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121. Ageing and epigenetics: linking neurodevelopmental and neurodegenerative disorders. (Abstract)

intellectual disability and cognitive ageing. Epigenetic pathways may strengthen the links between neurodevelopmental disorders and neurodegenerative diseases. WHAT THIS PAPER ADDS: DNA methylation has relevance to both neurological development and neurodegeneration. Links between epigenetics, genotype and phenotype are emerging.© 2019 Mac Keith Press. (...) Ageing and epigenetics: linking neurodevelopmental and neurodegenerative disorders. Epigenetics has classically been recognized as crucial to neurodevelopment and neurodevelopmental disorders. More recently its role in ageing processes, including neurodegenerative disorders has emerged, although far more research is required in this area, particularly in humans. Epigenetic processes that regulate gene expression comprise strata of DNA modification (e.g. methylation), histone modification (e.g

2019 Developmental Medicine and Child Neurology

122. Tumor-infiltrating T-cell Receptor-beta Repertoires are Linked to the Risk of Late Chemoradiation-induced Temporal Lobe Necrosis in Locally Advanced Nasopharyngeal Carcinoma. (Abstract)

Tumor-infiltrating T-cell Receptor-beta Repertoires are Linked to the Risk of Late Chemoradiation-induced Temporal Lobe Necrosis in Locally Advanced Nasopharyngeal Carcinoma. Temporal lobe necrosis (TLN), a late complication of nasopharyngeal carcinoma (NPC) after concurrent chemoradiotherapy (CCRT), causes permanent neurologic deficits. We aimed to investigate the risk factors for the development of CCRT-induced TLN in locally advanced NPC patients.The incidence of CCRT-induced TLN (...)  < .0001). We found that in the T4 NPC patients, univariate and multivariate analyses showed the radiation tolerance dose-volume effect was not an absolutely independent factor influencing TLN occurrence. However, increased TLN risk was observed in association with higher pre-CCRT baseline and post-CCRT neutrophil-to-lymphocyte ratios. There was also a link between intratumoral TCRbeta repertoire subtypes and TLN incidence. Combining the inherent TCRbeta genomic susceptibility with the clinical

2019 Biology and Physics

123. Emerging links between pediatric lysosomal storage diseases and adult parkinsonism. (Abstract)

role of lysosomes in neuronal homeostasis, neurological manifestations, including movement disorders, can accompany many lysosomal storage disorders. Over the last decade, evidence from genetics, clinical epidemiology, cell biology, and biochemistry have converged to implicate links between lysosomal storage disorders and adult-onset movement disorders. The strongest evidence comes from mutations in Glucocerebrosidase, which cause Gaucher's disease and are among the most common and potent risk (...) Emerging links between pediatric lysosomal storage diseases and adult parkinsonism. Lysosomal storage disorders comprise a clinically heterogeneous group of autosomal-recessive or X-linked genetic syndromes caused by disruption of lysosomal biogenesis or function resulting in accumulation of nondegraded substrates. Although lysosomal storage disorders are diagnosed predominantly in children, many show variable expressivity with clinical presentations possible later in life. Given the important

2019 Movement Disorders

124. A hexanucleotide repeat modifies expressivity of X-linked dystonia parkinsonism. (Abstract)

A hexanucleotide repeat modifies expressivity of X-linked dystonia parkinsonism. X-linked dystonia parkinsonism (XDP) is a neurodegenerative movement disorder caused by a single mutation: SINE-VNTR-Alu (SVA) retrotransposon insertion in TAF1. Recently, a (CCCTCT)n repeat within the SVA insertion has been reported as an age-at-onset (AAO) modifier in XDP. Here we investigate the role of this hexanucleotide repeat in modifying expressivity of XDP.We genotyped the hexanucleotide repeat in 355 XDP (...) expressivity in XDP. RN-dependent TAF1 repression and subsequent differences in TAF1 mRNA levels in patients may be potentiated in the brain through somatic variability leading to the neurological phenotype. ANN NEUROL 2019.© 2019 American Neurological Association.

2019 Annals of Neurology

125. Exploring causal pathways linking cerebral small vessel diseases burden to poststroke depressive symptoms with structural equation model analysis. (Abstract)

Exploring causal pathways linking cerebral small vessel diseases burden to poststroke depressive symptoms with structural equation model analysis. Cerebral small vessel diseases (SVD) are associated with poststroke depressive symptoms (PDS). The mechanisms underlying the association between SVD burden and PDS are unclear. This study investigated the clinical pathways linking SVD burden to PDS.A cohort of 563 patients with acute ischemic stroke were examined at three and fifteen months after (...) all four SVD markers in structural equation modeling (SEM). SEM was further employed to examine the direct and indirect linking pathways between SVD burden, infarct volumes, stroke severity, poststroke cognitive and physical dysfunctions, and PDS.The latent SVD burden was directly associated with more severe PDS at the 3-month follow-up (path coefficient=0.11), while SVD burden and PDS at the 15-month were mainly linked through PDS at the 3-month follow-up (path coefficient=0.48). The volume

2019 Journal of Affective Disorders

126. MRI brain lesions in asymptomatic boys with X-linked adrenoleukodystrophy. (Abstract)

MRI brain lesions in asymptomatic boys with X-linked adrenoleukodystrophy. To describe the brain MRI findings in asymptomatic patients with childhood cerebral adrenoleukodystrophy (CCALD).We retrospectively reviewed a series of biochemically or genetically confirmed cases of adrenoleukodystrophy followed at our institution between 2001 and 2015. We identified and analyzed 219 brain MRIs from 47 asymptomatic boys (median age 6.0 years). Patient age, MRI scan, and brain lesion characteristics (...) patients (r = -0.745; p < 0.0001). Older patients (median age 14.4 y/o) tended to undergo spontaneous arrest of disease. Early lesions grew 46× faster when still limited to the splenium, genu of the corpus callosum, or the brainstem (p = 0.001).We provide a description of CCALD lesion development in a cohort of asymptomatic boys. Understanding the early stages of CCALD is crucial to optimize treatments for children diagnosed by newborn screening.© 2019 American Academy of Neurology.

2019 Neurology

127. X-linked myotubular myopathy: A prospective international natural history study. (Abstract)

X-linked myotubular myopathy: A prospective international natural history study. Because X-linked myotubular myopathy (XLMTM) is a rare neuromuscular disease caused by mutations in the MTM1 gene with a large phenotypic heterogeneity, to ensure clinical trial readiness, it was mandatory to better quantify disease burden and determine best outcome measures.We designed an international prospective and longitudinal natural history study in patients with XLMTM and assessed muscle strength and motor (...) neutralizing activity was detected in 26% with 2 patients having an inhibitory titer >1:10.Our data confirm that XLMTM is slowly progressive for male survivors regardless of their phenotype and provide outcome validation and natural history data that can support clinical development in this population.NCT02057705.© 2019 American Academy of Neurology.

2019 Neurology

128. Headache: an important symptom possibly linked to white matter lesions in thalassaemia. (Abstract)

Headache: an important symptom possibly linked to white matter lesions in thalassaemia. Neurological manifestations are reported only occasionally in patients with thalassaemia and are given much less prominence than the complications related to anaemia and iron overload. White matter changes (WMCs) on magnetic resonance imaging (MRI) in patients with thalassaemia were first reported two decades ago but the significance of these lesions remains unclear. We studied the neurological and cognitive

2019 British journal of haematology

129. Succinate links atrial dysfunction and cardioembolic stroke. Full Text available with Trip Pro

underlying link between CE stroke and energy metabolism.© 2019 American Academy of Neurology. (...) Succinate links atrial dysfunction and cardioembolic stroke. To determine whether altered metabolic profiles represent a link between atrial dysfunction and cardioembolic (CE) stroke, and thus whether underlying dysfunctional atrial substrate may contribute to thromboembolism risk in CE stroke.A total of 144 metabolites were measured using liquid chromatography-tandem mass spectrometry in plasma samples collected within 9 hours of stroke onset in 367 acute stroke patients. Stroke subtype

2019 Neurology

130. Metoclopramide: risk of neurological adverse effects

Metoclopramide: risk of neurological adverse effects Metoclopramide: risk of neurological adverse effects - GOV.UK GOV.UK uses cookies to make the site simpler. or Search Metoclopramide: risk of neurological adverse effects Restricted dose and duration of use. Published 11 December 2014 From: Therapeutic area: , , , , , Contents Article date: August 2013 The European Medicines Agency’s Committee on Medicinal Products for Human Use has reviewed the benefits and risks of the antiemetic (...) metoclopramide. The review was done at the request of the French medicines regulatory agency (ANSM), following concerns over side effects and efficacy. The review confirmed the well known risks of neurological effects such as short-term extrapyramidal disorders and tardive dyskinesia. The conclusion of the review was that these risks outweigh the benefits in long-term or high-dose treatment. The EU review has recommended changes that include a restriction to the dose and duration of use to help minimise

2013 MHRA Drug Safety Update

131. Cohort study: Elderly in-hospital cardiac arrest patients who are resuscitated with neurological recovery experience favourable long-term survival similar to non-arrest heart failure patients

Cohort study: Elderly in-hospital cardiac arrest patients who are resuscitated with neurological recovery experience favourable long-term survival similar to non-arrest heart failure patients Elderly in-hospital cardiac arrest patients who are resuscitated with neurological recovery experience favourable long-term survival similar to non-arrest heart failure patients | BMJ Evidence-Based Medicine We use cookies to improve our service and to tailor our content and advertising to you. You can (...) cardiac arrest patients who are resuscitated with neurological recovery experience favourable long-term survival similar to non-arrest heart failure patients Article Text Prognosis Cohort study Elderly in-hospital cardiac arrest patients who are resuscitated with neurological recovery experience favourable long-term survival similar to non-arrest heart failure patients T Jared Bunch Statistics from Altmetric.com Commentary on: Chan PS , Nallamothu BK , Krumholz HM , et al . American Heart Association

2013 Evidence-Based Medicine

132. Tolvaptan (Samsca?): over-rapid increase in serum sodium risking serious neurological events

Tolvaptan (Samsca?): over-rapid increase in serum sodium risking serious neurological events Tolvaptan (Samsca▼): over-rapid increase in serum sodium risking serious neurological events - GOV.UK GOV.UK uses cookies to make the site simpler. or Search Tolvaptan (Samsca▼): over-rapid increase in serum sodium risking serious neurological events Careful monitoring of serum sodium important, co-administration of other drugs that may increase serum sodium not recommended. Published 11 December 2014 (...) . However, there have been reports of serious neurological events (see below: advice for healthcare professionals) in patients treated with tolvaptan where the correction of serum sodium has exceeded the suggested rate. Further information on the rates at which serum sodium should increase is also set out in the advice for healthcare professionals. Serum sodium should be closely monitored in patients receiving tolvaptan, especially those with very low serum sodium (<120 mmol/L) at baseline or where

2012 MHRA Drug Safety Update

133. Linking Digital Smartphone Behaviour With Brain Function

Information provided by (Responsible Party): University of Zurich Study Details Study Description Go to Brief Summary: This study will thus examine daily behaviour based on smartphone use and link it to the neurological and neuropsychological status as well as to neuroradiological studies that are part of the clinical routine. The study will examine behaviour changes before and after surgery, and how this change in measured behaviour with the smartphone relates to today's "gold standard", namely (...) Linking Digital Smartphone Behaviour With Brain Function Linking Digital Smartphone Behaviour With Brain Function - Full Text View - ClinicalTrials.gov Hide glossary Glossary Study record managers: refer to the if submitting registration or results information. Search for terms x × Study Record Detail Saved Studies Save this study Warning You have reached the maximum number of saved studies (100). Please remove one or more studies before adding more. Linking Digital Smartphone Behaviour

2018 Clinical Trials

134. A Study to Evaluate the Safety and Tolerability of V114 and Prevnar 13â„¢ in Healthy Infants (V114-031/PNEU-LINK)

A Study to Evaluate the Safety and Tolerability of V114 and Prevnar 13â„¢ in Healthy Infants (V114-031/PNEU-LINK) A Study to Evaluate the Safety and Tolerability of V114 and Prevnar 13™ in Healthy Infants (V114-031/PNEU-LINK) - Full Text View - ClinicalTrials.gov Hide glossary Glossary Study record managers: refer to the if submitting registration or results information. Search for terms x × Study Record Detail Saved Studies Save this study Warning You have reached the maximum number of saved (...) studies (100). Please remove one or more studies before adding more. A Study to Evaluate the Safety and Tolerability of V114 and Prevnar 13™ in Healthy Infants (V114-031/PNEU-LINK) The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. of clinical studies and talk to your health care provider before participating. Read our for details. ClinicalTrials.gov

2018 Clinical Trials

135. Lesional Evaluation of High Risk Patients With Neoatherosclerosis Treated With Rosuvastatin and Eicosapentaenoic Acid Using Optical Coherence Tomography(OCT)[LINK IT TWO]

Lesional Evaluation of High Risk Patients With Neoatherosclerosis Treated With Rosuvastatin and Eicosapentaenoic Acid Using Optical Coherence Tomography(OCT)[LINK IT TWO] Lesional Evaluation of High Risk Patients With Neoatherosclerosis Treated With Rosuvastatin and Eicosapentaenoic Acid Using Optical Coherence Tomography(OCT)[LINK IT TWO] - Full Text View - ClinicalTrials.gov Hide glossary Glossary Study record managers: refer to the if submitting registration or results information. Search (...) for terms x × Study Record Detail Saved Studies Save this study Warning You have reached the maximum number of saved studies (100). Please remove one or more studies before adding more. Lesional Evaluation of High Risk Patients With Neoatherosclerosis Treated With Rosuvastatin and Eicosapentaenoic Acid Using Optical Coherence Tomography(OCT)[LINK IT TWO] The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has

2018 Clinical Trials

136. Linking Cognitive Functioning to Multimodal Imaging in Multiple Sclerosis (MS)

Linking Cognitive Functioning to Multimodal Imaging in Multiple Sclerosis (MS) Linking Cognitive Functioning to Multimodal Imaging in Multiple Sclerosis (MS) - Full Text View - ClinicalTrials.gov Hide glossary Glossary Study record managers: refer to the if submitting registration or results information. Search for terms x × Study Record Detail Saved Studies Save this study Warning You have reached the maximum number of saved studies (100). Please remove one or more studies before adding more (...) . Linking Cognitive Functioning to Multimodal Imaging in Multiple Sclerosis (MS) The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. of clinical studies and talk to your health care provider before participating. Read our for details. ClinicalTrials.gov Identifier: NCT03723356 Recruitment Status : Recruiting First Posted : October 29, 2018 Last Update Posted

2018 Clinical Trials

137. Is interleukin-6 the link between low LDL cholesterol and increased non-cardiovascular mortality in the elderly? Full Text available with Trip Pro

Is interleukin-6 the link between low LDL cholesterol and increased non-cardiovascular mortality in the elderly? 29682295 2019 01 30 2053-3624 5 1 2018 Open heart Open Heart Is interleukin-6 the link between low LDL cholesterol and increased non-cardiovascular mortality in the elderly? e000789 10.1136/openhrt-2018-000789 DiNicolantonio James J JJ Mid America Heart Institute, Kansas, USA. McCarty Mark F MF Catalytic Longevity, Encinitas, California, USA. eng Editorial 2018 04 13 England Open (...) Biomarkers Prev. 2016 Aug;25(8):1231-9 27277846 Lancet. 1987 Aug 8;2(8554):298-301 2886765 Neurology. 2007 Mar 6;68(10):737-42 17182976 Metabolism. 1988 Sep;37(9):859-65 3419323 Arch Gerontol Geriatr. 2017 Nov;73:257-262 28866452 Lancet. 2012 Mar 31;379(9822):1214-24 22421340 BMJ. 1994 Feb 5;308(6925):373-9 8124144 J Natl Cancer Inst. 1982 Nov;69(5):989-96 6957662 Curr Opin Clin Nutr Metab Care. 2002 Mar;5(2):153-8 11844981 Ann Rheum Dis. 2017 Nov;76(11):1949-1952 28916714 Am J Epidemiol. 1992 Jun 1;135

2018 Open heart

138. Revealing a novel nociceptive network that links the subthalamic nucleus to pain processing Full Text available with Trip Pro

Revealing a novel nociceptive network that links the subthalamic nucleus to pain processing Pain is a prevalent symptom of Parkinson's disease, and is effectively treated by deep brain stimulation of the subthalamic nucleus (STN). However, the link between pain and the STN remains unclear. In the present work, using in vivo electrophysiology in rats, we report that STN neurons exhibit complex tonic and phasic responses to noxious stimuli. We also show that nociception is altered following (...) lesions of the STN, and characterize the role of the superior colliculus and the parabrachial nucleus in the transmission of nociceptive information to the STN, physiologically from both structures and anatomically in the case of the parabrachial nucleus. We show that STN nociceptive responses are abnormal in a rat model of PD, suggesting their dependence on the integrity of the nigrostriatal dopaminergic system. The STN-linked nociceptive network that we reveal is likely to be of considerable

2018 eLife

139. Modeling Congenital Disorders of N-Linked Glycoprotein Glycosylation in Drosophila melanogaster Full Text available with Trip Pro

Modeling Congenital Disorders of N-Linked Glycoprotein Glycosylation in Drosophila melanogaster Protein glycosylation, the enzymatic addition of N-linked or O-linked glycans to proteins, serves crucial functions in animal cells and requires the action of glycosyltransferases, glycosidases and nucleotide-sugar transporters, localized in the endoplasmic reticulum and Golgi apparatus. Congenital Disorders of Glycosylation (CDGs) comprise a family of multisystemic diseases caused by mutations (...) in genes encoding proteins involved in glycosylation pathways. CDGs are classified into two large groups. Type I CDGs affect the synthesis of the dolichol-linked Glc3Man9GlcNac2 precursor of N-linked glycosylation or its transfer to acceptor proteins. Type II CDG (CDG-II) diseases impair either the trimming of the N-linked oligosaccharide, the addition of terminal glycans or the biosynthesis of O-linked oligosaccharides, which occur in the Golgi apparatus. So far, over 100 distinct forms of CDGs

2018 Frontiers in genetics

140. To ERV Is Human: A Phenotype-Wide Scan Linking Polymorphic Human Endogenous Retrovirus-K Insertions to Complex Phenotypes Full Text available with Trip Pro

To ERV Is Human: A Phenotype-Wide Scan Linking Polymorphic Human Endogenous Retrovirus-K Insertions to Complex Phenotypes Approximately 8% of the human genome is comprised of endogenous retroviral insertions (ERVs) originating from historic retroviral integration into germ cells. The function of ERVs as regulators of gene expression is well established. Less well studied are insertional polymorphisms of ERVs and their contribution to the heritability of complex phenotypes. The most recent (...) integration of ERV, HERV-K, is expressed in a range of complex human conditions from cancer to neurologic diseases. Using an in-house computational pipeline and whole-genome sequencing data from the diverse 1,000 Genomes Phase 3 population (n = 2,504), we identified 46 polymorphic HERV-K insertions that are tagged by adjacent single nucleotide polymorphisms (SNPs). To test the potential role of polymorphic HERV-K in the heritability of complex diseases, existing databases were queried for enrichment

2018 Frontiers in genetics

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