rudyvdbrink/CitationDatabase huggingface dataset:
Inactivation of Prions and Amyloid Seeds with Hypochlorous Acid.
PLoS pathogens, 2016

Hypochlorous acid (HOCl) is produced naturally by neutrophils and other cells to kill conventional microbes in vivo. Synthetic preparations containing HOCl can also be effective as microbial disinfectants. Here we have tested whether HOCl can also inactivate prions and other self-propagating protein amyloid seeds. Prions are deadly pathogens that are notoriously difficult to inactivate, and standard microbial disinfection protocols are often inadequate. Recommended treatments for prion decontamination include strongly basic (pH ≥~12) sodium hypochlorite bleach, ≥1 N sodium hydroxide, and/or prolonged autoclaving. These treatments are damaging and/or unsuitable for many clinical, agricultural and environmental applications. We have tested the anti-prion activity of a weakly acidic aqueous formulation of HOCl (BrioHOCl) that poses no apparent hazard to either users or many surfaces. For example, BrioHOCl can be applied directly to skin and mucous membranes and has been aerosolized to treat entire rooms without apparent deleterious effects. Here, we demonstrate that immersion in BrioHOCl can inactivate not only a range of target microbes, including spores of Bacillus subtilis, but also prions in tissue suspensions and on stainless steel. Real-time quaking-induced conversion (RT-QuIC) assays showed that BrioHOCl treatments eliminated all detectable prion seeding activity of human Creutzfeldt-Jakob disease, bovine spongiform encephalopathy, cervine chronic wasting disease, sheep scrapie and hamster scrapie; these findings indicated reductions of ≥103- to 106-fold. Transgenic mouse bioassays showed that all detectable hamster-adapted scrapie infectivity in brain homogenates or on steel wires was eliminated, representing reductions of ≥~105.75-fold and >104-fold, respectively. Inactivation of RT-QuIC seeding activity correlated with free chlorine concentration and higher order aggregation or destruction of proteins generally, including prion protein. BrioHOCl treatments had similar effects on amyloids composed of human α-synuclein and a fragment of human tau. These results indicate that HOCl can block the self-propagating activity of prions and other amyloids.
Functional cooperation of α-synuclein and VAMP2 in synaptic vesicle recycling.
Proceedings of the National Academy of Sciences of the United States of America, 2019

The function of α-synuclein (α-syn) has been long debated, and two seemingly divergent views have emerged. In one, α-syn binds to VAMP2, acting as a SNARE chaperone-but with no effect on neurotransmission-while another posits that α-syn attenuates neurotransmitter release by restricting synaptic vesicle mobilization and recycling. Here, we show that α-syn-VAMP2 interactions are necessary for α-syn-induced synaptic attenuation. Our data connect divergent views and suggest a unified model of α-syn function.
The Role of Representation Strength of the Prime in Subliminal Visuomotor Priming.
Experimental psychology, 2017

This study investigated the role of representation strength of the prime in subliminal visuomotor priming in two experiments. Prime/target compatibility (compatible and incompatible) and preposed object type (jumbled lines, strong masking; and rectangular outlines, weak masking) were manipulated in Experiment 1. A significant negative compatibility effect (NCE) was observed in the rectangle condition, whereas no compatibility effect was found in the line condition. However, when a new variable, prime duration, was introduced in Experiment 2, the NCE was reversed with an increase in the prime duration in the rectangle condition, whereas the NCE was maintained in the line condition. This result is consistent with the claim that increasing the prime duration causes the prime representation to be too strong for inhibition in the rectangle condition but strong enough to reliably trigger inhibition in the line condition. The findings demonstrated that prime representation has a causal role in subliminal visuomotor priming.
Transcranial magnetic stimulation of early visual cortex suppresses conscious representations in a dichotomous manner without gradually decreasing their precision.
NeuroImage, 2017

Transcranial magnetic stimulation (TMS) of early visual cortex can suppresses visual perception at early stages of processing. The suppression can be measured both with objective forced-choice tasks and with subjective ratings of visual awareness, but there is lack of objective evidence on how and whether the TMS influences the quality of representations. Does TMS decrease the precision of representations in graded manner, or does it lead to dichotomous, "all-or-nothing" suppression. We resolved this question by using a continuous measure of the perceptual error: the observers had to perceive the orientation of a target (Landort-C) and to adjust the orientation of a probe to match that of the target. Mixture modeling was applied to estimate the probability of guess trials and the standard deviation of the non-guess trials. TMS delivered 60-150 ms after stimulus-onset influenced only the guessing rate, whereas the standard deviation (i.e., precision) was not affected. This suggests that TMS suppressed representations dichotomously without affecting their precision. The guessing probability correlated with subjective visibility ratings, suggesting that it measured visual awareness. In a control experiment, manipulation of the stimulus contrast affected the standard deviation of the errors, indicating that contrast has a gradual influence on the precision of representations. The findings suggest that TMS of early visual cortex suppresses perception in dichotomous manner by decreasing the signal-to-noise ratio by increasing the noise level, whereas reduction of the signal level (i.e., contrast) decreases the precision of representations.
Efficacy of combination therapy with erythropoietin and methylprednisolone in clinical recovery of severe relapse in multiple sclerosis.
Acta neurologica Belgica, 2014

Multiple sclerosis (MS) is a multifaceted disease in which genetic and environmental factors are involved. Although neurodegeneration aspect of MS has major influence in patients' disability, none of the available treatments have been shown to obviously reduce neurodegeneration. Recently, the role of Erythropoietin (EPO) as a neuroprotective and anti-inflammatory agent has been attracted tremendous interest. In the present randomized double-blind pilot study, we combined EPO with methylprednisolone (MPred) in severe motor relapsing-remitting MS (RR-MS) patients to target both inflammatory and neurodegenerative aspects of disease. Twenty patients with RR-MS in relapse phase were randomized into two groups. The case group (10 patients) received intravenous MPred (1,000 mg/24 h) and intravenous EPO (20,000 U/24 h) for five consecutive days, and the control group (10 patients) received just MPred at the same dose as the case group, and a placebo. Both groups were followed for 3 months by ambulatory index (AI), Expanded Disability Status Scale (EDSS) and by magnetic resonance imaging (MRI) parameters. Improvement in maximal distance walking, reflected by reduction in AI and EDSS, was observed in EPO group after second month and continued after 3 months. Furthermore, MRI data analysis showed significant reduction in the number of T2WI lesions in EPO group without any significant change in contrast enhancing and black hole lesions. There was no major side effect in EPO group. The results of this first therapeutic pilot trial in RR-MS patients are promising, but need to be validated in larger trials.
Anxiety Disorders in Williams Syndrome Contrasted with Intellectual Disability and the General Population: A Systematic Review and Meta-Analysis.
Journal of autism and developmental disorders, 2017

Individuals with specific genetic syndromes associated with intellectual disability (ID), such as Williams syndrome (WS), are at increased risk for developing anxiety disorders. A systematic literature review identified sixteen WS papers that could generate pooled prevalence estimates of anxiety disorders for WS. A meta-analysis compared these estimates with prevalence estimates for the heterogeneous ID population and the general population. Estimated rates of anxiety disorders in WS were high. WS individuals were four times more likely to experience anxiety than individuals with ID, and the risk was also heightened compared to the general population. The results provide further evidence of an unusual profile of high anxiety in WS.
Brain Connectivity Modulation After Exoskeleton-Assisted Gait in Chronic Hemiplegic Stroke Survivors: A Pilot Study.
American journal of physical medicine & rehabilitation, 2020

The aim of this study was to investigate electroencephalographic (EEG) connectivity short-term changes, quantified by node strength and betweenness centrality, induced by a single trial of exoskeleton-assisted gait in chronic stroke survivors.
PIEZO2 is required for mechanotransduction in human stem cell-derived touch receptors.
Nature neuroscience, 2015

Human sensory neurons are inaccessible for functional examination, and thus little is known about the mechanisms mediating touch sensation in humans. Here we demonstrate that the mechanosensitivity of human embryonic stem (hES) cell-derived touch receptors depends on PIEZO2. To recapitulate sensory neuron development in vitro, we established a multistep differentiation protocol and generated sensory neurons via the intermediate production of neural crest cells derived from hES cells or human induced pluripotent stem (hiPS) cells. The generated neurons express a distinct set of touch receptor-specific genes and convert mechanical stimuli into electrical signals, their most salient characteristic in vivo. Strikingly, mechanosensitivity is lost after CRISPR/Cas9-mediated PIEZO2 gene deletion. Our work establishes a model system that resembles human touch receptors, which may facilitate mechanistic analysis of other sensory subtypes and provide insight into developmental programs underlying sensory neuron diversity.
"I never forget a face, but in your case I'll be glad to make an exception": Intentional forgetting of emotional faces.
Canadian journal of experimental psychology = Revue canadienne de psychologie experimentale, 2014

The current study used the item-method directed forgetting paradigm to determine whether there are limits on the ability to intentionally forget angry faces. During the study phase, faces were presented, 1 at a time, each followed by an instruction to remember or forget. Following the presentation of all faces, participants performed a yes-no recognition test. In 2 experiments that varied only the presentation duration of the face (500 ms vs. 1,000 ms), we observed an overall directed forgetting effect, with greater recognition of faces studied with remember rather than forget instructions; the magnitude of this effect did not vary with emotional expression. We interpret these results in light of the proposal that priority processing of angry faces benefits the speed of forming an enduring long-term memory trace rather than increasing the strength of that trace.
Toll-like receptor-2, CD14 and heat-shock protein 70 in inflammatory lesions of rat experimental autoimmune neuritis.
Neuroscience, 2009

Experimental autoimmune neuritis (EAN) is a well-known animal model of Guillain-Barré syndrome (GBS) characterized by inflammation and demyelination in the peripheral nervous system. Toll-like receptors (TLRs) together with their co-receptors form the first line of the self-defense, and play important roles in innate immune responses and inflammation. TLRs can be activated by endogenous ligands, like heat shock protein 70 (HSP70). In this study, we examined the spatiotemporal expressions of TLR2, CD14 and Hsp70 in EAN rats using immunohistochemistry and RT-PCR. A significant up-regulation of TLR2, CD14 and Hsp70 was seen in sciatic nerves of EAN rats and correlated with disease severity. Furthermore, activated macrophages were the main cellular resource of TLR2, CD14 and Hsp70 in EAN. Our results suggest that TLR2-, CD14- or Hsp70-based immunomodulation might have potential in the control of unwanted innate immune system activation in inflammatory neuropathies.
Brain tumor-related epilepsy.
Current neuropharmacology, 2012

In patients with brain tumor (BT), seizures are the onset symptom in 20-40% of patients, while a further 20-45% of patients will present them during the course of the disease. These patients present a complex therapeutic profile and require a unique and multidisciplinary approach. The choice of antiepileptic drugs is challenging for this particular patient population because brain tumor-related epilepsy (BTRE) is often drug-resistant, has a strong impact on the quality of life and weighs heavily on public health expenditures.In BT patients, the presence of epilepsy is considered the most important risk factor for long-term disability. For this reason, the problem of the proper administration of medications and their potential side effects is of great importance, because good seizure control can significantly improve the patient's psychological and relational sphere. In these patients, new generation drugs such as gabapentin, lacosamide, levetiracetam, oxcarbazepine, pregabalin, topiramate, zonisamide are preferred because they have fewer drug interactions and cause fewer side effects. Among the recently marketed drugs, lacosamide has demonstrated promising results and should be considered a possible treatment option. Therefore, it is necessary to develop a customized treatment plan for each individual patient with BTRE. This requires a vision of patient management concerned not only with medical therapies (pharmacological, surgical, radiological, etc.) but also with emotional and psychological support for the individual as well as his or her family throughout all stages of the illness.
Optical Lace for Synthetic Afferent Neural Networks.
Science robotics, 2019

While vision dominates sensing in robots, animals with limited vision deftly navigate their environment using other forms of perception such as touch. Efforts have been made to apply artificial skins with tactile sensing to robots for similarly sophisticated mobile and manipulative skills. The ability to functionally mimic the afferent sensory neural network, required for distributed sensing and communication networks throughout the body is still missing. This limitation is partially due to the lack of cointegration of the mechanosensors in the body of the robot. In this paper, lacings of stretchable optical fibers distributed throughout 3D printed elastomer frameworks create a cointegrated body, sensing, and communication network. This soft, functional structure can localize deformation with sub-millimeter positional accuracy (Err = 0.71 mm), and sub-Newton force resolution (~0.3 N).
Modulation of SIRT1 expression in different neurodegenerative models and human pathologies.
Neuroscience, 2008

We examined the expression of SIRT1 in several experimental paradigms of human pathologies. We used a neuroblastoma cell line (B65), neuronal primary cultures (hippocampus and cerebellar granule cells) and in vivo approaches in rat and senescence murine models (SAM). Cell cultures and rats were treated with several well-know neurotoxins, i.e. rotenone, MPP(+), kainate and 3-nitropropionic acid. Subsequently, SIRT1 expression was compared in these different paradigms of neurotoxicity. The pattern of expression of SIRT1 in proliferating cell cultures (B65) was different to that in quiescent cell cultures. In the murine model of senescence (senescence-accelerated mice prone, SAMP8), SIRT1 expression progressively decreased, while in the control strain (senescence-accelerated mice resistant, SAMR1) it increased. Finally, we studied human samples of Parkinson's disease (PD), dementia with Lewy bodies (DLB) and Huntington's diseases (HD). SIRT1 expression decreased dramatically in HD, but there were no significant changes in Parkinson-related illnesses. In conclusion, SIRT1 expression may be a good sensor of toxic neuronal processes.
Two-step polymer- and liposome-enzyme prodrug therapies for cancer: PDEPT and PELT concepts and future perspectives.
Advanced drug delivery reviews, 2017

Polymer-directed enzyme prodrug therapy (PDEPT) and polymer enzyme liposome therapy (PELT) are two-step therapies developed to provide anticancer drugs site-selective intratumoral accumulation and release. Nanomedicines, such as polymer-drug conjugates and liposomal drugs, accumulate in the tumor site due to extravasation-dependent mechanism (enhanced permeability and retention - EPR - effect), and further need to cross the cellular membrane and release their payload in the intracellular compartment. The subsequent administration of a polymer-enzyme conjugate able to accumulate in the tumor tissue and to trigger the extracellular release of the active drug showed promising preclinical results. The development of polymer-enzyme, polymer-drug conjugates and liposomal drugs had undergone a vast advancement over the past decades. Several examples of enzyme mimics for in vivo therapy can be found in the literature. Moreover, polymer therapeutics often present an enzyme-sensitive mechanism of drug release. These nanomedicines can thus be optimal substrates for PDEPT and this review aims to provide new insights and stimuli toward the future perspectives of this promising combination.
The role of memantine in the treatment of psychiatric disorders other than the dementias: a review of current preclinical and clinical evidence.
CNS drugs, 2012

Memantine, a non-competitive NMDA receptor antagonist approved for Alzheimer's disease with a good safety profile, is increasingly being studied in a variety of non-dementia psychiatric disorders. We aimed to critically review relevant literature on the use of the drug in such disorders. We performed a PubMed search of the effects of memantine in animal models of psychiatric disorders and its effects in human studies of specific psychiatric disorders. The bulk of the data relates to the effects of memantine in major depressive disorder and schizophrenia, although more recent studies have provided data on the use of the drug in bipolar disorder as an add-on. Despite interesting preclinical data, results in major depression are not encouraging. Animal studies investigating the possible usefulness of memantine in schizophrenia are controversial; however, interesting findings were obtained in open studies of schizophrenia, but negative placebo-controlled, double-blind studies cast doubt on their validity. The effects of memantine in anxiety disorders have been poorly investigated, but data indicate that the use of the drug in obsessive-compulsive disorder and post-traumatic stress disorder holds promise, while findings relating to generalized anxiety disorder are rather disappointing. Results in eating disorders, catatonia, impulse control disorders (pathological gambling), substance and alcohol abuse/dependence, and attention-deficit hyperactivity disorder are inconclusive. In most psychiatric non-Alzheimer's disease conditions, the clinical data fail to support the usefulness of memantine as monotherapy or add-on treatment However, recent preclinical and clinical findings suggest that add-on memantine may show antimanic and mood-stabilizing effects in treatment-resistant bipolar disorder.
Longitudinal quantitative electroencephalographic study in mono-hemispheric stroke patients.
Neural regeneration research, 2019

The identification of individual factors modulating clinical recovery after a stroke is fundamental to personalize the therapeutic intervention to enhance the final clinical outcome. In this framework, electrophysiological factors are promising since are more directly related to neuroplasticity, which supports recovery in stroke patients, than neurovascular factors. In this retrospective observational study, we investigated brain neuronal activity assessed via spectral features and Higuchi's fractal dimension (HFD) of electroencephalographic signals in acute phase (2-10 days from symptom onset, T0) and sub-acute phase (2.5 months, T1) in 24 patients affected by unilateral middle cerebral artery stroke. Longitudinal assessment of the clinical deficits was performed using the National Institutes of Health Stroke Scale (NIHSS), together with the effective recovery calculated as the ratio between difference of NIHSS at T0 and T1 over the NIHSS value at T0. We observed that delta and alpha band electroencephalographic signal power changed between the two phases in both the hemispheres ipsilateral (ILH) and contralateral (CHL) to the lesion. Moreover, at T0, bilateral higher delta band power correlated with worse clinical conditions (Spearman's r
α2-containing GABA(A) receptors: a requirement for midazolam-escalated aggression and social approach in mice.
Psychopharmacology, 2015

Benzodiazepines (BZDs) are prescribed to reduce anxiety, agitation, and muscle spasms and for their sedative-hypnotic and anticonvulsant effects. Under specific conditions, BZDs escalate aggression in some individuals. Specific effects of BZDs have been linked to the α-subunit subtype composition of GABAA receptors.
Trauma-symptom profiles of adolescents in child welfare.
Child abuse & neglect, 2017

In the province of Ontario (Canada), over 28,900 adolescents are investigated by child welfare agencies each year because of suspected maltreatment. Exposure to childhood maltreatment represents a major threat to the psychological well-being of young people, particularly in terms of trauma-related stress. The present study investigated trauma symptom profiles among 479 adolescents (13-17 years) involved with the Canadian child welfare system between 2003 and 2010. Latent profile analysis identified three profiles using self-report data from the Trauma Symptom Checklist for Children. Most adolescents (59%, n=281) were classified into the profile depicting minimal trauma-related symptoms, 30% (n=144) were characterized by moderate trauma-related symptoms, and 11% (n=54) were in the profile reflecting severe trauma-related symptoms. Several variables predicted profile membership. Greater severity of sexual abuse and female sex were associated with a greater likelihood of belonging to the severe trauma symptom profile than both the moderate and the minimal trauma symptom profiles. In addition, having society ward status (compared to crown ward) was related to an increased likelihood of belonging to both the severe and moderate symptom profiles relative to the minimal symptom profile. This study provides some insight into the typologies of trauma experienced among child-welfare-involved adolescents and the set of factors which relate to the specific profiles. Findings are important for informing psychological assessment practices, as well as tailored interventions, for adolescents in the child welfare system.