococcosis either as a host or by responding to fungal antigens. To determine the infectivity of Cryptococcus neoformans var. grubii and Cryptococcus gattii in a human astrocytoma cell line and the induction of major histocompatibility complex (MHC) molecules...
March 24, 2017: Mycoses
https://www.readbyqxmd.com/read/28338071/phase-transition-nanodroplets-for-real-time-photoacoustic-ultrasound-dual-modality-imaging-and-photothermal-therapy-of-sentinel-lymph-node-in-breast-cancer
#14
Lu Yang, Juan Cheng, Yuli Chen, Shengjie Yu, Fengqiu Liu, Yang Sun, Yu Chen, Haitao Ran
Pathological status of lymph nodes (LNs) plays a critical role in staging and treatment for the patients with breast cancer. Sentinel lymph node biopsy has become the standard method in determining pathological status of axillary LNs. Therefore, the determination of sentinel lymph nodes (SLNs) and therapy of metastatic LNs are highly desirable in clinic. Herein, an unprecedented carbon nanoparticles (CNs)-incorporated liquid-gas phase-transition nanodroplets (CNPs) with strong near-infrared (NIR) absorption, good biocompatibility, excellent photoacoustic (PA) and ultrasound (US) contrast, and high photothermal-conversion efficiency are reported in this study...
March 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28337888/decitabine-treatment-for-acute-myeloid-leukemia-relapse-after-allogeneic-hematopoietic-stem-cell-transplantation
#15
X L Liu, X Zhao, C Wang, S J Gao, Y H Tan
Therapeutic options for patients with relapse of acute myeloid leukemia (AML) after allo-SCT are limited. Here, we present a case of a 49-year female with AML who underwent myeloablative allo-SCT from a matched sibling donor. Seven months after transplantation she developed cGVHD and suffered from extramedullary plus concurrent medullary relapse. The presence of CNS extramedullary disease is unique. Our patient was treated with decetabine. After one cycle the patient achieved complete remission and full donor chimerism without severe side effects or the occurrence of GVHD...
January 2017: Journal of Biological Regulators and Homeostatic Agents
https://www.readbyqxmd.com/read/28337644/cns-demyelination-with-tnf-%C3%AE-blockers
#16
REVIEW
Elissavet Kemanetzoglou, Elisabeth Andreadou
Tumor necrosis factor-α (TNF-α) blockers are a popular therapeutic choice in a number of inflammatory diseases. Thus far, five TNF- α blockers have been approved for clinical use (etanercept, infliximab, adalimumab, golimumab. and certolizumab). Despite being considered relatively safe, serious side effects associated with immune suppression have been reported, including central and peripheral nervous system (CNS) demyelinating disorders. It is still elusive whether these events are mere coincidence or a side effect of anti-TNF-α use...
April 2017: Current Neurology and Neuroscience Reports
https://www.readbyqxmd.com/read/28337585/background-gamma-radiation-and-childhood-cancer-in-germany-an-ecological-study
#17
Claudia Spix, Bernd Grosche, Martin Bleher, Peter Kaatsch, Peter Scholz-Kreisel, Maria Blettner
The relationship of low-dose background gamma radiation and childhood leukaemia was investigated in a number of studies. Results from these studies are inconclusive. Therefore, in the present study 25 years of German childhood cancer data were analyzed using interpolated background annual gamma dose rate per community in an ecological study. The main question was leukaemia; as exploratory questions we investigate central nervous system (CNS) tumours, thyroid carcinomas and diagnoses less likely to be related to radiation...
March 23, 2017: Radiation and Environmental Biophysics
https://www.readbyqxmd.com/read/28337172/bone-marrow-derived-cell-accumulation-in-the-spinal-cord-is-independent-of-peripheral-mobilization-in-a-mouse-model-of-amyotrophic-lateral-sclerosis
#18
Kyle Peake, John Manning, Coral-Ann Lewis, Kevin Tran, Fabio Rossi, Charles Krieger
Bone marrow-derived cells (BMDCs) are capable of migrating across the blood-brain barrier (BBB) and accumulating in the central nervous system (CNS) when transplanted into recipients conditioned with whole-body irradiation or chemotherapy. We used the chemotherapeutic agents busulfan and treosulfan to condition recipient mice for transplantation with bone marrow (BM) cells isolated from donor mice ubiquitously expressing green fluorescent protein. We attempted to increase the accumulation of BMDCs in the CNS by mobilization of BMDCs using either, or both, granulocyte colony-stimulating factor (GCSF) or plerixafor (AMD3100)...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28337127/nlrp3-inflammasome-in-neurological-diseases-from-functions-to-therapies
#19
REVIEW
Limin Song, Lei Pei, Shanglong Yao, Yan Wu, You Shang
Neuroinflammation has been identified as a causative factor of multiple neurological diseases. The nucleotide-binding oligomerization domain-, leucine-rich repeat- and pyrin domain-containing 3 (NLRP3) inflammasome, a subcellular multiprotein complex that is abundantly expressed in the central nervous system (CNS), can sense and be activated by a wide range of exogenous and endogenous stimuli such as microbes, aggregated and misfolded proteins, and adenosine triphosphate, which results in activation of caspase-1...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28337124/interleukin-4-protects-dopaminergic-neurons-in-vitro-but-is-dispensable-for-mptp-induced-neurodegeneration-in-vivo
#20
Laura Hühner, Jennifer Rilka, Ralf Gilsbach, Xiaolai Zhou, Venissa Machado, Björn Spittau
Microglia are involved in physiological as well as neuropathological processes in the central nervous system (CNS). Their functional states are often referred to as M1-like and M2-like activation, and are believed to contribute to neuroinflammation-mediated neurodegeneration or neuroprotection, respectively. Parkinson's disease (PD) is one the most common neurodegenerative disease and is characterized by the progressive loss of midbrain dopaminergic (mDA) neurons in the substantia nigra resulting in bradykinesia, tremor, and rigidity...
2017: Frontiers in Molecular Neuroscience
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