rudyvdbrink/CitationDatabase huggingface dataset:
The combined use of surgery and radiotherapy to treat patients with epidural cord compression due to metastatic disease: a cost-utility analysis.
Neuro-oncology, 2012

Neoplastic metastatic epidural spinal cord compression is a common complication of cancer that causes pain and progressive neurologic impairment. The previous standard treatment for this condition involved corticosteroids and radiotherapy (RT). Direct decompressive surgery with postoperative radiotherapy (S + RT) is now increasingly being chosen by clinicians to significantly improve patients' ability to walk and reduce their need for opioid analgesics and corticosteroids. A cost-utility analysis was conducted to compare S + RT with RT alone based on the landmark randomized clinical trial by Patchell et al. (2005). It was performed from the perspective of the Ontario Ministry of Health and Long-Term Care. Ontario-based costs were adjusted to 2010 US dollars. S + RT is more costly but also more effective than corticosteroids and RT alone, with an incremental cost-effectiveness ratio of US$250 307 per quality-adjusted life year (QALY) gained. First order probabilistic sensitivity analysis revealed that the probability of S + RT being cost-effective is 18.11%. The cost-effectiveness acceptability curve showed that there is a 91.11% probability of S + RT being cost-effective over RT alone at a willingness-to-pay of US$1 683 000 per QALY. In practice, the results of our study indicate that, by adopting the S + RT strategy, there would still be a chance of 18.11% of not paying extra at a willingness-to-pay of US$50 000 per QALY. Those results are sensitive to the costs of hospice palliative care. Our results suggest that adopting a standard S + RT approach for patients with MSCC is likely to increase health care costs but would result in improved outcomes.
Methyl-CpG binding-protein 2 function in cholinergic neurons mediates cardiac arrhythmogenesis.
Human molecular genetics, 2016

Sudden unexpected death occurs in one quarter of deaths in Rett Syndrome (RTT), a neurodevelopmental disorder caused by mutations in Methyl-CpG-binding protein 2 (MECP2). People with RTT show a variety of autonomic nervous system (ANS) abnormalities and mouse models show similar problems including QTc interval prolongation and hypothermia. To explore the role of cardiac problems in sudden death in RTT, we characterized cardiac rhythm in mice lacking Mecp2 function. Male and female mutant mice exhibited spontaneous cardiac rhythm abnormalities including bradycardic events, sinus pauses, atrioventricular block, premature ventricular contractions, non-sustained ventricular arrhythmias, and increased heart rate variability. Death was associated with spontaneous cardiac arrhythmias and complete conduction block. Atropine treatment reduced cardiac arrhythmias in mutant mice, implicating overactive parasympathetic tone. To explore the role of MeCP2 within the parasympathetic neurons, we selectively removed MeCP2 function from cholinergic neurons (MeCP2 ChAT KO), which recapitulated the cardiac rhythm abnormalities, hypothermia, and early death seen in RTT male mice. Conversely, restoring MeCP2 only in cholinergic neurons rescued these phenotypes. Thus, MeCP2 in cholinergic neurons is necessary and sufficient for autonomic cardiac control, thermoregulation, and survival, and targeting the overactive parasympathetic system may be a useful therapeutic strategy to prevent sudden unexpected death in RTT.
Recovery from ketamine-induced amnesia by blockade of GABA-A receptor in the medial prefrontal cortex of mice.
Neuroscience, 2017

Ketamine and other noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonists are known to induce deficits in learning and cognitive performance sensitive to prefrontal cortex (PFC) functions. The interaction of a glutamatergic and GABAergic systems is essential for many cognitive behaviors. In order to understand the effect of γ-aminobutyric acid (GABA)/glutamate interactions on learning and memory, we investigated the effects of intra medial prefrontal cortex (mPFC) injections of GABAergic agents on ketamine-induced amnesia using a one-trial passive avoidance task in mice. Pre-training systemic administration of ketamine (5, 10 and 15mg/kg, i.p.) dose-dependently decreased the memory acquisition of a one-trial passive avoidance task. Pre-training intra-mPFC injection of muscimol, GABAA receptor agonist (0.05, 0.1 and 0.2μg/mouse) and baclofen GABAB receptor agonist (0.05, 0.1, 0.5 and 1μg/mouse), impaired memory acquisition. However, co-pretreatment of different doses of muscimol and baclofen with a lower dose of ketamine (5mg/kg), which did not induce amnesia by itself, caused inhibition of memory formation. Our data showed that sole pre-training administration of bicuculline, GABA-A receptor antagonist and phaclofen GABA-B receptor antagonist into the mPFC, did not affect memory acquisition. In addition, the amnesia induced by pre-training ketamine (15mg/kg) was significantly decreased by the pretreatment of bicuculline (0.005, 0.1 and 0.5μg/mouse). It can be concluded that GABAergic system of the mPFC is involved in the ketamine-induced impairment of memory acquisition.
Behavioral outcomes of a novel, pelvic nerve damage rat model of fecal incontinence.
Neurogastroenterology and motility, 2018

Fecal incontinence (FI) has a multifactorial pathophysiology with a severe social impact. The most common cause for FI is pudendal nerve damage, which mostly occurs in women during or after labor. A better understanding of the pathophysiology is required to optimize treatment of FI. In this study, we evaluate the use of a novel pelvic nerve damage rat model of FI.
Gestational stress promotes pathological apneas and sex-specific disruption of respiratory control development in newborn rat.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013

Recurrent apneas are important causes of hospitalization and morbidity in newborns. Gestational stress (GS) compromises fetal brain development. Maternal stress and anxiety during gestation are linked to respiratory disorders in newborns; however, the mechanisms remain unknown. Here, we tested the hypothesis that repeated activation of the neuroendocrine response to stress during gestation is sufficient to disrupt the development of respiratory control and augment the occurrence of apneas in newborn rats. Pregnant dams were displaced and exposed to predator odor from days 9 to 19 of gestation. Control dams were undisturbed. Experiments were performed on male and female rats aged between 0 and 4 d old. Apnea frequency decreased with age but was consistently higher in stressed pups than controls. At day 4, GS augmented the proportion of apneas with O(2) desaturations by 12%. During acute hypoxia (12% O(2)), the reflexive increase in breathing augmented with age; however, this response was lower in stressed pups. Instability of respiratory rhythm recorded from medullary preparations decreased with age but was higher in stressed pups than controls. GS reduced medullary serotonin (5-HT) levels in newborn pups by 32%. Bath application of 5-HT and injection of 8-OH-DPAT [(±)-8-hydroxy-2-di-(n-propylamino) tetralin hydrobromide; 5-HT(1A) agonist; in vivo] reduced respiratory instability and apneas; these effects were greater in stressed pups than controls. Sex-specific effects were observed. We conclude that activation of the stress response during gestation is sufficient to disrupt respiratory control development and promote pathological apneas in newborn rats. A deficit in medullary 5-HT contributes to these effects.
Mental health morbidity among people subject to immigration detention in the UK: a feasibility study.
Epidemiology and psychiatric sciences, 2018

The UK has one of the largest systems of immigration detention in Europe.. Those detained include asylum-seekers and foreign national prisoners, groups with a higher prevalence of mental health vulnerabilities compared with the general population. In light of little published research on the mental health status of detainees in immigration removal centres (IRCs), the primary aim of this study was to explore whether it was feasible to conduct psychiatric research in such a setting. A secondary aim was to compare the mental health of those seeking asylum with the rest of the detainees.
Acute sleep deprivation delays the glucagon-like peptide 1 peak response to breakfast in healthy men.
Nutrition & diabetes, 2013

Previous experiments have demonstrated that acute sleep loss impairs glucose homeostasis and increases food intake in humans. The incretin hormone glucagon-like peptide 1 (GLP-1) enhances postprandial insulin secretion and promotes satiety. Hypothesizing that the detrimental metabolic effects of sleep curtailment imply alterations in GLP-1 signaling, we investigated 24-h serum total GLP-1 concentrations during total sleep deprivation (TSD) and a normal sleep/wake cycle (comprising ∼8 h of sleep) in 12 healthy young men.
A new approach for studying GPCR dimers: drug-induced inactivation and reactivation to reveal GPCR dimer function in vitro, in primary culture, and in vivo.
Pharmacology & therapeutics, 2012

GPCRs are a major family of homologous proteins and are key mediators of the effects of numerous endogenous neurotransmitters, hormones, cytokines, therapeutic drugs, and drugs-of-abuse. Despite the enormous amount of research on the pharmacological and biochemical properties of GPCRs, the question as to whether they exist as monomers, dimers, or higher order structures in the body is unanswered. The GPCR dimer field has been dominated by techniques involving recombinant cell lines expressing mutant receptors, often involving the solubilization of the receptors. These techniques cannot be applied in vivo or even to primary cell cultures. This review will focus on a novel approach to exploring the functional properties of homodimers. Studies of the 5-HT(7) and 5-HT(2A) serotonin receptors have revealed that binding of a pseudo-irreversible antagonist ("inactivator") to one of the orthosteric sites of a homodimer abolishes all receptor activity, and subsequent binding of a competitive antagonist to the orthosteric site of the second protomer releases the inactivator, allowing the receptor to return to an active state. This approach demonstrates allosteric crosstalk between protomers of native GPCR homodimers, indicating that GPCRs do exist and function as homodimers in both recombinant cells and rat primary astrocytes. This technique can be applied universally using intact recombinant or primary cells in culture, membrane homogenate preparations and, potentially, in vivo. The data obtained using the 5-HT(7) and 5-HT(2A) receptors are strongly supportive of a GPCR homodimer structure, with little evidence of monomer involvement in the function of these receptors.
Thermodynamically Stable, Photoreversible Pharmacology in Neurons with One- and Two-Photon Excitation.
Angewandte Chemie (International ed. in English), 2018

Photoswitchable bioprobes enable bidirectional control of cell physiology with different wavelengths of light. Many current photoswitches use cytotoxic UV light and are limited by the need for constant illumination owing to thermal relaxation in the dark. Now a photoswitchable tetrafluoroazobenzene(4FAB)-based ion channel antagonist has been developed that can be efficiently isomerized in two separate optical channels with visible light. Importantly, the metastable cis configuration showed very high stability in the dark over the course of days at room temperature. In neurons, the 4FAB antagonist reversibly blocks voltage-gated ion channels with violet and green light. Furthermore, photoswitching could also be achieved with two-photon excitation yielding high spatial resolution. 4FAB probes have the potential to enable long-term biological studies where both ON and OFF states can be maintained in the absence of irradiation.
Dialogues: The Science and Power of Storytelling.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2018

Skillful storytelling helps listeners understand the essence of complex concepts and ideas in meaningful and often personal ways. For this reason, storytelling is being embraced by scientists who not only want to connect more authentically with their audiences, but also want to understand how the brain processes this powerful form of communication. Here we present part of a conversation between a group of scientists actively engaged with the practice and/or the science of storytelling. We highlight the brain networks involved in the telling and hearing of stories and show how storytelling is being used well beyond the realm of public communication to add a deeper dimension to communication with our students and colleagues, as well as helping to make our profession more inclusive.
The influence of vibrissal somatosensory processing in rat superior colliculus on prey capture.
Neuroscience, 2011

The lateral part of intermediate layer of superior colliculus (SCl) is a critical substrate for successful predation by rats. Hunting-evoked expression of the activity marker Fos is concentrated in SCl while prey capture in rats with NMDA lesions in SCl is impaired. Particularly affected are rapid orienting and stereotyped sequences of actions associated with predation of fast moving prey. Such deficits are consistent with the view that the deep layers of SC are important for sensory guidance of movement. Although much of the relevant evidence involves visual control of movement, less is known about movement guidance by somatosensory input from vibrissae. Indeed, our impression is that prey contact with whiskers is a likely stimulus to trigger predation. Moreover, SCl receives whisker and orofacial somatosensory information directly from trigeminal complex, and indirectly from zona incerta, parvicelular reticular formation and somatosensory barrel cortex. To better understand sensory guidance of predation by vibrissal information we investigated prey capture by rats after whisker removal and the role of superior colliculus (SC) by comparing Fos expression after hunting with and without whiskers. Rats were allowed to hunt cockroaches, after which their whiskers were removed. Two days later they were allowed to hunt cockroaches again. Without whiskers the rats were less able to retain the cockroaches after capture and less able to pursue them in the event of the cockroach escaping. The predatory behaviour of rats with re-grown whiskers returned to normal. In parallel, Fos expression in SCl induced by predation was significantly reduced in whiskerless animals. We conclude that whiskers contribute to the efficiency of rat prey capture and that the loss of vibrissal input to SCl, as reflected by reduced Fos expression, could play a critical role in predatory deficits of whiskerless rats.
Fraction of IL-10+ and IL-17+ CD8 T cells is increased in MS patients in remission and during a relapse, but is not influenced by immune modulators.
Journal of neuroimmunology, 2013

In the present study, circulating proportions of CD8(+) T (Tc) cell subsets, including IL-17 (Tc17) and IL-10 (Tc10) producing cells, were assessed in relapsing-remitting MS (RRMS) patients and a possible effect of beta interferon (IFN-β), glatiramer acetate (GA), and vitamin D (VitD) on these cell subsets was investigated. We show that both Tc17 and Tc10 cell fractions are elevated in the circulation of RRMS patients in remission compared to healthy subjects and that these Tc subsets remain unaffected by current immune modulating regimens.
Focal epilepsy associated with dysembryoplastic neuroepithelial tumor in the area of the caudate nucleus.
Clinical neurology and neurosurgery, 2012

Dysembryoplastic neuroepithelial tumors (DNTs) are usually located within the supratentorial cortex, often in the temporal lobe and they are frequently associated with intractable complex partial seizures. DNTs in extracortical sites are rare. Thus far, 21 cases of 36 DNT-lesions occurring in these areas have been reported; only 8 out of them had epilepsy. We report a case of a 39-year-old woman who had pharmacoresistant epilepsy associated to a DNT in the caudate nucleus-periventricular area treated by lesionectomy. During a 4-year follow-up period, the patient was seizure free and the tumor did not recur. We discuss the hypothetical epileptogenic mechanism involved and we review the pertinent literature.
Mice with experimental antiphospholipid syndrome display hippocampal dysfunction and a reduction of dendritic complexity in hippocampal CA1 neurones.
Neuropathology and applied neurobiology, 2015

The antiphospholipid syndrome (APS) is an autoimmune disease characterized by high titres of auto-antibodies (aPL) leading to thrombosis and consequent infarcts. However, many affected patients develop neurological symptoms in the absence of stroke. Similarly, in a mouse model of this disease (eAPS), animals consistently develop behavioural abnormalities despite lack of ischemic brain injury. Therefore, the present study was designed to identify structural alterations of hippocampal neurones underlying the neurological symptoms in eAPS.
Apathy in Alzheimer's disease.
Current opinion in behavioral sciences, 2018

Apathy is the most common neuropsychiatric symptom in patients with Alzheimer's disease (AD). The presence of apathy has been related to greater caregiver distress, decreased quality of life, and increased morbidity. Here we review the most recent studies on this neuropsychiatric syndrome, focusing on prevalence, impact on quality of life, behavioural and neuroimaging studies, and treatment options. The results of some investigations on the behavioural and neuroanatomical profile of apathy in AD point to a role of frontostriatal circuits, specifically involving the anterior cingulate cortex. However, small and heterogeneous samples, lack of control for disease severity, and non-specific apathy scales complicate interpretation of results. Future studies might benefit from studying multiple dimensions of apathy within conceptual frameworks which allow for a deconstruction of underlying mechanisms.
A volumetric MRI study of limbic, associative and sensorimotor striatal subregions in schizophrenia.
Schizophrenia research, 2013

Cognitive and emotional functioning is mediated by frontal-subcortical feedback loops. The striatum, a component of this circuitry, thus is a possible neural substrate of schizophrenia. Striatum volume, however, is believed to be differentially influenced by neuroleptic treatment due to an anterior-posterior D2 receptor density gradient. We thus rigorously parcellated it into subregions in order to assess whether neuroleptic effect on group differences is regionally specific.
Anti-inflammatory (M2) macrophage media reduce transmission of oligomeric amyloid beta in differentiated SH-SY5Y cells.
Neurobiology of aging, 2017

Neuroinflammation plays an influential role in Alzheimer's disease (AD), although the mechanisms underlying this phenomenon remain largely unknown. Microglia are thought to be responsible for the majority of these effects and can be characterized into resting (M0), proinflammatory (M1), or anti-inflammatory (M2) functional phenotypes. We investigated the effects of conditioned macrophage media, as an analogue to microglia, on the transfer of oligomeric amyloid beta (oAβ) between differentiated SH-SY5Y cells. We also investigated how the different inflammatory environments related to intercellular and intracellular changes. We demonstrate that M2 products decrease interneuronal transfer of oAβ, while recombinant interleukin (IL)-4, IL-10, and IL-13 increase transfer. There were no alterations to the mRNA of a number of AD-related genes in response to the combination of oAβ and M0, M1, or M2, but several intracellular proteins, some relating to protein trafficking and the endosomal/lysosomal system, were altered. Stimulating microglia to an M2 phenotype may thus slow down the progression of AD and could be a target for future therapies.
Visual afterimages of emotional faces in high functioning autism.
Journal of autism and developmental disorders, 2012

Fixating an emotional facial expression can create afterimages, such that subsequent faces are seen as having the opposite expression of that fixated. Visual afterimages have been used to map the relationships among emotion categories, and this method was used here to compare ASD and matched control participants. Participants adapted to a facial expression for 45 s then saw a neutral face for 800 ms and chose a label to describe the latter. The ASD group showed evidence of afterimages, but atypical patterns of opposition: whereas fixating negative emotions uniformly evokes a positive afterimage in the control group, fixating negative emotions was more likely to evoke a negative afterimage in the ASD group. This study was the first to provide evidence of visual aftereffects in ASD and suggests a different psychological organization among emotions in those with ASD.
Temporal identity establishes columnar neuron morphology, connectivity, and function in a 
eLife, 2019

The insect central complex (CX) is a conserved brain region containing 60 + neuronal subtypes, several of which contribute to navigation. It is not known how CX neuronal diversity is generated or how developmental origin of subtypes relates to function. We mapped the developmental origin of four key CX subtypes and found that neurons with similar origin have similar axon/dendrite targeting. Moreover, we found that the temporal transcription factor (TTF) Eyeless/Pax6 regulates the development of two recurrently-connected CX subtypes: Eyeless loss simultaneously produces ectopic P-EN neurons with normal axon/dendrite projections, and reduces the number of E-PG neurons. Furthermore, transient loss of Eyeless during development impairs adult flies' capacity to perform celestial navigation. We conclude that neurons with similar developmental origin have similar connectivity, that Eyeless maintains equal E-PG and P-EN neuron number, and that Eyeless is required for the development of circuits that control adult navigation.
Ubiquitination of MBNL1 Is Required for Its Cytoplasmic Localization and Function in Promoting Neurite Outgrowth.
Cell reports, 2018

The Muscleblind-like protein family (MBNL) plays an important role in regulating the transition between differentiation and pluripotency and in the pathogenesis of myotonic dystrophy type 1 (DM1), a CTG expansion disorder. How different MBNL isoforms contribute to the differentiation and are affected in DM1 has not been investigated. Here, we show that the MBNL1 cytoplasmic, but not nuclear, isoform promotes neurite morphogenesis and reverses the morphological defects caused by expanded CUG RNA. Cytoplasmic MBNL1 is polyubiquitinated by lysine 63 (K63). Reduced cytoplasmic MBNL1 in the DM1 mouse brain is consistent with the reduced extent of K63 ubiquitination. Expanded CUG RNA induced the deubiqutination of cytoplasmic MBNL1, which resulted in nuclear translocation and morphological impairment that could be ameliorated by inhibiting K63-linked polyubiquitin chain degradation. Our results suggest that K63-linked ubiquitination of MBNL1 is required for its cytoplasmic localization and that deubiquitination of cytoplasmic MBNL1 is pathogenic in the DM1 brain.