rudyvdbrink/CitationDatabase huggingface dataset:
Charles Prosper Ollivier d'Angers (1796-1845) and his contributions to defining syringomyelia.
Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery, 2011

Distinguished as an anatomist, pathologist, and clinician, the Frenchman Charles Prosper Ollivier d'Angers dedicated his life to accelerating the forefront of neuroscience. At a young age, he explored the diseases and disorders of the spinal cord during a time when clinical neurological investigation scarcely existed. Ollivier d'Angers coined the term "syringomyelia."
Predicting therapeutic efficacy - experimental pain in human subjects.
Brain research reviews, 2009

The pharmaceutical industry faces tough times. Despite tremendous advances in the science and technology of new lead identification and optimization, attrition rates for novel drug candidates making it into the clinic remain unacceptably high. A seamless boundary between basic preclinical and clinical arms of the discovery process, embodying the concept of 'translational research' is viewed by many as the way forward. The rational application of human experimental pain models in early clinical development is reviewed. Capsaicin, UV-irradiation and electrical stimulation methods have each been used to establish experimental hyperalgesia in Phase-I human volunteers and the application of these approaches is discussed in the context of several pharmacological examples. However, data generated from such studies must be integrated into a well-conceived and executed series of Phase-II efficacy trials in patients in order to derive maximal benefit. The challenges involved in optimal Phase-II/III trial design are reviewed with specific attention to the issues of sample size and placebo response. Finally, the application and potential of cortical EEG studies are discussed as an objective alternative to more conventional pain assessment tools with specific examples of how this technique has been applied to the study of NSAID and opiate-based therapeutics.
Deficits in Mitochondrial Spare Respiratory Capacity Contribute to the Neuropsychological Changes of Alzheimer's Disease.
Journal of personalized medicine, 2020

Alzheimer's disease (AD) is diagnosed using neuropsychological testing, supported by amyloid and tau biomarkers and neuroimaging abnormalities. The cause of neuropsychological changes is not clear since they do not correlate with biomarkers. This study investigated if changes in cellular metabolism in AD correlate with neuropsychological changes. Fibroblasts were taken from 10 AD patients and 10 controls. Metabolic assessment included measuring total cellular ATP, extracellular lactate, mitochondrial membrane potential (MMP), mitochondrial respiration and glycolytic function. All participants were assessed with neuropsychological testing and brain structural MRI. AD patients had significantly lower scores in delayed and immediate recall, semantic memory, phonemic fluency and Mini Mental State Examination (MMSE). AD patients also had significantly smaller left hippocampal, left parietal, right parietal and anterior medial prefrontal cortical grey matter volumes. Fibroblast MMP, mitochondrial spare respiratory capacity (MSRC), glycolytic reserve, and extracellular lactate were found to be lower in AD patients. MSRC/MMP correlated significantly with semantic memory, immediate and delayed episodic recall. Correlations between MSRC and delayed episodic recall remained significant after controlling for age, education and brain reserve. Grey matter volumes did not correlate with MRSC/MMP. AD fibroblast metabolic assessment may represent an emergent disease biomarker of AD.
Use of a Mobile Phone App to Treat Depression Comorbid With Hypertension or Diabetes: A Pilot Study in Brazil and Peru.
JMIR mental health, 2019

Depression is underdiagnosed and undertreated in primary health care. When associated with chronic physical disorders, it worsens outcomes. There is a clear gap in the treatment of depression in low- and middle-income countries (LMICs), where specialists and funds are scarce. Interventions supported by mobile health (mHealth) technologies may help to reduce this gap. Mobile phones are widely used in LMICs, offering potentially feasible and affordable alternatives for the management of depression among individuals with chronic disorders.
Body Image in Young Gender Dysphoric Adults: A European Multi-Center Study.
Archives of sexual behavior, 2016

The alteration of sex-specific body features and the establishment of a satisfactory body image are known to be particularly relevant for individuals with Gender Dysphoria (GD). The aim of the study was to first develop new scales and examine the psychometric properties of the Hamburg Body Drawing Scale (Appelt & Strauß 1988). For the second part of this study, the satisfaction with different body features in young GD adults before cross-sex treatment were compared to female and male controls. Data collection took place within the context of the European Network for the Investigation of Gender Incongruence (ENIGI) including 135 female-to-male (FtMs) and 115 male-to-female (MtFs) young GD adults and 235 female and 379 male age-adjusted controls. The five female and six male body feature subscales revealed good internal consistency. The ENIGI sample reported less satisfaction with overall appearance (d = 0.30) and with all of their body features than controls, but no subgroup differences for sexual orientation (FtM and MtF) and Age of Onset (FtM) were found. Body dissatisfaction was higher with regard to sex-specific body features (largest effect sizes of d = 3.21 for Genitalia in FtMs and d = 2.85 for Androgen-responsive features and genitalia in MtFs) than with those that appeared less related to the natal sex (d = 0.64 for Facial features in FtMs and d = 0.59 for Body shape in MtFs). Not only medical body modifying interventions, but also psychosocial guidance with regard to body image might be helpful for GD individuals before transitioning.
Guillain-Barré syndrome mimics.
Brain and behavior, 2018

The Brighton Collaboration criteria have standardized the clinical and laboratory-supported diagnosis of Guillain-Barré syndrome (GBS) and Miller Fisher syndrome (MFS) in a way that is applicable in many parts of the world with variable resources. The caveat within the criteria, "absence of an identified alternative diagnosis for weakness" makes GBS a diagnosis of exclusion. Accurate diagnosis of GBS requires a good understanding of an updated, locally contextualised list of mimics, and features that distinguish them from GBS.
Neural basis of reward anticipation and its genetic determinants.
Proceedings of the National Academy of Sciences of the United States of America, 2016

Dysfunctional reward processing is implicated in various mental disorders, including attention deficit hyperactivity disorder (ADHD) and addictions. Such impairments might involve different components of the reward process, including brain activity during reward anticipation. We examined brain nodes engaged by reward anticipation in 1,544 adolescents and identified a network containing a core striatal node and cortical nodes facilitating outcome prediction and response preparation. Distinct nodes and functional connections were preferentially associated with either adolescent hyperactivity or alcohol consumption, thus conveying specificity of reward processing to clinically relevant behavior. We observed associations between the striatal node, hyperactivity, and the vacuolar protein sorting-associated protein 4A (VPS4A) gene in humans, and the causal role of Vps4 for hyperactivity was validated in Drosophila Our data provide a neurobehavioral model explaining the heterogeneity of reward-related behaviors and generate a hypothesis accounting for their enduring nature.
Personality traits and the risk for Parkinson disease: a prospective study.
European journal of epidemiology, 2016

In this study, we explored the association between the personality traits, neuroticism and introversion, and risk of Parkinson disease (PD). A population-based cohort study was conducted using questionnaire data from the Swedish Twin Registry for twins born 1926-1958 (n > 29,000). Personality traits were assessed in 1973 by a short form of Eysenck's Personality Inventory. The cohort was followed from 1974 to 2012 through Swedish patient and cause of death registers for PD ascertainment. Cox proportional hazards regression was used to estimate subsequent risk of PD, adjusting for attained age, sex and smoking. A mediation analysis was performed to further explore the role of smoking in the relationship between personality trait and PD. Confounding by familial factors was explored using a within-pair analysis. During a mean follow-up time of 36.8 years, 197 incident PD cases were identified. Both neuroticism and introversion were associated with an increased risk of PD after adjustment. Smoking was a significant mediator in the relationship between personality traits and PD that partly accounted for the effect of introversion, whereas it acted as a suppressor for the effect of neuroticism on PD risk. In the within-pair analyses, associations for neuroticism and introversion were attenuated. In conclusion, our study provides evidence that neuroticism is associated with an increased risk of PD that is in part suppressed by smoking. There was a weak association between introversion and PD and this effect was at least partly mediated through smoking. The observed effects may partly be explained by familial factors shared by twins.
Bilateral deep brain stimulation of the subthalamic nucleus effectively relieves dystonia secondary to Fahr's disease: a case report.
The International journal of neuroscience, 2013

Fahr's disease (FD) is a rare movement disorder characterized by bilateral intracranial calcifications that is refractory to most treatments. We present the case of a 26-year-old male with FD who was unable to walk independently and could not eat solid food because of poor swallowing capability and severe cervical dystonia. Injections of botulin toxin into the neck muscles, as well as biperiden, tiapride, amantadine, L-dopa and clonazepam were ineffective. Deep brain stimulation (DBS) was performed with two permanent electrodes containing four contact sites implanted bilaterally into the subthalamic nucleus (STN). The antidystonic effect was evident immediately after STN stimulation, and it was sustained during a 24-month follow-up period. There was a marked reduction of cervical dystonia, and he could eat solid food and was able to walk independently. This case demonstrates that DBS of the STN can be effective for the treatment of dystonia associated with FD.
Rapid Visuomotor Responses Reflect Value-Based Decisions.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2019

Cognitive decision-making is known to be sensitive to the values of potential options, which are the probability and size of rewards associated with different choices. Here, we examine whether rapid motor responses to perturbations of visual feedback about movement, which mediate low-level and involuntary feedback control loops, reflect computations associated with high-level value-based decision-making. In three experiments involving human participants, we varied the value associated with different potential targets for reaching movements by controlling the distributions of rewards across the targets (Experiment 1), the probability with which each target could be specified (Experiment 2), or both (Experiment 3). We found that the size of rapid and involuntary feedback responses to movement perturbations was strongly influenced by the relative value between targets. A statistical model of relative value that includes a term for risk sensitivity provided the best fit to the visuomotor response data, illustrating that feedback control policies are biased to favor more frequent task success at the expense of the overall extrinsic reward accumulated through movement. Importantly however, the regulation of rapid feedback responses was associated with successful pursuit of high-value task outcomes. This implies that when we move, the brain specifies a set of feedback control gains that enable low-level motor areas not only to generate efficient and accurate movement, but also to rapidly and adaptively respond to evolving sensory information in a manner consistent with value-based decision-making.
Comparative immunomodulatory properties of mesenchymal stem cells derived from human breast tumor and normal breast adipose tissue.
Cancer immunology, immunotherapy : CII, 2020

Mesenchymal stem cells (MSCs), one of the most important stromal cells in the tumor microenvironment, play a major role in the immunomodulation and development of tumors. In contrast to immunomodulatory effects of bone marrow-derived MSCs, resident MSCs were not well studied in tumor. The aim of this study was to compare the immunomodulatory properties and protein secretion profiles of MSCs isolated from breast tumor (T-MSC) and normal breast adipose tissue (N-MSC).
Sequential [(18)F]FDG µPET whole-brain imaging of central vestibular compensation: a model of deafferentation-induced brain plasticity.
Brain structure & function, 2016

Unilateral inner ear damage is followed by a rapid behavioural recovery due to central vestibular compensation. In this study, we utilized serial [(18)F]Fluoro-deoxyglucose ([(18)F]FDG)-µPET imaging in the rat to visualize changes in brain glucose metabolism during behavioural recovery after surgical and chemical unilateral labyrinthectomy, to determine the extent and time-course of the involvement of different brain regions in vestibular compensation and test previously described hypotheses of underlying mechanisms. Systematic patterns of relative changes of glucose metabolism (rCGM) were observed during vestibular compensation. A significant asymmetry of rCGM appeared in the vestibular nuclei, vestibulocerebellum, thalamus, multisensory vestibular cortex, hippocampus and amygdala in the acute phase of vestibular imbalance (4 h). This was followed by early vestibular compensation over 1-2 days where rCGM re-balanced between the vestibular nuclei, thalami and temporoparietal cortices and bilateral rCGM increase appeared in the hippocampus and amygdala. Subsequently over 2-7 days, rCGM increased in the ipsilesional spinal trigeminal nucleus and later (7-9 days) rCGM increased in the vestibulocerebellum bilaterally and the hypothalamus and persisted in the hippocampus. These systematic dynamic rCGM patterns during vestibular compensation, were confirmed in a second rat model of chemical unilateral labyrinthectomy by serial [(18)F]FDG-µPET. These findings show that deafferentation-induced plasticity after unilateral labyrinthectomy involves early mechanisms of re-balancing predominantly in the brainstem vestibular nuclei but also in thalamo-cortical and limbic areas, and indicate the contribution of spinocerebellar sensory inputs and vestibulocerebellar adaptation at the later stages of behavioural recovery.
Distinct microglial and macrophage distribution patterns in the concentric and lamellar lesions in Baló's disease and neuromyelitis optica spectrum disorders.
Brain pathology (Zurich, Switzerland), 2020

TMEM119 and purinergic receptor P2Y12 (P2RY12), which are not expressed by recruited peripheral blood macrophages, are proposed to discriminate microglia from macrophages. Therefore, we investigated the distribution patterns of microglia and macrophages in 10 concentric lesions from four autopsied Baló's disease cases and one neuromyelitis optica spectrum disorder (NMOSD) case, using quantitative immunohistochemistry for the markers TMEM119, P2RY12, CD68, CD163 and GLUT5. Three cases with Baló's disease had distal oligodendrogliopathy (DO) showing preferential loss of myelin-associated glycoprotein and early active demyelination in the outermost demyelinating layer (termed DMY-MO). In DMY-MO with DO, TMEM119-positive activated microglia expressing upregulated GLUT5 but markedly downregulated P2RY12 were significantly increased. These activated microglia expressed inducible nitric oxide synthase. Oligodendrocytes and their precursors showed apoptotic-like nuclear condensation in DMY-MO. TMEM119-negative and CD68/CD163-positive macrophages were distributed throughout the lesion center of DMY-MO with DO and these cells demonstrated foamy morphology only in the inner portion but not in the outer portion. In concentric demyelinating lesions from another Baló's case and lamellar demyelinating lesions in an NMOSD case, which had late active demyelination without DO, the densities of TMEM119-, GLUT5- and P2RY12-positive microglia with ramified morphology were significantly increased in myelinated layers but not in demyelinating layers. In particular, in the NMOSD case, TMEM119-positive microglia were confined to the outer portion of the myelinated layers. CD68-positive macrophages with foamy morphology also expressing CD163 accumulated in myelinated as well as in demyelinated layers. These findings suggest that activated microglia expressing TMEM119 and GLUT5, but not P2RY12, are associated with apoptosis of oligodendrocytes in the leading edge of Baló's concentric lesions with DO, whereas TMEM119-, GLUT5- and P2RY12-positive microglia with ramified morphology are associated with myelin preservation in concentric lesions without DO in Baló's disease and NMOSD. These two types of microglia appear to play distinct roles in the formation of concentric lesions.
Clinical significance of REM sleep behavior disorder in Parkinson's disease.
Sleep medicine, 2013

Rapid eye movement (REM) sleep behavior disorder (RBD) may be a risk factor for dementia development in patients with Parkinson's disease (PD); however, the role of subclinical RBD remains unknown. Patients with PD and clinical RBD, subclinical RBD, or with normal REM sleep were examined in a cross sectional study and a longitudinal follow-up.
Emergence of population bursts from simultaneous activation of small subsets of preBötzinger complex inspiratory neurons.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013

During rhythmic movements, central pattern generators (CPGs) trigger bursts of motor activity with precise timing. However, the number of neurons that must be activated within CPGs to generate motor output is unknown. In the mammalian breathing rhythm, a fundamentally important motor behavior, the preBötzinger Complex (preBötC) produces synchronous population-wide bursts of activity to control inspiratory movements. We probed mechanisms underlying inspiratory burst generation in the preBötC using holographic photolysis of caged glutamate in medullary slices from neonatal mice. With stimulation parameters determined to confine photoactivation to targeted neurons, simultaneous excitation of 4-9 targeted neurons could initiate ectopic, endogenous-like bursts with delays averaging 255 ms, placing a critical and novel boundary condition on the microcircuit underlying respiratory rhythmogenesis.
Leisure time physical activity reduces the association between TV-viewing and depressive symptoms: A large study among 59,401 Brazilian adults.
Journal of affective disorders, 2019

Both physical activity (PA) and TV-viewing are associated with depressive symptoms, but the combined association with depressive symptoms is unclear. Therefore, our aim was to analyze the joint association of PA and TV-viewing with depressive symptoms among a large cohort of adults.
Antibody neutralization poses a barrier to intravitreal adeno-associated viral vector gene delivery to non-human primates.
Gene therapy, 2015

Gene delivery vectors based on adeno-associated viruses (AAV) have exhibited promise in both preclinical disease models and human clinical trials for numerous disease targets, including the retinal degenerative disorders Leber's congenital amaurosis and choroideremia. One general challenge for AAV is that preexisting immunity, as well as subsequent development of immunity following vector administration, can severely inhibit systemic AAV vector gene delivery. However, the role of neutralizing antibodies (NABs) in AAV transduction of tissues considered to be immune privileged, such as the eye, is unclear in large animals. Intravitreal AAV administration allows for broad retinal delivery, but is more susceptible to interactions with the immune system than subretinal administration. To assess the effects of systemic anti-AAV antibody levels on intravitreal gene delivery, we quantified the anti-AAV antibodies present in sera from non-human primates before and after intravitreal injections with various AAV capsids. Analysis showed that intravitreal administration resulted in an increase in anti-AAV antibodies regardless of the capsid serotype, transgene or dosage of virus injected. For monkeys injected with wild-type AAV2 and/or an AAV2 mutant, the variable that most significantly affected the production of anti-AAV2 antibodies was the amount of virus delivered. In addition, post-injection antibody titers were highest against the serotype administered, but the antibodies were also cross-reactive against other AAV serotypes. Furthermore, NAB levels in serum correlated with those in vitreal fluid, demonstrating both that this route of administration exposes AAV capsid epitopes to the adaptive immune system and that serum measurements are predictive of vitreous fluid NAB titers. Moreover, the presence of preexisting NAB titers in the serum of monkeys correlated strongly (R=0.76) with weak, decaying or no transgene expression following intravitreal administration of AAV. Investigating anti-AAV antibody development will aid in understanding the interactions between gene therapy vectors and the immune system during ocular administration and can form a basis for future clinical studies applying intravitreal gene delivery.
Molecular mechanisms of epilepsy.
Nature neuroscience, 2015

Decades of experimental work have established an imbalance of excitation and inhibition as the leading mechanism of the transition from normal brain function to seizure. In epilepsy, these transitions are rare and abrupt. Transition processes incorporating positive feedback, such as activity-dependent disinhibition, could provide these uncommon timing features. A rapidly expanding array of genetic etiologies will help delineate the molecular mechanism(s). This delineation will entail quite a bit of cell biology. The genes discovered so far are more remarkable for their diversity than their similarities.
Dendrite branching and self-avoidance are controlled by Turtle, a conserved IgSF protein in Drosophila.
Development (Cambridge, England), 2009

The dendritic trees of neurons result from specific patterns of growth and branching, and dendrite branches of the same neuron avoid one another to spread over a particular receptive field. Recognition molecules on the surfaces of dendrites influence these patterning and avoidance processes by promoting attractive, repulsive or adhesive responses to specific cues. The Drosophila transmembrane protein Turtle (Tutl) and its orthologs in other species are conserved members of the immunoglobulin superfamily, the in vivo functions of which are unknown. In Drosophila sensory neurons, we show that the tutl gene is required to restrain dendrite branch formation in neurons with simple arbors, and to promote dendrite self-avoidance in neurons with complex arbors. The cytoplasmic tail of Tutl is dispensable for control of dendrite branching, suggesting that Tutl acts as a ligand or co-receptor for an unidentified recognition molecule to influence the architecture of dendrites and their coverage of receptive territories.