rudyvdbrink/CitationDatabase huggingface dataset:
Outcome prediction models in AQP4-IgG positive neuromyelitis optica spectrum disorders.
Brain : a journal of neurology, 2019

Pathogenic antibodies targeting the aquaporin-4 water channel on astrocytes are associated with relapsing inflammatory neuromyelitis optica spectrum disorders. The clinical phenotype is characterized by recurrent episodes of optic neuritis, longitudinally extensive transverse myelitis, area postrema attacks and less common brainstem and cerebral events. Patients often develop major residual disability from these attacks, so early diagnosis and initiation of attackpreventing medications is important. Accurate prediction of relapse would assist physicians in counselling patients, planning treatment and designing clinical trials. We used a large multicentre dataset of 441 patients from the UK, USA, Japan and Martinique who collectively experienced 1976 attacks, and applied sophisticated mathematical modelling to predict likelihood of relapse and disability at different time points. We found that Japanese patients had a lower risk of subsequent attacks except for brainstem and cerebral events, with an overall relative relapse risk of 0.681 (P = 0.001) compared to Caucasians and African patients, who had a higher likelihood of cerebral attacks, with a relative relapse risk of 3.309 (P = 0.009) compared to Caucasians. Female patients had a higher chance of relapse than male patients (P = 0.009), and patients with younger age of onset were more likely to have optic neuritis relapses (P < 0.001). Immunosuppressant drugs reduced and multiple sclerosis disease-modifying agents increased the likelihood of relapse (P < 0.001). Patients with optic neuritis at onset were more likely to develop blindness (P < 0.001), and those with older age of onset were more likely to develop ambulatory disability. Only 25% of long-term disability was related to initial onset attack, indicating the importance of early attack prevention. With respect to selection of patients for clinical trial design, there would be no gain in power by selecting recent onset patients and only a small gain by selecting patients with recent high disease activity. We provide risk estimates of relapse and disability for patients diagnosed and treated with immunosuppressive treatments over the subsequent 2, 3, 5 and 10 years according to type of attack at onset or the first 2-year course, ethnicity, sex and onset age. This study supports significant effects of onset age, onset phenotype and ethnicity on neuromyelitis optica spectrum disorders outcomes. Our results suggest that powering clinical treatment trials based upon relapse activity in the preceding 2 years may offer little benefit in the way of attack risk yet severely hamper clinical trial success.
Disruption of GABA(A)-mediated intracortical inhibition in patients with chorea-acanthocytosis.
Neuroscience letters, 2017

Chorea-acanthocytosis (Ch-Ac) is an autosomal recessive neurodegenerative disorder characterized by adult-onset chorea, acanthocytes in the peripheral blood, and Huntington's disease-like neuropsychiatric symptoms. Animal studies have shown mutation-related dysregulated cortical gamma-aminobutyric acid (GABA)ergic inhibitory networks in its pathophysiology. Herein we found that in patients with Ch-Ac there is a striking alteration of intracortical inhibitory circuits detected by using paired pulse transcranial magnetic stimulation protocols. Our findings show in vivo the functional disruption of GABA(A)-mediated networks in humans with Ch-Ac supporting the existing data in mice models with this condition.
Role of glutamate receptors in tetrabrominated diphenyl ether (BDE-47) neurotoxicity in mouse cerebellar granule neurons.
Toxicology letters, 2016

The polybrominated diphenyl ether (PBDE) flame retardants are developmental neurotoxicants, as evidenced by numerous in vitro, animal and human studies. PBDEs can alter the homeostasis of thyroid hormone and directly interact with brain cells. Induction of oxidative stress, leading to DNA damage and apoptotic cell death is a prominent mechanism of PBDE neurotoxicity, though other mechanisms have also been suggested. In the present study we investigated the potential role played by glutamate receptors in the in vitro neurotoxicity of the tetrabromodiphenyl ether BDE-47, one of the most abundant PBDE congeners. Toxicity of BDE-47 in mouse cerebellar neurons was diminished by antagonists of glutamate ionotropic receptors, but not by antagonists of glutamate metabotropic receptors. Antagonists of NMDA and AMPA/Kainate receptors also inhibited BDE-47-induced oxidative stress and increases in intracellular calcium. The calcium chelator BAPTA-AM also inhibited BDE-47 cytotoxicity and oxidative stress. BDE-47 caused a rapid increase of extracellular glutamate levels, which was not antagonized by any of the compounds tested. The results suggest that BDE-47, by still unknown mechanisms, increases extracellular glutamate which in turn activates ionotropic glutamate receptors leading to increased calcium levels, oxidative stress, and ultimately cell death.
Stigmatisation of those with mental health conditions in the acute general hospital setting. A qualitative framework synthesis.
Social science & medicine (1982), 2020

Patients with long-term mental health conditions often have complex physical, mental, and social needs. They are frequent users of the acute general healthcare system, but can experience stigmatising attitudes and behaviours, and structural discrimination. We wished to improve understanding of stigmatisation in the acute healthcare setting, to target areas for future intervention.
The somatosensory cortex of reeler mutant mice shows absent layering but intact formation and behavioral activation of columnar somatotopic maps.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010

Sensory information acquired via the large facial whiskers is processed and relayed in the whisker-to-barrel pathway, which shows multiple somatotopic maps of the receptor periphery. These maps consist of individual structural modules, the development of which may require intact cortical lamination. In the present study we examined the whisker-to-barrel pathway in the reeler mouse and thus used a model with disturbed cortical organization. A combination of histological (fluorescent Nissl and cytochrome oxidase staining) as well as molecular methods (c-Fos and laminar markers Rgs8, RORB, and ER81 expression) revealed wild type-equivalent modules in reeler. At the neocortical level, however, we found extensive alterations in the layout of the individual modules of the map. Nevertheless, they showed a columnar organization that included compartments equivalent to those of their wild-type counterparts. Moreover, all examined modules showed distinct activation as a consequence of behavioral whisker stimulation. Analysis of the magnitude of the cortical lamination defect surprisingly revealed an extensive disorganization, rather than an inversion, as assumed previously. Striking developmental plasticity of thalamic innervation, as suggested by vGluT2 immunohistochemistry, seems to ensure the proper formation of columnar modules and topological maps even under highly disorganized conditions.
REM Sleep Behavioral Events and Dreaming.
Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine, 2015

To clarify whether motor behaviors and/ or vocalizations during REM sleep, which do not yet fulfill diagnostic criteria for REM sleep behavior disorder (RBD) and were defined as REM sleep behavioral events (RBEs), correspond to dream enactments.
Transitional and translational studies of risk for anxiety.
Depression and anxiety, 2011

Adolescence reflects a period of increased rates of anxiety, depression, and suicide. Yet most teens emerge from this period with a healthy, positive outcome. In this article, we identify biological factors that may increase risk for some individuals during this developmental period by: (1) examining changes in neural circuitry underlying core phenotypic features of anxiety as healthy individuals transition into and out of adolescence; (2) examining genetic factors that may enhance the risk for psychopathology in one individual over another using translation from mouse models to human neuroimaging and behavior; and (3) examining the effects of early experiences on core phenotypic features of anxiety using human neuroimaging and behavioral approaches. Each of these approaches alone provides only limited information on genetic and environmental influences on complex human behavior across development. Together, they reflect an emerging field of translational developmental neuroscience in forming important bridges between animal models of neurodevelopmental and neuropsychiatric disorders.
Early social experience is critical for the development of cognitive control and dopamine modulation of prefrontal cortex function.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2013

Social experiences during youth are thought to be critical for proper social and cognitive development. Conversely, social insults during development can cause long-lasting behavioral impairments and increase the vulnerability for psychopathology later in life. To investigate the importance of social experience during the juvenile and early adolescent stage for the development of cognitive control capacities, rats were socially isolated from postnatal day 21 to 42 followed by re-socialization until they reached adulthood. Subsequently, two behavioral dimensions of impulsivity (impulsive action in the five-choice serial reaction time task (5-CSRTT) and impulsive choice in the delayed reward task) and decision making (in the rat gambling task) were assessed. In a separate group of animals, long-lasting cellular and synaptic changes in adult medial prefrontal cortex (PFC) pyramidal neurons were determined following social isolation. Juvenile and early adolescent social isolation resulted in impairments in impulsive action and decision making under novel or challenging circumstances. Moreover, socially isolated rats had a reduced response to enhancement of dopaminergic neurotransmission (using amphetamine or GBR12909) in the 5-CSRTT under challenging conditions. Impulsive choice was not affected by social isolation. These behavioral deficits were accompanied by a loss of sensitivity to dopamine of pyramidal neurons in the medial PFC. Our data show long-lasting deleterious effects of early social isolation on cognitive control and its neural substrates. Alterations in prefrontal cognitive control mechanisms may contribute to the enhanced risk for psychiatric disorders induced by aberrations in the early social environment.
Primary food reward and reward-predictive stimuli evoke different patterns of phasic dopamine signaling throughout the striatum.
The European journal of neuroscience, 2011

Phasic changes in dopamine activity play a critical role in learning and goal-directed behavior. Unpredicted reward and reward-predictive cues evoke phasic increases in the firing rate of the majority of midbrain dopamine neurons--results that predict uniformly broadcast increases in dopamine concentration throughout the striatum. However, measurement of dopamine concentration changes during reward has cast doubt on this prediction. We systematically measured phasic changes in dopamine in four striatal subregions [nucleus accumbens shell and core (Core), dorsomedial (DMS) and dorsolateral striatum] in response to stimuli known to activate a majority of dopamine neurons. We used fast-scan cyclic voltammetry in awake and behaving rats, which measures changes in dopamine on a similar timescale to the electrophysiological recordings that established a relationship between phasic dopamine activity and reward. Unlike the responses of midbrain dopamine neurons, unpredicted food reward and reward-predictive cues evoked a phasic increase in dopamine that was subregion specific. In rats with limited experience, unpredicted food reward evoked an increase exclusively in the Core. In rats trained on a discriminative stimulus paradigm, both unpredicted reward and reward-predictive cues evoked robust phasic dopamine in the Core and DMS. Thus, phasic dopamine release in select target structures is dynamic and dependent on context and experience. Because the four subregions assayed receive different inputs and have differential projection targets, the regional selectivity of phasic changes in dopamine has important implications for information flow through the striatum and plasticity that underlies learning and goal-directed behavior.
Two conventional protein kinase C isoforms, alpha and beta I, are involved in the ATP-induced activation of volume-regulated anion channel and glutamate release in cultured astrocytes.
Journal of neurochemistry, 2008

Volume-regulated anion channels (VRACs) are activated by cell swelling and are permeable to inorganic and small organic anions, including the excitatory amino acids glutamate and aspartate. In astrocytes, ATP potently enhances VRAC activity and glutamate release via a P2Y receptor-dependent mechanism. Our previous pharmacological study identified protein kinase C (PKC) as a major signaling enzyme in VRAC regulation by ATP. However, conflicting results obtained with potent PKC blockers prompted us to re-evaluate the involvement of PKC in regulation of astrocytic VRACs by using small interfering RNA (siRNA) and pharmacological inhibitors that selectively target individual PKC isoforms. In primary rat astrocyte cultures, application of hypoosmotic medium (30% reduction in osmolarity) and 20 microM ATP synergistically increased the release of excitatory amino acids, measured with a non-metabolized analog of L-glutamate, D-[(3)H]aspartate. Both Go6976, the selective inhibitor of Ca(2+)-sensitive PKCalpha, betaI/II, and gamma, and MP-20-28, a cell permeable pseudosubstrate inhibitory peptide of PKCalpha and betaI/II, reduced the effects of ATP on D-[(3)H]aspartate release by approximately 45-55%. Similar results were obtained with a mixture of siRNAs targeting rat PKCalpha and betaI. Surprisingly, down-regulation of individual alpha and betaI PKC isozymes by siRNA was completely ineffective. These data suggest that ATP regulates VRAC activity and volume-sensitive excitatory amino acid release via cooperative activation of PKCalpha and betaI.
Neurite architecture of the planum temporale predicts neurophysiological processing of auditory speech.
Science advances, 2018

The left hemispheric advantage in speech perception is reflected in faster neurophysiological processing. On the basis of postmortem data, it has been suggested that asymmetries in the organization of the intrinsic microcircuitry of the posterior temporal lobe may produce this leftward timing advantage. However, whether this hypothetical structure-function relationship exists in vivo has never been empirically validated. To test this assumption, we used in vivo neurite orientation dispersion and density imaging to quantify microcircuitry in terms of axon and dendrite complexity of the left and right planum temporale in 98 individuals. We found that a higher density of dendrites and axons in the temporal speech area is associated with faster neurophysiological processing of auditory speech, as reflected by electroencephalography. Our results imply that a higher density and higher number of synaptic contacts in the left posterior temporal lobe increase temporal precision and decrease latency of neurophysiological processes in this brain region.
Site-specific hydrogen sulfide-mediated central regulation of respiratory rhythm in medullary slices of neonatal rats.
Neuroscience, 2013

Hydrogen sulfide (H₂S) is involved in central regulation of respiratory rhythm at the level of the medulla oblongata. The present study was carried out to test our hypothesis that H₂S exerts site-specific regulatory action on respiratory rhythm in the medulla oblongata of neonatal rats. The rhythmic discharge of hypoglossal rootlets in medullary slices of neonatal rats was recorded. 200 μM NaHS (an H₂S donor) increased burst frequency (BF) in 900-μm slices containing the pre-Bötzinger complex (preBötC), whereas it caused diphasic responses in 1200-, 1400- and 1800-μm slices containing both the preBötC and part or all of the parafacial respiratory group (pFRG): an initial decrease in BF followed by an increase. The initial decrease in BF was no longer observed after unilateral lesion of the pFRG region in the 1400-μm slices. In addition, BF was increased by a unilateral micro-injection of NaHS into the preBötC region, but was decreased by an injection into the pFRG region. These data support our hypothesis that the regulatory action of H₂S on respiratory rhythm in the medulla oblongata is site-specific. The excitatory effect is caused by the preBötC, while the inhibitory effect is from the pFRG.
Surgical results of cranioplasty with a polymethylmethacrylate customized cranial implant in pediatric patients: a single-center experience.
Journal of neurosurgery. Pediatrics, 2016

OBJECTIVE Cranioplasty is a reconstructive procedure used to restore skull anatomy and repair skull defects. Optimal skull reconstruction is a challenge for neurosurgeons, and the strategy used to achieve the best result remains a topic of debate, especially in pediatric patients for whom the continuing skull growth makes the choice of material more difficult. When the native bone flap, which is universally accepted as the preferred option in pediatric patients, is unavailable, the authors' choice of prosthetic material is a polymethylmethacrylate (PMMA) implant designed using a custom-made technique. In this paper the authors present the results of their clinical series of 12 custom-made PMMA implants in pediatric patients. METHODS A retrospective study of the patients who had undergone cranioplasty at Gaslini Children's Hospital between 2006 and 2013 was conducted. A total of 12 consecutive cranioplasties in 12 patients was reviewed, in which a patient-specific PMMA implant was manufactured using a virtual 3D model and then transformed into a physical model using selective laser sintering or 3D printing. All patients or parents were administered a questionnaire to assess how the patient/parent judged the aesthetic result. RESULTS Patient age at craniectomy ranged from 5 months to 12.5 years, with a mean age of 84.33 months at cranioplasty. The mean extension of the custom-made plastic was 56.83 cm(2). The mean time between craniectomy and cranioplasty was 9.25 months. The mean follow-up duration was 55.7 months. No major complications were recorded; 3 patients experienced minor/moderate complications (prosthesis dislocation, granuloma formation, and fluid collection). CONCLUSIONS In this patient series, PMMA resulted in an extremely low complication rate and the custom-made technique was associated with an excellent grade of patient or parent satisfaction on long-term follow up.
TLR2 stimulation regulates the balance between regulatory T cell and Th17 function: a novel mechanism of reduced regulatory T cell function in multiple sclerosis.
Journal of immunology (Baltimore, Md. : 1950), 2015

CD4(+)CD25(hi) FOXP3(+) regulatory T cells (Tregs) maintain tolerance to self-Ags. Their defective function is involved in the pathogenesis of multiple sclerosis (MS), an inflammatory demyelinating disease of the CNS. However, the mechanisms of such defective function are poorly understood. Recently, we reported that stimulation of TLR2, which is preferentially expressed by human Tregs, reduces their suppressive function and skews them into a Th17-like phenotype. In this study, we tested the hypothesis that TLR2 activation is involved in reduced Treg function in MS. We found that Tregs from MS patients expressed higher levels of TLR2 compared with healthy controls, and stimulation with the synthetic lipopeptide Pam3Cys, an agonist of TLR1/2, reduced Treg function and induced Th17 skewing in MS patient samples more than in healthy controls. These data provide a novel mechanism underlying diminished Treg function in MS. Infections that activate TLR2 in vivo (specifically through TLR1/2 heterodimers) could shift the Treg/Th17 balance toward a proinflammatory state in MS, thereby promoting disease activity and progression.
Visual attention is not limited to the oculomotor range.
Proceedings of the National Academy of Sciences of the United States of America, 2019

Both patients with eye movement disorders and healthy participants whose oculomotor range had been experimentally reduced have been reported to show attentional deficits at locations unreachable by their eyes. Whereas previous studies were mainly based on the evaluation of reaction times, we measured visual sensitivity before saccadic eye movements and during fixation at locations either within or beyond participants' oculomotor range. Participants rotated their heads to prevent them from performing large rightward saccades. In this posture, an attentional cue was presented inside or outside their oculomotor range. Participants either made a saccade to the cue or maintained fixation while they discriminated the orientation of a visual noise patch. In contrast to previous reports, we found that the cue attracted visual attention regardless of whether it was presented within or beyond participants' oculomotor range during both fixation and saccade preparation. Moreover, when participants aimed to look to a cue that they could not reach with their eyes, we observed no benefit at their actual saccade endpoint. This demonstrates that spatial attention is not coupled to the executed oculomotor program but instead can be deployed unrestrictedly also toward locations to which no saccade can be executed. Our results are compatible with the view that covert and overt attentional orienting are guided by feedback projections of visual and visuomotor neurons of the gaze control system, irrespective of oculomotor limitations.
Moral distress in neuroscience nursing: an evolutionary concept analysis.
The Journal of neuroscience nursing : journal of the American Association of Neuroscience Nurses, 2012

Moral distress has been explored within a number of nursing contexts, including critical care, neuroscience, and end-of-life decision making. Although the antecedents and consequences of this concept continue to be uncovered, its unique attributes remain ambiguous. This analysis aims to clarify the concept of moral distress, contribute new insights about moral distress to nursing as a whole and to the subspecialty of neuroscience nursing in particular, and enhance advancements in nursing knowledge and practice. Literature published in English between 1987 and 2009 was searched using the Cumulative Index to Nursing and Allied Health Literature and Google Scholar databases. Eleven journal articles were used in the final analysis. Rodgers' evolutionary model of concept analysis was used in this study. Four comprehensive attributes were formulated to describe moral distress in neuroscience nursing: negative feelings, powerlessness, conflicting loyalties, and uncertainty. These attributes are intimately related, holding true meaning only when viewed within the context of one another and with respect to the historical and philosophical underpinnings of nursing praxis. This analysis demonstrates the fluidity, complexity, and multifacetedness of moral distress. Knowledge of the conceptual attributes presented herein will facilitate recognition and validation of personal experiences within the neuroscience nursing community.