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32,716,843
|
Revealing architectural order with quantitative label-free imaging and deep learning.
|
We report quantitative label-free imaging with phase and polarization (QLIPP) for simultaneous measurement of density, anisotropy, and orientation of structures in unlabeled live cells and tissue slices. We combine QLIPP with deep neural networks to predict fluorescence images of diverse cell and tissue structures. QLIPP images reveal anatomical regions and axon tract orientation in prenatal human brain tissue sections that are not visible using brightfield imaging. We report a variant of U-Net architecture, multi-channel 2.5D U-Net, for computationally efficient prediction of fluorescence images in three dimensions and over large fields of view. Further, we develop data normalization methods for accurate prediction of myelin distribution over large brain regions. We show that experimental defects in labeling the human tissue can be rescued with quantitative label-free imaging and neural network model. We anticipate that the proposed method will enable new studies of architectural order at spatial scales ranging from organelles to tissue.
|
eLife
| 2,020
| 7
| 0
| 0
|
33,238,377
|
Fatal Status Epilepticus in Dravet Syndrome.
|
Dravet Syndrome (DS) is burdened by high epilepsy-related premature mortality due to status epilepticus (SE). We surveyed centres within Europe through the Dravet Italia Onlus and EpiCARE network (European Reference Network for Rare and Complex Epilepsies). We collated responses on seven DS SCN1A+ patients who died following refractory SE (mean age 6.9 year, range 1.3-23.4 year); six were on valproate, clobazam, and stiripentol. All patients had previous SE. Fatal SE was always triggered by fever: either respiratory infection or one case of hexavalent vaccination. SE lasted between 80 min and 9 h and all patients received IV benzodiazepines. Four patients died during or within hours of SE; in three patients, SE was followed by coma with death occurring after 13-60 days. Our survey supports the hypothesis that unresponsive fever is a core characteristic feature of acute encephalopathy. We highlight the need for management protocols for prolonged seizures and SE in DS.
|
Brain sciences
| 2,020
| 11
| 0
| 0
|
32,542,710
|
Age-dependent dose calculations for common PET radionuclides and brain radiotracers in nonhuman primate computational models.
|
The combination of nonhuman primates (NHPs) with the state-of-the-art molecular imaging technologies allows for within-subject longitudinal research aiming at gaining new insights into human normal and disease conditions and provides an ideal foundation for future translational studies of new diagnostic tools, medical interventions, and therapies. However, radiation dose estimations for nonhuman primates from molecular imaging probes are lacking and are difficult to perform experimentally. The aim of this work is to construct age-dependent NHP computational model series to estimate the absorbed dose to NHP specimens in common molecular imaging procedures.
|
Medical physics
| 2,020
| 9
| 0
| 0
|
29,134,544
|
A broader phenotype of persistence emerges from individual differences in response to extinction.
|
The typical practice of averaging group performance during extinction gives the impression that responding declines gradually and homogeneously. However, previous studies of extinction in human infants have shown that some individuals persist in responding, whereas others abruptly cease responding. As predicted by theories of control, the infants who quickly resign typically display signs of sadness and despair when the expected reward is omitted. Using genetically diverse mice, here we observed a similar pattern of individual differences and the associated phenotypes. After learning to approach a food reward, upon extinction, some animals rapidly abandoned approach to the goal box, whereas other animals persisted in entering and searching the goal box. Interestingly, the persistent mice were slower to "give up" when confined to an inescapable pool of water (a test asserted to be indicative of susceptibility to depression) and exhibited a more extensive pattern of search for omitted rewards. Thus, extinction reveals a continuum in persistence, in which low values might reflect a susceptibility to the negative effects of stress and might predispose individuals to depression.
|
Psychonomic bulletin & review
| 2,018
| 10
| 0
| 0
|
32,969,847
|
Visual Outcomes in Leber Hereditary Optic Neuropathy Patients With the m.11778G>A (MTND4) Mitochondrial DNA Mutation.
|
Leber hereditary optic neuropathy (LHON) is a maternally inherited bilaterally blinding optic neuropathy, predominantly affecting otherwise healthy young individuals, mostly men. The visual prognosis is generally poor, with most patients worsening to at least 20/200 visual acuity. The m.11778G>A (MTND4) mitochondrial DNA mutation is the most common cause of LHON and is associated with poor outcomes and limited potential for meaningful visual recovery. Treatments for LHON are limited, and clinical trials are hampered by inadequate data regarding the natural history of visual loss and recovery. In this article, we review the current literature specifically related to visual function of LHON patients with the m.11778G>A mutation.
|
Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society
| 2,020
| 12
| 0
| 0
|
21,047,176
|
Spinal muscular atrophy due to double gene conversion event.
|
Spinal muscular atrophy (SMA) is an autosomal recessive disease characterized by degeneration of the anterior horn cells of the spinal cord. The survival motor neuron (SMN) gene has been identified as an SMA-determining gene. SMN exists as two copies in 5q13, and deletions in exons 7 and 8 of the telomeric copy (SMN(T)) occur in 95% of patients, regardless of disease severity. In a minority of patients, exon 7 but not exon 8 of SMN(T) appears deleted. We now report a patient with typical features of SMA type II who carried homozygous deletions of SMN(T) exon 7 and centromeric SMN (SMN(C)) exon 8 but retained SMN(T) exon 8 and SMN(C) exon 7. Sequence analysis demonstrated that SMN(C) exon 7 was adjacent to SMN(T) exon 8 on both SMN copies, indicating a double conversion. We confirm that sequence conversion is a common event in SMA and is associated with the milder form of the disease. The severity, however, can be modified in either positive or negative direction by other factors.
|
The International journal of neuroscience
| 2,011
| 2
| 0
| 0
|
29,447,028
|
Elastase as a potential biomarker for radiation-induced gut wall injury of the distal bowel in an experimental mouse model.
|
Traditionally, elastase has been used to study exocrine activity of the pancreas in patients with chronic pancreatitis and cystic fibrosis, and calprotectin as a marker for gut-wall inflammation in patients with inflammatory bowel disease. The aim of the study was to find out whether elastase and calprotectin could be used as inflammatory markers for radiation-induced gut wall injury of the distal bowel.
|
Acta oncologica (Stockholm, Sweden)
| 2,018
| 8
| 0
| 0
|
29,235,684
|
ON BECOMING ABLE TO PLAY: INDIVIDUAL CHILD PSYCHOANALYTIC PSYCHODRAMA AND THE DEVELOPMENT OF SYMBOLIZATION.
|
In this paper, the authors analyze the relevance and transformative potential of individual psychoanalytic psychodrama in the treatment of children with severe impairments in symbolization. Central features of this modality, including promoting the representation of early traumatic experiences, are presented and discussed. Specific features include double-envelope containment of the co-therapists' group and play leader, consequent diffraction of the transference-determining portrayal, gradual integration, and initial figuration of coexisting split-off fragments. Drawing on in-depth clinical material, the authors show how psychodrama tempers the potentially traumatic effects of the encounter with the object, allowing these patients to access the transitional area of play.
|
The Psychoanalytic quarterly
| 2,017
| 10
| 0
| 0
|
32,562,688
|
Giving meaning to the social world in autism spectrum disorders: Olfaction as a missing piece of the puzzle?
|
Altered social cognition is a core feature of Autism Spectrum Disorders (ASD). These impairments have been explained as the consequence of compromised social motivational mechanisms that limit social interest and activate a cascade of social deficits. Following this rational, we argue that approaches capable of surpassing ASD usual restraints (e.g., deficits in verbal abilities), and able to assign social meaning, could be more effective at responding to these difficulties. In this framework, we propose that olfaction, as well as cross-modal integration strategies involving both visual and olfactory domains, may have such potential. In fact, most of socioemotional processing deficits in ASD have been shown in an uni-modal perspective, mainly with visual stimuli. However, the social environment involves other modalities and is typically multisensorial. Given the potential of olfaction as a gateway for socioemotional information in ASD, we argue in favor of studying olfactory perception, as well as visuo-olfactory integration, given the potential of these approaches to drive effective interventions and give the access to a meaningful social world in ASD.
|
Neuroscience and biobehavioral reviews
| 2,020
| 9
| 0
| 0
|
32,986,284
|
Identification of intrinsic primary afferent neurons in mouse jejunum.
|
The gut is the only organ system with intrinsic neural reflexes. Intrinsic primary afferent neurons (IPANs) of the enteric nervous system initiate intrinsic reflexes, form gut-brain connections, and undergo considerable neuroplasticity to cause digestive diseases. They remain inaccessible to study in mice in the absence of a selective marker. Advillin is used as a marker for primary afferent neurons in dorsal root ganglia. The aim of this study was to test the hypothesis that advillin is expressed in IPANs of the mouse jejunum.
|
Neurogastroenterology and motility
| 2,020
| 12
| 0
| 0
|
32,817,435
|
Opportunities and limitations of genetically modified nonhuman primate models for neuroscience research.
|
The recently developed new genome-editing technologies, such as the CRISPR/Cas system, have opened the door for generating genetically modified nonhuman primate (NHP) models for basic neuroscience and brain disorders research. The complex circuit formation and experience-dependent refinement of the human brain are very difficult to model in vitro, and thus require use of in vivo whole-animal models. For many neurodevelopmental and psychiatric disorders, abnormal circuit formation and refinement might be at the center of their pathophysiology. Importantly, many of the critical circuits and regional cell populations implicated in higher human cognitive function and in many psychiatric disorders are not present in lower mammalian brains, while these analogous areas are replicated in NHP brains. Indeed, neuropsychiatric disorders represent a tremendous health and economic burden globally. The emerging field of genetically modified NHP models has the potential to transform our study of higher brain function and dramatically facilitate the development of effective treatment for human brain disorders. In this paper, we discuss the importance of developing such models, the infrastructure and training needed to maximize the impact of such models, and ethical standards required for using these models.
|
Proceedings of the National Academy of Sciences of the United States of America
| 2,020
| 9
| 0
| 0
|
30,785,216
|
Cardosin A endocytosis mediated by integrin leads to lysosome leakage and apoptosis of epithelial cells.
|
Cardosin A is an aspartic protease present in large amount in the pistils of cardoon flowers. This protease is known to contain an -Arg-Gly-Asp- (RGD) motif located on the molecular surface. In this study, we found that isolated recombinant cardosin A attached to human epithelial cells A549, mediated by the binding of its RGD motif to cell surface integrins. The cell bound cardosin A was internalized to endosomes and lysosomes and triggered the permeability of lysosomal membrane leading to apoptosis of the epithelial cells. These events are identical to those observed for three RGD-containing aspartic proteases, Saps 4-6, secreted by Candida albicans. Such a process, which has been called the Trojan Horse mechanism, is believed to benefit the invasion of C. albican into the epithelium of the host. The location of the RGD motifs of cardosin A and Saps 4-6 are on the opposite ends of the homologous three-dimensional structures, suggesting that the Trojan Horse mechanism is insensitive to the RGD position. Current finding also suggests that cardosin A may have a defensive function against the ingestion of cardoon flowers by human, insects, and other herbivores.
|
Proteins
| 2,019
| 6
| 0
| 0
|
33,197,641
|
Effects of reward associations on components of attentional network.
|
Previous research has revealed the influence of reward associations on attentional selection and control. The attentional network can be divided into three components according to its function: Alerting, orienting, and executive control. In the current research, we used training-test procedure and attention network test variant to investigate the effects of color-based reward associations on alerting (Experiment 1), orienting (Experiment 2), executive control (Experiment 3), as well as the interactions among these three networks (Experiment 4). The findings were as follows: Compared with colors previously associated with low reward, colors previously associated with high reward trigger stronger alerting and orienting effects (Experiments 1 and 2), and they had stronger interference effects when functioning as features of flanker distractor (Experiment 3). More importantly, reward associations had only a positive impact on the interaction of orienting by executive control but not on the interaction of alerting by executive control (Experiment 4). In summary, reward associations have different effects on the three attentional networks and can enhance the interaction of orienting by executive control.
|
Acta psychologica
| 2,021
| 1
| 0
| 0
|
28,721,539
|
[Computational neuroanatomy and microstructure imaging using magnetic resonance imaging].
|
Current computational neuroanatomy focuses on morphological measurements of the brain using standard magnetic resonance imaging (MRI) techniques. In comparison quantitative MRI (qMRI) typically provides a better tissue contrast and also greatly improves the sensitivity and specificity with respect to the microstructural characteristics of tissue.
|
Der Nervenarzt
| 2,017
| 8
| 0
| 0
|
32,458,204
|
Human VGF-Derived Antidepressant Neuropeptide TLQP62 Promotes SH-SY5Y Neurite Outgrowth.
|
TLQP62 is a neuropeptide derived from the neurotrophin-inducible VGF (non-acronymic) protein with antidepressant-like properties capable of inducing increased memory on the mouse hippocampus by promoting neurogenesis and synaptic plasticity through brain-derived neurotropic factor (BDNF) and its receptor tyrosine receptor kinase B (TrkB). Human SH-SY5Y neuroblastoma-derived cell line is widely used in neuroscience research and is known to undergo neurodifferentiation in the presence of all-trans retinoic acid by upregulating the expression of TrkB, making cells responsive to BDNF. As TLQP62 promotes BDNF expression, which in turn activates a BDNF/TrkB/CREB (cAMP response element-binding protein) pathway that upregulates VGF expression, there is a VGF-BDNF regulatory loop that seems to regulate neurogenesis. Therefore, here, we evaluate by morphological observation the ability of human TLQP62 to induce neuritogenesis of human SH-SY5Y neuroblastoma-derived cell line in a retinoic acid and BDFN-like way, making this cell line a suitable cell model for further studies concerning TLQP62 molecular mechanisms and signalling pathways. SIGNIFICANCE STATEMENT: VGF has been widely explored for its role in emotional behaviour and neuropsychiatric illness (Bartolomucci et al. 2011). Although VGF levels were found reduced in leukocytes of depressed patients, after antidepressant treatment or voluntary exercise, those levels were found to be restored in the hippocampus (Hunsberger et al. 2007; Thakker-Varia et al. 2007). Administration to hippocampal cells of TLQP62 produced an increase in synaptic charge that could explain this antidepressants effects (Alder et al. 2003). This interesting role of TLQP62 in the brain, especially in the hippocampus, makes this neuropeptide an attractive target for further investigation of its role in neurogenesis, learning, memory, and neurological disorders, and possible treatment development. Thus, the identification of a receptor(s) for this peptide and associated signalling pathway(s) is of high importance, as well as a proper cell model to perform those studies.
|
Journal of molecular neuroscience : MN
| 2,020
| 8
| 0
| 0
|
32,721,849
|
An overview of the role of interleukin-8 in colorectal cancer.
|
Colorectal Cancer (CRC), a common malignancy, is developing globally among people. Mutagenic insults activate peripheral nucleated cells to secrete chemokines in order to cause an inflammatory state. Despite the presence of multi-retrieving factors, elevated production of minor cytokines may speed-up the sever stages of the baseline inflammation targeting normal compensatory mechanism. IL-8 is a pro-inflammatory cytokine that is believed to be up-regulated in CRC to proceed primary condition into tumor behavior via induction of proliferation, angiogenesis and metastasis. Here, we assess the role of IL-8 in every step of CRC from signaling pathway and formation to invasion and discuss around new perspective therapy that targets IL-8 to manage CRC worldwide incidence and survival rate, more precisely.
|
Cytokine
| 2,020
| 11
| 0
| 0
|
31,185,924
|
CD36 gene polymorphism rs1761667 (G > A) is associated with hypertension and coronary artery disease in an Iranian population.
|
CD36 is associated with regulation of lipid metabolism, atherosclerosis, and blood pressure. Moreover, its variation may be involved in the development of hypertension and/or coronary artery disease (CAD). The present study was conducted to investigate the possible association of CD36 rs1761667 (G > A) polymorphism with hypertension and/or CAD in the southeastern of Iran.
|
BMC cardiovascular disorders
| 2,019
| 6
| 0
| 0
|
33,108,460
|
Correlated Brain Indexes of Semantic Prediction and Prediction Error: Brain Localization and Category Specificity.
|
With strong and valid predictions, grasping a message is easy, whereas more demanding processing is required in the absence of robust expectations. We here demonstrate that brain correlates of the interplay between prediction and perception mechanisms in the understanding of meaningful sentences. Sentence fragments that strongly predict subsequent words induced anticipatory brain activity preceding the expected words; this potential was absent if context did not strongly predict subsequent words. Subjective reports of certainty about upcoming words and objective corpus-based measures correlated with the size of the anticipatory signal, thus establishing its status as a semantic prediction potential (SPP). Crucially, there was an inverse correlation between the SPP and the N400 brain response. The main cortical generators of SPP and N400 were found in inferior prefrontal cortex and posterior temporal cortex, respectively. Interestingly, sentence meaning was reflected by both measures, with additional category-specific sources of SPPs and N400s falling into parieto-temporo-occipital (visual) and frontocentral (sensorimotor) areas for animal- and tool-related words, respectively. These results show that the well-known brain index of semantic comprehension, N400, has an antecedent with different brain localization but similar semantic discriminatory function. We discuss whether N400 dynamics may causally depend on mechanisms underlying SPP size and sources.
|
Cerebral cortex (New York, N.Y. : 1991)
| 2,021
| 2
| 0
| 0
|
32,621,840
|
Human Mpv17-like protein with a mitigating effect on mtDNA damage is involved in cAMP/PKA signaling in the mitochondrial matrix.
|
Human Mpv17-like protein (M-LPH/Mpv17L) is thought to play a role in minimizing mitochondrial dysfunction caused by mitochondrial DNA (mtDNA) damage. We have recently demonstrated that, in addition to an increase of mtDNA damage, M-LPH-knockout (M-LPH-KO) in HepG2 cells causes a significant reduction of mitochondrial transcription factor A (TFAM) protein, an essential factor for mtDNA maintenance, along with an increase in its phosphorylation. These intracellular changes suggested an association of M-LPH with the cAMP/PKA signaling pathway, as selective degradation of TFAM by mitochondrial protease is driven by protein kinase A (PKA)-dependent phosphorylation. In the present study, we observed that M-LPH-KO in HepG2 cells caused an increase in the level of mitochondrial cAMP and a reduction of total cellular cyclic nucleotide phosphodiesterase (PDE) activity. In vitro-synthesized M-LPH showed PDE activity, which was inhibited by IBMX, a non-selective inhibitor of PDE. Furthermore, M-LPH-KO promoted PKA-dependent phosphorylation of some mitochondrial proteins. Taken together, the present findings suggest that M-LPH, which has structural features atypical of PDE family members, might be a novel human PDE involved in cAMP/PKA signaling in the mitochondrial matrix.
|
Biochimica et biophysica acta. Molecular cell research
| 2,020
| 10
| 0
| 0
|
33,382,284
|
Awards for Distinguished Scientific Early Career Contributions to Psychology.
|
The Early Career Awards, given for the first time in 1974, recognize the large number of excellent early career psychologists. Recipients of this award may not have held a doctoral degree for more than nine years. For purposes of this award, psychology has been divided into 10 areas: animal learning and behavior, comparative; developmental; health; cognition/human learning; psychopathology; behavioral and cognitive neuroscience; perception/motor performance; social; applied research; and individual differences. Five areas are considered each year, with areas rotated in two-year cycles. The areas considered in 2020 were animal learning and behavior, comparative; developmental; health; cognition/human learning; and psychopathology. Each year, panels are selected for the areas under consideration, and these panels recommend nominees to the Committee on Scientific Awards. The 2020 recipients of the APA Scientific Contribution Awards were recognized by the 2019 Board of Scientific Affairs and selected by the 2019 Committee on Scientific Awards. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
|
The American psychologist
| 2,020
| 12
| 0
| 0
|
33,400,565
|
Understanding Human Cognitive Uniqueness.
|
Humanity has regarded itself as intellectually superior to other species for millennia, yet human cognitive uniqueness remains poorly understood. Here, we evaluate candidate traits plausibly underlying our distinctive cognition (including mental time travel, tool use, problem solving, social cognition, and communication) as well as domain generality, and we consider how human cognitive uniqueness may have evolved. We conclude that there are no traits present in humans and absent in other animals that in isolation explain our species' superior cognitive performance; rather, there are many cognitive domains in which humans possess unusually potent capabilities compared to those found in other species. Humans are flexible cognitive all-rounders, whose proficiency arises through interactions and reinforcement between cognitive domains at multiple scales.
|
Annual review of psychology
| 2,021
| 1
| 0
| 0
|
31,838,623
|
"How does Austria sleep?" self-reported sleep habits and complaints in an online survey.
|
During the past years, the prevalence of sleep problems has been increasing steadily in industrial societies and represents a major social and socioeconomic burden. The situation in Austria was last evaluated in 2007 by Zeitlhofer and colleagues in a representative sample of 1000 participants. In the current study, we sought to evaluate the sleep behaviour of the Austrian population in an ongoing online survey, in which we have collected data from 986 participants (66% women, mean age 40.9 ± 16.4 years) between March 2018 and May 2019. Sleep duration was appropriate in 52% of the respondents (i.e. 7-9 h per night). However, we found an alarmingly high number of self-reported sleep problems (46%), and only 31% of the participants classified themselves as "good sleepers" using a validated self-report questionnaire (Pittsburgh Sleep Quality Index, PSQI). Furthermore, many participants reported suffering from sleep problems for a very long time (86% > 6 months; 37% > 5 years) suggesting that currently available treatment options are either ineffective or not employed. Possible reasons for sleep problems could include irregular sleep-wake cycles, increased perceived stress levels, and the use of electronic devices just before sleep.
|
Sleep & breathing = Schlaf & Atmung
| 2,020
| 6
| 0
| 0
|
32,374,025
|
Fluctuations of consciousness, mood, and science: The interhemispheric switch and sticky switch models two decades on.
|
Science and medicine aim to identify verifiable and replicable truths. However, the paths to such truths are frequently characterized by swinging pendulums of opposing perspectives. This is especially so in human neuroscience and the brain-based clinical sciences, where the target of investigation is the most complex of all biological systems. This article overviews a set of interrelated neuroscientific and clinical hypotheses, models, experiments, and predictions with which I have been involved for the last two decades. Traversing visual neuroscience, consciousness science, genetics, chronobiology, and biological and clinical psychiatry, the work illustrates how developments in science and medicine can occur through a combination of synthesis, serendipity, and experimentation. The article also reflects on doing science with the inimitable John "Jack" Pettigrew, and outlines how Pettigrew and I conceived, proposed, tested, and developed two new scientific models-one on neural mechanisms of binocular rivalry, the other on the pathophysiology of bipolar disorder. I also provide an update on various aspects of our models and data, and describe lessons learned from Pettigrew on how perspectives in science exhibit their own fluctuations, ironically like the very phenomena on which we worked.
|
The Journal of comparative neurology
| 2,020
| 12
| 0
| 0
|
33,288,778
|
Sounds are remapped across saccades.
|
To achieve visual space constancy, our brain remaps eye-centered projections of visual objects across saccades. Here, we measured saccade trajectory curvature following the presentation of visual, auditory, and audiovisual distractors in a double-step saccade task to investigate if this stability mechanism also accounts for localized sounds. We found that saccade trajectories systematically curved away from the position at which either a light or a sound was presented, suggesting that both modalities are represented in eye-centered oculomotor centers. Importantly, the same effect was observed when the distractor preceded the execution of the first saccade. These results suggest that oculomotor centers keep track of visual, auditory and audiovisual objects by remapping their eye-centered representations across saccades. Furthermore, they argue for the existence of a supra-modal map which keeps track of multi-sensory object locations across our movements to create an impression of space constancy.
|
Scientific reports
| 2,020
| 12
| 0
| 0
|
32,819,897
|
Regional Mechanical Thrombectomy Imaging Protocol in Patients Presenting with Acute Ischemic Stroke during the COVID-19 Pandemic.
|
Chest CT is a rapid, useful additional screening tool for coronavirus disease 2019 (COVID-19) in emergent procedures. We describe the feasibility and interim outcome of implementing a modified imaging algorithm for COVID-19 risk stratification across a regional network of primary stroke centers in the work-up of acute ischemic stroke referrals for time-critical mechanical thrombectomy.
|
AJNR. American journal of neuroradiology
| 2,020
| 10
| 0
| 0
|
26,517,542
|
The potential for non-invasive brain stimulation to improve function after amputation.
|
Lower limb amputee rehabilitation has traditionally focussed on restoration of gait and balance through use of prosthetic limbs and mobility aids. Despite these efforts, some amputees continue to experience difficulties with mastering prosthetic mobility. Emerging techniques in rehabilitation, such as non-invasive brain stimulation (NIBS), may be an appropriate tool to enhance prosthetic rehabilitation outcomes by promoting "normal" brain reorganisation and function. The purpose of this review is to highlight the potential of NIBS to improve functional outcomes for lower limb amputees.
|
Disability and rehabilitation
| 2,016
| 7
| 0
| 0
|
33,197,557
|
X-linked cellular mosaicism underlies age-dependent occurrence of seizure-like events in mouse models of CDKL5 deficiency disorder.
|
CDKL5 deficiency disorder (CDD) is an infantile, epileptic encephalopathy presenting with early-onset seizures, intellectual disability, motor impairment, and autistic features. The disorder has been linked to mutations in the X-linked CDKL5, and mouse models of the disease recapitulate several aspects of CDD symptomology, including learning and memory impairments, motor deficits, and autistic-like features. Although early-onset epilepsy is one of the hallmark features of CDD, evidence of spontaneous seizure activity has only recently been described in Cdkl5-deficient heterozygous female mice, but the etiology, prevalence, and sex-specificity of this phenotype remain unknown. Here, we report the first observation of disturbance-associated seizure-like events in heterozygous female mice across two independent mouse models of CDD: Cdkl5 knockout mice and CDKL5 R59X knock-in mice. We find that both the prevalence and severity of this phenotype increase with aging, with a median onset around 28 weeks of age. Similar seizure-like events are not observed in hemizygous knockout male or homozygous knockout female littermates, suggesting that X-linked cellular mosaicism is a driving factor underlying these seizure-like events. Together, these findings not only contribute to our understanding of the effects of CDKL5 loss on seizure susceptibility, but also document a novel, pre-clinical phenotype for future therapeutic investigation.
|
Neurobiology of disease
| 2,021
| 1
| 0
| 0
|
34,457,634
|
Teaching Anatomy to Neuroscientific Health-Care Professionals: Are They Receiving the Best Anatomical Education?
|
University neuroanatomical courses seldom teach the anatomical-functional connectivity of the brain. White matter dissection improves understanding of brain connectivity, but until now has been restricted to neurosurgeons and in some cases to medical students, never to health-care non-medical professionals. Our aim was to teach white matter anatomy to medical and non-medical students to evaluate this technique in groups with different education. A standardized lab demonstration of white matter anatomy was performed with high appreciation rate in both groups, suggesting a suboptimal neuroanatomical education provided by basic course. We encourage to include this technique of teaching brain anatomy into basic neuroanatomical courses to improve the level of comprehension and competence in all health-care staff within the field of neuroscience.
|
Medical science educator
| 2,020
| 3
| 0
| 0
|
24,765,366
|
Multiple sclerosis in an adrenoleukodystrophy carrier.
|
X-linked adrenoleukodystrophy (X-ALD) is a rare inherited metabolic disorder, in which accumulation of very long chain fatty acids (VLCFAs) results in damage to the central nervous system. As the disease is X-linked, males are affected severely, but female carriers may also present with neurological symptoms. We report the case of a young adult female, who presented with episodic sensorimotor symptoms. Although she was a heterozygous female carrier of X-ALD, subsequent investigations confirmed a diagnosis of multiple sclerosis (MS). To the best of our knowledge, this is the first reported case of a female X-ALD carrier in which the clinical features were more consistent with co-existent MS than ALD-related pathology. The case serves as a reminder that alternative, more common diagnoses should also be considered in carriers of rare neurological syndromes.
|
Clinics and practice
| 2,011
| 9
| 0
| 0
|
33,110,101
|
Phosphorylation of Connexin36 near the C-terminus switches binding affinities for PDZ-domain and 14-3-3 proteins in vitro.
|
Connexin36 (Cx36) is the most abundant connexin in central nervous system neurons. It forms gap junction channels that act as electrical synapses. Similar to chemical synapses, Cx36-containing gap junctions undergo activity-dependent plasticity and complex regulation. Cx36 gap junctions represent multimolecular complexes and contain cytoskeletal, regulatory and scaffolding proteins, which regulate channel conductance, assembly and turnover. The amino acid sequence of mammalian Cx36 harbors a phosphorylation site for the Ca
|
Scientific reports
| 2,020
| 10
| 0
| 0
|
30,762,913
|
Increased picture-word interference in chronic and recreational users of cocaine.
|
The correct production of speech depends on the effective use of inhibitory control. Cocaine abuse has been linked to impaired inhibition in the verbal and nonverbal domains. The aim of this study was to evaluate the possible impairment of the inhibitory control process engaged in the production of language among chronic cocaine users, both in rehabilitation and recreational contexts.
|
Human psychopharmacology
| 2,019
| 3
| 0
| 0
|
32,932,137
|
Afterhyperpolarization amplitude in CA1 pyramidal cells of aged Long-Evans rats characterized for individual differences.
|
Altered neural excitability is considered a prominent contributing factor to cognitive decline during aging. A clear example is the excess neural activity observed in several temporal lobe structures of cognitively impaired older individuals in rodents and humans. At a cellular level, aging-related changes in mechanisms regulating intrinsic excitability have been well examined in pyramidal cells of the CA1 hippocampal subfield. Studies in the inbred Fisher 344 rat strain document an age-related increase in the slow afterhyperpolarization (AHP) that normally occurs after a burst of action potentials, and serves to reduce subsequent firing. We evaluated the status of the AHP in the outbred Long-Evans rat, a well-established model for studying individual differences in neurocognitive aging. In contrast to the findings reported in the Fisher 344 rats, in the Long-Evan rats we detected a selective reduction in AHP in cognitively impaired aged individuals. We discuss plausible scenarios to account for these differences and also discuss possible implications of these differences.
|
Neurobiology of aging
| 2,020
| 12
| 0
| 0
|
32,095,900
|
Retraction Note to: Stability of neuronal avalanches and long-range temporal correlations during the first year of life in human infant.
|
The authors have retracted this article Jannesari et al. (2019) because an incorrect version of the article was published in error. The manuscript has been republished as Jannesari et al. (2020). All authors agree to this retraction.
|
Brain structure & function
| 2,020
| 4
| 0
| 0
|
33,161,826
|
Improved Visual Function in a Case of Ultra-low Vision following Ischemic Encephalopathy Using Transcranial Electrical Stimulation; A Brief Report.
|
Cerebral visual impairment is amongst the key pathological causes of pediatric visual abnormalities often resulted from hypoxic-ischemic brain injury. Such an injury results in profound visual impairments which severely impairs patients' quality of life. Given the nature of the pathology, treatments are currently limited to rehabilitation strategies such as transcranial electrical stimulation and visual rehabilitation therapy.
|
Developmental neurorehabilitation
| 2,021
| 1
| 0
| 0
|
23,520,136
|
Homage to Rita Levi-Montalcini, the queen of modern neuroscience.
|
The first cell growth factor, nerve growth factor (NGF), was discovered by Rita Levi-Montalcini (RLM) in the early 1950s. Originally identified as neurite outgrowth-stimulating factor, later studies revealed that non-neuronal cells, including immune cells, endothelial cells, cardiomyocytes, pancreatic beta cells, prostate epithelial and adipose tissue cells, were also targets for and/or sources of NGF. Nerve growth factor is well recognised as mediating multiple biological phenomena, ranging from the neurotrophic through immunotrophic and epitheliotrophic to metabotrophic effects. Consequently, NGF and other members of the neurotrophin family are implicated in the pathogenesis of a large spectrum of neuronal and non-neuronal diseases, ranging from Alzheimer's and other neurodegenerative diseases to atherosclerosis and cardiometabolic disorders. Recent studies have demonstrated the therapeutic potentials of NGF in these conditions, including ocular and cutaneous diseases. NGF TrkA receptor antagonists emerged as novel drugs for pain, prostate and breast cancer, melanoma and urinary bladder syndromes. Here, we briefly describe the 'unpredictable' ideogenesis of the discovery of NGF, a eureka in the neuroscience.
|
Cell biology international
| 2,013
| 8
| 0
| 0
|
24,147,514
|
How will the growing threat of resistant hypertension impact the future treatment of high blood pressure?
|
Hypertension treatment and control efforts represent a major component of primary care with dedicated clinical guidelines and recommendations. However, high blood pressure (BP) control rates are complicated with the difficult to treat and resistant hypertensive patients. This category of patient, therefore, affects the development and implementation of the clinical guidelines. The recommendations of specific algorithms for resistant hypertension and difficult-to-treat patients with elevated BPs have been developed in consideration of new therapies and combination drug treatment. Hypertension treatment guidelines include and will continue to grade evidence from randomized clinical trials with detailed strategies on the management of these high-risk patients. Although resistant hypertension affects high BP control rates, the inclusion of refined pharmaceutical and device treatment strategies in evidence-based guidelines will be expected to have a significant impact on the clinical management of this high-risk patient population.
|
Expert review of cardiovascular therapy
| 2,013
| 11
| 0
| 0
|
33,517,649
|
COMPOSITION OF CEREBROSPINAL FLUID IN CLINICALLY NORMAL GRIZZLY BEARS (
|
Five cerebrospinal fluid (CSF) samples were collected from four clinically normal grizzly bears from the Washington State University Bear Research, Education, and Conservation Center. CSF samples were collected from the cerebellomedullary cisternal space. Samples were immediately processed and analyzed for microprotein content, red blood cells, white blood cells (WBCs), and differential cell count. Microprotein concentration (range 4.2-14.6 mg/dl; median, less than 6 mg/dl), total WBC count (range 0-2 cells/µl; median 2 cells/µl), and differential WBCs (predominance mononuclear cells) of the five CSF samples were comparable to previously published CSF analyses from clinically normal felines and canines. Providing documentation of CSF composition for clinically normal grizzly bears is important for neurologic disease diagnosis and treatment.
|
Journal of zoo and wildlife medicine : official publication of the American Association of Zoo Veterinarians
| 2,019
| 9
| 0
| 0
|
33,243,462
|
Role of the E3 ubiquitin ligase HRD1 in the regulation of serotonin transporter function.
|
To elucidate the regulation of serotonin transporter (SERT) function via its membrane trafficking, we investigated the involvement of the ubiquitin E3 ligase HRD1 (HMG-CoA reductase degradation protein), which participates in endoplasmic reticulum (ER)-associated degradation (ERAD), in the functional regulation of SERT. Cells transiently expressing wild-type SERT or a SERT C-terminal deletion mutant (SERTΔCT), a SERT protein predicted to be misfolded, were used for experiments. Studies using HRD1-overexpressing or HRD1-knockdown cells demonstrated that HRD1 is involved in SERT proteolysis. Overexpression of HRD1 promoted SERT ubiquitination, the effect of which was augmented by treatment with the proteasome inhibitor MG132. Immunoprecipitation studies revealed that HRD1 interacts with SERT in the presence of MG132. In addition, HRD1 was intracellularly colocalized with SERT, especially with aggregates of SERTΔCT in the ER. HRD1 also affected SERT uptake activity in accordance with the expression levels of the SERT protein. These results suggest that HRD1 contributes to the membrane trafficking and functional regulation of SERT through its involvement in ERAD-mediated SERT degradation.
|
Biochemical and biophysical research communications
| 2,021
| 1
| 0
| 0
|
18,550,792
|
Stimulation of fetal hypothalamus induces uterine contractions in pregnant rats at term.
|
The fetal brain is thought to have a role in the onset and progression of labor. Evidence also exists for fetal oxytocin release just before and during parturition. The present study examined whether activation of the fetal brain could induce uterine myometrial contractions through oxytocin receptors in the dam. Under urethane anesthesia, electrical stimulation of the hypothalamus of fetal rats that were still connected with the dams by an intact umbilical cord induced uterine contractions in term pregnant rats. Intraperitoneal injections of synthetic oxytocin in fetuses induced uterine contractions in the dams similar to those induced by electrical stimulation of the fetal hypothalamus. Maternal intravenous injections of an oxytocin antagonist immediately attenuated uterine contractions induced by fetal oxytocin injections and electrical stimulation of the fetal hypothalamus. These findings suggest the possibility that oxytocin released from the fetal hypothalamus is involved in parturition.
|
Biology of reproduction
| 2,008
| 10
| 0
| 0
|
33,795,948
|
Clinical Features of the Patients with Neuromyelitis Optica Spectrum Disorder.
|
Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory, demyelinating syndrome of the central nervous system (CNS) that predominantly affects the spinal cord and optic nerves. Since it was first described, new information about the pathophysiology gained momentum with the discovery of an antibody against Aquaporin-4, a water channel protein that is predominantly found in the astrocytes. In our study, we evaluated the clinical features of NMOSD and clinically related CNS disorders.
|
Noro psikiyatri arsivi
| 2,021
| 3
| 0
| 0
|
23,637,668
|
Traumatic neuroma in continuity injury model in rodents: a preliminary report.
|
Consistent with EBSJ's commitment to fostering quality research, we are pleased to feature some of the most highly rated abstracts from the 8th Annual AOSpine North America Fellows Forum in Banff Canada. Enhancing the quality of evidence in spine care means acknowledging and supporting the efforts of young researchers within our AOSpine North America network. We look forward to seeing more from these promising researchers in the future.
|
Evidence-based spine-care journal
| 2,010
| 8
| 0
| 0
|
33,189,388
|
Impact of Parental Exposure on Offspring Health in Humans.
|
The possibility that parental life experiences and environmental exposures influence mental and physical health across generations is an important concept in biology and medicine. Evidence from animal models has established the existence of a non-genetic mode of inheritance. This form of heredity involves transmission of the effects of parental exposure to the offspring through epigenetic changes in the germline. Studying the mechanisms of epigenetic inheritance in humans is challenging because it is difficult to obtain multigeneration cohorts, to collect reproductive cells in exposed parents, and to exclude psychosocial and cultural confounders. Nonetheless, epidemiological studies in humans exposed to famine, stress/trauma, or toxicants have provided evidence that parental exposure can impact the health of descendants, in some cases, across several generations. A few studies have also started to reveal epigenetic changes in the periphery and sperm after certain exposures. This article reviews these studies and evaluates the current evidence for the potential contribution of epigenetic factors to heredity in humans. The challenges and limitations of this fundamental biological process, its implications, and its societal relevance are also discussed.
|
Trends in genetics : TIG
| 2,021
| 4
| 0
| 0
|
31,261,968
|
The Lymphatic Headmaster of the Mast Cell-Related Splanchnic Inflammation in Portal Hypertension.
|
Portal hypertension is a common complication of liver disease, either acute or chronic. Consequently, in chronic liver disease, such as the hypertensive mesenteric venous pathology, the coexisting inflammatory response is classically characterized by the splanchnic blood circulation. However, a vascular lymphatic pathology is produced simultaneously with the splanchnic arterio-venous impairments. The pathological increase of the mesenteric venous pressure, by mechanotransduction of the venous endothelium hyperpressure, causes an inflammatory response involving the subendothelial mast cells and the lymphatic endothelium of the intestinal villi lacteal. In portal hypertension, the intestinal lymphatic inflammatory response through the development of mesenteric-systemic lymphatic collateral vessels favors the systemic diffusion of substances with a molecular pattern associated with damage and pathogens of intestinal origin. When the chronic hepatic insufficiency worsens the portal hypertensive inflammatory response, the splanchnic lymphatic system transports the hyperplasied intestinal mast cells to the mesenteric lymphatic complex. Then, an acquired immune response regulating a new hepato-intestinal metabolic scenario is activated. Therefore, reduction of the hepatic metabolism would reduce its key centralized functions, such as the metabolic, detoxifying and antioxidant functions which would try to be substituted by their peroxisome activity, among other functions of the mast cells.
|
Cells
| 2,019
| 6
| 0
| 0
|
33,277,559
|
Serotonin receptor 5-HT7 in Drosophila mushroom body neurons mediates larval appetitive olfactory learning.
|
Serotonin (5-HT) and dopamine are critical neuromodulators known to regulate a range of behaviors in invertebrates and mammals, such as learning and memory. Effects of both serotonin and dopamine are mediated largely through their downstream G-protein coupled receptors through cAMP-PKA signaling. While the role of dopamine in olfactory learning in Drosophila is well described, the function of serotonin and its downstream receptors on Drosophila olfactory learning remain largely unexplored. In this study we show that the output of serotonergic neurons, possibly through points of synaptic contacts on the mushroom body (MB), is essential for training during olfactory associative learning in Drosophila larvae. Additionally, we demonstrate that the regulation of olfactory associative learning by serotonin is mediated by its downstream receptor (d5-HT7) in a cAMP-dependent manner. We show that d5-HT7 expression specifically in the MB, an anatomical structure essential for olfactory learning in Drosophila, is critical for olfactory associative learning. Importantly our work shows that spatio-temporal restriction of d5-HT7 expression to the MB is sufficient to rescue olfactory learning deficits in a d5-HT7 null larvae. In summary, our results establish a critical, and previously unknown, role of d5-HT7 in olfactory learning.
|
Scientific reports
| 2,020
| 12
| 0
| 0
|
28,269,499
|
A time domain frequency-selective multivariate Granger causality approach.
|
The investigation of effective connectivity is one of the major topics in computational neuroscience to understand the interaction between spatially distributed neuronal units of the brain. Thus, a wide variety of methods has been developed during the last decades to investigate functional and effective connectivity in multivariate systems. Their spectrum ranges from model-based to model-free approaches with a clear separation into time and frequency range methods. We present in this simulation study a novel time domain approach based on Granger's principle of predictability, which allows frequency-selective considerations of directed interactions. It is based on a comparison of prediction errors of multivariate autoregressive models fitted to systematically modified time series. These modifications are based on signal decompositions, which enable a targeted cancellation of specific signal components with specific spectral properties. Depending on the embedded signal decomposition method, a frequency-selective or data-driven signal-adaptive Granger Causality Index may be derived.
|
Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference
| 2,016
| 8
| 0
| 0
|
32,880,057
|
Prefrontal resting-state connectivity and antidepressant response: no associations in the ELECT-TDCS trial.
|
Functional and structural MRI of prefrontal cortex (PFC) may provide putative biomarkers for predicting the treatment response to transcranial direct current stimulation (tDCS) in depression. A recent MRI study from ELECT-TDCS (Escitalopram versus Electrical Direct-Current Theror Depression Study) showed that depression improvement after tDCS was associated with gray matter volumes of PFC subregions. Based thereon, we investigated whether antidepressant effects of tDCS are similarly associated with baseline resting-state functional connectivity (rsFC). A subgroup of 51 patients underwent baseline rsFC-MRI. All patients of ELECT-TDCS were randomized to three treatment arms for 10 weeks (anodal-left, cathodal-right PFC tDCS plus placebo medication; escitalopram 10 mg/day for 3 weeks and 20 mg/day thereafter plus sham tDCS; and placebo medication plus sham tDCS). RsFC was calculated for various PFC regions and analyzed in relation to the individual antidepressant response. There was no significant association between baseline PFC connectivity of essential structural regions, nor any other PFC regions (after correction for multiple comparisons) and patients' individual antidepressant response. This study did not reveal an association between antidepressants effects of tDCS and baseline rsFC, unlike the gray matter volume findings. Thus, the antidepressant effects of tDCS may be differentially related to structural and functional MRI measurements.
|
European archives of psychiatry and clinical neuroscience
| 2,021
| 2
| 0
| 0
|
21,253,350
|
Functional residual capacity tool: A practical method to assess lung volume changes during pulmonary complications in mechanically ventilated patients.
|
In this report, we describe a patient in whom we used a functional residual capacity (FRC) tool available on a critical care ventilator to identify the loss of lung volume associated with pulmonary complications and increase in FRC with the application of a recruitment maneuver. The case report underlines the utility of the FRC tool in rapid visualization of the lung volume changes and the effects of application of corrective strategies in patients receiving mechanical ventilation.
|
Indian journal of critical care medicine : peer-reviewed, official publication of Indian Society of Critical Care Medicine
| 2,010
| 7
| 0
| 0
|
33,415,815
|
XCT 790 is a pharmacological aggrephagy inducer in a yeast model of proteotoxicity.
|
Aggrephagy is a selective autophagic degradation intracellular mechanism that clears toxic misfolded protein aggregates such as α-synuclein. Here, we identify and demonstrate that the small molecule, XCT 790 alleviates α-synuclein-mediated adverse effects in a yeast model of proteotoxicity. XCT 790 induced general autophagy and also enhanced starvation-induced autophagy. Mechanistically, we showed that XCT 790 clears toxic α-synuclein aggregates in an autophagy-dependent manner. Interestingly, XCT 790 did not demonstrate a synergistic effect on autophagy induction in the presence of another autophagy inducer such as 6-Bio.
|
Cell biology international
| 2,021
| 3
| 0
| 0
|
32,988,918
|
Diagnostic Accuracy of Pleural Fluid Cytology, Carcinoembryonic Antigen and C-Reactive Protein Together in Patients With Pulmonary Metastases and Malignant Pleural Effusion.
|
Pleural effusion (PE) has a heterogeneous aetiology, and differential diagnosis between benign and malignant disease may require invasive procedures in up to 60% of cases. The sensitivity of pleural cytology is limited, and several strategies have been tested to reduce the need of invasive diagnostic approaches. The aim of this study was to evaluate the usefulness of pleural fluid cytology, compared to, and combined with, carcinoembryonic antigen (CEA), C reactive protein (CRP), and lactate dehydrogenase (LDH) assay of pleural fluid (PF) in patients with a history of cancer, exudative non-purulent PE, and suspicion of malignant PE on imaging studies.
|
Anticancer research
| 2,020
| 10
| 0
| 0
|
33,194,488
|
Current Treatment Modalities for Calcified Coronary Artery Disease: A Review Article Comparing Novel Intravascular Lithotripsy and Traditional Rotational Atherectomy.
|
The coronary artery calcium score is considered the most useful marker for predicting coronary events. The high score reflects heavy calcification in the vessel, which is more challenging to treat with the percutaneous intervention (PCI). To prepare this type of heavily calcified lesion intravascular lithotripsy (IVL) technology can be used prior to PCI, which is based on the concept of converting electrical energy into mechanical energy. It harmlessly and selectively disrupts both the shallow and deep deposits of calcium. The balloon-based catheters of this system emit sonic waves that transfer to the adjacent tissue resulting in improvement in vessel compliance with the slightest soft tissue loss. Therefore, making the treatment of calcified lesions more feasible, effective, and also simplify complex lesions. The lesions considered for lithotripsy-enhanced balloon dilation include calcified coronary lesions and peripheral vasculature lesions. This article reviews the use of IVL in calcified coronary artery disease, its advantages, and disadvantages while comparing it with other techniques like high-pressure balloons and rotational atherectomy devices. A thorough search of databases like PubMed and Google Scholar was performed, which uncovered 35 peer review articles. Keywords utilized in the data search were calcified coronary artery disease, coronary lithotripsy, calcification, and calcified atherosclerotic plaque. According to rotational atherectomy and intravascular lithotripsy trials, the latter was safer, mainly by decreasing atheromatous embolization risk. Deciphering these studies, it seems like IVL is better at parameters like procedural and clinical success rate, acute lumen gain, and less residual stenosis except in-hospital major adverse cardiovascular events (MACE), which was better in rotational atherectomy (RA). However, when lesion crossings are present, the atherectomy technique is still considered as first-line therapy. In clinical practice, despite these encouraging data for treating calcified lesions, IVL is grossly underutilized because of substantial costs and perceived significant procedural risk effects on the cardiac rhythm like causing 'shock topics' and asynchronous cardiac pacing. More longer-term clinical data and extensive researches are required to validate its safety and efficiency.
|
Cureus
| 2,020
| 10
| 0
| 0
|
26,679,068
|
Congenital Spinal Malformation and Stroke: Aneurysmal Dilatations and Bilateral Rotational Vertebral Artery Occlusion.
|
A 30-year-old woman suffered from acute vertebrobasilar stroke. Cranial tomography (CT) scans showed multiple vertebral abnormalities suggestive of congenital spine malformation, and angiographic CT revealed aneurysmal dilatations (ADs) at segment V2 of both vertebral arteries (VAs). Dynamic neuroimaging tests including angiography and angio-CT were performed and showed occlusion of both VAs at the point of the ADs with contralateral rotation of the neck. The presence of a bony structure causing the artery compression was excluded and embolic phenomena originating at the AD was proposed as the likely source of stroke. Even if infrequent, the presence of craniocervical anomalies should be considered in vertebrobasilar stroke of indeterminate etiology.
|
Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association
| 2,016
| 3
| 0
| 0
|
33,483,938
|
Effects of Fingolimod and Natalizumab on Brain T1-/T2-Weighted and Magnetization Transfer Ratios: a 2-Year Study.
|
Fingolimod and natalizumab significantly reduce disease activity in relapsing-remitting multiple sclerosis (RRMS) and could promote tissue repair and neuroprotection. The ratio between conventional T1- and T2-weighted sequences (T1w/T2w-ratio) and magnetization transfer ratio (MTR) allow to quantify brain microstructural tissue abnormalities. Here, we compared fingolimod and natalizumab effects on brain T1w/T2w-ratio and MTR in RRMS over 2 years of treatment. RRMS patients starting fingolimod (n = 25) or natalizumab (n = 30) underwent 3T brain MRI scans at baseline (T0), month 6 (M6), month 12 (M12), and month 24 (M24). White matter (WM) lesions, normal-appearing (NA) WM, and gray matter (GM) T1w/T2w-ratio and MTR were estimated and compared between groups using linear mixed models. No baseline demographic, clinical, and MRI difference was found between groups. In natalizumab patients, lesion T1w/T2w-ratio and MTR significantly increased at M6 vs. T0 (p ≤ 0.035) and decreased at subsequent timepoints (p ≤ 0.037). In fingolimod patients, lesion T1w/T2w-ratio increased at M12 vs. T0 (p = 0.010), while MTR gradually increased at subsequent timepoints vs. T0 (p ≤ 0.027). Natalizumab stabilized NAWM and GM T1w/T2w-ratio and MTR. In fingolimod patients, NAWM T1w/T2w-ratio and MTR significantly increased at M24 vs. M12 (p ≤ 0.001). A significant GM T1w/T2w-ratio decrease at M6 vs. T0 (p = 0.014) and increase at M24 vs. M6 (p = 0.008) occurred, whereas GM MTR was significantly higher at M24 vs. previous timepoints (p ≤ 0.017) with significant between-group differences (p ≤ 0.034). Natalizumab may promote an early recovery of lesional damage and prevent microstructural damage accumulation in NAWM and GM during the first 2 years of treatment. Fingolimod enhances tissue damage recovery being visible after 6 months in lesions and after 2 years in NAWM and GM.
|
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics
| 2,021
| 4
| 0
| 0
|
32,687,884
|
Incubation of depression: ECM assembly and parvalbumin interneurons after stress.
|
The extracellular space is occupied by a complex network of proteins creating a mesh-like assembly known as the extracellular matrix (ECM). ECM assembles into dense net-like structures, perineuronal nets (PNNs), that envelope cell somas and proximal neurites of predominantly parvalbumin
|
Neuroscience and biobehavioral reviews
| 2,020
| 11
| 0
| 0
|
32,221,749
|
Atypical Development of Attentional Control Associates with Later Adaptive Functioning, Autism and ADHD Traits.
|
Autism is frequently associated with difficulties with top-down attentional control, which impact on individuals' mental health and quality of life. The developmental processes involved in these attentional difficulties are not well understood. Using a data-driven approach, 2 samples (N = 294 and 412) of infants at elevated and typical likelihood of autism were grouped according to profiles of parent report of attention at 10, 15 and 25 months. In contrast to the normative profile of increases in attentional control scores between infancy and toddlerhood, a minority (7-9%) showed plateauing attentional control scores between 10 and 25 months. Consistent with pre-registered hypotheses, plateaued growth of attentional control was associated with elevated autism and ADHD traits, and lower adaptive functioning at age 3 years.
|
Journal of autism and developmental disorders
| 2,020
| 11
| 0
| 0
|
33,581,379
|
Optimized repetitive transcranial magnetic stimulation techniques for the treatment of major depression: A proof of concept study.
|
Although effective in major depressive disorder (MDD), repetitive transcranial magnetic stimulation (rTMS) is costly and complex, limiting accessibility. To address this, we tested the feasibility of novel rTMS techniques with cost-saving opportunities, such as an open-room setting, large non-focal parabolic coils, and custom-built coil arms. We employed a low-frequency (LF) 1 Hz stimulation protocol (360 pulses per session), delivered on the most affordable FDA-approved device. MDD participants received an initial accelerated rTMS course (arTMS) of 6 sessions/day over 5 days (30 total), followed by a tapering course of daily sessions (up to 25) to decrease the odds of relapse. The self-reported Beck Depression Inventory II (BDI-II) was used to measure severity of depression. Forty-eight (48) patients completed the arTMS course. No serious adverse events occurred, and all patients reported manageable pain levels. Response and remission rates were 35.4% and 27.1% on the BDI-II, respectively, at the end of the tapering course. Repeated measures ANOVA showed significant changes of BDI-II scores over time. Even though our protocol will require further improvements, some of the concepts we introduced here could help guide the design of future trials aiming at increasing accessibility to rTMS.
|
Psychiatry research
| 2,021
| 4
| 0
| 0
|
18,345,974
|
Management of epilepsy in tuberous sclerosis complex.
|
Tuberous sclerosis complex (TSC) is an inherited disorder resulting from mutations in one of two genes, TSC1 (Hamartin) and TSC2 (Tuberin). These two proteins form a cytosolic complex that inhibits the mTOR pathway that controls cell growth and proliferation. Pathologically, abnormalities of neuronal migration, cellular differentiation and excessive cellular proliferation all contribute to the formation of the different brain lesions of TSC. Seizure is the most common presenting symptom. Seizures can be present in the first year of life and up to one third of children develop infantile spasms. Seizures usually have a focal or multifocal origin, are often resistant to antiepileptic drugs and have a negative impact on the neurocognitive development. Vigabatrin has proved to be effective against infantile spasms due to TSC. New evidence suggests that it is possible to noninvasively identify using multimodality techniques, TSC children who are likely to become seizure-free following surgical treatment. Understanding the mechanisms of epileptogenesis and the possible role of the mTOR pathway in this process might increase the availability of novel and targeted therapies.
|
Expert review of neurotherapeutics
| 2,008
| 3
| 0
| 0
|
32,858,045
|
Language context tunes brain network for language control in bilingual language production.
|
When bilinguals intend to speak in their first (L1) or second language (L2) according to the environment, a brain network involving cortical-subcortical regions is recruited to resolve cross-language interference. Research has found that the activation of these brain regions varies with language contexts. However, previous studies have not yet examined adaptive changes in the interactions of brain regions for different language contexts. To address this gap, we adopted extended unified structural equation modeling (euSEM) to identify the connectivity patterns of the bilingual control network. Twenty-one unbalanced Chinese-English bilinguals were instructed to name pictures in L1-single, L2-single, and dual-language contexts while undergoing functional magnetic resonance imaging (fMRI). We found that unbalanced bilinguals relied on a more functional integrated brain network, which was reflected by clearer core-periphery structures and increased global efficiency, in dual-language and L2-single contexts compared to L1-single context. Furthermore, the pattern of brain connectivity in the dual-language context was more similar to that in the L1-single context than the L2-single context. More importantly, we found more similarities between the connectivity patterns of dual-language and L1-single contexts in bilinguals with lower inhibitory control abilities. These findings provide the first connectivity evidence for the effect of language context on the bilingual language control network, which inhibits the base language and underpins bilinguals' change along the monolingual-bilingual mode continuum.
|
Neuropsychologia
| 2,020
| 10
| 0
| 0
|
25,054,298
|
Brain metastases as a cause of malignant cerebrospinal fluid ascites: case report and review of the literature.
|
The development of cerebrospinal fluid ascites after a ventriculo-peritoneal shunt operation is an extremely rare complication. There have been only sporadic case reports and small series reviews published in regards to this condition. They are usually found in the context of primary brain tumors, usually affecting the pediatric population. We present an unusual case of a patient with known metastatic breast carcinoma to the brain who develops malignant cerebrospinal fluid ascites after a ventriculo-peritoneal shunt insertion. This is the first known adult case of a metastatic breast primary to the brain causing tumor dissemination via a ventriculo-peritoneal shunt.
|
CNS oncology
| 2,012
| 9
| 0
| 0
|
32,964,492
|
GDNF/RET Signaling Pathway Activation Eliminates Lewy Body Pathology in Midbrain Dopamine Neurons.
|
Parkinson's disease (PD) is associated with proteostasis disturbances and accumulation of misfolded α-synuclein (α-syn), a cytosolic protein present in high concentrations at pre-synaptic neuronal terminals. It is a primary constituent of intracellular protein aggregates known as Lewy neurites or Lewy bodies. Progression of Lewy pathology caused by the prion-like self-templating properties of misfolded α-syn is a characteristic feature in the brains of PD patients. Glial cell line-derived neurotrophic factor (GDNF) promotes survival of mature dopamine (DA) neurons in vitro and in vivo. However, the data on its effect on Lewy pathology is controversial.
|
Movement disorders : official journal of the Movement Disorder Society
| 2,020
| 12
| 0
| 0
|
25,045,237
|
A case report of preoperative and postoperative 7.0T brain MRI in a patient with a small cell glioblastoma.
|
A 45-yr-old female patient was admitted with one-month history of headache and progressive left hemiparesis. Brain magnetic resonance imaging (MRI) demonstrated a mass lesion in her right frontal lobe. Her brain tumor was confirmed as a small cell glioblastoma. Her follow-up brain MRI, taken at 8 months after her initial surgery demonstrated tumor recurrence in the right frontal lobe. Contrast-enhanced 7.0T brain magnetic resonance imaging (MRI) was safely performed before surgery and at the time of recurrence. Compared with 1.5T and 3.0T brain MRI, 7.0T MRI showed sharpened images of the brain tumor contexture with detailed anatomical information. The fused images of 7.0T and 1.5T brain MRI taken at the time of recurrence demonstrated no significant discrepancy in the positions of the anterior and the posterior commissures. It is suggested that 7.0T MRI can be safely utilized for better images of the maligant gliomas before and after surgery.
|
Journal of Korean medical science
| 2,014
| 7
| 0
| 0
|
12,929,740
|
Perinatal asphyxia in the guinea pig leads to morphologic but not neurologic, cognitive, or behavioral changes.
|
In a recent publication, we described neurodegeneration along with neurotransmitter deficits and impaired differentiation in the guinea pig 3 months following severe perinatal asphyxia (PA). We were therefore interested in the clinical features in terms of neurology, cognitive functions, and behavior.
|
Journal of investigative medicine : the official publication of the American Federation for Clinical Research
| 2,003
| 7
| 0
| 0
|
32,270,385
|
Cross-Cultural Adaptation to Australia of the KONTAKT© Social Skills Group Training Program for Youth with Autism Spectrum Disorder: A Feasibility Study.
|
This study investigated the feasibility and cultural validity of KONTAKT©, a manualised social skills group training, in improving the social functioning of adolescents with autism spectrum disorder (ASD). KONTAKT© was delivered to 17 adolescents (m
|
Journal of autism and developmental disorders
| 2,020
| 12
| 0
| 0
|
32,735,782
|
Cannabidiol for the treatment of cannabis use disorder: a phase 2a, double-blind, placebo-controlled, randomised, adaptive Bayesian trial.
|
Background A substantial and unmet clinical need exists for pharmacological treatment of cannabis use disorders. Cannabidiol could offer a novel treatment, but it is unclear which doses might be efficacious or safe. Therefore, we aimed to identify efficacious doses and eliminate inefficacious doses in a phase 2a trial using an adaptive Bayesian design.
|
The lancet. Psychiatry
| 2,020
| 10
| 0
| 0
|
32,643,116
|
Increased miR-20b Level in High Grade Cervical Intraepithelial Neoplasia.
|
Cervical cancer is a common malignant tumor worldwide ranking fourth in incidence and mortality among females, which was reduced significantly by cytology screening and human papilloma virus (HPV) DNA testing. The specificity of cytology is high; however, the sensitivity is low, in contrast to the HPV DNA testing. Despite the success of these measures, new biomarkers are still considered to aim increasing sensitivity and specificity of screening and diagnosis. Significant alterations in microRNA (miRNA) expression have been detected in several cancers with variable consistency. To investigate the stratification role of miRNAs between normal epithelium and cervical intraepithelial neoplasia (CIN2-3), we screened the expression of 667 miRNAs to identify significant markers (n = 10), out of them 9 miRNAs were applied in the study (miR-20b, -24, -26a, -29b, -99a, -100, -147, -212, -515-3p) along with RNU48 and U6 as the references. To benchmark the miRNAs, 22 paired (tumor-free and tumor tissue pairs) laser microdissection-obtained cervical formalin fixed, paraffin embedded tissue samples were assayed. The expression of miR-20b was 2.4 times higher in CIN2-3 samples as compared to normal tissues (p < 0.0001). In the HPV16-positive subsets of the samples (n = 13), miR-20b showed 2.9-times elevation (p < 0.001), whereas miR-515 was 1.15-times downregulated (p < 0.05) in CIN2-3 as compared to normal tissue. These results suggest the potential value of miR-20b as a statification biomarker in order to differentiate neoplastic and non-tumorous cases.
|
Pathology oncology research : POR
| 2,020
| 10
| 0
| 0
|
30,135,749
|
Internet-delivered cognitive behavioral therapy for posttraumatic stress disorder in international humanitarian aid workers: Study protocol.
|
Humanitarian aid workers are likely to be exposed or witness complex emergencies. Posttraumatic stress disorder (PTSD) is one of the most widespread and most commonly studied mental health problems after exposure to adversities and trauma. However, face-to-face treatment has limited utilization in the resource-constrained settings where humanitarian aid workers often operate. Internet-delivered cognitive behavioral therapy (iCBT) is a treatment option with the potential to improve the access to evidence-based care for humanitarian aid workers. Until now, only a few studies have evaluated iCBT in the treatment of PTSD. No studies have yet explored the feasibility of iCBT for humanitarian aid workers with PTSD. The aim of this study is to investigate the participants' experiences and progress with the treatment, in order to determine whether TELLUS is acceptable for humanitarian aid workers.
|
Internet interventions
| 2,017
| 12
| 0
| 0
|
32,892,719
|
Biportal endoscopic technique in the treatment of spinal stenosis: early clinical experiences and results.
|
Minimally invasive procedures in spine surgery have undergone significant development in recent times. A demand emerged from both surgeons and patients to develop and perform these types of surgeries in order to prevent biomechanical and surgical complications. Our study aimed to present early clinical results of a biportal endoscopy technique in the treatment of degenerative spinal stenosis.
|
Neurological research
| 2,020
| 12
| 0
| 0
|
29,738,958
|
Predictive values and specificity of electroencephalographic findings in autoimmune encephalitis diagnosis.
|
Early diagnosis of autoimmune encephalitis (AE) to not delay treatment is challenging but needed in practice. Most previous evidences of electroencephalographic (EEG) findings in AE were derived from descriptive studies. Given paucity of evidence of specific EEG findings to help with early diagnosis of AE, this study aimed to ascertain specific EEG findings and assess their predictive values in diagnosis of AE.
|
Epilepsy & behavior : E&B
| 2,018
| 7
| 0
| 0
|
33,458,577
|
Alpha-sarcoglycanopathy presenting as myalgia and hyperCKemia in two adults with a long-term follow-up. Case reports.
|
Two patients with a paucisymptomatic hyperckemia underwent a skeletal muscle biopsy and massive gene panel to investigate mutations associated with inherited muscle disorders. In the SGCA gene, sequence analyses revealed a homozygous c.850C > T/p.Arg284Cys in patient 1 and two heterozygous variants (c.739G > A/p.Val247Met and c.850C > T/p.Arg284Cys) in patient 2. Combination of histology and immunofluorence studies showed minimal changes for muscular proteins including the α-sarcoglycan. These two cases highlight the advantages of next-generation sequencing in the differential diagnosis of mild myopathic conditions before considering the more invasive muscle biopsy in sarcoglycanopathies.
|
Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology
| 2,020
| 12
| 0
| 0
|
32,716,133
|
A systematic review of the clinical and genetic characteristics of Chinese patients with cystic fibrosis.
|
To investigate and summarize the clinical and genetic characteristics of Chinese cystic fibrosis (CF) patients to improve clinicians' understanding and decrease the rates of misdiagnosis and missed diagnoses in China.
|
Pediatric pulmonology
| 2,020
| 11
| 0
| 0
|
33,125,571
|
Botulinum toxin therapy of dystonia.
|
Botulinum toxin (BT) is used to treat a large number of muscle hyperactivity syndromes. Its use in dystonia, however, is still one of the most important indications for BT therapy. When BT is injected into dystonic muscles, it produces a peripheral paresis which is localised, well controllable and follows a distinct and predictable time course of around 3 months. Adverse effects are always transient and usually mild, long-term application is safe. With this profile BT can be used to treat cranial dystonia, cervical dystonia and limb dystonia including writer's and musician's cramps. The recent introduction of BT high dose therapy also allows to treat more wide-spread dystonia including segmental and generalised dystonia. BT can easily be combined with other anti-dystonic treatments such as deep brain stimulation and intrathecal baclofen application. Best treatment results are obtained when BT therapy is integrated in the multimodal and long-term 'multilayer concept of treatment of dystonia'. The biggest challenge for the future will be to deliver state of the art BT therapy to all dystonia patients in need, regardless of whether they live in developed countries or beyond.
|
Journal of neural transmission (Vienna, Austria : 1996)
| 2,021
| 4
| 0
| 0
|
33,076,223
|
Validation of the Human-Animal Interaction Scale (HAIS) in Czech Language.
|
Human-Animal interaction (HAI) refers to any contact between humans and animals. Despite the lack of standardized measures of evaluation, one possible tool is the Human Animal Interaction Scale (HAIS). This study aimed to evaluate it in Czech language and to verify its use in clinical settings. One group of participants included 85 non-clinical volunteers; the second included 22 clinical participants, who were hospitalized in a long-term inpatient department All participants filled out the HAIS, the Companion Animal Bonding Scale (CABS) and the Companion Animal Semantic Differential (CASD). The Czech HAIS achieved similarly good psychometric properties as the original scale. The Cronbach's alpha showed strong internal consistency (α = 0.920) in the sample of volunteers, but low internal consistency (α = 0.656) in the group of clinical participants. In non-clinical volunteers, all scales and subscales correlated mutually at the
|
International journal of environmental research and public health
| 2,020
| 10
| 0
| 0
|
32,744,806
|
Synthesis, Computational Studies and Assessment of in Vitro Activity of Squalene Derivatives as Carbonic Anhydrase Inhibitors.
|
We report novel molecules incorporating the nontoxic squalene scaffold and different carbonic anhydrase inhibitors (CAIs). Potent inhibitory action, in the low-nanomolar range, was detected against isoforms hCA II for sulfonamide derivatives, which proved to be selective against this isoform over the tumor-associate hCA IX and XII isoforms. On the other hand, coumarin derivatives showed weak potency but high selectivity against the tumor-associated isoform CA IX. These compounds are interesting candidates for preclinical evaluation in glaucoma or various tumors in which the two enzymes are involved. In addition, an in silico study of inhibitor-bound hCA II revealed extensive interactions with the hydrophobic pocket of the active site and provided molecular insights into the binding properties of these new inhibitors.
|
ChemMedChem
| 2,020
| 11
| 0
| 0
|
33,236,937
|
The effect of visual uncertainty on implicit motor adaptation.
|
Sensorimotor adaptation is influenced by both the size and variance of error information. In the present study, we varied visual uncertainty and error size in a factorial manner and evaluated their joint effect on adaptation, using a feedback method that avoids inherent limitations with standard visuomotor tasks. Uncertainty attenuated adaptation, but only when the error was small. This striking interaction highlights a novel constraint for models of sensorimotor adaptation. Sensorimotor adaptation is driven by sensory prediction errors, the difference between the predicted and actual feedback. When the position of the feedback is made uncertain, motor adaptation is attenuated. This effect, in the context of optimal sensory integration models, has been attributed to the motor system discounting noisy feedback and thus reducing the learning rate. In its simplest form, optimal integration predicts that uncertainty would result in reduced learning for all error sizes. However, these predictions remain untested since manipulations of error size in standard visuomotor tasks introduce confounds in the degree to which performance is influenced by other learning processes such as strategy use. Here, we used a novel visuomotor task that isolates the contribution of implicit adaptation, independent of error size. In two experiments, we varied feedback uncertainty and error size in a factorial manner. At odds with the basic predictions derived from the optimal integration theory, the results show that uncertainty attenuated learning only when the error size was small but had no effect when the error size was large. We discuss possible mechanisms that may account for this interaction, considering how uncertainty may interact with the relevance assigned to the error signal or how the output of the adaptation system in terms of recalibrating the sensorimotor map may be modified by uncertainty.
|
Journal of neurophysiology
| 2,021
| 1
| 0
| 0
|
25,558,208
|
An unusual cause of high peak airway pressure: Interpretation of displayed alarms.
|
Airway pressure monitoring is critical in modern day anesthesia ventilators to detect and warn high or low pressure conditions in the breathing system. We report a scenario leading to unexpectedly very high peak inspiratory pressure in the intraoperative period and describe the mechanism for high priority alarm activation. We also discuss the role of a blocked bacterial filter in causing sustained display of increased airway pressure. This scenario is a very good example for understanding the unique safety feature present in the Dräger ventilators and the attending anesthesiologist must have an adequate knowledge of the functioning and safety feature of the ventilators they are using to interpret the alarms in the perioperative to prevent unnecessary anxiety and intervention.
|
Saudi journal of anaesthesia
| 2,015
| 1
| 0
| 0
|
32,655,149
|
Nest construction and presence do not alter territorial aggression in male threespine stickleback.
|
Constructing a nest within a mating territory provides a clear benefit to the resident, particularly by improving the opportunity to mate. It is unclear whether animals who use nests exclusively for reproductive purposes account for either the effort invested or the resulting increase in mating potential when valuing their territories. We sought to explicitly reveal a nest's added subjective resource value through within-group comparison of aggressive behaviour before and after nest construction. An increase in aggression following construction would indicate that the resident perceives greater subjective value in his territory, and thus values the nest. Threespine stickleback,
|
Animal behaviour
| 2,020
| 8
| 0
| 0
|
26,889,895
|
Commentary: Transdiagnostic neuroscience of child and adolescent mental disorders--differentiating decision-making in attention-deficit/hyperactivity disorder, conduct disorder, depression and anxiety. A commentary on Sonuga-Barke et al. (2016).
|
Sonuga-Barke, Cortese, Fairchild, and Stringaris offer us new insights not only on the neuropsychological processes and neurobiological mechanisms involved in the decision-making process but also how some of the most relevant child mental disorders might impact this process through a very comprehensive review of the pertinent literature. Although it is difficult to select specific points for discussing in a so dense review, I would like to highlight some aspects for 'whetting readers appetite' and seduce them to be in contact with the fascinating neurobiology behind an essential aspect of our lives.
|
Journal of child psychology and psychiatry, and allied disciplines
| 2,016
| 3
| 0
| 0
|
32,599,451
|
MicroRNA-19a-PTEN Axis Is Involved in the Developmental Decline of Axon Regenerative Capacity in Retinal Ganglion Cells.
|
Irreversible blindness from glaucoma and optic neuropathies is attributed to retinal ganglion cells (RGCs) losing the ability to regenerate axons. While several transcription factors and proteins have demonstrated enhancement of axon regeneration after optic nerve injury, mechanisms contributing to the age-related decline in axon regenerative capacity remain elusive. In this study, we show that microRNAs are differentially expressed during RGC development and identify microRNA-19a (miR-19a) as a heterochronic marker; developmental decline of miR-19a relieves suppression of phosphatase and tensin homolog (PTEN), a key regulator of axon regeneration, and serves as a temporal indicator of decreasing axon regenerative capacity. Intravitreal injection of miR-19a promotes axon regeneration after optic nerve crush in adult mice, and it increases axon extension in RGCs isolated from aged human donors. This study uncovers a previously unrecognized involvement of the miR-19a-PTEN axis in RGC axon regeneration, and it demonstrates therapeutic potential of microRNA-mediated restoration of axon regenerative capacity in optic neuropathies.
|
Molecular therapy. Nucleic acids
| 2,020
| 9
| 0
| 0
|
33,875,655
|
Transcriptomic analysis to identify genes associated with selective hippocampal vulnerability in Alzheimer's disease.
|
Selective vulnerability of different brain regions is seen in many neurodegenerative disorders. The hippocampus and cortex are selectively vulnerable in Alzheimer's disease (AD), however the degree of involvement of the different brain regions differs among patients. We classified corticolimbic patterns of neurofibrillary tangles in postmortem tissue to capture extreme and representative phenotypes. We combined bulk RNA sequencing with digital pathology to examine hippocampal vulnerability in AD. We identified hippocampal gene expression changes associated with hippocampal vulnerability and used machine learning to identify genes that were associated with AD neuropathology, including SERPINA5, RYBP, SLC38A2, FEM1B, and PYDC1. Further histologic and biochemical analyses suggested SERPINA5 expression is associated with tau expression in the brain. Our study highlights the importance of embracing heterogeneity of the human brain in disease to identify disease-relevant gene expression.
|
Nature communications
| 2,021
| 4
| 0
| 0
|
33,413,001
|
"Protenuria in SLE: Is it always lupus?".
|
Proteinuria is one of the most typical manifestations of kidney involvement in Systemic Lupus Erythematosus (SLE). We report the case of a 23-year-old woman with a 6-year-long history of SLE presenting with proteinuria after a three-year remission on hydroxychloroquine. Kidney histological examination showed alterations inconsistent with lupus nephritis and suggestive of hydroxychloroquine toxicity or Fabry disease. The latter was confirmed by genetic assay.
|
Lupus
| 2,021
| 4
| 0
| 0
|
33,868,560
|
Acute Cryptogenic Stroke During West Nile Virus Infection: Case Report.
|
West Nile virus is an emerging infection in North America but has not traditionally been associated with acute vascular events. We report a 57-year-old healthy male who developed pharyngitis and a corporeal rash, followed 1 week later by an acute cryptogenic stroke. Following successful endovascular thrombectomy, cerebrospinal fluid analysis revealed acute West Nile virus infection. While severe cases of vasculopathy have been described with flavivirus infection, stroke associated with relatively mild symptoms has not been. Given increasing evidence that viral and bacterial infections of many varieties may be stroke triggers, West Nile virus and other flaviviruses may represent an uncommon but underappreciated trigger of cryptogenic stroke. We review indirect evidence that viral endothelial tropism or a nonspecific peri-infectious inflammatory state may be causative mechanisms.
|
The Neurohospitalist
| 2,021
| 1
| 0
| 0
|
29,057,179
|
Chiari I Malformation and Spinal Cord Ischemia in a Cadaver.
|
With advanced imaging, the Chiari I malformation (CIM) is more frequently diagnosed than in the past when this entity was identified most commonly at autopsy. Herein, we report the rare case of an adult cadaver found not only to have CIM but also adjacent spinal cord ischemia. This case is discussed in the context of chronic compression of the spinal cord by a CIM and the need for close monitoring of these patients.
|
Cureus
| 2,017
| 8
| 0
| 0
|
32,559,008
|
A comparative evaluation of different neuromyelitis optica spectrum disorder sets of criteria.
|
Three different sets of criteria have been proposed for the diagnosis of neuromyelitis optica spectrum disorder (NMOSD). The objective was to compare the specificity, sensitivity and diagnostic accuracy of the three different sets of NMOSD criteria in patients presenting with inflammatory disorders of the central nervous system suggestive of NMOSD.
|
European journal of neurology
| 2,020
| 11
| 0
| 0
|
33,160,275
|
The relationship between perceived stress and emotional distress during the COVID-19 outbreak: Effects of boredom proneness and coping style.
|
The outbreak of a novel coronavirus (COVID-19) pandemic was a great threat to the physical and mental health of the general population. Our research aimed to investigate the relationship between perceived stress and emotional distress during the initial outbreak. Furthermore, potential risks and protective factors, i.e., coping and boredom proneness, of stress-related emotional distress were also explored. Data from 3233 participants in China were collected through an online survey platform during the initial outbreak of the COVID-19 from January 31 to February 9 in 2020. Results showed that higher perceived stress was associated with more emotional distress including depression, fear, compulsion-anxiety, neurasthenia, and hypochondria. Boredom proneness significantly and positively mediated the relationship between perceived stress and emotional distress. Moreover, coping style moderated the stress-emotional distress relationship, i.e., individuals who mainly adopted positive coping strategies suffered fewer symptoms of depression, compulsion-anxiety, and neurasthenia under stress, while negative coping strategies aggravated emotional distress. These results from the present study provide practical value for mental health intervention during the emergent public health events.
|
Journal of anxiety disorders
| 2,021
| 1
| 0
| 0
|
33,534,022
|
The role of delta and theta oscillations during ego-motion in healthy adult volunteers.
|
The successful cortical processing of multisensory input typically requires the integration of data represented in different reference systems to perform many fundamental tasks, such as bipedal locomotion. Animal studies have provided insights into the integration processes performed by the neocortex and have identified region specific tuning curves for different reference frames during ego-motion. Yet, there remains almost no data on this topic in humans.In this study, an experiment originally performed in animal research with the aim to identify brain regions modulated by the position of the head and eyes relative to a translational ego-motion was adapted for humans. Subjects sitting on a motion platform were accelerated along a translational pathway with either eyes and head aligned or a 20° yaw-plane offset relative to the motion direction while EEG was recorded.Using a distributed source localization approach, it was found that activity in area PFm, a part of Brodmann area 40, was modulated by the congruency of translational motion direction, eye, and head position. In addition, an asymmetry between the hemispheres in the opercular-insular region was observed during the cortical processing of the vestibular input. A frequency specific analysis revealed that low-frequency oscillations in the delta- and theta-band are modulated by vestibular stimulation. Source-localization estimated that the observed low-frequency oscillations are generated by vestibular core-regions, such as the parieto-opercular region and frontal areas like the mid-orbital gyrus and the medial frontal gyrus.
|
Experimental brain research
| 2,021
| 4
| 0
| 0
|
33,779,593
|
Measuring Nucleotide Binding to Intact, Functional Membrane Proteins in Real Time.
|
We have developed a method to measure binding of adenine nucleotides to intact, functional transmembrane receptors in a cellular or membrane environment. This method combines expression of proteins tagged with the fluorescent non-canonical amino acid ANAP, and FRET between ANAP and fluorescent (trinitrophenyl) nucleotide derivatives. We present examples of nucleotide binding to ANAP-tagged KATP ion channels measured in unroofed plasma membranes and excised, inside-out membrane patches under voltage clamp. The latter allows for simultaneous measurements of ligand binding and channel current, a direct readout of protein function. Data treatment and analysis are discussed extensively, along with potential pitfalls and artefacts. This method provides rich mechanistic insights into the ligand-dependent gating of KATP channels and can readily be adapted to the study of other nucleotide-regulated proteins or any receptor for which a suitable fluorescent ligand can be identified.
|
Journal of visualized experiments : JoVE
| 2,021
| 3
| 0
| 0
|
32,587,999
|
Reduced odor detection and hedonic changes in asymptomatic university students as SARS-CoV-2 emerged locally.
|
Aerosol droplets have emerged as the primary mode of SARS-Cov-2 transmission and can be spread by infectious asymptomatic/pre-symptomatic persons rendering indicators of latent viral infection essential. Olfactory impairment is now a recognized symptom of COVID-19 and is rapidly becoming one of the most reliable indicators of the disease. We compared olfaction data from asymptomatic students, who were assessed as SARS-CoV-2 was unknowingly spreading locally, to students tested prior to the arrival of the virus. This study was naturalistic by design as testing occurred in the context of four research studies, all of which used the same inclusion/exclusion criteria and the same protocol to objectively assess odor detection, identification, and hedonics with physiological tests. Data from students (Cohort II; N=22) with probable SARS-CoV-2 exposure were compared to students tested just prior to local virus transmission (Cohort I; N=25), and a normative sample of students assessed over the previous four years (N=272). Students in Cohort II demonstrated significantly reduced odor detection sensitivity compared to students in Cohort I (t=2.60; P=.01; d=0.77; CI, 0.17, 1.36), with a distribution skewed towards reduced detection sensitivity (D=0.38; P=.005). Categorically, the exposed group was significantly more likely to have hyposmia (OR=7.74; CI, 3.1, 19.40), particularly the subgroup assessed in the final week before campus closure (OR=13.61; CI, 3.40, 35.66;). The exposed cohort also rated odors as less unpleasant (P<.001, CLES=0.77). A limitation of our study is that participants were not tested for COVID-19 as testing was unavailable in the area. Objective measures of olfaction may detect olfactory impairment in asymptomatic persons who are otherwise unaware of smell loss. The development of cost-effective, objective olfaction tests that could be self-administered regularly could aid in early detection of SARS-CoV-2 exposure, which is vital to combatting this pandemic.
|
medRxiv : the preprint server for health sciences
| 2,020
| 9
| 0
| 0
|
23,348,593
|
Electroencephalogram γ-band activity during the perception of music key levels.
|
An interdisciplinary research field, music perception involves various disciplines, such as psychology, neuroscience, and even physics. Research on music perception offers us a window into the mechanism of the brain. In music perception, the same distance of key shift in different directions tends to be perceived as different degrees of change. It, however, still remains unclear whether directional asymmetry is specific to key shift perception or a general phenomenon of key perception. Using both behavioral and electroencephalogram methods, this study examined Chinese nonmusicians' subjective ratings and electroencephalogram γ-band activity related to a piece of music performed at three different key levels and presented in three separate performances, none of which contained a key shift. This study showed that directional asymmetry is a general phenomenon of key level perception rather than specific to key shift perception. Furthermore, a counterclockwisely modulated key is related to stronger γ-band spectral power than a clockwisely modulated key.
|
Neuroreport
| 2,013
| 3
| 0
| 0
|
32,681,751
|
Predominant and novel de novo variants in 29 individuals with ALG13 deficiency: Clinical description, biomarker status, biochemical analysis, and treatment suggestions.
|
Asparagine-linked glycosylation 13 homolog (ALG13) encodes a nonredundant, highly conserved, X-linked uridine diphosphate (UDP)-N-acetylglucosaminyltransferase required for the synthesis of lipid linked oligosaccharide precursor and proper N-linked glycosylation. De novo variants in ALG13 underlie a form of early infantile epileptic encephalopathy known as EIEE36, but given its essential role in glycosylation, it is also considered a congenital disorder of glycosylation (CDG), ALG13-CDG. Twenty-four previously reported ALG13-CDG cases had de novo variants, but surprisingly, unlike most forms of CDG, ALG13-CDG did not show the anticipated glycosylation defects, typically detected by altered transferrin glycosylation. Structural homology modeling of two recurrent de novo variants, p.A81T and p.N107S, suggests both are likely to impact the function of ALG13. Using a corresponding ALG13-deficient yeast strain, we show that expressing yeast ALG13 with either of the highly conserved hotspot variants rescues the observed growth defect, but not its glycosylation abnormality. We present molecular and clinical data on 29 previously unreported individuals with de novo variants in ALG13. This more than doubles the number of known cases. A key finding is that a vast majority of the individuals presents with West syndrome, a feature shared with other CDG types. Among these, the initial epileptic spasms best responded to adrenocorticotropic hormone or prednisolone, while clobazam and felbamate showed promise for continued epilepsy treatment. A ketogenic diet seems to play an important role in the treatment of these individuals.
|
Journal of inherited metabolic disease
| 2,020
| 11
| 0
| 0
|
32,657,780
|
Interacting hepatic PAI-1/tPA gene regulatory pathways influence impaired fibrinolysis severity in obesity.
|
Fibrinolysis is initiated by tissue-type plasminogen activator (tPA) and inhibited by plasminogen activator inhibitor 1 (PAI-1). In obese humans, plasma PAI-1 and tPA proteins are increased, but PAI-1 dominates, leading to reduced fibrinolysis and thrombosis. To understand tPA-PAI-1 regulation in obesity, we focused on hepatocytes, a functionally important source of tPA and PAI-1 that sense obesity-induced metabolic stress. We showed that obese mice, like humans, had reduced fibrinolysis and increased plasma PAI-1 and tPA, due largely to their increased hepatocyte expression. A decrease in the PAI-1 (SERPINE1) gene corepressor Rev-Erbα increased PAI-1, which then increased the tPA gene PLAT via a PAI-1/LRP1/PKA/p-CREB1 pathway. This pathway was partially counterbalanced by increased DACH1, a PLAT-negative regulator. We focused on the PAI-1/PLAT pathway, which mitigates the reduction in fibrinolysis in obesity. Thus, silencing hepatocyte PAI-1, CREB1, or tPA in obese mice lowered plasma tPA and further impaired fibrinolysis. The PAI-1/PLAT pathway was present in primary human hepatocytes, and associations among PAI-1, tPA, and PLAT in livers from obese and lean humans were consistent with these findings. Knowledge of PAI-1 and tPA regulation in hepatocytes in obesity may suggest therapeutic strategies for improving fibrinolysis and lowering the risk of thrombosis in this setting.
|
The Journal of clinical investigation
| 2,020
| 8
| 0
| 0
|
33,419,453
|
Association between polygenic risk score of Alzheimer's disease and plasma phosphorylated tau in individuals from the Alzheimer's Disease Neuroimaging Initiative.
|
Recent studies suggest that plasma phosphorylated tau181 (p-tau181) is a highly specific biomarker for Alzheimer's disease (AD)-related tau pathology. It has great potential for the diagnostic and prognostic evaluation of AD, since it identifies AD with the same accuracy as tau PET and CSF p-tau181 and predicts the development of AD dementia in cognitively unimpaired (CU) individuals and in those with mild cognitive impairment (MCI). Plasma p-tau181 may also be used as a biomarker in studies exploring disease pathogenesis, such as genetic or environmental risk factors for AD-type tau pathology. The aim of the present study was to investigate the relation between polygenic risk scores (PRSs) for AD and plasma p-tau181.
|
Alzheimer's research & therapy
| 2,021
| 1
| 0
| 0
|
30,174,999
|
Duplication of the Alar Ligaments: A Case Report.
|
The alar ligament is one of the two strongest ligaments stabilizing the craniocervical junction. The literature describes many variations of the attachment, insertion, shape, and orientation of the alar ligament and an understanding of these variations is vital as they can lead to altered biomechanics or misinterpretation on imaging. Herein, we report, to our knowledge, the first case of duplication of the alar ligaments and discuss the anatomical variations present in the literature.
|
Cureus
| 2,018
| 6
| 0
| 0
|
33,303,861
|
Region-specific Foxp2 deletions in cortex, striatum or cerebellum cannot explain vocalization deficits observed in spontaneous global knockouts.
|
FOXP2 has been identified as a gene related to speech in humans, based on rare mutations that yield significant impairments in speech at the level of both motor performance and language comprehension. Disruptions of the murine orthologue Foxp2 in mouse pups have been shown to interfere with production of ultrasonic vocalizations (USVs). However, it remains unclear which structures are responsible for these deficits. Here, we show that conditional knockout mice with selective Foxp2 deletions targeting the cerebral cortex, striatum or cerebellum, three key sites of motor control with robust neural gene expression, do not recapture the profile of pup USV deficits observed in mice with global disruptions of this gene. Moreover, we observed that global Foxp2 knockout pups show substantive reductions in USV production as well as an overproduction of short broadband noise "clicks", which was not present in the brain region-specific knockouts. These data indicate that deficits of Foxp2 expression in the cortex, striatum or cerebellum cannot solely explain the disrupted vocalization behaviours in global Foxp2 knockouts. Our findings raise the possibility that the impact of Foxp2 disruption on USV is mediated at least in part by effects of this gene on the anatomical prerequisites for vocalizing.
|
Scientific reports
| 2,020
| 12
| 0
| 0
|
32,538,485
|
Increasing excitation versus decreasing inhibition in auditory cortex: consequences on the discrimination performance between communication sounds.
|
Enhancing cortical excitability can be achieved by either reducing intracortical inhibition or by enhancing intracortical excitation. Here we compare the consequences of reducing intracortical inhibition and of enhancing intracortical excitation on the processing of communication sounds in the primary auditory cortex. Local application of gabazine and of AMPA enlarged the spectrotemporal receptive fields and increased the responses to communication to the same extent. The Mutual Information (an index of the cortical neurons' ability to discriminate between natural sounds) was increased in both cases, as were the noise and signal correlations. Spike-timing reliability was only increased after gabazine application and post-excitation suppression was affected in the opposite way: it was increased when reducing the intracortical inhibition but was eliminated by enhancing the excitation. A computational model suggests that these results can be explained by an additive effect vs. a multiplicative effect ABSTRACT: The level of excitability of cortical circuits is often viewed as one of the critical factors controlling perceptive performance. In theory, enhancing cortical excitability can be achieved either by reducing inhibitory currents or by increasing excitatory currents. Here, we evaluated whether reducing inhibitory currents or increasing excitatory currents in auditory cortex similarly affects the neurons' ability to discriminate between communication sounds. We attenuated the inhibitory currents by application of gabazine (GBZ), and increased the excitatory currents by applying AMPA in the auditory cortex while testing frequency receptive fields and responses to communication sounds. GBZ and AMPA enlarged the receptive fields and increased the responses to communication sounds to the same extent. The spike-timing reliability of neuronal responses was largely increased when attenuating the intracortical inhibition but not after increasing the excitation. The discriminative abilities of cortical cells increased in both cases but this increase was more pronounced after attenuating the inhibition. The shape of the response to communication sounds was modified in the opposite direction: reducing inhibition increased post-excitation suppression whereas this suppression tended to disappear when increasing the excitation. A computational model indicates that the additive effect promoted by AMPA vs. the multiplicative effect of GBZ on neuronal responses, together with the dynamics of spontaneous cortical activity, can explain these differences. Thus, although apparently equivalent for increasing cortical excitability, acting on inhibition vs. on excitation impacts differently the cortical ability to discriminate natural stimuli, and only modulating inhibition changed efficiently the cortical representation of communication sounds.
|
The Journal of physiology
| 2,020
| 9
| 0
| 0
|
32,404,360
|
Caffeine-Induced Psychosis and a Review of Statutory Approaches to Involuntary Intoxication.
|
Caffeine is the most commonly ingested psychoactive substance in the world. Although caffeine-use disorder is not recognized as a formal diagnosis in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, five disorders related to caffeine use are enumerated therein. An evolving literature suggests that caffeine is one of many licit substances that may cause psychotic symptoms in higher doses. Here, we present a case in which a defendant ingested large quantities of caffeine, which result in transient psychosis and a successful affirmative defense of involuntary intoxication. The purpose of this article is to summarize states' statutory approaches to involuntary intoxication, given that the term is defined variably, if defined at all. Evaluators must be careful to apply jurisdictionally appropriate standards in involuntary intoxication defenses because the bar for this total defense differs across localities.
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The journal of the American Academy of Psychiatry and the Law
| 2,020
| 9
| 0
| 0
|
32,928,526
|
Need for systematic screening for IGD in adolescent psychiatric inpatients.
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Psychiatric comorbidities are frequent in adolescents with internet gaming disorder (IGD). In contrast, the proportion of IGD among adolescents hospitalized for a psychiatric disorder has not been documented yet. In addition, parental ratings of IGD could be useful for diagnosis, but very few data exist on this issue. The objectives of this study were to: (1) assess the prevalence of IGD among adolescent psychiatric inpatients, using the Ten-Item Internet Gaming Disorder Test (IGDT-10), and (2) assess the parental version developed for this study (IGDT-10-P). A total of 102 patients, aged from 12 to 17 years old, were included from four psychiatric units of the French region Auvergne-Rhône-Alpes, during a 6-month inclusion period. Adolescents completed the IGDT-10 while one of their parents completed the IGDT-10-P. The inclusion rate among the eligible population was 57.95%. The prevalence of IGD in the sample, based on the IGDT-10 and IGDT-10-P, was 6.00% and 12.79%, respectively. Psychometric features of the IGDT-10-P indicated excellent internal consistency, a good model fit to the one factor model in confirmatory factor analysis, a strong correlation with gaming time, and a moderate correlation with the IGDT-10. Our results support the need for a systematic screening of IGD among adolescents hospitalized for a psychiatric disorder. Future studies should aim to confirm and explain the prevalence gap between self- and parent-reported criteria.
|
L'Encephale
| 2,020
| 12
| 0
| 0
|
33,172,287
|
Is Timing of Tracheotomy a Factor Influencing the Clinical Course in COVID-19 Patients?
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The timing of tracheotomy is a complex decision that requires understanding of the relative risks and benefits as compared with prolonging intubation. The role of tracheotomy during the COVID-19 pandemic remains to be determined. There is no evidence that early tracheostomy improves patient's clinical course and it is not impact on the natural history of these patients. In our opinion, the tracheotomy should be proposed in stable COVID-19 patients after 18th days after orotracheal intubation when the viral load is finished. Only in the case of patients with difficult of intubation do we perform earlier tracheotomies.
|
Ear, nose, & throat journal
| 2,021
| 4
| 0
| 0
|
29,500,482
|
Correction to: Reducing task-based fMRI scanning time using simultaneous multislice echo planar imaging.
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The original version of this article contained a mistake. The correct Affiliation 2 is Semmelweis University, János Szentágothai PhD School, MR Research Centre, Balassa Street 6, Budapest 1083, Hungary.
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Neuroradiology
| 2,018
| 5
| 0
| 0
|
31,639,356
|
Drosophila Neuroscience: Should I Land or Should I Jump?
|
Information about behavioral states can be integrated in decision-making circuits. In Drosophila, the behavioral state - flying versus not flying - determines whether flies land or jump by dynamically coupling visual information to pre-motor descending neurons.
|
Current biology : CB
| 2,019
| 10
| 0
| 0
|
33,302,777
|
Take a Seat and Get Into Its Shoes! When Humans Spontaneously Represent Visual Scenes From the Point of View of Inanimate Objects.
|
Human description of the surrounding world may spontaneously rely on others' perspective, which is a crucial component of social cognition. In five studies, participants were asked to describe the spatial relations between objects in visual scenes including, or not, other agents. In Experiment 1, a substantial proportion of participants used an other-centered perspective in the presence of another agent, replicating classical findings. To our own surprise, we also observed that an even greater number of participants used an other-centered perspective when the human agent was replaced by an armchair. In order to explore this phenomenon, Experiments 2 to 5 compared the respective strength of chair-centered and agent-centered perspectives and/or set them into conflict. A significant proportion of participants spontaneously took the seat's perspective even when it may not be sat on (Experiments 3 and 4) and even when the seat was not referred to (Experiments 4 and 5). Altogether, these findings suggest that perspective taking may spontaneously apply to inanimate objects. These results question whether such tendencies originate from social cognitive skills-as classically assumed-or reveal a nonsocial phenomenon. Future works should specifically test the widely assumed social nature of spontaneous perspective-taking.
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Perception
| 2,020
| 12
| 0
| 0
|
33,232,577
|
A Guide to Fluorescence Lifetime Microscopy and Förster's Resonance Energy Transfer in Neuroscience.
|
Fluorescence lifetime microscopy (FLIM) and Förster's resonance energy transfer (FRET) are advanced optical tools that neuroscientists can employ to interrogate the structure and function of complex biological systems in vitro and in vivo using light. In neurobiology they are primarily used to study protein-protein interactions, to study conformational changes in protein complexes, and to monitor genetically encoded FRET-based biosensors. These methods are ideally suited to optically monitor changes in neurons that are triggered optogenetically. Utilization of this technique by neuroscientists has been limited, since a broad understanding of FLIM and FRET requires familiarity with the interactions of light and matter on a quantum mechanical level, and because the ultra-fast instrumentation used to measure fluorescent lifetimes and resonance energy transfer are more at home in a physics lab than in a biology lab. In this overview, we aim to help neuroscientists overcome these obstacles and thus feel more comfortable with the FLIM-FRET method. Our goal is to aid researchers in the neuroscience community to achieve a better understanding of the fundamentals of FLIM-FRET and encourage them to fully leverage its powerful ability as a research tool. Published 2020. U.S. Government.
|
Current protocols in neuroscience
| 2,020
| 12
| 0
| 0
|
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