rudyvdbrink/CitationDatabase huggingface dataset:
Advances in colonic motor complexes in mice.
American journal of physiology. Gastrointestinal and liver physiology, 2021

The primary functions of the gastrointestinal (GI) tract are to absorb nutrients, water, and electrolytes that are essential for life. This is accompanied by the capability of the GI tract to mix ingested content to maximize absorption and effectively excrete waste material. There have been major advances in understanding intrinsic neural mechanisms involved in GI motility. This review highlights major advances over the past few decades in our understanding of colonic motor complexes (CMCs), the major intrinsic neural patterns that control GI motility. CMCs are generated by rhythmic coordinated firing of large populations of myenteric neurons. Initially, it was thought that serotonin release from the mucosa was required for CMC generation. However, careful experiments have now shown that neither the mucosa nor endogenous serotonin are required, although, evidence suggests enteroendocrine (EC) cells modulate CMCs. The frequency and extent of propagation of CMCs are highly dependent on mechanical stimuli (circumferential stretch). In summary, the isolated mouse colon emerges as a good model to investigate intrinsic mechanisms underlying colonic motility and provides an excellent preparation to explore potential therapeutic agents on colonic motility, in a highly controlled in vitro environment. In addition, during CMCs, the mouse colon facilitates investigations into the emergence of dynamic assemblies of extensive neural networks, applicable to the nervous system of different organisms.
Recalling the firedog: Individual differences in associative memory for unitized and nonunitized associations among older adults.
Hippocampus, 2020

Memory deficits in aging are characterized by impaired hippocampus-mediated relational binding-the formation of links between items in memory. By reducing reliance on relational binding, unitization of two items into one concept enhances associative recognition among older adults. Can a similar enhancement be obtained when probing memory with recall? This question has yet to be examined, because recall has been assumed to rely predominantly on relational binding. Inspired by recent evidence challenging this assumption, we investigated individual differences in older adults' recall of unitized and nonunitized associations. Compared with successfully aging individuals, older adults with mild memory deficits, typically mediated by the hippocampus, were impaired in recall of paired-associates in a task which relies on relational binding (study: "PLAY-TUNNEL"; test: PLAY-T?). In stark contrast, the two groups showed similar performance when items were unitized into a novel compound word (study: "LOVEGIGGLE"; test: LOVEG?). Thus, boosting nonrelational aspects of recall enhances associative memory among aging individuals with subtle memory impairments to comparable levels as successfully aging older adults.
Endosomal Dysfunction Induced by Directly Overactivating Rab5 Recapitulates Prodromal and Neurodegenerative Features of Alzheimer's Disease.
Cell reports, 2020

Neuronal endosomal dysfunction, the earliest known pathobiology specific to Alzheimer's disease (AD), is mediated by the aberrant activation of Rab5 triggered by APP-β secretase cleaved C-terminal fragment (APP-βCTF). To distinguish pathophysiological consequences specific to overactivated Rab5 itself, we activate Rab5 independently from APP-βCTF in the PA-Rab5 mouse model. We report that Rab5 overactivation alone recapitulates diverse prodromal and degenerative features of AD. Modest neuron-specific transgenic Rab5 expression inducing hyperactivation of Rab5 comparable to that in AD brain reproduces AD-related Rab5-endosomal enlargement and mistrafficking, hippocampal synaptic plasticity deficits via accelerated AMPAR endocytosis and dendritic spine loss, and tau hyperphosphorylation via activated glycogen synthase kinase-3β. Importantly, Rab5-mediated endosomal dysfunction induces progressive cholinergic neurodegeneration and impairs hippocampal-dependent memory. Aberrant neuronal Rab5-endosome signaling, therefore, drives a pathogenic cascade distinct from β-amyloid-related neurotoxicity, which includes prodromal and neurodegenerative features of AD, and suggests Rab5 overactivation as a potential therapeutic target.
Correction to: The unexplained success of stentplasty vasospasm treatment : Insights using Mechanistic Mathematical Modeling.
Clinical neuroradiology, 2019

Correction to: Clin Neuroradiol 2019 https://doi.org/10.1007/s00062-019-00776-2 The original version of this article unfortunately contained a mistake. The Acknowledgements were missing. The correct information is given ….
Predictive validity of the Italian parental questionnaire for developmental evaluation at age 4 (QS4-G).
Journal of paediatrics and child health, 2015

To examine whether the results at 4 years of age of the developmental questionnaire QS4-G can predict the outcome of cognitive, neuropsychological and academic abilities 4-6 years later. The QS4-G is a validated parental questionnaire designed for the screening and surveillance of the neuropsychological and behavioural developmental status of 4-year-olds (93 questions).
Designed PKC-targeting bryostatin analogs modulate innate immunity and neuroinflammation.
Cell chemical biology, 2021

Neuroinflammation characterizes multiple neurologic diseases, including primary inflammatory conditions such as multiple sclerosis and classical neurodegenerative diseases. Aberrant activation of the innate immune system contributes to disease progression, but drugs modulating innate immunity, particularly within the central nervous system (CNS), are lacking. The CNS-penetrant natural product bryostatin-1 attenuates neuroinflammation by targeting innate myeloid cells. Supplies of natural bryostatin-1 are limited, but a recent scalable good manufacturing practice (GMP) synthesis has enabled access to it and its analogs (bryologs), the latter providing a path to more efficacious, better tolerated, and more accessible agents. Here, we show that multiple synthetically accessible bryologs replicate the anti-inflammatory effects of bryostatin-1 on innate immune cells in vitro, and a lead bryolog attenuates neuroinflammation in vivo, actions mechanistically dependent on protein kinase C (PKC) binding. Our findings identify bryologs as promising drug candidates for targeting innate immunity in neuroinflammation and create a platform for evaluation of synthetic PKC modulators in neuroinflammatory diseases.
A Neurite Outgrowth Assay and Neurotoxicity Assessment with Human Neural Progenitor Cell-Derived Neurons.
Journal of visualized experiments : JoVE, 2020

Neurite outgrowth assay and neurotoxicity assessment are two major studies that can be performed using the presented method herein. This protocol provides reliable analysis of neuronal morphology together with quantitative measurements of modifications on neurite length and synaptic protein localization and abundance upon treatment with small molecule compounds. In addition to the application of the presented method in neurite outgrowth studies, neurotoxicity assessment can be performed to assess, distinguish and rank commercial chemical compounds based on their potential developmental neurotoxicity effect. Even though cell lines are nowadays widely used in compound screening assays in neuroscience, they often differ genetically and phenotypically from their tissue origin. Primary cells, on the other hand, maintain important markers and functions observed in vivo. Therefore, due to the translation potential and physiological relevance that these cells could offer neurite outgrowth assay and neurotoxicity assessment can considerably benefit from using human neural progenitor cells (hNPCs) as the primary human cell model. The presented method herein can be utilized to screen for the ability of compounds to induce neurite outgrowth and neurotoxicity by taking advantage of the human neural progenitor cell-derived neurons, a cell model closely representing human biology."
Comparing Safety and Efficacy of Dabigatran and Factor Xa Inhibitors for Stroke Prevention in Hemophiliacs with Non-Valvular Atrial Fibrillation.
Journal of atrial fibrillation, 2019

Atrial fibrillation, a progressively rising global health problem, is also rising in Hemophiliacs due to an increase in life expectancy in them. While treating Hemophiliacs with AF, deciding eligibility, choosing the anticoagulant based on risk-benefit ratio are tough decisions for physicians to make. This review paper aims to explore and compare existing studies, reviews and consensus papers to assess the safety of different Novel Oral Anticoagulants (NOACS) in this population.
Cerebellar Degeneration Increases Visual Influence on Dynamic Estimates of Verticality.
Current biology : CB, 2018

Our perception of verticality relies on combining sensory information from multiple sources. Neuronal recordings in animals implicate the cerebellum in the process, yet disease of the human cerebellum was not found to affect this perception. Here we show that a perceptual disturbance of verticality is indeed present in people with a genetically determined and pure form of cerebellar degeneration (spinocerebellar ataxia type 6; SCA 6), but is only revealed under dynamic visual conditions. Participants were required to continuously orient a visually displayed bar to vertical while the bar angle was perturbed by a low-frequency random signal and a random dot pattern rotated in their visual periphery. The random dot pattern was rotated at one of two velocities (4°/s and 16°/s), traveling with either coherent or noisy motion. Perceived vertical was biased by visual rotation in healthy participants, particularly in a more elderly group, but SCA 6 participants were biased more than both groups. The bias was reduced by visual noise, but more so for SCA 6 participants than young controls. Distortion of verticality by visual rotation stems from the stimulus creating an illusion of self-rotation. We modeled this process using a maximum-likelihood sensory cue-combination model operating on noisy visual- and vestibular-rotation signals. The observed effects of visual rotation and visual noise could be compellingly explained by cerebellar degeneration, and to a lesser extent aging, causing an increase in central vestibular noise. This is consistent with the human cerebellum operating on dynamic vestibular signals to inform the process that estimates which way is up.
Electronic Implementation of Integrated End-of-life Care: A Local Approach.
International journal of integrated care, 2017

The Liverpool Care Pathway for the Dying Patient is an instrument to deliver integrated care for patients in their last hours of life. Originally a paper-based system, this study investigates the feasibility of an electronic version.
Melatonin treatment reverses cognitive and endocrine deficits evoked by a 24-h light exposure in adult zebrafish.
Neuroscience letters, 2020

Melatonin is an important pineal hormone that regulates human and animal circadian rhythms and sleep. Mounting clinical and rodent evidence indicates that melatonin also modulates affective behaviors and cognition. The zebrafish (Danio rerio) is rapidly becoming a powerful novel model organism in translational neuroscience research. Here, we evaluate the effects of a 24-h melatonin treatment on behavior and physiology of adult zebrafish with circadian rhythm disturbed by a 24-h light exposure. While such light exposure evoked overt cognitive and neuroendocrine (cortisol) deficits in zebrafish, these effects were reversed by a 24-h melatonin treatment. Collectively, these findings suggest a positive modulation of affective and cognitive phenotypes in zebrafish by melatonin, and reinforce the growing utility of zebrafish models for studying circadian, cognitive and behavioral processes and their neuroendocrine regulation in vivo.
Treating TB human neuroectodermal cell line with retinoic acid induces the appearance of neuron-like voltage-gated ionic currents.
Brain research, 2019

TB is a cell line derived from the cerebrospinal fluid sample of a patient with primary leptomeningeal melanomatosis. Our previous immunological and ultrastructural analysis revealed that TB cells differentiate towards a neuronal phenotype when grown in vitro up to 7 days in presence of 10 µM all-trans retinoic acid (RA). Recently, we reported that TB cells are sensitive to the cytotoxic effects of β-amyloid peptides, activating the cytosolic phospholipase A2. To date, it is not known if RA, in addition to inducing morphological changes, also causes functional modification in TB cells, by regulating voltage-gated ionic currents. To this purpose, we performed electrophysiological characterization of undifferentiated (TB) and differentiated (RA-TB) cells by means of whole-cell patch clamp recordings. Upon depolarizing stimuli, both groups displayed voltage-gated K
Microbleeds and the Effect of Anticoagulation in Patients With Embolic Stroke of Undetermined Source: An Exploratory Analysis of the NAVIGATE ESUS Randomized Clinical Trial.
JAMA neurology, 2021

The reported associations of cerebral microbleeds with recurrent stroke and intracerebral hemorrhage have raised concerns regarding antithrombotic treatment in patients with a history of stroke and microbleeds on magnetic resonance imaging.
Simvastatin Prevents Long-Term Cognitive Deficits in Sepsis Survivor Rats by Reducing Neuroinflammation and Neurodegeneration.
Neurotoxicity research, 2020

Sepsis-associated encephalopathy causes brain dysfunction that can result in cognitive impairments in sepsis survivor patients. In previous work, we showed that simvastatin attenuated oxidative stress in brain structures related to memory in septic rats. However, there is still a need to evaluate the long-term impact of simvastatin administration on brain neurodegenerative processes and cognitive damage in sepsis survivors. Here, we investigated the possible neuroprotective role of simvastatin in neuroinflammation, and neurodegeneration conditions of brain structures related to memory in rats at 10 days after sepsis survival. Male Wistar rats (250-300 g) were submitted to cecal ligation and puncture (CLP, n = 42) or remained as non-manipulated (naïve, n = 30). Both groups were treated (before and after the surgery) by gavage with simvastatin (20 mg/kg) or an equivalent volume of saline and observed for 10 days. Simvastatin-treated rats that survived to sepsis showed a reduction in the levels of nitrate, IL1-β, and IL-6 and an increase in Bcl-2 protein expression in the prefrontal cortex and hippocampus, and synaptophysin only in the hippocampus. Immunofluorescence revealed a reduction of glial activation, neurodegeneration, apoptosis, and amyloid aggregates confirmed by quantification of GFAP, Iba-1, phospho Ser
Contrast enhanced ultrasound (CEUS) applications in neurosurgical and neurological settings - New scenarios for brain and spinal cord ultrasonography. A systematic review.
Clinical neurology and neurosurgery, 2020

Contrast-enhanced ultrasound (CEUS) is a real-time, feasible technique. Both intraoperatively and bedside, it satisfies the need for serial assessment and easy performability. Initially employed in neuro-oncology, it has recently overcome this first application. We aimed to evaluate the literature and give a comprehensive view of its use in the fields listed below. A systematic review of all pertinent literature was performed via PubMed access according PRISMA P guidelines. Studies not involving human adults and not reporting original data were excluded. Cross-check of references of selected articles was performed to complete bibliographical research. 67 articles were then grouped by field of application: Oncology (26 articles) further subdivided in a) cranial tumors (23 articles) and b) spinal tumors (3 articles); Vascular (31 articles), divided in three sections: a) aneurysms, AVMs and AVFs surgery (6 articles), b) cerebral perfusion assessment and acute stroke patients management (15 articles), c) carotid plaques treatment (10 articles); TBI (2 articles); Pediatrics (4 articles); Peripheral nerve surgery (2 articles) and others (2 articles). CEUS versatility across the aforementioned areas was analyzed, underlining its complementarity to other well-settled imaging techniques. This review is focused on reporting CEUS advantages and disadvantages, suggesting a further broadening of the already numerous applications.
Immunological reactions following intracerebroventricular transplantation of adrenal medulla.
Restorative neurology and neuroscience, 1994

Immunological reactions after intracerebroventricular syn-, allo- and xenogenic transplantation of adrenal medulla were investigated histologically. In xenografts only, T cell infiltration and graft rejection were observed. Syngrafts and allografts were not rejected and were not infiltrated by T cells, although expression of MHC class II antigen was observed at all survival times. Major histocompatibility complex (MHC) class I immunoreactivity was strongly expressed in adrenal cortex syngrafts, which could play a role in the rejection of grafts containing mixed cell populations. The survival of chromaffin cells in allografts was decreased as compared to syngrafts, and there were fewer allograft animals with large numbers of surviving chromaffin cells. There was some increased cellularity (microglia and macrophages) in allografts even though no T cell infiltration was found. Therefore, it appears that this limited survival of intracerebral adrenal medulla allografts is not due to T cell-mediated graft rejection.
Kv4.1, a Key Ion Channel For Low Frequency Firing of Dentate Granule Cells, Is Crucial for Pattern Separation.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2020

The dentate gyrus (DG) in the hippocampus may play key roles in remembering distinct episodes through pattern separation, which may be subserved by the sparse firing properties of granule cells (GCs) in the DG. Low intrinsic excitability is characteristic of mature GCs, but ion channel mechanisms are not fully understood. Here, we investigated ionic channel mechanisms for firing frequency regulation in hippocampal GCs using male and female mice, and identified Kv4.1 as a key player. Immunofluorescence analysis showed that Kv4.1 was preferentially expressed in the DG, and its expression level determined by Western blot analysis was higher at 8-week than 3-week-old mice, suggesting a developmental regulation of Kv4.1 expression. With respect to firing frequency, GCs are categorized into two distinctive groups: low-frequency (LF) and high-frequency (HF) firing GCs. Input resistance (
A mathematical model of negative covariability of inter-columnar excitatory synaptic actions caused by presynaptic inhibition.
The European journal of neuroscience, 2013

We previously showed that a positive covariability between intracortical excitatory synaptic actions onto the two layer three pyramidal cells (PCs) located in mutually adjacent columns is changed into a negative covariability by column-wise presynaptic inhibition of intracortical inputs, implicated as a basis for the desynchronization of inter-columnar synaptic actions. Here we investigated how the inter-columnar desynchronization is modulated by the strength of presynaptic inhibition or other factors, by using a mathematical model. Based on our previous findings on the paired-pulse depression (PPD) of intracortical excitatory postsynaptic currents (EPSCs) evoked in PCs located in the stimulated home column (HC) but no PPD in PCs located in the adjacent column (AC), a mathematical model of synaptic connections between PCs and inhibitory interneurons was constructed. When the paired-pulse ratio (PPR) was decreased beyond 0.80, the correlation coefficient between the two second EPSC amplitudes in the paired PCs located in the HC and AC and that in the paired PCs located in the same HC exhibited opposite changes, and reached a global negative maximum and local positive maximum, respectively, at almost the same PPR (0.40). At this PPR, the desynchronization between the two cell assemblies in mutually adjacent columns would be maximized. These positive and negative covariabilities were not produced without background oscillatory synchronization across columns and were enhanced by increasing the synchronization magnitude, indicating that the synchronization leads to the desynchronization. We propose that a slow oscillatory synchronization across columns may emerge following the liberation from the column-wise presynaptic inhibition of inter-columnar synaptic inputs.
Quality and Clinical Care Development in Spine Surgery-Connecting the Dots: An Expanded Clinical Narrative.
Global spine journal, 2020

Our health care system is an evidenced-based quality-centric environment. Pursuit of quality is a process that encompasses knowledge development and care advancements through collaboration and expertise. Depicted here is the foundational knowledge, process, and contributions that hallmark successful clinical quality programs. Beginning with methodology, followed by process and form, we create the foundational knowledge and exemplars demonstrating framework and continuum of process in pursuit and attainment of successful clinical quality and care development for patients. Although our protocol has been devised for complex spine care, this could be implemented across all health care specialties to provide individualized and high-quality care for all current and future patients, all while creating a culture of accountability for physicians.
Global REACH 2018: renal oxygen delivery is maintained during early acclimatization to 4,330 m.
American journal of physiology. Renal physiology, 2020

Early acclimatization to high altitude is characterized by various respiratory, hematological, and cardiovascular adaptations that serve to restore oxygen delivery to tissue. However, less is understood about renal function and the role of renal oxygen delivery (RDO
(D620N) VPS35 causes the impairment of Wnt/β-catenin signaling cascade and mitochondrial dysfunction in a PARK17 knockin mouse model.
Cell death & disease, 2020

Patients with familial type 17 of Parkinson's disease (PARK17) manifest autosomal dominant pattern and late-onset parkinsonian syndromes. Heterozygous (D620N) mutation of vacuolar protein sorting 35 (VPS35) is genetic cause of PARK17. We prepared heterozygous VPS35
The Understanding of Pediatric Akinetic Mutism.
Cureus, 2021

Pediatric akinetic mutism syndrome is a clinical disease resulting from cerebellar injury and characterized by the absence of speech or reduced speech, emotional lability, there may also be hypotonia, oropharyngeal dysfunction/dysphagia, bladder and intestinal incontinence, or other behavioral disorders and neurological signals. It is described as the most recurrent complication in children, after posterior fossa tumor surgery, mainly related to cerebellar midline injuries. An increasing number of research and prospective reviews have provided valuable information on cerebellar mutism syndrome in recent years. The purpose of this review was to elucidate the pathophysiological basis and the predictive factors for this syndrome. Most cases of mutism are due to injury cerebellar tracts and cerebellar-cerebral circuits, involving particularly distinct points of the dentate-thalamus-cortical and dentato-rubro-thalamus-cortical. Advanced neuroimaging techniques, such as tractography and perfusion studies, have contributed to demonstrating changes in these pathways in patients with pediatric cerebellar mutism.