rudyvdbrink/CitationDatabase huggingface dataset:
Effect of corticosteroid (triamcinolone acetonide) and chlorhexidin on chemotherapy- induced oxidative stress in buccal mucosa of rats.
Ear, nose, & throat journal, 2020

Oral mucositis (OM) refers to erythematous and ulcerative lesions of the oral mucosa. This pathology can occur by various causes. Cancer therapy is one of the well-known causes of OM such as chemotherapy and/or with radiation therapy. It has been widely mentioned that oxidative stress parameters such as lipid peroxidation (LP) levels increase during cancer process. Glutathione (GSH) is one of the major intracellular enzymes to detoxify oxidant molecules. The aim of this study was to investigate and compare the effects of Triamcinolone Acetonide (TA), a synthetic steroid chlorhexidine (CHX), a chemical antiseptic, on 5- fluorouracil (5-FU), a chemotherapeutic agent and soft abrasion induced OM in buccal mucosa of rats.OM was induced in rats through a combination of 5-FU treatment and mild abrasion of the cheek pouch with a wire brush. Buccal mucosa lipid peroxidation (LP) levels were higher (p< 0.05) in 5-FU group than in control although LP levels were lower (p<0.05) in TA group than in control group. The reduced glutathione levels were lower (p<0.05) in 5-FU group than in the control group although its level was higher (p<0.05) in TA and CHX groups than in the 5-FU group. Glutathione peroxidase activity was also higher (p<0.05) in TA group than the 5- FU group. In histopathological analyses, treatment with TA reduced 5-FU induced inflammatory cell infiltration and ulceration (p<0.001) but not with CHX.In conclusion, we observed that TA and CHX treatment modulated chemotherapy induced oxidative injury in the rat OM. However, only TA histopathologically ameliorated the 5-FU induced OM of rats. These findings suggest that TA is a useful agent for management of experimental oxidative injury and OM caused by the chemotherapy.
Early-life-trauma triggers interferon-β resistance and neurodegeneration in a multiple sclerosis model via downregulated β1-adrenergic signaling.
Nature communications, 2021

Environmental triggers have important functions in multiple sclerosis (MS) susceptibility, phenotype, and trajectory. Exposure to early life trauma (ELT) has been associated with higher relapse rates in MS patients; however, the underlying mechanisms are not well-defined. Here we show ELT induces mechanistic and phenotypical alterations during experimental autoimmune encephalitis (EAE). ELT sustains downregulation of immune cell adrenergic receptors, which can be attributed to chronic norepinephrine circulation. ELT-subjected mice exhibit interferon-β resistance and neurodegeneration driven by lymphotoxin and CXCR2 involvement. These phenotypic changes are observed in control EAE mice treated with β1 adrenergic receptor antagonist. Conversely, β1 adrenergic receptor agonist treatment to ELT mice abrogates phenotype changes via restoration of immune cell β1 adrenergic receptor function. Our results indicate that ELT alters EAE phenotype via downregulation of β1 adrenergic signaling in immune cells. These results have implications for the effect of environmental factors in provoking disease heterogeneity and might enable prediction of long-term outcomes in MS.
Optogenetic TDP-43 nucleation induces persistent insoluble species and progressive motor dysfunction in vivo.
Neurobiology of disease, 2020

TDP-43 is a predominantly nuclear DNA/RNA binding protein that is often mislocalized into insoluble cytoplasmic inclusions in post-mortem patient tissue in a variety of neurodegenerative disorders including Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal dementia (FTD). The underlying causes of TDP-43 proteinopathies remain unclear, but recent studies indicate the formation of these protein assemblies is driven by aberrant phase transitions of RNA deficient TDP-43. Technical limitations have prevented our ability to understand how TDP-43 proteinopathy relates to disease pathogenesis. Current animal models of TDP-43 proteinopathy often rely on overexpression of wild-type TDP-43 to non-physiological levels that may initiate neurotoxicity through nuclear gain of function mechanisms, or by the expression of disease-causing mutations found in only a fraction of ALS patients. New technologies allowing for light-responsive control of subcellular protein crowding provide a promising approach to drive intracellular protein aggregation, as we have previously demonstrated in vitro. Here we present a model for the optogenetic induction of TDP-43 proteinopathy in Drosophila that recapitulates key features of patient pathology, including detergent insoluble cytoplamsic inclusions and progressive motor dysfunction.
Dual-Task in Large Perceptual Space Reveals Subclinical Hemispatial Neglect.
Journal of the International Neuropsychological Society : JINS, 2020

Both clinically observable and subclinical hemispatial neglect are related to functional disability. The aim of the present study was to examine whether increasing task complexity improves sensitivity in assessment and whether it enables the identification of subclinical neglect.
Molecular imaging of Alzheimer's disease-related gamma-secretase in mice and nonhuman primates.
The Journal of experimental medicine, 2020

The pathogenesis of Alzheimer's disease (AD) is primarily driven by brain accumulation of the amyloid-β-42 (Aβ42) peptide generated from the amyloid-β precursor protein (APP) via cleavages by β- and γ-secretase. γ-Secretase is a prime drug target for AD; however, its brain regional expression and distribution remain largely unknown. Here, we are aimed at developing molecular imaging tools for visualizing γ-secretase. We used our recently developed γ-secretase modulators (GSMs) and synthesized our GSM-based imaging agent, [11C]SGSM-15606. We subsequently performed molecular imaging in rodents, including AD transgenic animals, and macaques, which revealed that our probe displayed good brain uptake and selectivity, stable metabolism, and appropriate kinetics and distribution for imaging γ-secretase in the brain. Interestingly, rodents and macaques shared certain brain areas with high γ-secretase expression, suggesting a functional conservation of γ-secretase. Collectively, we have provided the first molecular brain imaging of γ-secretase, which may not only accelerate our drug discovery for AD but also advance our understanding of AD.
Systemic involvement in adult-onset leukoencephalopathy with intracranial calcifications and cysts (Labrune syndrome) with a novel mutation of the SNORD118 gene.
European journal of neurology, 2020

Although Labrune syndrome is a well-known disorder characterized by a typical neuroradiological triad, namely leukoencephalopathy, intracranial calcifications and cysts, there are no reports of systemic involvement in this disorder. This paper attempts to describe a peculiar clinical manifestation related to a novel mutation in the SNORD118 gene.
Bright light exposure before bedtime impairs response inhibition the following morning: a non-randomized crossover study.
Chronobiology international, 2018

Bright light exposure in the late evening can affect cognitive function the following morning either by changing the biological clock and/or disturbing sleep, but the evidence for this effect is scarce, and the underlying mechanism remains unknown. In this study, we first aimed to evaluate the effect of bright light exposure before bedtime on frontal lobe activity the following morning using near-infrared spectroscopy (NIRS) during a Go/NoGo task. Second, we aimed to evaluate the effects of bright light exposure before bedtime on polysomnographic measures and on a frontal lobe function test the following morning.
Leucine-rich repeat kinase 2-linked Parkinson's disease: clinical and molecular findings.
Journal of movement disorders, 2010

Mutations in Leucine-rich repeat kinase 2 (LRRK2) gene are the most common cause of sporadic and familial late onset Parkinson's disease (PD). The G2019S common mutation has been identified about 1% of sporadic cases and 4-7% of familial cases. Over 50 variants have since been identified in LRRK2, and at least 7 of these are confirmed to be pathogenic. In addition to pathogenic mutations, several common polymorphisms in the LRRK2 gene (G2385R and R1628P) have been identified that may explain up to 10% of sporadic PD in Asian populations. LRRK2 is a large complex multidomain protein with 2,527-amino-acid and the molecular weight is 286 kDa. LRRK2 multidomain protein consists of a catalytic core domain, kinase domain and a number of putative protein-protein interaction domains. LRRK2 mutations found in PD families, including the G2019S and I2020T mutations show increased intrinsic kinase activity, when assessed with myelin basic protein as substrate. The modification of LRRK2 GTPase and kinase activity affecting residues in the ROC, COR and mitogen-activated protein kinase kinase kinases domains is believed to lead to neuronal cell death, but the pathways involved remain unclear. A number of in vivo models in C. elegans, D. melanogaster and mice have been developed to study the patho/physiological function of LRRK2. Based on current literature, a toxic gain of function in LRRK2 kinase activity is a possible pathophysiologic mechanism and thus inhibition of kinase activity in experimental models offers a potential therapeutic strategy for LRRK2-linked PD.
Friedreich cardiomyopathy is a desminopathy.
Free neuropathology, 2021

Heart disease is an integral part of Friedreich ataxia (FA) and the most common cause of death in this autosomal recessive disease. The result of the mutation is lack of frataxin, a small mitochondrial protein. The clinical and pathological phenotypes of FA are complex, involving brain, spinal cord, dorsal root ganglia, sensory nerves, heart, and endocrine pancreas. The hypothesis is that frataxin deficiency causes downstream changes in the proteome of the affected tissues, including the heart. A proteomic analysis of heart proteins in FA cardiomyopathy by antibody microarray, Western blots, immunohistochemistry, and double-label laser scanning confocal immunofluorescence microscopy revealed upregulation of desmin and its chaperone protein, αB-crystallin. In normal hearts, these two proteins are co-localized at intercalated discs and Z discs. In FA, desmin and αB-crystallin aggregate, causing chaotic modification of intercalated discs, clustering of mitochondria, and destruction of the contractile apparatus of cardiomyocytes. Western blots of tissue lysates in FA cardiomyopathy reveal a truncated desmin isoprotein that migrates at a lower molecular weight range than wild type desmin. While desmin and αB-crystallin are not mutated in FA, the accumulation of these proteins in FA hearts allows the conclusion that FA cardiomyopathy is a desminopathy akin to desmin myopathy of skeletal muscle.
Delayed Identification of Cortical Superficial Siderosis in a Patient with Recurrent Transient Focal Neurological Symptoms: A Case Report.
Cureus, 2019

Cortical superficial siderosis (cSS), also referred to as sulcal siderosis, is a neurological condition characterized by hemosiderin subpial deposits in the cortical sulci over the convexities of cerebral hemispheres. These deposits are further found sparingly in the spinal cord, brainstem, and cerebellum. Patients typically present with transient focal neurological symptoms that make cSS challenging to differentiate from other acute neurological processes such as transient ischemic attacks (TIA), focal seizures, and acute convexity subarachnoid hemorrhage (cSAH). This condition is presently recognized as a characteristic feature of the age-associated disorder referred to as cerebral amyloid angiopathy (CAA). This paper describes a patient who presented with transient neurologic symptoms, first suspected to be secondary to acute subarachnoid hemorrhage (SAH), found to have cSS and cerebral amyloid angiopathy.
Pro-social preference in an automated operant two-choice reward task under different housing conditions: Exploratory studies on pro-social decision making.
Developmental cognitive neuroscience, 2020

In this study, we aimed to develop a behavioral task that measures pro-social decision making in rats. A fully automated, operant pro-social two-choice task is introduced that quantifies pro-social preferences for a mutual food reward in a set-up with tightly controlled task contingencies. Pairs of same-sex adult Wistar rats were placed in an operant chamber divided into two compartments (one rat per compartment), separated by a transparent barrier with holes that allowed the rats to see, hear, smell, but not touch each other. Test rats could earn a sucrose pellet either for themselves (own reward) or for themselves and the partner (both reward) by means of lever pressing. On average, male rats showed a 60 % preference for the lever that yielded a food reward for both themselves and their partner. In contrast, females did not show lever preference, regardless of the estrous cycle phase. Next, the impact of juvenile environmental factors on male rat social decision making was studied. Males were group-housed from postnatal day 26 onwards in complex housing Marlau™ cages that provided social and physical enrichment and stimulation in the form of novelty. Complex housed males did not show a preference for the pro-social lever.
Skeletal muscle mTORC1 regulates neuromuscular junction stability.
Journal of cachexia, sarcopenia and muscle, 2020

Skeletal muscle is a plastic tissue that can adapt to different stimuli. It is well established that Mammalian Target of Rapamycin Complex 1 (mTORC1) signalling is a key modulator in mediating increases in skeletal muscle mass and function. However, the role of mTORC1 signalling in adult skeletal muscle homeostasis is still not well defined.
Delineating the Nature and Correlates of Social Dysfunction after Childhood Traumatic Brain Injury Using Common Data Elements: Evidence from an International Multi-Cohort Study.
Journal of neurotrauma, 2021

Although childhood traumatic brain injury (TBI) has been linked to heightened risk of impaired social skills and behavior, current evidence is weakened by small studies of variable methodological quality. To address these weaknesses, this international multi-cohort study involved synthesis of data from two large observational cohort studies of complicated mild-severe child TBI in Australia and North America. Both studies adopted a unified approach to data collection and coding procedures, providing the opportunity to merge datasets from multiple, well-characterized cohorts for which gold standard measures of social outcomes were collected during the chronic recovery phase. The study involved 218 children, including 33 children with severe TBI, 83 children with complicated mild-moderate TBI, 59 children with orthopedic injury, and 43 age- and sex-matched typically developing control children. All injured children were recruited from academic children's hospitals and underwent direct cognitive assessments including measures of theory of mind (ToM) at least 1-year post- injury. Parents rated their child's social adjustment using standardized measures of social skills, communication and behavior. Results showed a brain-injury specific effect on ToM abilities, such that children with both complicated mild to moderate and severe TBI displayed significantly poorer ToM than children without TBI. In mediator models, poorer ToM predicted poorer parent-rated self-direction and social skills, as well as more frequent behavioral symptoms. The ToM mediated the effect of severe TBI on parent ratings of communication and social skills, as well as on overall behavior symptoms. The findings suggest that deficits in ToM are evident across the spectrum of TBI severity and represent one mechanism linking severe child TBI to long-term social adjustment difficulties. The findings underscore the value of large-scale data harmonization projects to increase the quality of evidence regarding the outcomes of TBI. Clinical and scientific implications are discussed.
Prediction of mild parkinsonism revealed by neural oscillatory changes and machine learning.
Journal of neurophysiology, 2020

Neural oscillatory changes within and across different frequency bands are thought to underlie motor dysfunction in Parkinson's disease (PD) and may serve as biomarkers for closed-loop deep brain stimulation (DBS) approaches. Here, we used neural oscillatory signals derived from chronically implanted cortical and subcortical electrode arrays as features to train machine learning algorithms to discriminate between naive and mild PD states in a nonhuman primate model. Local field potential (LFP) data were collected over several months from a 12-channel subdural electrocorticography (ECoG) grid and a 6-channel custom array implanted in the subthalamic nucleus (STN). Relative to the naive state, the PD state showed elevated primary motor cortex (M1) and STN power in the beta, high gamma, and high-frequency oscillation (HFO) bands and decreased power in the delta band. Theta power was found to be decreased in STN but not M1. In the PD state there was elevated beta-HFO phase-amplitude coupling (PAC) in the STN. We applied machine learning with support vector machines with radial basis function (SVM-RBF) kernel and
Synthesis of polyenylpyrrole derivatives with selective growth inhibitory activity against T-cell acute lymphoblastic leukemia cells.
Bioorganic & medicinal chemistry letters, 2021

T-cell acute lymphoblastic leukemia (T-ALL) is a hardly curable disease with a high relapse rate. 20 analogs were synthesized based on the structures of two kinds of fungi-derived polyenylpyrrole products (rumbrin (1) and auxarconjugatin-B (2)) to suppress the growth of T-ALL-derived cell line CCRF-CEM and tested for growth-inhibiting activity. The octatetraenylpyrrole analog gave an IC
The Neurobiology of Health Communication.
Psychosomatic medicine, 2017

This issue of Psychosomatic Medicine describes findings from an innovative study by Kang et al that used neuroimaging methods to quantify neural responses to health communications. Findings indicated that sedentary individuals who hold self-transcendent values show attenuated limbic threat responses to communications about the benefits of physical activity. Furthermore, participants who were instructed to articulate such values showed some evidence of additional blunting of the same neural response. In this editorial, we provide context for the interpretation of these findings within the existing research using the brain-as-predictor approach, and other recent trends within biobehavioral medicine involving the use of neuroscience methods in the service of health behavior change.
Electroretinography may reveal cognitive impairment among a cohort of subjects at risk of a major psychiatric disorder.
Psychiatry research, 2020

Almost a third of the offspring of parents diagnosed with schizophrenia or bipolar disorder could develop a mental disorder or related symptoms. The objectives of this study were to test the existence of two distinct subgroups of youth at-risk, according to their retinal response to luminance measured with electroretinography (ERG), and to relate the resulting cluster memberships with the cognitive clusters previously reported.
The role of neuronal excitability, allocation to an engram and memory linking in the behavioral generation of a false memory in mice.
Neurobiology of learning and memory, 2020

Memory is a constructive, not reproductive, process that is prone to errors. Errors in memory, though, may originate from normally adaptive memory processes. At the extreme of memory distortion is falsely "remembering" an event that did not occur. False memories are well-studied in cognitive psychology, but have received relatively less attention in neuroscience. Here, we took advantage of mechanistic insights into how neurons are allocated or recruited into an engram (memory trace) to generate a false memory in mice using only behavioral manipulations. At the time of an event, neurons compete for allocation to an engram supporting the memory for this event; neurons with higher excitability win this competition (Han et al., 2007). Even after the event, these allocated "engram neurons" remain temporarily (~6 h) more excitable than neighboring neurons. Should a similar event occur in this 6 h period of heightened engram neuron excitability, an overlapping population of neurons will be co-allocated to this second engram, which serves to functionally link the two memories (Rashid et al., 2016). Here, we applied this principle of co-allocation and found that mice develop a false fear memory to a neutral stimulus if exposed to this stimulus shortly (3 h), but not a longer time (24 h), after cued fear conditioning. Similar to co-allocation, the generation of this false memory depended on the post-training excitability of engram neurons such that these neurons remained more excitable during exposure to the neutral stimulus at 3 h but not 24 h. Optogenetically silencing engram neurons 3 h after cued fear conditioning impaired formation of a false fear memory to the neutral stimulus, while optogenetically activating engram neurons 24 h after cued fear conditioning created a false fear memory. These results suggest that some false memories may originate from normally adaptive mnemonic processes such as neuronal excitability-dependent allocation and memory linking.
Gradient theories of brain activation: A novel application to studying the parental brain.
Current behavioral neuroscience reports, 2019

Parental brain research primarily employs general-linear-model-based (GLM-based) analyses to assess blood-oxygenation-level-dependent responses to infant auditory and visual cues, reporting common responses in shared cortical and subcortical structures. However, this approach does not reveal intermixed neural substrates related to different sensory modalities. We consider this notion in studying the parental brain.
A randomized controlled trial of a Group psychological intervention to increase locus of control for alcohol consumption among Alcohol-Misusing Short-term (male) Prisoners (GASP).
Addiction (Abingdon, England), 2020

Reducing alcohol misuse by male prisoners is an important global issue. Control of drinking behaviour could be a useful target for intervention in this population, and locus of control could be a causal factor in this. We aimed to assess the effect of a clinical psychologist-facilitated group intervention on male prisoners' locus of control of drinking behaviour.
Pharmacological Treatment of Mood Disorders and Comorbid Addictions: A Systematic Review and Meta-Analysis: Traitement Pharmacologique des Troubles de L'humeur et des Dépendances Comorbides: Une Revue Systématique et une Méta-Analyse.
Canadian journal of psychiatry. Revue canadienne de psychiatrie, 2020

Addiction comorbidity is an important clinical challenge in mood disorders, but the best way of pharmacologically treating people with mood disorders and addictions remains unclear. The aim of this study was to assess the efficacy of pharmacological treatments for mood and addiction symptoms in people with mood disorders and addiction comorbidity.
Improving Visual Function after Mild Traumatic Brain Injury Using a Vision Therapy Program: Case Reports.
Brain sciences, 2020

This case report describes the outcome of vision therapy for three patients who were referred to therapy due to visual symptoms after mild traumatic brain injury (MTBI). The criterion for inclusion was a high score (>21p) on the Convergence Insufficiency Symptom Survey (CISS) scale. The vision therapy program (VTP) included both face-to-face sessions and home-based tasks. Cases #1 and #2 had a substantial CISS scale evaluation improvement, and case #2 normalized the CISS scale score from 36 to 19. All patients agreed that vision therapy helped them understand their own vision and changes in their vision, which helped their overall recovery after MTBI. Rehabilitation professionals have an important role in screening for vision impairments and treating functional vision challenges after mild traumatic brain injury.