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https://www.readbyqxmd.com/read/28434044/faulty-rna-splicing-consequences-and-therapeutic-opportunities-in-brain-and-muscle-disorders
#1
REVIEW
Vittoria Pagliarini, Piergiorgio La Rosa, Claudio Sette
Alternative splicing is a powerful mechanism that largely expands the coding potential of eukaryotic genomes. Indeed, its complex and flexible regulation is exploited by cells to adapt to various environmental conditions, through production of protein variants displaying different functions. Such flexibility, however, is accompanied by high risk of errors, and dysregulation of splicing is now recognized as an important factor in human diseases. Notably, the RNA-based nature of splicing, which involves high specificity through base pair recognition, offers a remarkable therapeutic opportunity by allowing design of tools with elevated target selectivity...
April 22, 2017: Human Genetics
https://www.readbyqxmd.com/read/28434004/what-do-medical-students-know-about-deep-brain-stimulation
#2
Andreas Wloch, Assel Saryyeva, Hans E Heissler, Christoph Schrader, H Holger Capelle, Joachim K Krauss
BACKGROUND: Deep brain stimulation (DBS) is an established therapy for movement disorders. It is currently under investigation in neuropsychiatric disorders. Neurophobia is a common phenomenon that might have a negative impact in medical education. Little is known about medical students' knowledge about DBS when they enter university and what they learn about it during their medical formation. METHODS: A 10-item questionnaire was designed. Questions addressed indications for DBS, costs of DBS, complications, the percentage of Parkinson disease (PD) patients who might profit from DBS, etc...
April 22, 2017: Stereotactic and Functional Neurosurgery
https://www.readbyqxmd.com/read/28433987/radiofrequency-lesions-through-deep-brain-stimulation-electrodes-in-movement-disorders-case-report-and-review-of-the-literature
#3
Javier Pérez-Suárez, Cristina V Torres Díaz, Lydia López Manzanares, Marta Navas García, Jesús Pastor, Patricia Barrio Fernández, Rafael G de Sola
BACKGROUND: Although there are few reports of radiofrequency lesions performed through deep brain stimulation (DBS) electrodes in patients with movement disorders, experience with this method is scarce. METHODS: We present 2 patients who had been previously treated with DBS of subthalamic nuclei (STN) and the ventral intermediate (VIM) nucleus of the thalamus for Parkinson's disease and essential tremor, respectively, and underwent a radiofrequency lesion through their DBS electrodes after developing a hardware infection...
April 22, 2017: Stereotactic and Functional Neurosurgery
https://www.readbyqxmd.com/read/28433943/acute-lung-injury-leads-to-depression-like-symptoms-through-upregulation-of-neutrophilic-and-neuronal-nadph-oxidase-signaling-in-a-murine-model
#4
Ahmed Nadeem, Nahid Siddiqui, Naif O Al-Harbi, Sabry M Attia, Shakir D AlSharari, Sheikh F Ahmad
There is an increased prevalence of comorbid major depressive disorders with a number of inflammatory conditions which is thought to result from activation of the immune system. Acute lung injury (ALI) in humans has been also shown to be associated with depression previously. However, no study has explored the mechanism behind ALI-induced depression. NADPH oxidase (NOX-2) derived reactive oxygen species (ROS) are associated with neuropsychiatric disorders including depression. ROS generation via NOX-2 is also shown to be involved in the pathogenesis of ALI...
April 20, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28433855/the-electrophysiology-of-neurohiv-a-systematic-review-of-eeg-and-meg-studies-in-people-with-hiv-infection-since-the-advent-of-highly-active-antiretroviral-therapy
#5
Ana Lucia Fernández-Cruz, Lesley K Fellows
OBJECTIVE: The Human Immunodeficiency Virus (HIV) has an impact on the brain, even when the infection is well-controlled with modern highly-active antiretroviral therapy (HAART). While dementia is rare in those on HAART, milder cognitive impairment is common. The causes, patterns, and evolution of brain dysfunction in people living with HIV remain uncertain. We evaluate whether electrophysiological methods provide informative measures of brain dysfunction in this population. METHODS: A systematic literature search identified studies that used EEG or MEG to evaluate persons living with HIV published between 1996 (when HAART became available) and 2016...
March 31, 2017: Clinical Neurophysiology: Official Journal of the International Federation of Clinical Neurophysiology
https://www.readbyqxmd.com/read/28433741/loss-of-the-neurodevelopmental-gene-zswim6-alters-striatal-morphology-and-motor-regulation
#6
David J Tischfield, Dave K Saraswat, Andrew Furash, Stephen C Fowler, Marc V Fuccillo, Stewart A Anderson
The zinc-finger SWIM domain-containing protein 6 (ZSWIM6) is a protein of unknown function that has been associated with schizophrenia and limited educational attainment by three independent genome-wide association studies. Additionally, a putatively causal point mutation in ZSWIM6 has been identified in several cases of acromelic frontonasal dysostosis with severe intellectual disability. Despite the growing number of studies implicating ZSWIM6 as an important regulator of brain development, its role in this process has never been examined...
April 19, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28433711/mdh2-is-an-rna-binding-protein-involved-in-downregulation-of-sodium-channel-scn1a-expression-under-seizure-condition
#7
Yong-Hong Chen, Shu-Jing Liu, Mei-Mei Gao, Tao Zeng, Guo-Wang Lin, Na-Na Tan, Hui-Ling Tang, Ping Lu, Tao Su, Wei-Wen Sun, Long-Chang Xie, Yong-Hong Yi, Yue-Sheng Long
Voltage-gated sodium channel α-subunit type I (NaV1.1, encoded by SCN1A gene) plays a critical role in the excitability of brain. Downregulation of SCN1A expression is associated with epilepsy, a common neurological disorder characterized by recurrent seizures. Here we reveal a novel role of malate dehydrogenase 2 (MDH2) in the posttanscriptional regulation of SCN1A expression under seizure condition. We identified that MDH2 was an RNA binding protein that could bind two of the four conserved regions in the 3' UTRs of SCN1A...
April 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28433458/linking-the-biological-underpinnings-of-depression-role-of-mitochondria-interactions-with-melatonin-inflammation-sirtuins-tryptophan-catabolites-dna-repair-and-oxidative-and-nitrosative-stress-with-consequences-for-classification-and-cognition
#8
REVIEW
George Anderson
The pathophysiological underpinnings of neuroprogressive processes in recurrent major depressive disorder (rMDD) are reviewed. A wide array of biochemical processes underlie MDD presentations and their shift to a recurrent, neuroprogressive course, including: increased immune-inflammation, tryptophan catabolites (TRYCATs), mitochondrial dysfunction, aryl hydrocarbonn receptor activation, and oxidative and nitrosative stress (O&NS), as well as decreased sirtuins and melatonergic pathway activity. These biochemical changes may have their roots in central, systemic and/or peripheral sites, including in the gut, as well as in developmental processes, such as prenatal stressors and breastfeeding consequences...
April 19, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28433457/spatial-and-temporal-expression-patterns-of-genes-around-nine-neuroticism-associated-loci
#9
Kazutaka Ohi, Takamitsu Shimada, Toshiki Yasuyama, Kohei Kimura, Takashi Uehara, Yasuhiro Kawasaki
Neuroticism is a high-order personality trait. Individuals with higher neuroticism have increased risks of various psychiatric disorders and physical health outcomes. Neuroticism is related to physiological differences in the brain. A recent genome-wide association study identified nine distinct genomic loci that contribute to neuroticism. Brain development and function depend on the precise regulation of gene expression, which is differentially regulated across brain regions and developmental stages. Using multiple publicly available human post-mortem databases, we investigated, in brain and non-brain tissues and across several developmental life stages, the spatial and temporal expression patterns of genes arising from nine neuroticism-associated loci...
April 19, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28433456/cytokine-alterations-and-cognitive-impairment-in-major-depressive-disorder-from-putative-mechanisms-to-novel-treatment-targets
#10
REVIEW
Błażej Misiak, Jan Aleksander Beszłej, Kamila Kotowicz, Monika Szewczuk-Bogusławska, Jerzy Samochowiec, Jolanta Kucharska-Mazur, Dorota Frydecka
Overwhelming evidence indicates the involvement of immune-inflammatory processes in the pathophysiology of major depressive disorder (MDD). Peripheral cytokine alterations serve as one of most consistently reported indices of subthreshold inflammatory state observed in MDD. Although cytokines cannot pass directly through the blood-brain barrier, a number of transport mechanisms have been reported. In addition, peripheral cytokines may impact central nervous system via downstream effectors of their biological activity...
April 19, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28433417/mechanistic-insights-into-epigenetic-modulation-of-ethanol-consumption
#11
Igor Ponomarev, Claire E Stelly, Hitoshi Morikawa, Yuri A Blednov, R Dayne Mayfield, R Adron Harris
There is growing evidence that small-molecule inhibitors of epigenetic modulators, such as histone deacetylases (HDAC) and DNA methyltransferases (DNMT), can reduce voluntary ethanol consumption in animal models, but molecular and cellular processes underlying this behavioral effect are poorly understood. We used C57BL/6J male mice to investigate the effects of two FDA-approved drugs, decitabine (a DNMT inhibitor) and SAHA (an HDAC inhibitor), on ethanol consumption using two tests: binge-like drinking in the dark (DID) and chronic intermittent every other day (EOD) drinking...
March 12, 2017: Alcohol
https://www.readbyqxmd.com/read/28433109/pathogenesis-of-wilson-disease
#12
Ivo Florin Scheiber, Radan Brůha, Petr Dušek
Wilson disease is an autosomal-recessive disorder originating from a genetic defect in the copper-transporting ATPase ATP7B that is required for biliary copper secretion and loading of ceruloplasmin with copper. Impaired ATP7B function in Wilson disease results in excessive accumulation of copper in liver, brain, and other tissues. Toxic copper deposits may induce oxidative stress, modify expression of genes, directly inhibit proteins, and impair mitochondrial function, leading to hepatic, neuropsychiatric, renal, musculoskeletal, and other symptoms...
2017: Handbook of Clinical Neurology
https://www.readbyqxmd.com/read/28433099/other-organ-involvement-and-clinical-aspects-of-wilson-disease
#13
Karolina Dzieżyc, Tomasz Litwin, Anna Członkowska
Wilson disease (WD) is a rare disorder of copper metabolism that presents mainly with hepatic and neuropsychiatric features. Copper accumulates not only in the liver and brain, but also in other organs. Liver injury can also be the cause of secondary impairment of other tissues. Therefore, the clinical manifestation of WD may be renal, cardiac, skin, osteoarticular, or endocrinologic and include other organ disturbances. Renal abnormalities include tubular dysfunction (e.g., renal tubular acidosis, aminoaciduria) and nephrolithiasis...
2017: Handbook of Clinical Neurology
https://www.readbyqxmd.com/read/28433096/wilson-disease-neurologic-features
#14
Anna Członkowska, Tomasz Litwin, Grzegorz Chabik
Wilson disease (WD) is a neurodegenerative disorder, which presents as a spectrum of neurologic manifestations that includes tremor, bradykinesia, rigidity, dystonia, chorea, dysarthria, and dysphagia, together with a combination of neurologic symptoms that can easily lead to misdiagnosis. An early diagnosis of WD, and appropriate anticopper treatment, usually leads to a marked improvement in patient health. Conversely, delayed diagnosis can result in persistent pathology, which, left untreated, can ultimately prove lethal...
2017: Handbook of Clinical Neurology
https://www.readbyqxmd.com/read/28433093/impact-of-a-common-genetic-variation-associated-with-putamen-volume-on-neural-mechanisms-of-attention-deficit-hyperactivity-disorder
#15
Bing Xu, Tianye Jia, Christine Macare, Tobias Banaschewski, Arun L W Bokde, Uli Bromberg, Christian Büchel, Anna Cattrell, Patricia J Conrod, Herta Flor, Vincent Frouin, Jürgen Gallinat, Hugh Garavan, Penny Gowland, Andreas Heinz, Bernd Ittermann, Jean-Luc Martinot, Marie-Laure Paillère Martinot, Frauke Nees, Dimitri Papadopoulos Orfanos, Tomáš Paus, Luise Poustka, Michael N Smolka, Henrik Walter, Robert Whelan, Gunter Schumann, Sylvane Desrivières
OBJECTIVE: In a recent genomewide association study of subcortical brain volumes, a common genetic variation at rs945270 was identified as having the strongest effect on putamen volume, a brain measurement linked to familial risk for attention-deficit/hyperactivity disorder (ADHD). To determine whether rs945270 might be a genetic determinant of ADHD, its effects on ADHD-related symptoms and neural mechanisms of ADHD, such as response inhibition and reward sensitivity, were explored. METHOD: A large population sample of 1,834 14-year-old adolescents was used to test the effects of rs945270 on ADHD symptoms assessed through the Strengths and Difficulties Questionnaire and region-of-interest analyses of putamen activation by functional magnetic resonance imaging using the stop signal and monetary incentive delay tasks, assessing response inhibition and reward sensitivity, respectively...
May 2017: Journal of the American Academy of Child and Adolescent Psychiatry
https://www.readbyqxmd.com/read/28433092/behavioral-and-neural-sustained-attention-deficits-in-disruptive-mood-dysregulation-disorder-and-attention-deficit-hyperactivity-disorder
#16
David Pagliaccio, Jillian Lee Wiggins, Nancy E Adleman, Alexa Curhan, Susan Zhang, Kenneth E Towbin, Melissa A Brotman, Daniel S Pine, Ellen Leibenluft
OBJECTIVE: Disruptive mood dysregulation disorder (DMDD), characterized by severe irritability, and attention-deficit/hyperactivity disorder (ADHD) are highly comorbid. This is the first study to characterize neural and behavioral similarities and differences in attentional functioning across these disorders. METHOD: Twenty-seven healthy volunteers, 31 patients with DMDD, and 25 patients with ADHD (8 to 18 years old) completed a functional magnetic resonance imaging attention task...
May 2017: Journal of the American Academy of Child and Adolescent Psychiatry
https://www.readbyqxmd.com/read/28432758/specificity-and-sensitivity-of-magnetic-resonance-imaging-findings-in-the-diagnosis-of-progressive-supranuclear-palsy
#17
REVIEW
Stephen Bacchi, Ivana Chim, Sandy Patel
Progressive supranuclear palsy (PSP) is a neurodegenerative condition that can only be diagnosed conclusively on pathological examination. Currently, the diagnosis is based upon the National Institute of Neurological Disorders and Stroke and the Society for PSP criteria. These criteria consist of purely clinical findings. Elements of brain MRI that are being investigated for this role include identifying structural features on conventional MRI, volume changes, signal abnormalities and diffusion changes. The aim of this study is to conduct a systematic search to identify which MRI findings have evidence to support their sensitivity/specificity/accuracy in the diagnosis of PSP...
April 22, 2017: Journal of Medical Imaging and Radiation Oncology
https://www.readbyqxmd.com/read/28432303/closed-loop-deep-brain-stimulation-by-pulsatile-delayed-feedback-with-increased-gap-between-pulse-phases
#18
Oleksandr V Popovych, Borys Lysyansky, Peter A Tass
Computationally it was shown that desynchronizing delayed feedback stimulation methods are effective closed-loop techniques for the control of synchronization in ensembles of interacting oscillators. We here computationally design stimulation signals for electrical stimulation of neuronal tissue that preserve the desynchronizing delayed feedback characteristics and comply with mandatory charge deposit-related safety requirements. For this, the amplitude of the high-frequency (HF) train of biphasic charge-balanced pulses used by the standard HF deep brain stimulation (DBS) is modulated by the smooth feedback signals...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28432029/suppression-of-reward-induced-dopamine-release-in-the-nucleus-accumbens-in-animal-models-of-depression-differential-responses-to-drug-treatment
#19
Saki Minami, Hiroshi Satoyoshi, Soichiro Ide, Takeshi Inoue, Mitsuhiro Yoshioka, Masabumi Minami
Anhedonia, the loss of interest or pleasure in previously enjoyable activities, is a core symptom of major depressive disorder, suggesting that the brain reward system may be dysfunctional in this condition. Neurochemical changes in the mesolimbic dopamine (DA) system are not fully understood in animal models of depression. We investigated reward (30% sucrose intake)-induced DA release in the nucleus accumbens (NAc) and the effect of chronic treatment with the antidepressant escitalopram (5mg/kg, intraperitoneally twice daily for 3 weeks) in two animal models of depression...
April 18, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28431870/the-effect-of-hypertonic-saline-and-mannitol-on-coagulation-in-moderate-traumatic-brain-injury-patients
#20
Haifeng Wang, Hongshi Cao, Xiaohong Zhang, Liang Ge, Li Bie
BACKGROUND: Hyperosmolar therapy, using either hypertonic saline (HTS) or mannitol (MT), is considered the treatment of choice for intracranial hypertension, a disorder characterized by high intracranial pressure (ICP). However, hyperosmolar agents have been postulated to impair coagulation and platelet function. The aim of this study was to identify whether HTS and MT could affect coagulation in moderate traumatic brain injury (TBI) patients. METHODS: In this prospective and randomized double-blind study, we included adult patients with moderate TBI...
April 14, 2017: American Journal of Emergency Medicine
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