rudyvdbrink/CitationDatabase huggingface dataset:
Identification and characterization of synthetic chondroitin-4-sulfate binding peptides in neuronal functions.
Scientific reports, 2019

Chondroitin sulfate proteoglycans (CSPGs), up-regulated in and around the glial scar after mammalian spinal cord injury, have been suggested to be key inhibitory molecules for functional recovery by impeding axonal regrowth/sprouting and synaptic rearrangements. CSPG-mediated inhibition is mainly associated with the glycosaminoglycan chains of CSPGs, and chondroitin-4-sulfate (C4S) is the predominant sulfated structure that regulates axonal guidance and growth in the adult nervous system. With the aim to find molecules that neutralize the inhibitory functions of C4S, we screened a phage display library for peptides binding to C4S. From the phage clones binding to C4S we selected three peptides for further analysis. We observed that these peptides bind to C4S, but not chondroitin-6-sulfate, heparin sulfate or dermatan sulfate, in a concentration-dependent and saturable manner, whereas the scrambled peptides showed highly reduced or no binding to C4S. The C4S-binding peptides, but not their scrambled counterparts, when added to cultures of mouse cerebellar neurons and human neuroblastoma cells, neutralized the inhibitory functions of the C4S- and CSPG-coated substrate on cell adhesion, neuronal migration and neurite outgrowth. These results indicate that the C4S-binding peptides neutralize several inhibitory functions of CSPGs, suggesting that they may be beneficial in repairing mammalian nervous system injuries.
One-year mirror-image study of the impact of olanzapine long-acting injection on healthcare resource utilization and costs in severe schizophrenia.
Psychiatry research, 2018

Olanzapine long-acting injections (OLAIs) are often prescribed to patients with severe schizophrenia who are typically excluded from randomized clinical trials. To date, no mirror-image study has examined the impact of OLAIs on healthcare resource utilizations in these patients. We conducted a retrospective, one-year mirror-image study of OLAIs on 40 patients with severe schizophrenic disorder. Illness severity was defined by failure to respond to two sequential antipsychotics. Outcomes included: (i) healthcare resource utilizations via hospitalization admissions, bed days, outpatient visits, and inpatient service costs computations (ii) clinical efficacy through changes in the Brief Psychiatric Rating Scale (BPRS) and in the Clinical Global Impression-Schizophrenia Scale (CGI-SCH), and (iii) adverse effects. After one year, OLAIs were associated with significant decreases of 65.7%, 86.2% and 86.2% in hospitalization admissions, bed days, and inpatient service costs respectively. A significant mean change of -0.47 and -0.63 was determined the BPRS and the CGI-SCH scores, respectively. There were no significant differences in the number of outpatient visits and adverse effects, except for post-injection sedation/delirium syndrome whose incidence was 0.30% per injection. This mirror-image study provides the first evidence that prescribing OLAIs reduces in a cost-effective manner average bed days and hospital admissions in patients with severe schizophrenia.
Pupillometry as an indicator of L-DOPA dosages in Parkinson's disease patients.
Journal of neural transmission (Vienna, Austria : 1996), 2018

Dopamine was shown to induce mydriasis by excitation of alpha-adrenergic receptors at the dilator pupillae muscle. Pupilla diameter may thus serve as an indirect measure of peripheral pharmacokinetics of L-DOPA and dopamine. The aim of this study is to evaluate the effect of L-DOPA dosage on pupillometric parameters in Parkinson's disease (PD) patients. Sixteen PD patients and 14 healthy control subjects (CS) were studied. The statistical analysis revealed significant differences between CS and PD patients for the mean maximum and minimum pupil diameters (p = 0.017, p = 0.028, respectively), with higher values found in PD. Moreover, a significant dose-response relationship was found between the maximum pupil diameter and both the morning L-DOPA dose (R
Gabapentin for chronic neuropathic pain and fibromyalgia in adults.
The Cochrane database of systematic reviews, 2011

This review updates parts of two earlier Cochrane reviews investigating effects of gabapentin in chronic neuropathic pain (pain due to nerve damage). Antiepileptic drugs are used to manage pain, predominantly for chronic neuropathic pain, especially when the pain is lancinating or burning.
Role of orexin-1 receptors in the dorsal hippocampus (CA1 region) in expression and extinction of the morphine-induced conditioned place preference in the rats.
Peptides, 2018

Orexinergic system is involved in reward processing and drug addiction. Objectives here, we investigated the effect of intra-hippocampal CA1 administration of orexin-1 receptor (OX1r) antagonist on the expression, and extinction of morphine-induced place preference in rats. Conditioned place preference (CPP) was induced by subcutaneous injection of morphine (5 mg/kg) during a 3-day conditioning phase. Two experimental plots were designed; SB334867 as a selective OX1r antagonist was dissolved in 12% DMSO, prepared in solutions with different concentrations (3, 30, and 300 nM), and microinjected into the CA1 and some neighboring regions (0.5 μl/side), bilaterally. CPP score and locomotor activity were recorded during the CPP test. Results demonstrated that intra-CA1 administration of the OX1r antagonist attenuates the expression of morphine-induced CPP. Furthermore, higher concentrations of SB334867 facilitated the extinction period of morphine-induced CPP and reduced its latency. Nevertheless, solely administration of DMSO did not have any influence on the CPP scores and locomotion in both phases. Our findings suggest that OX1rs in the CA1 region of the hippocampus are involved in the expression of morphine CPP. Moreover, blockade of OX1rs could facilitate extinction and may extinguish the ability of drug-related cues. It seems that the antagonist might be considered as a propitious therapeutic agent in suppressing drug-seeking behaviors.
Accelerated long-term forgetting over three months in asymptomatic APOE ɛ4 carriers.
Annals of clinical and translational neurology, 2021

Accelerated long-term forgetting (ALF) refers to a rapid loss of information over days or weeks despite normal acquisition/encoding. Notwithstanding its potential relevance as a presymptomatic marker of cognitive dysfunction, no study has addressed the relationship between ALF and Alzheimer's disease (AD) biomarkers. We examined ALF in APOE ɛ4 carriers versus noncarriers, and its relationships with AD cerebrospinal fluid (CSF) biomarkers. We found ALF over three months in APOE ɛ4 carriers (F(1,19) = 5.60; P < 0.05; Cohen's d = 1.08), and this performance was associated with abnormal levels of the CSF Aβ
Evaluation of PARKIN gene variants in West Bengal Parkinson's disease patients.
Journal of human genetics, 2015

Little information is available regarding the molecular pathogenesis of Parkinson's disease (PD) among the Bengalee population in West Bengal, India. This study was undertaken to determine the contribution of Parkin variants in well-defined ethnically identical Bengalee population of India and further to describe the clinical spectrum associated with these mutations. A total of 150 unrelated PD patients and 150 controls were recruited for the study. The entire cohort was screened for mutations in all the 12 exons of the gene along with flanking splice junctions by polymerase chain reaction and DNA sequencing. Eleven nucleotide variants including two novel changes were detected. Cerebrospinal fluid (CSF) parkin protein expression of the novel mutation, Val186Ile (found in heterozygous condition in one patient only) was almost 2.7 folds lower than the controls and other PD patients. Molecular characterization of polymorphisms Ser167Asn and Val380Leu depicted that homozygous Ser167 and Val380 are significantly associated with the disease. We did not find any linkage disequilibrium among the SNPs, the low r(2) for every pair of single-nucleotide polymorphisms (SNPs) indicated that these SNPs cannot be tagged by each other. Another novel intronic change, IVS8+48C>T was present in almost equally in PD patients and controls. Among the ethnically defined Bengalee population of West Bengal, occurrence of Parkin mutation is 4% (6/150) of the PD patient pool supported with decreased folds of expression of CSF PARKIN protein. Parkin polymorphisms, Ser167 and Val380 are risk factors for the progression of the disease, and their frequency is greatly influenced by ethnic origin.
Expanding the clinical phenotype of the ultra-rare Skraban-Deardorff syndrome: Two novel individuals with WDR26 loss-of-function variants and a literature review.
American journal of medical genetics. Part A, 2021

De novo variants in the WDR26 gene leading to haploinsufficiency have recently been associated with Skraban-Deardorff syndrome. This condition is an ultra-rare autosomal dominant neurodevelopmental disorder characterized by a broad range of clinical signs, including intellectual disability (ID), developmental delay (DD), seizures, abnormal facial features, feeding difficulties, and minor skeletal anomalies. Currently, 18 cases have been reported in the literature and for only 15 of them a clinical description is available. Here, we describe a child with Skraban-Deardorff syndrome associated with the WDR26 pathogenic de novo variant NM_025160.6:c.69dupC, p.(Gly24ArgfsTer48), and an adult associated with the pathogenic de novo variant c.1076G > A, p.(Trp359Ter). The adult patient was a 29-year-old female with detailed information on clinical history and pharmacological treatments since birth, providing an opportunity to map disease progression and patient management. By comparing our cases with published reports of Skraban-Deardorff syndrome, we provide a genetic and clinical summary of this ultrarare condition, describe the clinical management from childhood to adult age, and further expand on the clinical phenotype.
Comprehensive assessment of multiple biases in small RNA sequencing reveals significant differences in the performance of widely used methods.
BMC genomics, 2019

RNA sequencing offers advantages over other quantification methods for microRNA (miRNA), yet numerous biases make reliable quantification challenging. Previous evaluations of these biases have focused on adapter ligation bias with limited evaluation of reverse transcription bias or amplification bias. Furthermore, evaluations of the quantification of isomiRs (miRNA isoforms) or the influence of starting amount on performance have been very limited. No study had yet evaluated the quantification of isomiRs of altered length or compared the consistency of results derived from multiple moderate starting inputs. We therefore evaluated quantifications of miRNA and isomiRs using four library preparation kits, with various starting amounts, as well as quantifications following removal of duplicate reads using unique molecular identifiers (UMIs) to mitigate reverse transcription and amplification biases.
P2X7 purinoceptors contribute to the death of Schwann cells transplanted into the spinal cord.
Cell death & disease, 2013

The potential to use Schwann cells (SCs) in neural repair for patients suffering from neurotrauma and neurodegenerative diseases is well recognized. However, significant cell death after transplantation hinders the clinical translation of SC-based therapies. Various factors may contribute to the death of transplanted cells. It is known that prolonged activation of P2X7 purinoceptors (P2X7R) can lead to death of certain types of cells. In this study, we show that rat SCs express P2X7R and exposure of cultured SCs to high concentrations of ATP (3-5 mM) or a P2X7R agonist, 2'(3')-O-(4-benzoylbenzoyl)ATP (BzATP) induced significant cell death rapidly. High concentrations of ATP and BzATP increased ethidium uptake by SCs, indicating increased membrane permeability to large molecules, a typical feature of prolonged P2X7R activation. SC death, as well as ethidium uptake, induced by ATP was blocked by an irreversible P2X7R antagonist oxidized ATP (oxATP) or a reversible P2X7R antagonist A438079. oxATP also significantly inhibits the increase of intracellular free calcium induced by minimolar ATP concentrations. Furthermore, ATP did not cause death of SCs isolated from P2X7R-knockout mice. All these results suggest that P2X7R is responsible for ATP-induced SC death in vitro. When rat SCs were treated with oxATP before transplantation into uninjured rat spinal cord, 35% more SCs survived than untreated SCs 1 week after transplantation. Moreover, 58% more SCs isolated from P2X7R-knockout mice survived after being transplanted into rat spinal cord than SCs from wild-type mice. This further confirms that P2X7R is involved in the death of transplanted SCs. These results indicate that targeting P2X7R on SCs could be a potential strategy to improve the survival of transplanted cells. As many other types of cells, including neural stem cells, also express P2X7R, deactivating P2X7R may improve the survival of other types of transplanted cells.
Affective blindsight in the absence of input from face processing regions in occipital-temporal cortex.
Neuropsychologia, 2019

Previous research suggests that the implicit recognition of emotional expressions may be carried out by pathways that bypass primary visual cortex (V1) and project to the amygdala. Some of the strongest evidence supporting this claim comes from case studies of "affective blindsight" in which patients with V1 damage can correctly guess whether an unseen face was depicting a fearful or happy expression. In the current study, we report a new case of affective blindsight in patient MC who is cortically blind following extensive bilateral lesions to V1, as well as face and object processing regions in her ventral visual stream. Despite her large lesions, MC has preserved motion perception which is related to sparing of the motion sensitive region MT+ in both hemispheres. To examine affective blindsight in MC we asked her to perform gender and emotion discrimination tasks in which she had to guess, using a two-alternative forced-choice procedure, whether the face presented was male or female, happy or fearful, or happy or angry. In addition, we also tested MC in a four-alternative forced-choice target localization task. Results indicated that MC was not able to determine the gender of the faces (53% accuracy), or localize targets in a forced-choice task. However, she was able to determine, at above chance levels, whether the face presented was depicting a happy or fearful (67%, p = .006), or a happy or angry (64%, p = .025) expression. Interestingly, although MC was better than chance at discriminating between emotions in faces when asked to make rapid judgments, her performance fell to chance when she was asked to provide subjective confidence ratings about her performance. These data lend further support to the idea that there is a non-conscious visual pathway that bypasses V1 which is capable of processing affective signals from facial expressions without input from higher-order face and object processing regions in the ventral visual stream.
Prolonged stay at the paediatric intensive care unit associated with paediatric delirium.
European child & adolescent psychiatry, 2010

The objective of this study was to investigate, under circumstances of routine care, the impact of paediatric delirium (PD) on length of stay in the paediatric intensive care unit (PICU) as well as on direct financial costs. A five-year prospective observational study (2002-2007) was carried out in a tertiary eight-bed PICU in the Netherlands. Critically ill children aged 1 to 18 years who were acutely, non-electively and consecutively admitted to the PICU and detected as having PD in routine care were compared to critically ill children aged 1 to 18 years without signs of PD. PD, population characteristics and severity of illness at admission were used as predictors for length of PICU stay. Differences in length of stay yielded short-term, direct medical costs associated with PD. Forty-nine children with and 98 children without PD were included. PD prolonged length of PICU stay with 2.39 days, independent of severity of illness, age, gender, mechanical ventilation and medical indication for admission (B = 0.38, P < 0.001). PD increased direct medical costs with 1.5%. The results suggest a negative prognostic influence of PD on duration of PICU stay in routine care, resulting in an increase of direct medical costs.
Breastfeeding and maternal sensitivity predict early infant temperament.
Acta paediatrica (Oslo, Norway : 1992), 2015

Research findings are inconclusive when it comes to whether breastfeeding is associated with the mother-infant relationship or infant temperament. We examined the association between breastfeeding at three months postpartum and infant temperament at 18 months postpartum and whether this link was affected by the mothers' anxiety and mediated by her sensitivity.
Brain insulin dysregulation: implication for neurological and neuropsychiatric disorders.
Molecular neurobiology, 2013

Arduous efforts have been made in the last three decades to elucidate the role of insulin in the brain. A growing number of evidences show that insulin is involved in several physiological function of the brain such as food intake and weight control, reproduction, learning and memory, neuromodulation and neuroprotection. In addition, it is now clear that insulin and insulin disturbances particularly diabetes mellitus may contribute or in some cases play the main role in development and progression of neurodegenerative and neuropsychiatric disorders. Focusing on the molecular mechanisms, this review summarizes the recent findings on the involvement of insulin dysfunction in neurological disorders like Alzheimer's disease, Parkinson's disease and Huntington's disease and also mental disorders like depression and psychosis sharing features of neuroinflammation and neurodegeneration.
The novel antiepileptic drug imepitoin compares favourably to other GABA-mimetic drugs in a seizure threshold model in mice and dogs.
Pharmacological research, 2013

Recently, the imidazolinone derivative imepitoin has been approved for treatment of canine epilepsy. Imepitoin acts as a low-affinity partial agonist at the benzodiazepine (BZD) site of the GABAA receptor and is the first compound with such mechanism that has been developed as an antiepileptic drug (AED). This mechanism offers several advantages compared to full agonists, including less severe adverse effects and a lack of tolerance and dependence liability, which has been demonstrated in rodents, dogs, and nonhuman primates. In clinical trials in epileptic dogs, imepitoin was shown to be an effective and safe AED. Recently, seizures in dogs have been proposed as a translational platform for human therapeutic trials on new epilepsy treatments. In the present study, we compared the anticonvulsant efficacy of imepitoin, phenobarbital and the high-affinity partial BZD agonist abecarnil in the timed i.v. pentylenetetrazole (PTZ) seizure threshold test in dogs and, for comparison, in mice. Furthermore, adverse effects of treatments were compared in both species. All drugs dose-dependently increased the PTZ threshold in both species, but anticonvulsant efficacy was higher in dogs than mice. At the doses selected for this study, imepitoin was slightly less potent than phenobarbital in increasing seizure threshold, but markedly more tolerable in both species. Effective doses of imepitoin in the PTZ seizure model were in the same range as those suppressing spontaneous recurrent seizures in epileptic dogs. The study demonstrates that low-affinity partial agonists at the benzodiazepine site of the GABAA receptor, such as imepitoin, offer advantages as a new category of AEDs.
Chronic mild stress-induced protein dysregulations correlated with susceptibility and resiliency to depression or anxiety revealed by quantitative proteomics of the rat prefrontal cortex.
Translational psychiatry, 2021

Chronic stress is a significant risk factor for depression as well as anxiety disorders. Yet, the stress-induced specific and common molecular dysregulations of these disorders have not been fully understood. Previously, we constructed a chronic mild stress (CMS) rat model to separate and obtain depression-susceptible, anxiety-susceptible, and insusceptible groups. In this study, the prefrontal cortical proteomes of the three stressed groups were comparatively profiled utilizing isobaric tags for relative and absolute quantitation (iTRAQ)-coupled tandem mass spectrometry approach. A total of 212 protein dysregulations were identified, potentially correlating to susceptibility or resilience to CMS-induced depression or anxiety, and thus might serve as potential protein targets for further investigation. In addition, independent analysis by parallel reaction monitoring identified changes in Gfap, Rhog, Gnai2, Ppp1r1b, and Uqcrh; Tubb6, Urod, Cul1, Spred1, and Gpcpd1; Acadl, Ppp1r1a, Grm2, Mtor, Lsm8, Cplx2, and Tsta3 that were distinctly correlated to depression-susceptible, anxiety-susceptible, or insusceptible groups, respectively. This suggested that identical CMS had different effects on the protein regulation system of the rat prefrontal cortex. Collectively, the present proteomics study of the prefrontal cortex established a significant molecular basis and offered new insights into the specificity and commonality of pathophysiologic mechanisms underlying susceptibility and resiliency to stress-induced depression or anxiety.
Brivaracetam as add-on treatment in focal epilepsy: A real-world time-based analysis.
Epilepsia, 2021

The study assessed the clinical response to add-on brivaracetam (BRV) in real-world practice by means of time-to-baseline seizure count methodology. Patients with focal epilepsy who were prescribed add-on BRV were identified. Primary endpoint was the time-to-baseline seizure count defined as the number of days until each patient experienced the number of focal seizures that occurred in the 90 days before BRV initiation. Subgroup analysis was performed according to levetiracetam (LEV) status (naive vs prior use). Three-hundred eighty-seven patients were included. The overall median time-to-baseline seizure count was 150 (95% confidence interval [CI] = 130-175) days. The median time-to-baseline seizure count was 198 (lower limit of 95% CI = 168) days for LEV-naive patients, 126 (95% CI = 105-150) days for patients with prior LEV use and withdrawal due to insufficient efficacy, and 170 (95% CI = 128-291) days for patients who discontinued LEV due to adverse events (P = .002). The number of prior antiseizure medications (adjusted hazard ratio [
MR-Eye: High-Resolution Microscopy Coil MRI for the Assessment of the Orbit and Periorbital Structures, Part 1: Technique and Anatomy.
AJNR. American journal of neuroradiology, 2020

Microscopy coil MR imaging of the orbits has been described previously as a technique for anatomic depiction. In the first part of this 2-part series, the improvement in spatial resolution that the technique offers compared with conventional MR imaging of the orbits is demonstrated. We provide a guide to implementing the technique, sharing pearls and pitfalls gleaned from our own practice to make implementation of microscopy coil MR imaging at your own center easy. As a quick reference guide to the small-scale structures encountered when reading the studies, a short anatomy section is included, which doubles as a showcase for the high-quality imaging that can be obtained. In the second part, our experience of microscopy coil MR imaging in day-to-day clinical practice takes it far beyond being a useful anatomic educational tool. Through a series of interesting cases, we highlight the added benefit of microscopy coil MR imaging compared with standard orbital MR imaging.