rudyvdbrink/CitationDatabase huggingface dataset:
Designing in vivo concentration gradients with discrete controlled release: a computational model.
Journal of neural engineering, 2010

One promising neurorehabilitation therapy involves presenting neurotrophins directly into the brain to induce growth of new neural connections. The precise control of neurotrophin concentration gradients deep within neural tissue that would be necessary for such a therapy is not currently possible, however. Here we evaluate the theoretical potential of a novel method of drug delivery, discrete controlled release (DCR), to control effective neurotrophin concentration gradients in an isotropic region of neocortex. We do so by constructing computational models of neurotrophin concentration profiles resulting from discrete release locations into the cortex and then optimizing their design for uniform concentration gradients. The resulting model indicates that by rationally selecting initial neurotrophin concentrations for drug-releasing electrode coatings in a square 16-electrode array, nearly uniform concentration gradients (i.e. planar concentration profiles) from one edge of the electrode array to the other should be obtainable. DCR therefore represents a promising new method of precisely directing neuronal growth in vivo over a wider spatial profile than would be possible with single release points.
Biallelic MFSD2A variants associated with congenital microcephaly, developmental delay, and recognizable neuroimaging features.
European journal of human genetics : EJHG, 2020

Major Facilitator Superfamily Domain containing 2a (MFSD2A) is an essential endothelial lipid transporter at the blood-brain barrier. Biallelic variants affecting function in MFSD2A cause autosomal recessive primary microcephaly 15 (MCPH15, OMIM# 616486). We sought to expand our knowledge of the phenotypic spectrum of MCPH15 and demonstrate the underlying mechanism of inactivation of the MFSD2A transporter. We carried out detailed analysis of the clinical and neuroradiological features of a series of 27 MCPH15 cases, including eight new individuals from seven unrelated families. Genetic investigation was performed through exome sequencing (ES). Structural insights on the human Mfsd2a model and in-vitro biochemical assays were used to investigate the functional impact of the identified variants. All patients had primary microcephaly and severe developmental delay. Brain MRI showed variable degrees of white matter reduction, ventricular enlargement, callosal hypodysgenesis, and pontine and vermian hypoplasia. ES led to the identification of six novel biallelic MFSD2A variants (NG_053084.1, NM_032793.5: c.556+1G>A, c.748G>T; p.(Val250Phe), c.750_753del; p.(Cys251SerfsTer3), c.977G>A; p.(Arg326His), c.1386_1435del; p.(Gln462HisfsTer17), and c.1478C>T; p.(Pro493Leu)) and two recurrent variants (NM_032793.5: c.593C>T; p.(Thr198Met) and c.476C>T; p.(Thr159Met)). All these variants and the previously reported NM_032793.5: c.490C>A; p.(Pro164Thr) resulted in either reduced MFSD2A expression and/or transport activity. Our study further delineates the phenotypic spectrum of MCPH15, refining its clinical and neuroradiological characterization and supporting that MFSD2A deficiency causes early prenatal brain developmental disruption. We also show that poor MFSD2A expression despite normal transporter activity is a relevant pathomechanism in MCPH15.
Personal protective equipment for reducing the risk of COVID-19 infection among health care workers involved in emergency trauma surgery during the pandemic: An umbrella review.
The journal of trauma and acute care surgery, 2021

Health care facilities in low- and middle-income countries are inadequately resourced to adhere to current COVID-19 prevention recommendations. Recommendations for surgical emergency trauma care measures need to be adequately informed by available evidence and adapt to particular settings. To inform future recommendations, we set to summarize the effects of different personal protective equipment (PPE) on the risk of COVID-19 infection in health personnel caring for trauma surgery patients.
Blunted neural and psychological stress processing predicts future grey matter atrophy in multiple sclerosis.
Neurobiology of stress, 2020

Multiple sclerosis (MS) is characterized by two neuropathological key aspects: inflammation and neurodegeneration. Clinical studies support a prospective link between psychological stress and subsequent inflammatory disease activity. However, it is unknown if a similar link exists for grey matter (GM) degeneration as the key driver of irreversible disability.
The Brentano Illusion Test (BRIT): An implicit task of perceptual processing for the assessment of visual field defects in neglect patients.
Neuropsychological rehabilitation, 2021

In brain damaged patients with unilateral spatial neglect (USN), the differential diagnosis between the presence and absence of a unilateral visual half-field deficit (VHFD) is hampered by the similarity of their phenomenology. The absence of stimuli detection in the contralateral visual field, indeed, can be due to the co-occurrence of USN and VHFD or the sole presence of the USN. The disentangling of the two conditions is required to devise more specific rehabilitation programmes. Daini et al. [2002. Exploring the syndrome of spatial unilateral neglect through an illusion of length.
T
Neurobiology of disease, 2021

Abnormalities in thyroid hormones (TH) availability and/or metabolism have been hypothesized to contribute to Alzheimer's disease (AD) and to be a risk factor for stroke. Recently, 3-iodothyronamine (T
Cell-Type-Specific Outcome Representation in the Primary Motor Cortex.
Neuron, 2020

Adaptive movements are critical for animal survival. To guide future actions, the brain monitors various outcomes, including achievement of movement and appetitive goals. The nature of these outcome signals and their neuronal and network realization in the motor cortex (M1), which directs skilled movements, is largely unknown. Using a dexterity task, calcium imaging, optogenetic perturbations, and behavioral manipulations, we studied outcome signals in the murine forelimb M1. We found two populations of layer 2-3 neurons, termed success- and failure-related neurons, that develop with training, and report end results of trials. In these neurons, prolonged responses were recorded after success or failure trials independent of reward and kinematics. In addition, the initial state of layer 5 pyramidal tract neurons contained a memory trace of the previous trial's outcome. Intertrial cortical activity was needed to learn new task requirements. These M1 layer-specific performance outcome signals may support reinforcement motor learning of skilled behavior.
Associations Between Gender, Resiliency Factors, and Anxiety in Neuro-ICU Caregivers: a Prospective Study.
International journal of behavioral medicine, 2020

Informal caregivers of patients admitted to the neuroscience intensive care unit (Neuro-ICU) are at risk for developing chronic anxiety. Resiliency factors may reduce risk, yet their differential effects for female and male caregivers have not been studied in this population. We aim to examine interactions between gender and baseline resiliency factors and anxiety at baseline, 3 months, and 6 months.
Comorbid anxiety-like behavior in a rat model of colitis is mediated by an upregulation of corticolimbic fatty acid amide hydrolase.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2021

Peripheral inflammatory conditions, including those localized to the gastrointestinal tract, are highly comorbid with psychiatric disorders such as anxiety and depression. These behavioral symptoms are poorly managed by conventional treatments for inflammatory diseases and contribute to quality of life impairments. Peripheral inflammation is associated with sustained elevations in circulating glucocorticoid hormones, which can modulate central processes, including those involved in the regulation of emotional behavior. The endocannabinoid (eCB) system is exquisitely sensitive to these hormonal changes and is a significant regulator of emotional behavior. The impact of peripheral inflammation on central eCB function, and whether this is related to the development of these behavioral comorbidities remains to be determined. To examine this, we employed the trinitrobenzene sulfonic acid-induced model of colonic inflammation (colitis) in adult, male, Sprague Dawley rats to produce sustained peripheral inflammation. Colitis produced increases in behavioral measures of anxiety and elevations in circulating corticosterone. These alterations were accompanied by elevated hydrolytic activity of the enzyme fatty acid amide hydrolase (FAAH), which hydrolyzes the eCB anandamide (AEA), throughout multiple corticolimbic brain regions. This elevation of FAAH activity was associated with broad reductions in the content of AEA, whose decline was driven by central corticotropin releasing factor type 1 receptor signaling. Colitis-induced anxiety was reversed following acute central inhibition of FAAH, suggesting that the reductions in AEA produced by colitis contributed to the generation of anxiety. These data provide a novel perspective for the pharmacological management of psychiatric comorbidities of chronic inflammatory conditions through modulation of eCB signaling.
Homozygote loss-of-function variants in the human COCH gene underlie hearing loss.
European journal of human genetics : EJHG, 2021

Since 1999, the COCH gene encoding cochlin, has been linked to the autosomal dominant non-syndromic hearing loss, DFNA9, with or without vestibular abnormalities. The hearing impairment associated with the variants affecting gene function has been attributed to a dominant-negative effect. Mutant cochlin was seen to accumulate intracellularly, with the formation of aggregates both inside and outside the cells, in contrast to the wild-type cochlin that is normally secreted. While additional recessive variants in the COCH gene (DFNB110) have recently been reported, the mechanism of the loss-of-function (LOF) effect of the COCH gene product remains unknown. In this study, we used COS7 cell lines to investigate the consequences of a novel homozygous frameshift variant on RNA transcription, and on cochlin translation. Our results indicate a LOF effect of the variant and a major decrease in cochlin translation. This data have a dramatic impact on the accuracy of genetic counseling for both heterozygote and homozygote carriers of LOF variants in COCH.
Sex differences in stroke co-morbidities.
Experimental neurology, 2020

Males and females possess distinct biological differences that manifest in diverse risk profiles for acute and chronic diseases. A well-documented example of this is ischemic stroke. It has been demonstrated that older females have greater prevalence of, and worse outcome after, ischemic stroke than do males and younger females. Loss of estrogen after menopause is heavily implicated as a contributing factor for this phenomenon; however, there is mounting evidence to suggest that certain risk factors tend to occur more often in older females, such as hypertension and atrial fibrillation, while others more adversely affect females than they do males, such as diabetes and smoking. Sex-specific risk factors, such as oral contraceptive use and menopause, could also contribute to the discrepancy in stroke prevalence and outcome. Additionally, there is evidence to suggest that females tend to present with more nontraditional symptoms of acute stroke than do males, making it more difficult for clinicians to correctly identify the occurrence of a stroke, which may delay the administration of thrombolytic intervention. Finally, certain sociodemographic factors, such as the fact that females were more likely to live alone prior to stroke, may contribute to poorer recovery in females. This review will explore the various co-morbidities and sociodemographic factors that contribute to the greater prevalence of and poorer outcome after stroke in older females and will highlight the critical need for considering sex as a predisposing biological variable in stroke studies.
The effects of audiovisual distraction on the muscle sympathetic responses to experimental muscle pain.
Experimental brain research, 2018

Pain elicited by intramuscular infusion of hypertonic saline solution causes muscle sympathetic nerve activity (MSNA) to increase in some subjects, yet decrease in others. Although the direction of the response is not predictable based on baseline physiological and psychological parameters, we know that it results from sustained functional changes in specific brain regions that are responsible for the behavioral and cardiovascular responses to psychological stressors, as well as those involved in attention. The aim of this study was to investigate whether MSNA responses to experimental muscle pain in humans could be altered with an audiovisual stimulus that served to distract them from the pain. MSNA was recorded from the left common peroneal nerve of 20 young healthy individuals during a 45-min intramuscular infusion of hypertonic saline solution into the ipsilateral tibialis anterior muscle. The distracting stimulus commenced 15 min after the start of the infusion and lasted for 15 min. Fifteen subjects showed an increase in mean burst amplitude of MSNA (to 176.4 ± 7.9% of baseline), while five showed a decrease (to 73.1 ± 5.2% of baseline); distraction had no effect on these profiles. These results indicate that even though the subjects were attending to the audiovisual stimulus, and were presumably distracted from the pain, it failed to alter the MSNA responses to muscle pain.
Treatment of human airway epithelial Calu-3 cells with a peptide-nucleic acid (PNA) targeting the microRNA miR-101-3p is associated with increased expression of the cystic fibrosis Transmembrane Conductance Regulator () gene.
European journal of medicinal chemistry, 2021

Since the identification of microRNAs (miRNAs) involved in the regulation of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene, miRNAs known to down-regulate the expression of the CFTR and associated proteins have been investigated as potential therapeutic targets. Here we show that miR-101-3p, targeting the 3'-UTR sequence of the CFTR mRNA, can be selectively inhibited by a peptide nucleic acid (PNA) carrying a full complementary sequence. With respect to clinical relevance of microRNA targeting, it is expected that reduction in concentration of miRNAs (the anti-miRNA approach) could be associated with increasing amounts of target mRNAs. Consistently to this hypothesis, we report that PNA-mediated inhibition of miR-101-3p was accompanied by CFTR up-regulation. Next Generation Sequencing (NGS) was performed in order to verify the effects of the anti-miR-101-3p PNA on the Calu-3 miRNome. Upon inhibition of miR-101-3p we observed a fold change (FC) expression <2 of the majority of miRNAs (403/479, 84.13%), whereas we identified a list of dysregulated miRNAs, suggesting that specific miRNA inhibition (in our case miR-101-3p) might be accompanied by alteration of expression of other miRNAs, some of them known to be involved in Cystic Fibrosis (CF), such as miR-155-5p and miR-125b-5p.
Convalescent Memory T Cell Immunity in Individuals with Mild or Asymptomatic SARS-CoV-2 Infection May Result from an Evolutionarily Adapted Immune Response to Coronavirus and the 'Common Cold'.
Medical science monitor : international medical journal of experimental and clinical research, 2020

Recent studies have shown a significant level of T cell immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in convalescent coronavirus disease 2019 (COVID-19) patients and unexposed healthy individuals. Also, SARS-CoV-2-reactive T memory cells occur in unexposed healthy individuals from endemic coronaviruses that cause the 'common cold.' The finding of the expression of adaptive SARS-CoV-2-reactive T memory cells in unexposed healthy individuals may be due to multiple cross-reactive viral protein targets following previous exposure to endemic human coronavirus infections. The opinion of the authors is that determination of protein sequence homologies across seemingly disparate viral protein libraries may provide epitope-matching data that link SARS-CoV-2-reactive T memory cell signatures to prior administration of cross-reacting vaccines to common viral pathogens. Exposure to SARS-CoV-2 initiates diverse cellular immune responses, including the associated 'cytokine storm'. Therefore, it is possible that the intact virus possesses a required degree of conformational matching, or stereoselectivity, to effectively target its receptor on multiple cell types. Therefore, conformational matching may be viewed as an evolving mechanism of viral infection and viral replication by an evolutionary modification of the angiotensin-converting enzyme 2 (ACE2) receptor required for SARS-CoV-2 binding and host cell entry. The authors propose that convalescent memory T cell immunity in individuals with mild or asymptomatic SARS-CoV-2 infection may result from an evolutionarily adapted immune response to coronavirus and the 'common cold'.
Dr. Peter Emil Becker and the Third Reich.
American journal of medical genetics. Part A, 2013

In 1985 the physician after whom Becker Muscular Dystrophy is named, German neurologist Dr. Peter Emil Becker (1908-2000), published an autobiographical article in the American Journal of Medical Genetics in which he disavowed any association with the Nazi Party. A closer look at the evidence, however, suggests otherwise. Review of war records and related sources raise concern for Dr. Becker's affiliation with the Nazi Party and his contributions to its ideology.
Imaging nervous system activity with voltage-sensitive dyes.
Current protocols in neuroscience, 2003

Optical recording with a voltage-sensitive dye is advantageous where membrane potential must be recorded in many sites at once. This unit describes methods for making voltage-sensitive dye measurements on different preparations to study (1) how a neuron integrates its synaptic input into its action potential output by measuring membrane potential everywhere synaptic input occurs and where spikes are initiated; (2) how a nervous system generates a behavior in Aplysia abdominal ganglion; and (3) responses to sensory stimuli and generation of motor output in the vertebrate brain by simultaneous measurement of population signals from many areas. The approach is three-pronged: (1) find the dye with the largest signal-to-noise ratio; (2) reduce extraneous sources of noise; and (3) maximize the number of photons measured to reduce the relative shot noise. A discussion of optical recording methods including the choice of dyes, light sources, optics, cameras, and minimizing noise is also provided.
The basics of mitochondrial cAMP signalling: Where, when, why.
Cell calcium, 2021

Cytosolic cAMP signalling in live cells has been extensively investigated in the past, while only in the last decade the existence of an intramitochondrial autonomous cAMP homeostatic system began to emerge. Thanks to the development of novel tools to investigate cAMP dynamics and cAMP/PKA-dependent phosphorylation within the matrix and in other mitochondrial compartments, it is now possible to address directly and in intact living cells a series of questions that until now could be addressed only by indirect approaches, in isolated organelles or through subcellular fractionation studies. In this contribution we discuss the mechanisms that regulate cAMP dynamics at the surface and inside mitochondria, and its crosstalk with organelle Ca
μDrop: Multi-analyte portable electrochemical-sensing device for blood-based detection of cleaved tau and neuron filament light in traumatic brain injury patients.
Biosensors & bioelectronics, 2021

Over 27 million individuals are affected every year worldwide with central nervous system (CNS) injuries. These injuries include but are not limited to traumatic brain injury (TBI) and spinal cord injury (SCI). CNS injuries remain a significant public health concern which demands reliable tools for rapid, on-sight, on-field, and point-of-care diagnostic (POC) solutions. To address these challenges, we developed a low-cost, open-source, hand-held, portable, and POC detection technology, termed as MicroDrop (μDrop), which can simultaneously detect up to eight target biomolecules and display results in both analog and digital formats. The data acquired is stored wirelessly in a cloud server for further investigation and statistical analysis. Multiplexing capability of μDrop and immuno-biosensors detects and quantifies Cleaved-Tau Protein (C-Tau) and Neuron-Filament (NFL) proteins in the blood of TBI patients. Immuno-biosensors rapidly sense the two target proteins in less than 30 min, with μDrop and a conventional potentiostat. C-Tau and NFL were selectively detected with μDrop within the dynamic range of 10 pg/mL - 100 ng/mL and the sensitivity range of 47 μA/pg mm
Use of Peripheral Sensory Information for Central Nervous Control of Arm Movement by Octopus vulgaris.
Current biology : CB, 2020

Octopuses are active predators with highly flexible bodies and rich behavioral repertoires [1-3]. They display advanced cognitive abilities, and the size of their large nervous system rivals that of many mammals. However, only one third of the neurons constitute the CNS, while the rest are located in an elaborate PNS, including eight arms, each containing myriad sensory receptors of various modalities [2-4]. This led early workers to question the extent to which the CNS is privy to non-visual sensory input from the periphery and to suggest that it has limited capacity to finely control arm movement [3-5]. This conclusion seemed reasonable considering the size of the PNS and the results of early behavioral tests [3, 6-8]. We recently demonstrated that octopuses use visual information to control goal-directed complex single arm movements [9]. However, that study did not establish whether animals use information from the arm itself [9-12]. We here report on development of two-choice, single-arm mazes that test the ability of octopuses to perform operant learning tasks that mimic normal tactile exploration behavior and require the non-peripheral neural circuitry to use focal sensory information originating in single arms [1, 10]. We show that the CNS of the octopus uses peripheral information about arm motion as well as tactile input to accomplish learning tasks that entail directed control of movement. We conclude that although octopus arms have a great capacity to act independently, they are also subject to central control, allowing well-organized, purposeful behavior of the organism as a whole.
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European journal of nuclear medicine and molecular imaging, 2020

Second-generation tau radiotracers for use with positron emission tomography (PET) have been developed for visualization of tau deposits in vivo. For several β-amyloid and first-generation tau-PET radiotracers, it has been shown that early-phase images can be used as a surrogate of neuronal injury. Therefore, we investigated the performance of early acquisitions of the novel tau-PET radiotracer [