Seizure-related complication rate in a residential population with epilepsy and intellectual disability (ECOMRAID-trial).

INTRODUCTION: The aim of the ECOMRAID trial (Epileptic seizure related Complication RAte in residential population of persons with epilepsy and Intellectual Disability) was to study seizure-related complications (status epilepticus, respiratory complications, or other severe complications) in people with epilepsy and intellectual disability living in a residential setting. The results of the present study are a prerequisite for performing a prospective study into the effectiveness of nocturnal surveillance patients with high risk for Sudden unexpected death in epilepsy (SUDEP). MATERIAL AND METHODS: A retrospective study was conducted in three general residential care institutions and one residential specialized epilepsy clinic. In this 5-year cohort, we collected the following data: age (at inclusion and in case of death), sex, type of residential care, different types of complications, rescue/emergency medication administration, transfers to another department (internal midcare / monitoring unit or general hospital) and a self-designed SUDEP risk score. Our primary research questions were to assess the number of patients who experienced seizure-related complications and their individual complication rates. The secondary research questions were to document the relationship of these complications with the SUDEP risk score, with the type of residential living, and with the frequency of interventions by caregivers. RESULTS: We included 370 patients (1790 patient-years) and in 135 of them, we found 717 seizure-related complications. The following complication rates were found: all complications: at 36%, status epilepticus: at 13%, respiratory complications: at 5%, and other complications at 26%. In residential care institutions, we found fewer patients with complications compared to the specialized epilepsy clinic (all complications 24% vs 42%, OR 0.44, p < 0.01; status epilepticus 5% vs 17%, OR 0.27, p < 0.01; other: complications 19% vs 30%, OR 0.56, p < 0.05). In residential care institutions, we found more "other complications" than in the specialized epilepsy clinic (89% vs 71%, OR 3.13, p < 0.0001). The annual frequency of all complications together was higher in residential care institutions (range 0 to 21 vs 0 to 10, p < 0.05). Rescue medication was given to 75% of the patients, but more often in the specialized epilepsy clinic (median 2.6 vs 0.5 times/patient/year, p < 0.001). In the specialized epilepsy clinic, more patients were transferred to a midcare / monitoring unit or general hospital (56% vs 9%, OR 13.44, p < 0.0001) with higher yearly frequencies (median 0.2 vs 0.0, p < 0.001). There were no reported cases of SUDEP. The median SUDEP risk score was higher in the specialized epilepsy clinic (5 vs 4, p < 0.05) and was weakly correlated with the status epilepticus (ρ = 0.20, p < 0.001) and (total) complication rate (ρ = 0.18, p < 0.001). CONCLUSION: We found seizure-related complications in more than one-third of the patients with epilepsy and intellectual disability living in a residential setting over a period of 5 years. The data also quantify seizure-related complications in patients with epilepsy and intellectual disability.

Dark Sweet Cherry (Prunus avium) Anthocyanins Suppressed ERK1/2-Akt/mTOR Cell Signaling and Oxidative Stress: Implications for TNBC Growth and Invasion.

This study aimed to assess dark sweet cherry (DSC) total polyphenols (WE) and anthocyanins (ACN) against metastatic breast cancer (BC). The WE and ACN anticancer activity and underlying mechanisms were assessed in vitro using 4T1 BC cells. A pilot study using a BALB/C mouse syngeneic model bearing 4T1 tumors assessed the anti-metastatic potential of ACN in vivo. ACN inhibited cell viability with higher potency than WE and reduced reactive oxygen species (ROS) (IC50 = 58.6 µg cyanidin 3-glucoside equivalent (C3G)/mL or 122 µM). ACN induced p38 stress-related intrinsic apoptosis, leading to caspase-3 cleavage and total PARP decrease. ACN suppressed ERK1/2 and Akt/mTOR signaling pathways, which are abnormally activated in BC and promote motility and invasion. This was consistent with suppression of VCAM-1 mRNA, Scr phosphorylation and 88.6% reduction of cells migrating to wounded area. The pilot in vivo results supported the ACN-mediated suppression of angiogenesis in tumors and lungs. ACN also lowered Cenpf mRNA in lungs, associated with lung metastasis lesions and poor survival. Results demonstrated the dual Akt-ERK inhibitory role of ACN and suppression of their downstream pro-invasive targets. These results encourage a larger scale in vivo study to confirm that ACN may help to fight BC invasion and metastasis.

Dark Sweet Cherry (Prunus avium) Phenolics Enriched in Anthocyanins Induced Apoptosis in MDA-MB-453 Breast Cancer Cells through MAPK-Dependent Signaling and Reduced Invasion via Akt and PLCγ-1 Downregulation.

Dark sweet cherries (DSCs) are rich source of phenolics known to exert anticancer and anti-invasive activities. This study elucidated the molecular mechanisms underlying the activity of DSC phenolics against MDA-MB-453 breast cancer cells In Vitro. Cells were treated with DSC phenolics in whole extract (WE), and fractions enriched in anthocyanins (ACN) and proanthocyanidins (PCN) at concentrations that inhibited cell growth by 50%. Results showed that DSC phenolics suppressed Akt and PLCγ-1 activation, and inhibited cell motility and invasion, but only ACN reached significance. The extrinsic and intrinsic apoptotic pathways were also activated by DSC phenolics via caspase-8 cleavage and increased Bax/Bcl-2 ratio, with ACN exhibiting significant activation and stronger PARP-1 cleavage. Furthermore, sustained activation of mitogen-activated protein kinases (MAPKs) ERK1/2 and p38 was observed wherein ERK1/2 (U0126) and p38 (SB203580) inhibitors confirmed crosstalk ERK1/2-Akt and MAPK intrinsic mitochondrial pathways. In conclusion, DSC phenolics inhibited MDA-MB-453 breast cancer cells by targeting cell signaling pathways that induce apoptosis and suppress cell invasion, with ACN showing enhanced chemopreventive activities.

Dysphagia, dysarthria and aphasia following a first acute ischaemic stroke: incidence and associated factors.

BACKGROUND AND PURPOSE: Dysphagia, dysarthria and aphasia are common symptoms following acute stroke; however, limited data are available from recent prospective clinical trials. The aim of this study was to determine the incidence and associated factors of dysphagia, dysarthria and aphasia following a first acute ischaemic stroke in patients admitted to a comprehensive stroke center. METHODS: All first ischaemic stroke patients admitted to the Stroke Unit of Ghent University Hospital within 48 h after symptom onset were enrolled in this prospective study between March 2018 and October 2019. Dysphagia and communication screenings were performed within 3 days after admission. When dysphagia, dysarthria and/or aphasia were assumed, standardized assessments were performed. Incidence rates were calculated as point estimates (%) with 95% confidence intervals (CI). Associated factors were calculated via multivariate binary logistic regression analyses. RESULTS: Dysphagia, dysarthria and aphasia were present in 23% (95% CI, 17-31), 44% (95% CI, 37-52) and 23% (95% CI, 17-30), respectively of 151 first ischaemic stroke patients [67 female, mean age 67 (SD 14) years]. Separate multivariate binary logistic regression analyses showed that dysphagia, dysarthria and aphasia were significantly associated with age-adjusted stroke severity at baseline [odds ratio (OR), 1.16; 95% CI, 1.09-1.23; OR, 1.13; 95% CI, 1.07-1.20 and OR, 1.11; 95% CI, 1.05-1.17 respectively]. Corrected for stroke severity, the risk for aphasia increased by 4% per year of age (OR, 1.04; 95% CI, 1.00-1.07). Adjusted for age and stroke severity, aphasia was significantly associated with large artery atherosclerosis as stroke etiology (OR, 3.91; 95% CI, 1.18-12.98). CONCLUSIONS: This trial showed a high incidence of dysphagia, dysarthria and aphasia following acute ischaemic stroke. Stroke severity was an associated factor for all three symptoms.

Neurological manifestations and neuro-invasive mechanisms of the severe acute respiratory syndrome coronavirus type 2.

BACKGROUND AND PURPOSE: Infections with coronaviruses are not always confined to the respiratory tract and various neurological manifestations have been reported. The aim of this study was to perform a review to describe neurological manifestations in patients with COVID-19 and possible neuro-invasive mechanisms of Sars-CoV-2. METHODS: PubMed, Web of Science and COVID-dedicated databases were searched for the combination of COVID-19 terminology and neurology terminology up to 10 May 2020. Social media channels were followed up between 15 March and 10 May 2020 for postings with the same scope. Neurological manifestations were extracted from the identified papers and combined to provide a useful summary for the neurologist in clinical practice. RESULTS: Neurological manifestations potentially related to COVID-19 have been reported in large studies, case series and case reports and include acute cerebrovascular diseases, impaired consciousness, cranial nerve manifestations and autoimmune disorders such as the Guillain-Barré syndrome often present in patients with more severe COVID-19. Cranial nerve symptoms such as olfactory and gustatory dysfunctions are highly prevalent in patients with mild to moderate COVID-19 even without associated nasal symptoms and often present in an early stage of the disease. CONCLUSION: Physicians should be aware of the neurological manifestations in patients with COVID-19, especially when rapid clinical deterioration occurs. The neurological symptoms in COVID-19 patients may be due to direct viral neurological injury or indirect neuroinflammatory and autoimmune mechanisms. No antiviral treatments against the virus or vaccines for its prevention are available and the long-term consequences of the infection on human health remain uncertain especially with regard to the neurological system.

Neurophysiological investigations of drug resistant epilepsy patients treated with vagus nerve stimulation to differentiate responders from non-responders.

BACKGROUND AND PURPOSE: In patients treated with vagus nerve stimulation (VNS) for drug resistant epilepsy (DRE), up to a third of patients will eventually not respond to the therapy. As VNS therapy requires surgery for device implantation, prediction of response prior to surgery is desirable. It is hypothesized that neurophysiological investigations related to the mechanisms of action of VNS may help to differentiate VNS responders from non-responders prior to the initiation of therapy. METHODS: In a prospective series of DRE patients, polysomnography, heart rate variability (HRV) and cognitive event related potentials were recorded. Polysomnography and HRV were repeated after 1 year of treatment with VNS. Polysomnography, HRV and cognitive event related potentials were compared between VNS responders (≥50% reduction in seizure frequency) and non-responders. RESULTS: Fifteen out of 30 patients became VNS responders after 1 year of VNS treatment. Prior to treatment with VNS, the amount of deep sleep (NREM 3), the HRV high frequency (HF) power and the P3b amplitude were significantly different in responders compared to non-responders (P = 0.007; P = 0.001; P = 0.03). CONCLUSION: Three neurophysiological parameters, NREM 3, HRV HF and P3b amplitude, were found to be significantly different in DRE patients who became responders to VNS treatment prior to initiation of their treatment with VNS. These non-invasive recordings may be used as characteristics for response in future studies and help avoid unsuccessful implantations. Mechanistically these findings may be related to changes in brain regions involved in the so-called vagal afferent network.

Structural Characterization of Cranberry Arabinoxyloglucan Oligosaccharides.

Cranberry ( Vaccinium macrocarpon) products are widely available in North American food, juice, and dietary supplement markets. The use of cranberry is popular for the prevention of urinary tract infections (UTIs) and other reported health benefits. Preliminary findings by our research group indicate that arabinoxyloglucan oligosaccharides are present in cranberry products and may contribute to the antiadhesion properties of urine produced after cranberry consumption, but relatively little is known regarding the oligosaccharide components of cranberry. This report describes the isolation from two cranberry sources and the complete structure elucidation of two arabinoxyloglucan oligosaccharides through the use of carbohydrate-specific NMR spectroscopic and chemical derivatization methods. These compounds were identified as the heptasaccharide ß-d-glucopyranosyl-(1→4)-[α-d-xylopyranosyl-(1→6)]-ß-d-glucopyranosyl-(1→4)-ß-d-glucopyranosyl-(1→4)-[α-l-arabinofuranosyl-(1→2)-α-d-xylopyranosyl-(1→6)]-ß-d-glucopyranose (1) and the octasaccharide ß-d-glucopyranosyl-(1→4)-[α-l-arabinofuranosyl-(1→2)-α-d-xylopyranosyl-(1→6)]-ß-d-glucopyranosyl-(1→4)-ß-d-glucopyranosyl-(1→4)-[α-l-arabinofuranosyl-(1→2)-α-d-xylopyranosyl-(1→6)]-ß-d-glucopyranose (2). Selected fractions and the isolated compounds were subjected to antimicrobial, cell viability, and E. coli antiadhesion assays. Results indicated that enriched fractions and purified compounds lacked antimicrobial and cytotoxic effects, supporting the potential use of such compounds for disease prevention without the risk for resistance development. Preliminary antiadhesion results indicated that mixtures of oligosaccharides exhibited greater antiadhesion properties than purified fractions or pure compounds. The potential use of cranberry oligosaccharides for the prevention of UTIs warrants continued investigations of this complex compound series.

Evaluating the evidence for non-monotonic dose-response relationships: A systematic literature review and (re-)analysis of in vivo toxicity data in the area of food safety.

This study aims to evaluate the evidence for the existence of non-monotonic dose-responses (NMDRs) of substances in the area of food safety. This review was performed following the systematic review methodology with the aim to identify in vivo studies published between January 2002 and February 2015 containing evidence for potential NMDRs. Inclusion and reliability criteria were defined and used to select relevant and reliable studies. A set of six checkpoints was developed to establish the likelihood that the data retrieved contained evidence for NMDR. In this review, 49 in vivo studies were identified as relevant and reliable, of which 42 were used for dose-response analysis. These studies contained 179 in vivo dose-response datasets with at least five dose groups (and a control group) as fewer doses cannot provide evidence for NMDR. These datasets were extracted and analyzed using the PROAST software package. The resulting dose-response relationships were evaluated for possible evidence of NMDRs by applying the six checkpoints. In total, 10 out of the 179 in vivo datasets fulfilled all six checkpoints. While these datasets could be considered as providing evidence for NMDR, replicated studies would still be needed to check if the results can be reproduced to rule out that the non-monotonicity was caused by incidental anomalies in that specific study. This approach, combining a systematic review with a set of checkpoints, is new and appears useful for future evaluations of the dose response datasets regarding evidence of non-monotonicity.

Evaluation of MEG vs EEG after sleep deprivation in epilepsy.

OBJECTIVE: MEG and EEG after sleep deprivation (EEG-SD) are applied as diagnostic tools in the evaluation of patients with possible epilepsy. There is no gold standard to check whether the diagnosis based on these two modalities is correct. The best standard available is the long-term follow-up of patients. As follow-up of an earlier study in which the additional value of MEG vs EEG-SD diagnosis was evaluated, we investigated the long-term validity of MEG-based and EEG-SD-based diagnosis. MATERIALS AND METHODS: Data collected from 46 patients were used in a comparative study of the last known diagnosis against the original one of 8 years ago. RESULTS: Long-term (3-8 years) sensitivity of sharp phenomena (combining spikes and sharp waves) in routine MEG and in EEG-SD for the diagnosis epilepsy is 71% and 62%, respectively. When compared to the original study, this hardly changed. Over time, uncertainty on diagnosis diminishes. CONCLUSION: MEG as well as EEG-SD are robust long-term predictors for epilepsy.

Cognitive deterioration in adult epilepsy: clinical characteristics of "Accelerated Cognitive Ageing".

OBJECTIVES: "Epileptic dementia" is reported in adults with childhood-onset refractory epilepsy. Cognitive deterioration can also occur in a "second-hit model". MATERIALS AND METHODS: We studied the clinical and neuropsychological characteristics of patients with cognitive deterioration (≥1 SD discrepancy between current IQ and premorbid IQ). Memory function, reaction time and processing speed were also evaluated. Analyses were performed to investigate which clinical characteristics correlated with cognitive deterioration. RESULTS: Twenty-seven patients were included with a mean age of 55.7 years old, an average age at epilepsy onset of 33.9 years and a mean duration of 21.8 years. Over 40% had experienced at least one status epilepticus. About 77.8% had at least one comorbid disease (most of (cardio)vascular origin). Cognitive deterioration scores were significant for both Performance IQ and Full Scale IQ, but not for Verbal IQ. Impairments in fluid functions primarily affected the IQ-scores. Memory was not impaired. Epilepsy factors explained 7% of the variance in deterioration, whereas 38% was explained by relatively low premorbid IQ and educational level, high age at seizure onset and older age. CONCLUSIONS: A subgroup of patients with localization-related epilepsy exhibits cognitive decline characterized by deterioration in PIQ and FSIQ, but with preserved higher order functions (VIQ and memory). Patients typically have epilepsia tarda, comorbid pathology, relatively low educational level and older age. These are factors known to increase the vulnerability of the brain by diminishing cognitive reserve. Cognitive deterioration may develop according to a stepwise "second-hit model", affecting and accelerating the cognitive ageing process.

The effect of neuropeptide FF in the amygdala kindling model.

OBJECTIVE: Neuropeptide FF (NPFF) and its receptors (NPFF1 R and NPFF2 R) are differentially distributed throughout the central nervous system. NPFF reduces cortical excitability in rats when administered intracerebroventricularly (i.c.v.), and both NPFF and NPFF1 R antagonists attenuate pilocarpine-induced limbic seizures. In this study, our aim was to determine whether NPFF exerts anticonvulsant or anti-epileptogenic effects in the rat amygdala kindling model for temporal lobe seizures. METHODS: Male Wistar rats were implanted with a recording/stimulation electrode in the right amygdala and a cannula in the left lateral ventricle. In a first group of animals, the afterdischarge threshold (ADT) was determined after a single i.c.v. infusion of saline (n = 8) or NPFF (1 nmol/h for 2 h; n = 10). Subsequently, daily infusion of saline (n = 8) or NPFF (1 nmol/h for 2 h; i.c.v.; n = 9) was performed, followed by a kindling stimulus (ADT+200 µA). Afterdischarge duration and seizure severity were evaluated after every kindling stimulus. A second group of rats (n = 7) were fully kindled, and the effect of saline or a high dose of NPFF (10 nmol/h for 2 h, i.c.v.) on ADT and the generalized seizure threshold (GST) was subsequently determined. RESULTS: In naive rats, NPFF significantly increased the ADT compared to control (435 ± 72 µA vs 131 ± 23 µA [P < 0.05]). When rats underwent daily stimulations above the ADT, NPFF did not delay or prevent kindling acquisition. Furthermore, a high dose of NPFF did not alter ADT or GST in fully kindled rats. CONCLUSIONS: I.c.v. administration of NPFF reduced excitability in the amygdala in naive, but not in fully kindled rats, and had no effect on kindling acquisition.

Changes in the frequency of benign focal spikes accompany changes in central information processing speed: a prospective 2-year follow-up study.

We prospectively examined whether changes in the frequency of benign focal spikes accompany changes in cognition. Twenty-six children with benign focal spikes (19 with Rolandic epilepsy) and learning difficulties were examined with repeated 24-hour EEG recordings, three cognitive tests on central information processing speed (CIPS), and questionnaires on cognition and behavior at baseline, 6months, and 2years. Antiepileptic drug changes were allowed when estimated necessary by the treating physician. At baseline, a lower CIPS was correlated with a higher frequency of diurnal interictal epileptiform discharges (IEDs) and with worse academic achievement. At follow-up, there was a significant correlation between changes in CIPS and EEG changes in wakefulness (in the same direction) when the EEG outcome was dichotomized in IED frequency "increased" or "not increased". Behavioral problems were more often observed in patients with higher frequency of IEDs in sleep at baseline and in those with ongoing IEDs compared with those with EEG remission (without or with sporadic IEDs in the recording) at the end of the study period. No changes were observed in the results of the questionnaires. A lower diurnal IED frequency at baseline, lack of serial IEDs, and occurrence of only unilateral IEDs were correlated with a higher chance of EEG remission at 2-year follow-up. Electroencephalography remission could not be predicted from other epilepsy variables except from seizure freedom in the last six months. Our results confirm the nonbenign character of 'benign' focal spikes. Whether an early and stable EEG remission can be achieved through antiepileptic treatment and whether this is of benefit for cognitive development should be examined in prospective placebo-controlled randomized trials.

Development of a fluorometric microplate antiadhesion assay using uropathogenic Escherichia coli and human uroepithelial cells.

A fluorometric microplate assay has been developed to determine Escherichia (E.) coli adhesion to uroepithelial cells (UEC). P-fimbriated E. coli were labeled with BacLight Green and preincubated 30 min with human urine or standard. Fluorescent-E. coli were added to UEC in mircoplates at a 400:1 ratio, incubated 1 h, and washed, and the fluorescence intensity was measured. Specific labeling and adherence were confirmed by flow cytometry. A myricetin (1) standard curve (0-30 µg/mL) was developed; the lower limit of detection was 0.1 µg/mL, and half-maximal inhibitory concentration was 0.88 µg/mL (intra- and interassay coefficients of variance were <10% and <15%, respectively). Vaccinium macrocarpon (cranberry) extracts, quercetin (2), and procyanidins B1 (3), B2 (4), and C1 (5) showed similar inhibition. Antiadhesion activity of urine samples from subjects (n = 12) consuming placebo or V. macrocarpon beverage determined using this assay was positively correlated (R(2) = 0.78; p < 0.01) with a radiolabeled-E. coli assay.

Guidance for the preparation of neurological management guidelines by EFNS scientific task forces - revised recommendations 2012.

This paper is meant to provide guidance to anyone wishing to write a neurological guideline for diagnosis or treatment, and is directed at the Scientist Panels and task forces of the European Federation of Neurological Societies (EFNS). It substitutes the previous guidance paper from 2004. It contains several new aspects: the guidance is now based on a change of the grading system for evidence and for the resulting recommendations, and has adopted The Grading of Recommendations, Assessment, Development and Evaluation system (GRADE). The process of grading the quality of evidence and strength of recommendations can now be improved and made more transparent. The task forces embarking on the development of a guideline must now make clearer and more transparent choices about outcomes considered most relevant when searching the literature and evaluating their findings. Thus, the outcomes chosen will be more critical, more patient-oriented and easier to translate into simple recommendations. This paper also provides updated practical recommendations for planning a guideline task force within the framework of the EFNS. Finally, this paper hopes to find the approval also by the relevant bodies of our future organization, the European Academy of Neurology.

Intensity-dependent modulatory effects of vagus nerve stimulation on cortical excitability.

OBJECTIVES: Vagus nerve stimulation (VNS) is an effective treatment for refractory epilepsy. It remains unknown whether VNS efficacy is dependent on output current intensity. The present study investigated the effect of various VNS output current intensities on cortical excitability in the motor cortex stimulation rat model. The hypothesis was that output current intensities in the lower range are sufficient to significantly affect cortical excitability. MATERIAL AND METHODS: VNS at four output current intensities (0 mA, 0.25 mA, 0.5 mA and 1 mA) was randomly administered in rats (n = 15) on four consecutive days. Per output current intensity, the animals underwent five-one-hour periods: (i) baseline, (ii) VNS1, (iii) wash-out1, (iv) VNS2 and (v) wash-out2. After each one-hour period, the motor seizure threshold (MST) was measured and compared to baseline (i.e. ∆MSTbaseline , ∆MSTVNS 1 , ∆MSTwash-out1 , ∆MSTVNS 2 and ∆MSTwash-out2 ). Finally, the mean ∆MSTbaseline , mean ∆MSTwash-out1 , mean ∆MSTwash-out2 and mean ∆MSTVNS per VNS output current intensity were calculated. RESULTS: No differences were found between the mean ∆MSTbaseline , mean ∆MSTwash-out1 and mean ∆MSTwash-out2 within each VNS output current intensity. The mean ∆MSTVNS at 0 mA, 0.25 mA, 0.5 mA and 1 mA was 15.3 ± 14.6 µA, 101.8 ± 23.5 µA, 108.1 ± 24.4 µA and 85.7 ± 18.1 µA respectively. The mean ∆MSTVNS at 0.25 mA, 0.5 mA and 1 mA were significantly larger compared to the mean ∆MSTVNS at 0 mA (P = 0.002 for 0.25 mA; P = 0.001 for 0.5 mA; P = 0.011 for 1 mA). CONCLUSIONS: This study confirms efficacy of VNS in the motor cortex stimulation rat model and indicates that, of the output current intensities tested, 0.25 mA is sufficient to decrease cortical excitability and higher output current intensities may not be required.

Subgroup classification in patients with psychogenic non-epileptic seizures.

INTRODUCTION: In this open non-controlled clinical cohort study, the applicability of a theoretical model for the diagnosis of psychogenic non-epileptic seizures (PNES) was studied in order to define a general psychological profile and to specify possible subgroups. METHODS: Forty PNES patients were assessed with a PNES "test battery" consisting of eleven psychological instruments, e.g., a trauma checklist, the global cognitive level, mental flexibility, speed of information processing, personality factors, dissociation, daily hassles and stress and coping factors. RESULTS: The total PNES group was characterized by multiple trauma, personality vulnerability (in a lesser extent, neuropsychological vulnerabilities), no increased dissociation, many complaints about daily hassles that may trigger seizures and negative coping strategies that may contribute to prolongation of the seizures. Using factor analysis, specific subgroups were revealed: a 'psychotrauma subgroup', a 'high vulnerability somatizing subgroup' (with high and low cognitive levels) and a 'high vulnerability sensitive personality problem subgroup'. CONCLUSION: Using a theoretical model in PNES diagnosis, PNES seem to be a symptom of distinct underlying etiological factors with different accents in the model. Hence, describing a general profile seems to conceal specific subgroups with subsequent treatment implications. This study identified three factors, representing two dimensions of the model, that are essential for subgroup classification: psychological etiology (psychotrauma or not), vulnerability, e.g., the somatization tendency, and sensitive personality problems/characteristics ('novelty seeking'). For treatment, this means that interventions could be tailored to the main underlying etiological problem. Also, further research could focus on differentiating subgroups with subsequent treatment indications and possible different prognoses.

Development and validation of a sensitive, high-throughput bioassay for the adhesion of radiolabeled E. coli to uroepithelial cells in vitro.

Vaccinium macrocarpon (cranberry) products have been used to prevent uropathogenic Escherichia (E.) coli adherence to uroepithelial cells (UEC) and may help reduce risk of urinary tract infection. Reported herein are the development and validation of an assay to assess antiadhesion activity of V. macrocarpon extracts and human urine. P-fimbriated E. coli (CFT073) was labeled with ³H-uridine, then co-incubated with HTB-4 UEC at a 400:1 ratio. V. macrocarpon extracts (0-17 mg proanthocyanidins/mL) were added to ³H-labeled E. coli before co-incubating with UEC. The assay yielded a sensitive inhibition curve: the lower limit of detection and half-maximal inhibitory concentration were 0.43 and 1.59 mg proanthocyanidins/mL for V. macrocarpon extract CEP 55; intra- and interassay coefficients of variance were <10% and <15%, respectively. V. macrocarpon extract CEP 3283 showed identical adhesion inhibition. Serial dilutions of urine from human participants who consumed V. macrocarpon beverages showed a linear decrease in antiadhesion activity. Antiadhesion assays conducted with urine from a human intervention study also showed good agreement with results obtained using the hemagglutination assay. Therefore, a sensitive, high-throughput, biologically relevant antiadhesion assay using ³H-E. coli co-incubated with UEC is reported, which can be used for studying the action of V. macrocarpon bioactives.

A framework to integrate EEG-correlated fMRI and intracerebral recordings.

EEG-correlated functional MRI (EEG-fMRI) has been used to indicate brain regions associated with interictal epileptiform discharges (IEDs). This technique enables the delineation of the complete epileptiform network, including multifocal and deeply situated cortical areas. Before EEG-fMRI can be used as an additional diagnostic tool in the preoperative work-up, its added value should be assessed in relation to intracranial EEG recorded from depth electrodes (SEEG) or from the cortex (ECoG), currently the clinical standard. In this study, we propose a framework for the analysis of the SEEG data to investigate in a quantitative way whether EEG-fMRI reflects the same cortical areas as identified by the IEDs present in SEEG recordings. For that purpose, the data of both modalities were analyzed with a general linear model at the same time scale and within the same spatial domain. The IEDs were used as predictors in the model, yielding for EEG-fMRI the brain voxels that were related to the IEDs and, similarly for SEEG, the electrodes that were involved. Finally, the results of the regression analysis were projected on the anatomical MRI of the patients. To explore the usefulness of this quantitative approach, a sample of five patients was studied who both underwent EEG-fMRI and SEEG recordings. For clinical validation, the results of the SEEG analysis were compared to the standard visual review of IEDs in SEEG and to the identified seizure onset zone, the resected area, and outcome of surgery. SEEG analysis revealed a spatial pattern for the most frequent and dominant IEDs present in the data of all patients. The electrodes with the highest correlation values were in good concordance with the electrodes that showed maximal amplitude during those events in the SEEG recordings. These results indicate that the analysis of SEEG data at the time scale of EEG-fMRI, using the same type of regression model, is a promising way to validate EEG-fMRI data. In fact, the BOLD areas with a positive hemodynamic response function were closely related to the spatial pattern of IEDs in the SEEG recordings in four of the five patients. The areas of significant BOLD that were not located in the vicinity of depth electrodes, were mainly characterized by negative hemodynamic responses. Furthermore, the area with a positive hemodynamic response function overlapped with the resected area in three patients, while it was located at the edge of the resection area for one. To conclude, the results of this study encourage the application of EEG-fMRI to guide the implantation of depth electrodes as prerequisite for successful epilepsy surgery.

Dietary intake and risk assessment of elements for 1- and 2-year-old children in the Netherlands.

In 2017, a total diet study (TDS) was conducted in the Netherlands to determine the intake of elements by 1- and 2-year-old children. Concentrations of 47 elements were analysed and long-term dietary intake was calculated for 24 elements. The 95th percentile (P95) intake estimates were compared with a tolerable daily or weekly intake (TDI or TWI) or tolerable upper intake level (UL), or a margin of exposure (MOE) was calculated. The P95 intake of cadmium and zinc exceeded the TWI or UL, respectively, and the P95 intake of inorganic arsenic and lead resulted in low MOEs. Food subgroups contributing most to the intake were "potatoes" for cadmium, "milk and milk-based beverages" for zinc, "concentrated fruit juices" and "rice" for inorganic arsenic, and "candies" for lead. For inorganic mercury, it could not be established if the intake was (too) high. P95 intake estimates of the other elements for which a risk characterisation could be performed were below the health-based guidance values. It was noted that the P50 intake estimate of manganese was a factor of 3 higher than the adequate intake level. Due to the absence of a UL, it is not clear if this intake is of concern.

Pigmented potato consumption alters oxidative stress and inflammatory damage in men.

Pigmented potatoes contain high concentrations of antioxidants, including phenolic acids, anthocyanins, and carotenoids. These bioactive compounds have been implicated in the inhibition or prevention of cellular oxidative damage and chronic disease susceptibility. We assessed the effects of pigmented potato consumption on oxidative stress and inflammation biomarkers in adult males. Free-living healthy men (18-40 y; n = 12/group) consumed 150 g of cooked white- (WP), yellow- (YP), or purple-flesh potatoes (PP) once per day for 6 wk in a randomized study. Blood was collected at baseline and wk 6 to analyze total antioxidant capacity (TAC), DNA damage as assessed by plasma 8-hydroxydeoxyguanosine (8-OHdG), protein oxidation, lipid peroxidation, C-reactive protein (CRP), inflammatory cytokines, lymphoproliferation, NK cytotoxicity, and phenotypes. Potatoes were analyzed for TAC, phenolic acids, anthocyanins, and carotenoids. Compared with the WP group, the YP group had higher concentrations of phenolic acids (P < 0.002) and carotenoids (P < 0.001), whereas the PP group had higher concentrations of phenolic acids (P < 0.002) and anthocyanins (P < 0.001). Men who consumed YP and PP tended to have lower (P < 0.08) plasma IL-6 compared with those consuming WP. The PP group tended to have a lower plasma CRP concentration than the WP group (P = 0.07). The 8-OHdG concentration was lower in men who consumed either YP or PP compared with WP. Pigmented potato consumption reduced inflammation and DNA damage in healthy adult males. This offers consumers an improved nutritional choice in potato consumption.