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https://www.readbyqxmd.com/read/29792572/galnac-sirna-conjugates-leading-the-way-for-delivery-of-rnai-therapeutics
#1
Aaron D Springer, Steven F Dowdy
Short-interfering RNA (siRNA)-induced RNAi responses have great potential to treat a wide variety of human diseases from cancer to pandemic viral outbreaks to Parkinson's Disease. However, before siRNAs can become drugs, they must overcome a billion years of evolutionary defenses designed to keep invading RNAs on the outside cells from getting to the inside of cells. Not surprisingly, significant effort has been placed in developing a wide array of delivery technologies. Foremost of these has been the development of N-acetylgalactosamine (GalNAc) siRNA conjugates for delivery to liver...
May 24, 2018: Nucleic Acid Therapeutics
https://www.readbyqxmd.com/read/29789378/subthalamic-nucleus-neurons-differentially-encode-early-and-late-aspects-of-speech-production
#2
W J Lipski, A Alhourani, T Pirnia, P W Jones, C Dastolfo-Hromack, L B Helou, D J Crammond, S Shaiman, M W Dickey, L L Holt, R S Turner, J A Fiez, R M Richardson
Basal ganglia-thalamocortical loops mediate all motor behavior, yet little detail is known about the role of basal ganglia nuclei in speech production. Using intracranial recording during deep brain stimulation surgery in humans with Parkinson's disease, we tested the hypothesis that the firing rate of subthalamic nucleus neurons is modulated in sync with motor execution aspects of speech. Nearly half of seventy-nine unit recordings exhibited firing rate modulation, during a syllable reading task across twelve subjects (male and female)...
May 22, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29784843/high-dose-and-delayed-treatment-with-bile-acids-ineffective-in-rml-prion-infected-mice
#3
Grant Norman, Jody Campeau, Valerie L Sim
Prion diseases are a group of neurodegenerative diseases associated with the misfolding of the cellular prion protein (PrPC ) into the infectious form (PrPSc ). There are currently no treatments for prion disease. Bile acids have the ability to protect hepatocytes from apoptosis and are neuroprotective in animal models of other protein folding neurodegenerative diseases including Huntington's, Parkinson's, and Alzheimer's disease. Importantly, bile acids are approved for clinical use in patients with cirrhosis, and have recently been shown to be safe and possibly effective in pilot trials of patients with amyotrophic lateral sclerosis (ALS)...
May 21, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29784534/presynaptic-dopaminergic-neuroimaging-in-rem-sleep-behavior-disorder-a-systematic-review-and-meta-analysis
#4
REVIEW
Matteo Bauckneht, Andrea Chincarini, Fabrizio De Carli, Michele Terzaghi, Silvia Morbelli, Flavio Nobili, Dario Arnaldi
The presence of polysomnography-confirmed REM sleep behavior disorder (RBD) is the stronger risk factor for having prodromal Parkinson disease (PD), followed by abnormal presynaptic dopaminergic radionuclide neuroimaging. Aim of the review is to conduct a meta-analysis of literature data regarding presynaptic dopaminergic neuroimaging in RBD. A literature search was conducted, resulting in 16 papers that met the inclusion criteria. Clinical and neuroimaging data were extracted. The studies are heterogeneous, especially for neuroimaging methodology...
April 22, 2018: Sleep Medicine Reviews
https://www.readbyqxmd.com/read/29783988/tolerogenic-bone-marrow-derived-dendritic-cells-induce-neuroprotective-regulatory-t-cells-in-a-model-of-parkinson-s-disease
#5
Charles R Schutt, Howard E Gendelman, R Lee Mosley
BACKGROUND: Administration of granulocyte-macrophage colony-stimulating factor (GM-CSF) increases regulatory T cell (Treg) number and function with control of neuroinflammation and neuronal protection in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson's disease (PD). Recently, we demonstrated in an early phase 1 clinical trial that GM-CSF also improves motor skills in PD patients. However, the mechanisms of Treg induction and its effects on neuroprotective responses remain unknown...
May 21, 2018: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/29783690/echinacoside-an-inestimable-natural-product-in-treatment-of-neurological-and-other-disorders
#6
REVIEW
Jingjing Liu, Lingling Yang, Yanhong Dong, Bo Zhang, Xueqin Ma
Echinacoside (ECH), a natural phenylethanoid glycoside, was first isolated from Echinacea angustifolia DC. (Compositae) sixty years ago. It was found to possess numerous pharmacologically beneficial activities for human health, especially the neuroprotective and cardiovascular effects. Although ECH showed promising potential for treatment of Parkinson's and Alzheimer's diseases, some important issues arose. These included the identification of active metabolites as having poor bioavailability in prototype form, the definite molecular signal pathways or targets of ECH with the above effects, and limited reliable clinical trials...
May 18, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29780852/parkinson-s-patients-with-dyskinesia-switched-from-immediate-release-amantadine-to-open-label-ads-5102
#7
Stuart H Isaacson, Stanley Fahn, Rajesh Pahwa, Caroline M Tanner, Alberto J Espay, Claudia Trenkwalder, Charles H Adler, Rajiv Patni, Reed Johnson
Background: ADS-5102 (amantadine) extended release capsules (GOCOVRI™) are a treatment for dyskinesia in patients with Parkinson's disease (PD). ADS-5102 reduced dyskinesia and OFF time in phase 3 controlled trials of up to six months. Amantadine immediate release (IR) is used for dyskinesia, but suboptimal durability and tolerability limit its clinical utility. Methods: In an ongoing, open-label, phase 3 study in the US and Western Europe (NCT02202551), patients with PD received 274 mg of ADS-5102 (equivalent to 340 mg amantadine HCl) once daily at bedtime for up to two years...
March 2018: Movement Disorders Clinical Practice
https://www.readbyqxmd.com/read/29780572/cognitive-training-and-transcranial-direct-current-stimulation-for-mild-cognitive-impairment-in-parkinson-s-disease-a-randomized-controlled-trial
#8
Blake J Lawrence, Natalie Gasson, Andrew R Johnson, Leon Booth, Andrea M Loftus
This study examined whether standard cognitive training, tailored cognitive training, transcranial direct current stimulation (tDCS), standard cognitive training + tDCS, or tailored cognitive training + tDCS improved cognitive function and functional outcomes in participants with PD and mild cognitive impairment (PD-MCI). Forty-two participants with PD-MCI were randomized to one of six groups: (1) standard cognitive training, (2) tailored cognitive training, (3) tDCS, (4) standard cognitive training + tDCS, (5) tailored cognitive training + tDCS, or (6) a control group...
2018: Parkinson's Disease
https://www.readbyqxmd.com/read/29779721/evaluation-of-an-ontology-based-system-for-computerized-cognitive-rehabilitation
#9
Anna Alloni, Silvana Quaglini, Silvia Panzarasa, Elena Sinforiani, Sara Bernini
OBJECTIVES: This paper describes the results of a randomized clinical trial about the effectiveness of a computerized rehabilitation treatment on a sample of 31 patients affected by Parkinson disease. METHODS: Computerized exercises were administered by the therapists to the intervention group (n = 17) through the CoRe tool, which automatically generates a big variety of exercises leveraging on a stimuli set (words, sounds and images) organized into a dedicated ontology...
July 2018: International Journal of Medical Informatics
https://www.readbyqxmd.com/read/29778803/age-affects-reinforcement-learning-through-dopamine-based-learning-imbalance-and-high-decision-noise-not-through-parkinsonian-mechanisms
#10
Ravi B Sojitra, Itamar Lerner, Jessica R Petok, Mark A Gluck
Probabilistic reinforcement learning declines in healthy cognitive aging. While some findings suggest impairments are especially conspicuous in learning from rewards, resembling deficits in Parkinson's disease, others also show impairments in learning from punishments. To reconcile these findings, we tested 252 adults from 3 age groups on a probabilistic reinforcement learning task, analyzed trial-by-trial performance with a Q-reinforcement learning model, and correlated both fitted model parameters and behavior to polymorphisms in dopamine-related genes...
April 19, 2018: Neurobiology of Aging
https://www.readbyqxmd.com/read/29774765/-staying-safe-a-narrative-review-of-falls-prevention-in-people-with-parkinson-s-pdsafe
#11
Sophia Hulbert, Lynn Rochester, Alice Nieuwboer, Vicki Goodwin, Carolyn Fitton, Kim Chivers-Seymour, Ann Ashburn
BACKGROUND: Parkinson's disease demonstrates a spectrum of motor and non-motor symptoms. Falling is common and disabling. Current medical management shows minimal impact to reduce falls or fall-related risk factors, such as deficits in gait, strength, and postural instability. Despite evidence supporting rehabilitation in reducing fall risk factors, the most appropriate intervention to reduce overall fall rate remains inconclusive. This article aims to 1) synthesise current evidence and conceptual models of falls rehabilitation in Parkinson's in a narrative review; and based on this evidence, 2) introduce the treatment protocol used in the falls prevention and multi-centre clinical trial "PDSAFE"...
May 18, 2018: Disability and Rehabilitation
https://www.readbyqxmd.com/read/29772496/vibrotactile-feedback-alters-dynamics-of-static-postural-control-in-persons-with-parkinson-s-disease-but-not-older-adults-at-high-fall-risk
#12
Carleigh M High, Hannah F McHugh, Stephen C Mills, Shinichi Amano, Jane E Freund, Srikant Vallabhajosula
BACKGROUND: Aging and Parkinson's disease are often associated with impaired postural control. Providing extrinsic feedback via vibrotactile sensation could supplement intrinsic feedback to maintain postural control. RESEARCH QUESTION: We investigated the postural control response to vibrotactile feedback provided at the trunk during challenging stance conditions in older adults at high fall risk and individuals with Parkinson's disease compared to healthy older adults...
May 8, 2018: Gait & Posture
https://www.readbyqxmd.com/read/29770251/review-of-the-neurological-benefits-of-phytocannabinoids
#13
REVIEW
Joseph Maroon, Jeff Bost
Background: Numerous physical, psychological, and emotional benefits have been attributed to marijuana since its first reported use in 2,600 BC in a Chinese pharmacopoeia. The phytocannabinoids, cannabidiol (CBD), and delta-9-tetrahydrocannabinol (Δ9-THC) are the most studied extracts from cannabis sativa subspecies hemp and marijuana. CBD and Δ9-THC interact uniquely with the endocannabinoid system (ECS). Through direct and indirect actions, intrinsic endocannabinoids and plant-based phytocannabinoids modulate and influence a variety of physiological systems influenced by the ECS...
2018: Surgical Neurology International
https://www.readbyqxmd.com/read/29764704/current-understanding-of-neuroinflammation-after-traumatic-brain-injury-and-cell-based-therapeutic-opportunities
#14
REVIEW
Ye Xiong, Asim Mahmood, Michael Chopp
Traumatic brain injury (TBI) remains a major cause of death and disability worldwide. Increasing evidence indicates that TBI is an important risk factor for neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and chronic traumatic encephalopathy. Despite improved supportive and rehabilitative care of TBI patients, unfortunately, all late phase clinical trials in TBI have yet to yield a safe and effective neuroprotective treatment. The disappointing clinical trials may be attributed to variability in treatment approaches and heterogeneity of the population of TBI patients as well as a race against time to prevent or reduce inexorable cell death...
April 24, 2018: Chinese Journal of Traumatology, Zhonghua Chuang Shang za Zhi
https://www.readbyqxmd.com/read/29764353/non-motor-parkinson-disease-new-concepts-and-personalised-management
#15
Nataliya Titova, K Ray Chaudhuri
Most patients with Parkinson disease (PD) have non-motor symptoms (NMS), and on average these can range from four to 19 different symptoms. NMS dominate the prodromal phase of PD and some may serve as clinical biomarkers of PD. NMS can be dopaminergic, non-dopaminergic, of genetic origin or drug induced. Clinical assessment of NMS should include the NMS Questionnaire (completed by patients) for screening, as recommended by the International Parkinson and Movement Disorders Society and other international societies...
May 21, 2018: Medical Journal of Australia
https://www.readbyqxmd.com/read/29759930/diagnostic-criteria-for-camptocormia-in-parkinson-s-disease-a-consensus-based-proposal
#16
Alfonso Fasano, Christian Geroin, Alfredo Berardelli, Bastiaan R Bloem, Alberto J Espay, Mark Hallett, Anthony E Lang, Michele Tinazzi
INTRODUCTION: Camptocormia is defined as an involuntary, marked flexion of the thoracolumbar spine appearing during standing or walking and resolving in the supine position or when leaning against a wall. However, there is no established agreement on the minimum degree of forward flexion needed to diagnose camptocormia. Likewise, the current definition does not categorize camptocormia on the basis of the bending fulcrum. METHODS: We performed a survey among movement disorders experts to identify camptocormia using images of patients with variable degrees and types of forward trunk flexion by fulcrum (upper and lower fulcra)...
May 8, 2018: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/29759929/entacapone-and-prostate-cancer-in-parkinson-s-disease-patients-a-large-veterans-affairs-healthcare-system-study
#17
Jacqueline M Major, Diane Dong, Francesca Cunningham, Kunthel By, Kwan Hur, David C Shih, Rong Jiang, Gerald D Podskalny, XiangMing Wei, Simone Pinheiro, Steven T Bird, Stephine Keeton, David J Graham
BACKGROUND: An increased incidence of prostate cancer was observed in Parkinson's disease (PD) patients treated with entacapone during a pre-approval randomized clinical trial; the relation has not been robustly investigated in the U.S. ambulatory setting. OBJECTIVE: To investigate whether entacapone is associated with prostate cancer and to assess whether the associations are correlated with advanced disease at the time of cancer diagnosis. METHODS: Using data from the Department of Veterans Affairs healthcare system, new-user cohorts were created of PD patients treated with add-on entacapone or add-on dopamine agonist/monoamine oxidase B inhibitors between January 2000 and December 2014...
May 5, 2018: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/29758999/movement-disorders-associated-with-antipsychotic-medication-in-people-with-schizophrenia-an-overview-of-cochrane-reviews-and-meta-analysis
#18
Davide Martino, Vikram Karnik, Sydney Osland, Thomas R E Barnes, Tamara M Pringsheim
Movement disorders associated with antipsychotic medications are relatively common, stigmatising, and potentially disabling. Their prevalence in people with psychosis who are prescribed second-generation antipsychotics (SGAs) is uncertain, as is their level of recognition by clinicinas. We conducted meta-analyses of randomised controlled trials included in the Cochrane Database of Systematic Reviews on schizophrenia and schizophrenia-like psychoses to estimate the prevalence of new-onset dystonia, akathisia, parkinsonism, and tremor with SGAs (amisulpride, asenapine, aripiprazole, clozapine, olanzapine, paliperidone, quetiapine, risperidone, L-sulpiride, and ziprasidone) approved in Canada and the UK, comparing them with haloperidol and chlorpromazine...
January 1, 2018: Canadian Journal of Psychiatry. Revue Canadienne de Psychiatrie
https://www.readbyqxmd.com/read/29756335/treatment-of-restless-legs-syndrome-evidence-based-review-and-implications-for-clinical-practice-revised-2017-%C3%A2
#19
REVIEW
Juliane Winkelmann, Richard P Allen, Birgit Högl, Yuichi Inoue, Wolfgang Oertel, Aaro V Salminen, John W Winkelman, Claudia Trenkwalder, Cristina Sampaio
The objective of the current review was to update the previous evidence-based medicine review of treatments for restless legs syndrome published in 2008. All randomized, controlled trials (level I) with a high quality score published between January 2007 and January 2017 were reviewed. Forty new studies qualified for efficacy review. Pregabalin, gabapentin enacarbil, and oxycodone/naloxone, which did not appear in the previous review, have accrued data to be considered efficacious. Likewise, new data enable the modification of the level of efficacy for rotigotine from likely efficacious to efficacious...
May 14, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/29755339/therapeutic-potential-of-a-prolyl-hydroxylase-inhibitor-fg-4592-for-parkinson-s-diseases-in-vitro-and-in-vivo-regulation-of-redox-biology-and-mitochondrial-function
#20
Xuan Li, Xin-Xin Cui, Ya-Jing Chen, Ting-Ting Wu, Huaxi Xu, Huiyong Yin, Yun-Cheng Wu
As the main transcription factor that regulates the cellular responses to hypoxia, Hypoxia-inducible factor-1α (HIF-1α) plays an important role in the pathogenesis of Parkinson's disease (PD). HIF-1α is normally degraded through ubiquitination after hydroxylation by prolyl hydroxylases (PHD). Emerging evidence has suggested that HIF PHD inhibitors (HIF-PHI) may have neuroprotective effects on PD through increasing HIF-1α levels. However, the therapeutic benefit of HIF-PHI for PD remains poorly explored due to the lack of proper clinical compounds and understanding of the underlying molecular mechanisms...
2018: Frontiers in Aging Neuroscience
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