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https://www.readbyqxmd.com/read/29224179/antidiabetic-polypill-improves-central-pathology-and-cognitive-impairment-in-a-mixed-model-of-alzheimer-s-disease-and-type-2-diabetes
#1
Carmen Infante-Garcia, Juan Jose Ramos-Rodriguez, Carmen Hierro-Bujalance, Esperanza Ortegon, Eleanor Pickett, Rosemary Jackson, Fernando Hernandez-Pacho, Tara Spires-Jones, Monica Garcia-Alloza
Type 2 diabetes (T2D) is an important risk factor to suffer dementia, being Alzheimer's disease (AD) as the most common form. Both AD and T2D are closely related to aging and with a growing elderly population it might be of relevance to explore new therapeutic approaches that may slow or prevent central complications associated with metabolic disorders. Therefore, we propose the use of the antidiabetic polypill (PP), a pharmacological cocktail, commonly used by T2D patients that include metformin, aspirin, simvastatin, and an angiotensin-converting enzyme inhibitor...
December 9, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/29222408/brain-insulin-resistance-impairs-hippocampal-synaptic-plasticity-and-memory-by-increasing-glua1-palmitoylation-through-foxo3a
#2
Matteo Spinelli, Salvatore Fusco, Marco Mainardi, Federico Scala, Francesca Natale, Rosita Lapenta, Andrea Mattera, Marco Rinaudo, Domenica Donatella Li Puma, Cristian Ripoli, Alfonso Grassi, Marcello D'Ascenzo, Claudio Grassi
High-fat diet (HFD) and metabolic diseases cause detrimental effects on hippocampal synaptic plasticity, learning, and memory through molecular mechanisms still poorly understood. Here, we demonstrate that HFD increases palmitic acid deposition in the hippocampus and induces hippocampal insulin resistance leading to FoxO3a-mediated overexpression of the palmitoyltransferase zDHHC3. The excess of palmitic acid along with higher zDHHC3 levels causes hyper-palmitoylation of AMPA glutamate receptor subunit GluA1, hindering its activity-dependent trafficking to the plasma membrane...
December 8, 2017: Nature Communications
https://www.readbyqxmd.com/read/29222403/common-pathophysiology-in-multiple-mouse-models-of-pitt-hopkins-syndrome
#3
Courtney Thaxton, Alexander D Kloth, Ellen P Clark, Sheryl S Moy, Raymond A Chitwood, Benjamin D Philpot
Mutations or deletions of the transcription factor TCF4 are linked to Pitt-Hopkins syndrome (PTHS) and schizophrenia, suggesting that the precise pathogenic mutations dictate cellular, synaptic, and behavioral consequences. Here we generated two novel mouse models of PTHS-one that mimics the most common pathogenic TCF4 point mutation (human R580W, mouse R579W) and one that deletes three pathogenic arginines-and explored phenotypes of these lines alongside models of pan-cellular or CNS-specific heterozygous Tcf4 disruption...
December 8, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29222297/current-treatment-algorithm-for-the-management-of-patients-with-myelofibrosis-jak-inhibitors-and-beyond
#4
REVIEW
Claire N Harrison, Donal P McLornan
Myelofibrosis (MF) is a heterogeneous disorder characterized by splenomegaly, constitutional symptoms, ineffective hematopoiesis, and an inherent risk of leukemic transformation. The past decade has seen a massive shift in available therapeutic options for our patients and we are learning how and when to use novel agents, either alone or in combination, during the disease course. This has translated into improved management of splenomegaly, significant amelioration in disease-related symptom burden for many, and may lead to improved survival...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222285/five-lessons-learned-about-long-term-pain-management-in-adults-with-sickle-cell-disease
#5
REVIEW
Joshua J Field
Chronic pain affects one-half of adults with sickle cell disease (SCD). Despite the prevalence of chronic pain, few studies have been performed to determine the best practices for this patient population. Although the pathophysiology of chronic pain in SCD may be different from other chronic pain syndromes, many of the guidelines outlined in the pain literature and elsewhere are applicable; some were consensus-adopted in the 2014 National Heart, Lung, and Blood Institute SCD Guidelines. Recommended practices, such as controlled substance agreements and monitoring of urine, may seem unnecessary or counterproductive to hematologists...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29221855/toll-like-receptor-4-regulates-anxiety-like-behavior-and-darpp-32-phosphorylation
#6
T Femenia, Y Qian, T Arentsen, H Forssberg, R Diaz Heijtz
Toll-like receptors (TLRs) play a crucial role in early innate immune responses to inflammatory agents and pathogens. In the brain, some members of the TLR family are expressed in glial cells and neurons. In particular, TLR4 has been involved in learning and memory processes, stress-induced adaptations, and pathogenesis of neurodegenerative disorders. However, the role of TLR4 in emotional behaviors and their underlying mechanisms are poorly understood. In this study, we investigated the role of TLR4 in emotional and social behavior by using different behavioral approaches, and assessed potential molecular alterations in important brain areas involved in emotional responses...
December 5, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29221774/sleep-dependent-motor-sequence-memory-consolidation-in-individuals-with-periodic-limb-movements
#7
Valya Sergeeva, Jeremy Viczko, Laura B Ray, Adrian M Owen, Stuart M Fogel
Periodic limb movements (PLMs) during sleep increase with age and are associated with striatal neurodegeneration and dopamine deficiency. Limb movements are often associated with disruptions to non-rapid eye movement (NREM) sleep. Motor skill memory consolidation recruits the striatum, and learning-dependent striatal activation is associated with NREM sleep. Therefore, we investigated whether de novo individuals who significantly experience elevated levels of PLMs but have not been formally diagnosed with periodic limb movement disorder had learning and sleep-related memory deficits and whether these deficits were related to sleep quality and symptom severity...
December 2017: Sleep Medicine
https://www.readbyqxmd.com/read/29220673/de-novo-variants-in-gria4-lead-to-intellectual-disability-with-or-without-seizures-and-gait-abnormalities
#8
Sonja Martin, Adam Chamberlin, Deepali N Shinde, Maja Hempel, Tim M Strom, Allison Schreiber, Jessika Johannsen, Lilian Bomme Ousager, Martin J Larsen, Lars Kjaersgaard Hansen, Ali Fatemi, Julie S Cohen, Johannes Lemke, Kristina P Sørensen, Katherine L Helbig, Davor Lessel, Rami Abou Jamra
Using trio whole-exome sequencing, we have identified de novo heterozygous pathogenic variants in GRIA4 in five unrelated individuals with intellectual disability and other symptoms. GRIA4 encodes an AMPA receptor subunit known as GluR4, which is found on excitatory glutamatergic synapses and is important for learning and memory. Four of the variants are located in the highly conserved SYTANLAAF motif in the transmembrane protein M3, and the fifth is in an extra-cellular domain. Molecular modeling of the altered protein showed that three of the variants in the SYTANLAAF motif orient toward the center of the pore region and most likely lead to disturbance of the gating mechanism...
December 7, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/29218830/effectiveness-of-vocabulary-intervention-for-older-children-with-developmental-language-disorder
#9
Lisa Wright, Tim Pring, Susan Ebbels
BACKGROUND: Children with developmental language disorder (DLD) frequently have difficulties with word learning and understanding vocabulary. For these children, this can significantly impact on social interactions, daily activities and academic progress. Although there is literature providing a rationale for targeting word learning in such children, there is little evidence for the effectiveness of specific interventions in this area for children with identified DLD. AIMS: To establish whether direct one-to-one intervention for children with DLD over 9 years of age leads to improved abilities to identify, comprehend, define, and use nouns and verbs targeted in intervention as compared with non-targeted control items and whether or not the participants' rating of their own knowledge of the words changes with intervention...
December 7, 2017: International Journal of Language & Communication Disorders
https://www.readbyqxmd.com/read/29218767/maternal-communicative-behaviours-and-interaction-quality-as-predictors-of-language-development-findings-from-a-community-based-study-of-slow-to-talk-toddlers
#10
Laura J Conway, Penny A Levickis, Jodie Smith, Fiona Mensah, Melissa Wake, Sheena Reilly
BACKGROUND: Identifying risk and protective factors for language development informs interventions for children with developmental language disorder (DLD). Maternal responsive and intrusive communicative behaviours are associated with language development. Mother-child interaction quality may influence how children use these behaviours in language learning. AIMS: To identify (1) communicative behaviours and interaction quality associated with language outcomes; (2) whether the association between a maternal intrusive behaviour (directive) and child language scores changed alongside a maternal responsive behaviour (expansion); and (3) whether interaction quality modified these associations...
December 7, 2017: International Journal of Language & Communication Disorders
https://www.readbyqxmd.com/read/29218394/modulation-of-sphingosine-1-phosphate-s1p-attenuates-spatial-learning-and-memory-impairments-in-the-valproic-acid-rat-model-of-autism
#11
Hongmei Wu, Quanzhi Zhang, Jingquan Gao, Caihong Sun, Jia Wang, Wei Xia, Yonggang Cao, Yanqiu Hao, Lijie Wu
RATIONALE: Autism spectrum disorders (ASD) are a set of pervasive neurodevelopmental disorders that manifest in early childhood, and it is growing up to be a major cause of disability in children. However, the etiology and treatment of ASD are not well understood. In our previous study, we found that serum levels of sphingosine 1-phosphate (S1P) were increased significantly in children with autism, indicating that S1P levels may be involved in ASD. OBJECTIVE: The objective of this study was to identify a link between increased levels of S1P and neurobehavioral changes in autism...
December 7, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/29217875/deep-auto-context-convolutional-neural-networks-for-standard-dose-pet-image-estimation-from-low-dose-pet-mri
#12
Lei Xiang, Yu Qiao, Dong Nie, Le An, Qian Wang, Dinggang Shen
Positron emission tomography (PET) is an essential technique in many clinical applications such as tumor detection and brain disorder diagnosis. In order to obtain high-quality PET images, a standard-dose radioactive tracer is needed, which inevitably causes the risk of radiation exposure damage. For reducing the patient's exposure to radiation and maintaining the high quality of PET images, in this paper, we propose a deep learning architecture to estimate the high-quality standard-dose PET (SPET) image from the combination of the low-quality low-dose PET (LPET) image and the accompanying T1-weighted acquisition from magnetic resonance imaging (MRI)...
December 6, 2017: Neurocomputing
https://www.readbyqxmd.com/read/29217836/drug-development-for-neurodevelopmental-disorders-lessons-learned-from-fragile-x-syndrome
#13
REVIEW
Elizabeth M Berry-Kravis, Lothar Lindemann, Aia E Jønch, George Apostol, Mark F Bear, Randall L Carpenter, Jacqueline N Crawley, Aurore Curie, Vincent Des Portes, Farah Hossain, Fabrizio Gasparini, Baltazar Gomez-Mancilla, David Hessl, Eva Loth, Sebastian H Scharf, Paul P Wang, Florian Von Raison, Randi Hagerman, Will Spooren, Sébastien Jacquemont
Neurodevelopmental disorders such as fragile X syndrome (FXS) result in lifelong cognitive and behavioural deficits and represent a major public health burden. FXS is the most frequent monogenic form of intellectual disability and autism, and the underlying pathophysiology linked to its causal gene, FMR1, has been the focus of intense research. Key alterations in synaptic function thought to underlie this neurodevelopmental disorder have been characterized and rescued in animal models of FXS using genetic and pharmacological approaches...
December 8, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/29217683/insulin-like-growth-factor-ii-targets-the-mtor-pathway-to-reverse-autism-like-phenotypes-in-mice
#14
Adam B Steinmetz, Sarah A Stern, Amy S Kohtz, Giannina Descalzi, Cristina M Alberini
Autism spectrum disorder (ASD) is a developmental disability characterized by impairments in social interaction and repetitive behavior, and is also associated with cognitive deficits. There is no current treatment that can ameliorate most of the ASD symptomatology; thus, identifying novel therapies is urgently needed. We used male BTBR T+Itpr3tf /J (BTBR) mice, a model that reproduces most of the core behavioral phenotypes of ASD, to test the effects of systemic administration of insulin like growth factor II (IGF-II), a polypeptide that crosses the blood brain barrier and acts as a cognitive enhancer...
December 6, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29217410/munc18-1-haploinsufficiency-impairs-learning-and-memory-by-reduced-synaptic-vesicular-release-in-a-model-of-ohtahara-syndrome
#15
Albert Orock, Sreemathi Logan, Ferenc Deak
Ohtahara syndrome, also known as type 4 of Early Infantile Epileptic Encephalopathy with suppression bursts (EIEE-4) is currently an untreatable disorder that presents with seizures and impaired cognition. EIEE-4 patients have mutations most frequently in the STXBP1 gene encoding a Sec protein, munc18-1. The exact molecular mechanism of how these munc18-1 mutations cause impaired cognition, remains elusive. The leading haploinsufficiency hypothesis posits that mutations in munc18-1 render the protein unstable leading to its degradation...
December 4, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29217357/tempol-prevents-post-traumatic-stress-disorder-induced-memory-impairment
#16
Karem H Alzoubi, Abeer M Rababa'h, Omar N Yaqoub
Post-traumatic stress disorder (PTSD) is a mental health disorder that can develop after a terrifying or life threatening event. Multiple symptoms are noticed in patients with PTSD including cognitive impairment, which was shown to be is associated with oxidative stress. Tempol is a highly efficient membrane-permeable antioxidant. In this study, we investigated the possible protective effect of tempol on PTSD-induced memory impairment. To test this hypothesis, we used single prolonged stress (SPS) model (2h restrain, 20min forced swimming, 15min rest, and 1-2min diethyl ether exposure) as a model of PTSD...
December 4, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/29216235/association-between-memory-impairment-and-brain-metabolite-concentrations-in-north-korean-refugees-with-posttraumatic-stress-disorder
#17
Jung Eun Shin, Chi-Hoon Choi, Jong Min Lee, Jun Soo Kwon, So Hee Lee, Hyun-Chung Kim, Na Young Han, Soo-Hee Choi, So Young Yoo
Individuals with posttraumatic stress disorder (PTSD) had experiences of enormous psychological stress that can result in neurocognitive and neurochemical changes. To date, the causal relationship between them remains unclear. The present study is to investigate the association between neurocognitive characteristics and neural metabolite concentrations in North Korean refugees with PTSD. A total of 53 North Korean refugees with or without PTSD underwent neurocognitive function tests. For neural metabolite scanning, magnetic resonance spectroscopy of the hippocampus and anterior cingulate cortex (ACC) has been conducted...
2017: PloS One
https://www.readbyqxmd.com/read/29214567/natural-history-trial-readiness-and-gene-discovery-advances-in-patient-registries-for-neuromuscular-disease
#18
Rachel Thompson, Agata Robertson, Hanns Lochmüller
Inherited neuromuscular diseases (NMDs) are genetic disorders that affect the skeletal muscles or the nerves controlling muscle function. With a new generation of diagnostic options and recent advances in translational research improving the opportunities for therapy development for these rare conditions, capturing patient information in databases collecting a range of clinical and genetic data together with contact details has assumed an increasingly important role in trial planning and recruitment as well as natural history data collection...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29214565/intellectual-disability-rare-disorders-a-diagnostic-challenge
#19
Malin Kvarnung, Ann Nordgren
Rare disorders constitute a large and heterogeneous group of diagnoses of which many cause chronic disabilities with significant impact on the lives of affected individuals and their families as well as on the health-care system. Each individual disorder is rare, but when considered as a group, rare disorders are common with a total prevalence of approximately 6-8%. The clinical presentation of these disorders includes a broad diversity of symptoms and signs, often involving the nervous system and resulting in symptoms such as intellectual disability, neuropsychiatric disorders, epilepsy and motor dysfunction...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29214257/piceatannol-attenuates-behavioral-disorder-and-neurological-deficits-in-aging-mice-via-activating-the-nrf2-pathway
#20
Yan Zhang, Li-Hong Zhang, Xi Chen, Ning Zhang, Guang Li
Aging is a complex process that is accompanied by neurological damage. Chronic injection of d-galactose (d-gal) can accelerate the aging process similar to natural aging and is commonly used to build an aging model to investigate aging. In the present study, the effects of piceatannol on d-gal-induced aging in mice were evaluated. Piceatannol treatment showed an observable anti-aging effect. Results obtained in vivo showed that piceatannol retained spontaneous motor activity and enhanced spatial learning and memory abilities in mice in which aging was induced by d-gal...
December 7, 2017: Food & Function
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