rudyvdbrink/CitationDatabase huggingface dataset:
Transient receptor potential vanilloid 1, vanilloid 2 and melastatin 8 immunoreactive nerve fibers in human skin from individuals with and without Norrbottnian congenital insensitivity to pain.
Neuroscience, 2009

Transient receptor potential vanilloid 1 (TRPV1), vanilloid 2 (TRPV2) and melastatin 8 (TRPM8) are thermosensitive cation channels expressed on primary sensory neurons. In contrast to TRPV1, which is present on nociceptive primary afferents and keratinocytes in human skin, less is known about the distribution of TRPV2 and TRPM8 in this tissue. Immunohistochemistry of human forearm skin identified TRPV2 and TRPM8 immunoreactive nerve fibers in epidermis-papillary dermis and around blood vessels and hair follicles in dermis, although these nerve fibers were less abundant than TRPV1 immunoreactive nerve fibers throughout the skin. The TRPV2 and TRPM8 immunoreactive nerve fibers also showed immunoreactivity for calcitonin gene-related peptide (CGRP) and to a lesser extent substance P (SP). Neither of the TRP ion channels co-localized with neurofilament 200 kDa (NF200), vasoactive intestinal peptide (VIP) or tyrosine hydroxylase (TH). Nerve fibers immunoreactive for TRPV1, TRPV2, TRPM8, CGRP and SP were absent or substantially reduced in number in individuals with Norrbottnian congenital insensitivity to pain, an autosomal disease selectively affecting the development of C-fiber and Adelta-fiber primary afferents. Quantitative real time PCR detected mRNA transcripts encoding TRPV1 and TRPV2, but not TRPM8, in skin from healthy volunteers, suggesting that these ion channels are also expressed extraneuronally. In conclusion, nerve fibers in human skin express TRPV1, TRPV2 and TRPM8 that co-localize with the sensory neuropeptides CGRP and SP, but not with NF200, VIP or TH. A dramatic loss of such nerve fibers was seen in skin from individuals with Norrbottnian congenital insensitivity to pain, further suggesting that these ion channels are expressed primarily on nociceptive primary sensory neurons in human skin.
A 3D neurovascular microfluidic model consisting of neurons, astrocytes and cerebral endothelial cells as a blood-brain barrier.
Lab on a chip, 2017

The neurovascular unit is a complex, interdependent system composed of neurons and neural supporting cells, such as astrocytes, as well as cells that comprise the vascular system including endothelial cells, pericytes, and smooth muscle cells. Each cell type in the neurovascular unit plays an essential role, either in transmitting and processing neural signals or in maintaining the appropriate microenvironmental conditions for healthy neural function. In vitro neurovascular models can be useful for understanding the different roles and functions of the cells composing the neurovascular unit, as well as for assessing the effects on neural function of therapeutic compounds after crossing the endothelial barrier. Here, we report a novel three-dimensional neurovascular microfluidic model consisting of primary rat astrocytes and neurons together with human cerebral microvascular endothelial cells. These three cell types in our neurovascular chip (NVC) show distinct cell type-specific morphological characteristics and functional properties. In particular, morphological and functional analysis of neurons enables quantitative assessment of neuronal responses, while human cerebral endothelial cells form monolayers with size-selective permeability similar to existing in vitro blood-brain barrier (BBB) models.
Foundational Elements of School-Specific Augmented Medical Education.
Medical science educator, 2019

Recent efforts to enrich the medical education experience recommended interinstitutional and collaborative efforts. Within this context, the author describes a model for school-specific augmented medical education. The evidence-backed conceptual model is composed of six foundational elements, which include the following: technology-enriched learning environments, analytics to drive instructional interventions, cognitive neuroscience and educational psychology research (the Science of Learning), self-regulated learning strategies, competency-based approaches, and blended learning instructional design. Harnessing the creativity of our leadership, medical educators, and learners is fundamental to improving the learning experience for all. This model could be used to meaningfully guide implementation processes.
Randomized trial of custom orthoses and footwear on foot pain and plantar pressure in diabetic peripheral arterial disease.
Diabetic medicine : a journal of the British Diabetic Association, 2009

Custom-made foot orthoses reduce plantar pressure, ulceration and amputation in patients with diabetes mellitus. There is limited evidence of their effect on foot pain. In a randomized, single-blind, sham-controlled trial, the efficacy of custom orthoses on foot pain and plantar pressure in diabetic patients with peripheral arterial disease was investigated.
Biotechnical development of genetic addiction risk score (GARS) and selective evidence for inclusion of polymorphic allelic risk in substance use disorder (SUD).
Journal of systems and integrative neuroscience, 2020

Research into the neurogenetic basis of addiction identified and characterized by Reward Deficiency Syndrome (RDS) includes all drug and non-drug addictive, obsessive and compulsive behaviors. We are proposing herein that a new model for the prevention and treatment of Substance Use Disorder (SUD) a subset of RDS behaviors, based on objective biologic evidence, should be given serious consideration in the face of a drug epidemic. The development of the Genetic Addiction Risk Score (GARS) followed seminal research in 1990, whereby, Blum's group identified the first genetic association with severe alcoholism published in JAMA. While it is true that no one to date has provided adequate RDS free controls there have been many studies using case -controls whereby SUD has been eliminated. We argue that this deficiency needs to be addressed in the field and if adopted appropriately many spurious results would be eliminated reducing confusion regarding the role of genetics in addiction. However, an estimation, based on these previous literature results provided herein, while not representative of all association studies known to date, this sampling of case- control studies displays significant associations between alcohol and drug risk. In fact, we present a total of
[Informations on psychotropics and their adaptations for patients suffering from mental disorders in France during the SARS-CoV-2 epidemic].
L'Encephale, 2020

The 2019-20 coronavirus pandemic (SARS-CoV-2; severe acute respiratory syndrome coronavirus 2) has dramatic consequences on populations in terms of morbidity and mortality and in social terms, the general confinement of almost half of the world's population being a situation unprecedented in history, which is difficult today to measure the impact at the individual and collective levels. More specifically, it affects people with various risk factors, which are more frequent in patients suffering from psychiatric disorders. Psychiatrists need to know: (i) how to identify, the risks associated with the prescription of psychotropic drugs and which can prove to be counterproductive in their association with COVID-19 (coronavirus disease 2019), (ii) how to assess in terms of benefit/risk ratio, the implication of any hasty and brutal modification on psychotropic drugs that can induce confusion for a differential diagnosis with the evolution of COVID-19. We carried out a review of the literature aimed at assessing the specific benefit/risk ratio of psychotropic treatments in patients suffering from COVID-19. Clinically, symptoms suggestive of COVID-19 (fever, cough, dyspnea, digestive signs) can be caused by various psychotropic drugs and require vigilance to avoid false negatives and false positives. In infected patients, psychotropic drugs should be used with caution, especially in the elderly, considering the pulmonary risk. Lithium and Clozapine, which are the reference drugs in bipolar disorder and resistant schizophrenia, warrant specific attention. For these two treatments the possibility of a reduction in the dosage - in case of minimal infectious signs and in a situation, which does not allow rapid control - should ideally be considered taking into account the clinical response (even biological; plasma concentrations) observed in the face of previous dose reductions. Tobacco is well identified for its effects as an inducer of CYP1A2 enzyme. In a COVID+ patient, the consequences of an abrupt cessation of smoking, particularly related with the appearance of respiratory symptoms (cough, dyspnea), must therefore be anticipated for patients receiving psychotropics metabolized by CYP1A2. Plasma concentrations of these drugs are expected to decrease and can be related to an increase risk of relapse. The symptomatic treatments used in COVID-19 have frequent interactions with the most used psychotropics. If there is no curative treatment for infection to SARS-CoV-2, the interactions of the various molecules currently tested with several classes of psychotropic drugs (antidepressants, antipsychotics) are important to consider because of the risk of changes in cardiac conduction. Specific knowledge on COVID-19 remains poor today, but we must recommend rigor in this context in the use of psychotropic drugs, to avoid adding, in patients suffering from psychiatric disorders, potentially vulnerable in the epidemic context, an iatrogenic risk or loss of efficiency.
The Hierarchical Organization of the Default, Dorsal Attention and Salience Networks in Adolescents and Young Adults.
Cerebral cortex (New York, N.Y. : 1991), 2018

An important characteristic of spontaneous brain activity is the anticorrelation between the core default network (cDN) and the dorsal attention network (DAN) and the salience network (SN). This anticorrelation may constitute a key aspect of functional anatomy and is implicated in several brain disorders. We used dynamic causal modeling to assess the hypothesis that a causal hierarchy underlies this anticorrelation structure, using resting-state fMRI of healthy adolescent and young adults (N = 404). Our analysis revealed an asymmetric effective connectivity, such that the regions in the SN and DAN exerted an inhibitory influence on the cDN regions; whereas the cDN exerted an excitatory influence on the SN and DAN regions. The relative strength of efferent versus afferent connections places the SN at the apex of the hierarchy, suggesting that the SN modulates anticorrelated networks with descending hierarchical connections. In short, this study of directed neuronal coupling reveals a causal hierarchical architecture that generates or orchestrates anticorrelation of brain activity. These new findings shed light on functional integration of intrinsic brain networks at rest and speak to future dynamic causal modeling studies of large-scale networks.
The modulatory role of nicotine on cognitive and non-cognitive functions.
Brain research, 2019

Nicotine, as the main component of tobacco, plays a key role in various behaviors of both humans and animals including reward, addiction, learning and memory, anxiety, pain as well as body weight and temperature. Nicotine exerts its function by activating nicotinic acetylcholine receptors (nAChRs) which one highly expressed throughout the nervous system. The mesocorticolimbic dopamine system mediates the processing of reward, learning and memory behaviors produced by nicotine. In addition, some structures of the central nervous system, such as the hippocampus and amygdala, have a major role in mediation of nicotine properties. Furthermore, the effect of nicotine in modulation of cognitive and non-cognitive functions can produce by other neurochemical systems such as opioid, dopamine, glutamate, cannabinoids, GABA and serotonin as well as nitric oxide. The present review will explain involvement of these neurotransmitters on cognitive and non-cognitive functions induced by nicotine.
Activity-dependent alpha-cleavage of nectin-1 is mediated by a disintegrin and metalloprotease 10 (ADAM10).
The Journal of biological chemistry, 2010

Nectin-1 is known to undergo ectodomain shedding by alpha-secretase and subsequent proteolytic processing by gamma-secretase. How secretase-mediated cleavage of nectin-1 is regulated in neuronal cells and how nectin-1 cleavage affects synaptic adhesion is poorly understood. We have investigated alpha-and gamma-secretase-mediated processing of nectin-1 in primary cortical neurons and identified which protease acts as a alpha-secretase. We report here that NMDA receptor activation, but not stimulation of AMPA or metabotropic glutamate receptors, resulted in robust alpha- and gamma-secretase cleavage of nectin-1 in mature cortical neurons. Cleavage of nectin-1 required influx of Ca(2+) through the NMDA receptor, and activation of calmodulin, but was not dependent on calcium/calmodulin-dependent protein kinase II (CaMKII) activation. We found that ADAM10 is the major secretase responsible for nectin-1 ectodomain cleavage in neurons and the brain. These observations suggest that alpha- and gamma-secretase processing of nectin-1 is a Ca(2+)/calmodulin-regulated event that occurs under conditions of activity-dependent synaptic plasticity and ADAM10 and gamma-secretase are responsible for these cleavage events.
Encoding of fear learning and memory in distributed neuronal circuits.
Nature neuroscience, 2014

How sensory information is transformed by learning into adaptive behaviors is a fundamental question in neuroscience. Studies of auditory fear conditioning have revealed much about the formation and expression of emotional memories and have provided important insights into this question. Classical work focused on the amygdala as a central structure for fear conditioning. Recent advances, however, have identified new circuits and neural coding strategies mediating fear learning and the expression of fear behaviors. One area of research has identified key brain regions and neuronal coding mechanisms that regulate the formation, specificity and strength of fear memories. Other work has discovered critical circuits and neuronal dynamics by which fear memories are expressed through a medial prefrontal cortex pathway and coordinated activity across interconnected brain regions. Here we review these recent advances alongside prior work to provide a working model of the extended circuits and neuronal coding mechanisms mediating fear learning and memory.
Cognitive and methodological considerations on the effects of musical expertise on speech segmentation.
Annals of the New York Academy of Sciences, 2012

Both speech and music are constituted by sequences of sound elements that unfold in time and require listeners to engage cognitive functions such as sequencing, attention, and memory. We recently ran a set of experiments with the aim of testing the effect of musical expertise on a rather high cognitive function: speech segmentation. Here, we will present the main concepts underlying the investigation of speech segmentation as well as its link to music and musical expertise. Interestingly, our results seem to show that musical training and expertise have effects on brain plasticity that may go beyond primary regions. Moreover, to facilitate and improve future research in this domain, we will here describe several delicate methodological precautions that need to be taken into account (e.g., the choice of stimuli, participants, data analyses). Finally, we will give some possible future directions to better understand the impact that music may have on speech processing.
De novo variants in PAK1 lead to intellectual disability with macrocephaly and seizures.
Brain : a journal of neurology, 2019

Using trio exome sequencing, we identified de novo heterozygous missense variants in PAK1 in four unrelated individuals with intellectual disability, macrocephaly and seizures. PAK1 encodes the p21-activated kinase, a major driver of neuronal development in humans and other organisms. In normal neurons, PAK1 dimers reside in a trans-inhibited conformation, where each autoinhibitory domain covers the kinase domain of the other monomer. Upon GTPase binding via CDC42 or RAC1, the PAK1 dimers dissociate and become activated. All identified variants are located within or close to the autoinhibitory switch domain that is necessary for trans-inhibition of resting PAK1 dimers. Protein modelling supports a model of reduced ability of regular autoinhibition, suggesting a gain of function mechanism for the identified missense variants. Alleviated dissociation into monomers, autophosphorylation and activation of PAK1 influences the actin dynamics of neurite outgrowth. Based on our clinical and genetic data, as well as the role of PAK1 in brain development, we suggest that gain of function pathogenic de novo missense variants in PAK1 lead to moderate-to-severe intellectual disability, macrocephaly caused by the presence of megalencephaly and ventriculomegaly, (febrile) seizures and autism-like behaviour.
CT perfusion in acute stroke calls: A pictorial review and differential diagnoses.
Journal of medical imaging and radiation oncology, 2016

CT perfusion is increasingly utilised in hyperacute stroke to facilitate diagnosis and patient selection for reperfusion therapies. This review article demonstrates eight examples of how CT perfusion can be used to diagnose stroke mimics and small volume infarcts, which can be easily missed on non-contrast CT, and to suggest the presence of an ischaemic penumbra. Radiologists involved in stroke management must understand the importance of rapid imaging acquisition and be confident in the prospective interpretation of this powerful diagnostic tool as we move into a new era of hyperacute stroke care.
Neurosteroid biosynthetic pathways changes in prefrontal cortex in Alzheimer's disease.
Neurobiology of aging, 2011

Expression of the genes for enzymes involved in neurosteroid biosynthesis was studied in human prefrontal cortex (PFC) in the course of Alzheimer's disease (AD) (n=49). Quantitative RT-PCR (qPCR) revealed that mRNA levels of diazepam binding inhibitor (DBI), which is involved in the first step of steroidogenesis and in GABAergic transmission, were increased, as were mRNA levels for several neurosteroid biosynthetic enzymes. Aromatase, 17β-hydroxysteroid dehydrogenase type 1 (HSD17B1) and aldo-keto reductase 1C2 (AKR1C2), were all increased in the late stages of AD. Several GABA-A subunits were significantly reduced in AD. Increased expression of aromatase in the PFC was confirmed by immunohistochemistry and was found to be localized predominantly in astrocytes. These data suggest a role for estrogens and allopregnanolone produced by astrocytes in the PFC in AD, possibly as part of a rescue program. The reduced gene expression of some synaptic and extra-synaptic GABA-A subunits may indicate a deficit of modulation of GABA-A receptors by neuroactive steroids, which may contribute to the neuropsychiatric characteristics of this disease.
Characterization of the decision network for wing expansion in Drosophila using targeted expression of the TRPM8 channel.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009

After emergence, adult flies and other insects select a suitable perch and expand their wings. Wing expansion is governed by the hormone bursicon and can be delayed under adverse environmental conditions. How environmental factors delay bursicon release and alter perch selection and expansion behaviors has not been investigated in detail. Here we provide evidence that in Drosophila the motor programs underlying perch selection and wing expansion have different environmental dependencies. Using physical manipulations, we demonstrate that the decision to perch is based primarily on environmental valuations and is incrementally delayed under conditions of increasing perturbation and confinement. In contrast, the all-or-none motor patterns underlying wing expansion are relatively invariant in length regardless of environmental conditions. Using a novel technique for targeted activation of neurons, we show that the highly stereotyped wing expansion motor patterns can be initiated by stimulation of N(CCAP), a small network of central neurons that regulates the release of bursicon. Activation of this network using the cold-sensitive rat TRPM8 channel is sufficient to trigger all essential behavioral and somatic processes required for wing expansion. The delay of wing expansion under adverse circumstances thus couples an environmentally sensitive decision network to a command-like network that initiates a fixed action pattern. Because N(CCAP) mediates environmentally insensitive ecdysis-related behaviors in Drosophila development before adult emergence, the study of wing expansion promises insights not only into how networks mediate behavioral choices, but also into how decision networks develop.
Public Engagement and Neurology: An Update.
Brain sciences, 2021

Public engagement (PE) is defined as the involvement of "specialists who listen, develop their understanding, and interact with non-specialists in non-profit activities of educational, cultural, and social nature to engage the public in science-related matters". The public health relevance of PE consists in building up a scientifically literate society, able to participate in and support scientific and technological developments and their implications for educational settings. Neurological disorders account for 35% of all diseases. PE could have a positive impact on the lives of people affected by neurological diseases.
A novel GRN mutation (GRN c.708+6_+9delTGAG) in frontotemporal lobar degeneration with TDP-43-positive inclusions: clinicopathologic report of 6 cases.
Journal of neuropathology and experimental neurology, 2014

Understanding of frontotemporal lobar degeneration, the underlying pathology most often linked to the clinical diagnosis of frontotemporal dementia, is rapidly increasing. Mutations in 7 known genes (MAPT, GRN, C9orf72, VCP, CHMP2B, and, rarely, TARDBP and FUS) are associated with frontotemporal dementia, and the pathologic classification of frontotemporal lobar degeneration has recently been modified to reflect these discoveries. Mutations in one of these genes (GRN), which encodes progranulin, have been implicated in up to a quarter of cases of frontotemporal lobar degeneration with TDP-43 (TAR DNA-binding protein 43)-positive inclusions; currently, there are more than 60 known pathogenic mutations of the gene. We present the clinical, pathologic, and genetic findings on 6 cases from 4 families, 5 of which were shown to have a novel GRN c.708+6_+9delTGAG mutation.
Adolf Meyer: the neuroanatomist and neuropsychiatrist behind Meyer's loop and its significance in neurosurgery.
Brain : a journal of neurology, 2020

Psychiatrist Adolf Meyer’s work as a neuroanatomist is less well-known among the medical community. Using manuscripts by Harvey Cushing and by Meyer himself, Schijns and Koehler explore how Meyer’s anatomical studies enabled him to describe the temporal loop of the optic radiation, known today as ‘Meyer’s loop’.