Dynamic flow and shear stress as key parameters for intestinal cells morphology and polarization in an organ-on-a-chip model.

Gut-on-a-chip microfluidic devices have emerged as versatile and practical systems for modeling the human intestine in vitro. Cells cultured under microfluidic conditions experience the effect of shear stress, used as a biomechanical cue to promote a faster cell polarization in Caco-2 cells when compared with static culture conditions. However, published systems to date have utilized a constant flow rate that fails to account for changes in cell shear stress ([Formula: see text]) resulting from changes in cell elongation that occur with differentiation. In this study, computational fluid dynamics (CFD) simulations predict that cells with villi-like morphology experience a [Formula: see text] higher than bulge-like cells at the initial growth stages. Therefore, we investigated the use of a dynamic flow rate to maintain a constant [Formula: see text] across the experiment. Microscopic assessment of cell morphology and dome formation confirmed the initiation of Caco-2 polarization within three days. Next, adopting our dynamic approach, we evaluated whether the following decreased flow could still contribute to complete cell differentiation if compared with the standard constant flow methodology. Caco-2 cells polarized under both conditions, secreted mucin-2 and villin and formed tight junctions and crypt-villi structures. Gene expression was not impacted using the dynamic flow rate. In conclusion, our dynamic flow approach still facilitates cell differentiation while enabling a reduced consumption of reagents.

Models of the Gut for Analyzing the Impact of Food and Drugs.

Models of the human gastrointestinal tract (GIT) can be powerful tools for examining the biological interactions of food products and pharmaceuticals. This can be done under normal healthy conditions or using models of disease-many of which have no curative therapy. This report outlines the field of gastrointestinal modeling, with a particular focus on the intestine. Traditional in vivo animal models are compared to a range of in vitro models. In vitro systems are elaborated over time, recently culminating with microfluidic intestines-on-chips (IsOC) and 3D bioengineered models. Macroscale models are also reviewed for their important contribution in the microbiota studies. Lastly, it is discussed how in silico approaches may have utility in predicting and interpreting experimental data. The various advantages and limitations of the different systems are contrasted. It is posited that only through complementary use of these models will salient research questions be able to be addressed.

Effect of short-term transcutaneous trigeminal nerve stimulation on EEG activity in drug-resistant epilepsy.

BACKGROUND: Transcutaneous trigeminal nerve stimulation (TNS) has antiepileptic effects in patients with drug-resistant epilepsy (DRE). However, whether and how TNS is able to modulate the electroencephalogram (EEG) background activity in patients with DRE is still unknown. OBJECTIVES: To investigate the effect of short-term TNS on EEG background activity in DRE by qualitative and quantitative analyses. METHODS: Twenty-nine DRE patients participated in the study. Twenty-two were randomly divided into a "sham-TNS" or "real-TNS" group; seven patients underwent stimulation of the median nerve (MNS) at the wrist. Real-TNS was delivered bilaterally to the infraorbital nerve (trains of 1-20 mA, 120 Hz, cyclic modality for 20 min). The sham-TNS protocol mimicked the real-TNS one but at a zero intensity. For MNS, the same parameters as real-TNS were used. EEG was continuously acquired for 40 min: 10' pre, 20' during and 10' post stimulation. EEG was visually inspected for interictal epileptiform discharge (IEDs) changes and processed by spectral analysis for changes in mean frequency and absolute power of each frequency band. RESULTS: A significant increase of EEG absolute alpha power was observed during real-TNS compared with the sham-TNS (F34,680 = 1.748; p = 0.006). Conversely, no significant effects were noticed either for quantitative analysis of other frequency bands or for IEDs detection. MNS proved unable to modulate EEG activity. CONCLUSIONS: Short-term TNS induces an acute and specific effect on background EEG of DRE by increasing the absolute alpha band power. EEG alpha rhythm enhancement may index a cortical functional inhibition and act as a seizure-preventing mechanism.

Paradoxical Effect of Levetiracetam in Newly Diagnosed Type II Focal Cortical Dysplasia.

A paradoxical effect of antiepileptic drugs was defined as an increased seizure frequency or severity occurring shortly after introducing a drug considered effective for that kind of epilepsy. In addition, this effect should occur at nontoxic drug serum levels. So far, pathophysiological mechanisms underlying this phenomenon have not been clarified. Recent evidence suggests that the variability of drug effects may depend on precise intrinsic properties of dynamic networks involving the drug and its binding site. Although several reports of paradoxical seizure exacerbation have been reported for levetiracetam (LEV), a possible association with focal cortical dysplasia has never been described nor investigated. In this report, we document a paradoxical effect induced by LEV monotherapy in a patient with type II focal cortical dysplasia at LEV serum levels within the therapeutic range. A hint of pathophysiological hypothesis underlying this potential relationship will be also suggested.

Advances in clinical determinants and neurological manifestations of B vitamin deficiency in adults.

B vitamin deficiency is a leading cause of neurological impairment and disability throughout the world. Multiple B vitamin deficiencies often coexist, and thus an understanding of the complex relationships between the different biochemical pathways regulated in the brain by these vitamins may facilitate prompter diagnosis and improved treatment. Particular populations at risk for multiple B vitamin deficiencies include the elderly, people with alcoholism, patients with heart failure, patients with recent obesity surgery, and vegetarians/vegans. Recently, new clinical settings that predispose individuals to B vitamin deficiency have been highlighted. Moreover, other data indicate a possible pathogenetic role of subclinical chronic B vitamin deficiency in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. In light of these findings, this review examines the clinical manifestations of B vitamin deficiency and the effect of B vitamin deficiency on the adult nervous system. The interrelationships of multiple B vitamin deficiencies are emphasized, along with the clinical phenotypes related to B vitamin deficiencies. Recent advances in the clinical determinants and diagnostic clues of B vitamin deficiency, as well as the suggested therapies for B vitamin disorders, are described.

Predictors for being offered epilepsy surgery: 5-year experience of a tertiary referral centre.

OBJECTIVES: To define factors that predict whether patients with pharmacoresistant focal epilepsy are offered epilepsy surgery (including invasive EEG) and the main reasons for not proceeding with these after non-invasive presurgical evaluation. METHODS: We retrospectively analysed data from 612 consecutive patients with focal epilepsy admitted to a video-EEG Telemetry Unit for presurgical evaluation, and used a multivariate logistic regression model to assess the predictive value of factors for being offered potentially curative surgery. RESULTS: In the multivariate analysis, bilateral lesions on MRI (OR: 0.10; 95% CI 0.03 to 0.24), no lesion (OR: 0.33; 95% CI 0.22 to 0.49) or extratemporal lobe epilepsy (OR: 0.30; 95% CI 0.20 to 0.45) were the only factors that significantly reduced the probability of being offered surgery. 32% of patients who were offered epilepsy surgery decided against proceeding. CONCLUSIONS: There was a low chance (<10%) of being offered surgery if there were bilateral lesions on MRI and extratemporal lobe epilepsy. Patients should be given advice on the risk/benefit ratio and of realistic outcomes of epilepsy surgery; this may help reduce the number of patients who refuse surgery after comprehensive workup.

The utility of polysomnography for the diagnosis of NREM parasomnias: an observational study over 4 years of clinical practice.

Polysomnography (PSG) is considered the gold standard for diagnosis of non-rapid eye movement (NREM) parasomnias, however its diagnostic yield has been rarely reported. We aimed to assess the diagnostic value of polysomnography in different categories of patients with suspected NREM parasomnia and define variables that can affect the outcome. 124 adults referred for polysomnography for suspected NREM parasomnia were retrospectively identified and divided into clinical categories based on their history. Each polysomnography was analysed for features of NREM parasomnia or different sleep disorders and for presence of potential precipitants. The impact on the outcome of number of recording nights and concomitant consumption of benzodiazepines and antidepressants was assessed. Overall, PSG confirmed NREM parasomnias in 60.5 % patients and showed a different sleep disorder in another 16 %. Precipitants were found in 21 % of the 124 patients. However, PSG showed limited value when the NREM parasomnia was clinically uncomplicated, since it rarely revealed a different diagnosis or unsuspected precipitants (5 % respectively), but became essential for people with unusual features in the history where different or overlapping diagnoses (18 %) or unsuspected precipitants (24 %) were commonly identified. Taking benzodiazepines or antidepressants during the PSG reduced the diagnostic yield. PSG has a high diagnostic yield in patients with suspected NREM parasomnia, and can reveal a different diagnosis or precipitants in over 40 % of people with complicated or atypical presentation or those with a history of epilepsy. We suggest that PSG should be performed for one night in the first instance, with leg electrodes and respiratory measurements and after benzodiazepine and antidepressant withdrawal.

Gelastic seizures: incidence, clinical and EEG features in adult patients undergoing video-EEG telemetry.

This study aimed to determine clinical features of adult patients with gelastic seizures recorded on video -electroencephalography (EEG) over a 5-year period. We screened video-EEG telemetry reports for the occurrence of the term "gelastic" seizures, and assessed the semiology, EEG features, and duration of those seizures. Gelastic seizures were identified in 19 (0.8%) of 2,446 admissions. The presumed epileptogenic zone was in the hypothalamus in one third of the cases, temporal lobe epilepsy was diagnosed in another third, and the remainder of the cases presenting with gelastic seizures were classified as frontal, parietal lobe epilepsy or remained undetermined or were multifocal. Gelastic seizures were embedded in a semiology, with part of the seizure showing features of automotor seizures. A small proportion of patients underwent epilepsy surgery. Outcome of epilepsy surgery was related to the underlying pathology; two patients with hippocampal sclerosis had good outcomes following temporal lobe resection and one of four patients with hypothalamic hamartomas undergoing gamma knife surgery had a good outcome.