Epileptiform Activity in Alcohol Dependent Patients and Possibilities of Its Indirect Measurement

Background: Alcohol dependence during withdrawal and also in abstinent period in many cases is related to reduced inhibitory functions and kindling that may appear in the form of psychosensory symptoms similar to temporal lobe epilepsy frequently in conditions of normal EEG and without seizures. Because temporal lobe epileptic activity tend to spread between hemispheres, it is possible to suppose that measures reflecting interhemispheric information transfer such as electrodermal activity (EDA) might be related to the psychosensory symptoms. Methods and Findings: We have performed measurement of bilateral EDA, psychosensory symptoms (LSCL-33) and alcohol craving (ACQ) in 34 alcohol dependent patients and 32 healthy controls. The results in alcohol dependent patients show that during rest conditions the psychosensory symptoms (LSCL-33) are related to EDA transinformation (PTI) between left and right EDA records (Spearman r = 0.44, p,0.01). Conclusions: The result may present potentially useful clinical finding suggesting a possibility to indirectly assess epileptiform changes in alcohol dependent patients

Subclinical Epileptiform Process in Patients with Unipolar Depression and Its Indirect Psychophysiological Manifestations

BACKGROUND: According to recent clinical findings epileptiform activity in temporolimbic structures may cause depressive and other psychiatric symptoms that may occur independently of any seizure in patient's history. In addition in these patients subclinical seizure-like activity with indirect clinical manifestations likely may occur in a form of various forms of cognitive, affective, memory, sensory, behavioral and somatic symptoms (the so-called complex partial seizure-like symptoms). A typical characteristic of epileptiform changes is increased neural synchrony related to spreading of epileptiform activity between hemispheres even in subclinical conditions i.e. without seizures. These findings suggest a hypothesis that measures reflecting a level of synchronization and information transfer between hemispheres could reflect spreading of epileptiform activity and might be related to complex partial seizure-like symptoms. METHODS AND FINDINGS: Suitable data for such analysis may provide various physiological signals reflecting brain laterality, as for example bilateral electrodermal activity (EDA) that is closely related to limbic modulation influences. With this purpose we have performed measurement and analysis of bilateral EDA and compared the results with psychometric measures of complex partial seizure-like symptoms, depression and actually experienced stress in 44 patients with unipolar depression and 35 healthy controls. The results in unipolar depressive patients show that during rest conditions the patients with higher level of complex partial seizure like symptoms (CPSI) display increased level of EDA transinformation (PTI) calculated between left and right EDA records (Spearman correlation between CPSI and PTI is r = 0.43, p = 0.004). CONCLUSIONS: The result may present potentially useful clinical finding suggesting that increased EDA transinformation (PTI) could indirectly indicate increased neural synchrony as a possible indicator of epileptiform activity in unipolar depressive patients treated by serotoninergic antidepresants

Biological Designer Self-Assembling Peptide Nanofiber Scaffolds Significantly Enhance Osteoblast Proliferation, Differentiation and 3-D Migration

A class of self-assembling peptide nanofiber scaffolds has been shown to be an excellent biological material for 3-dimension cell culture and stimulating cell migration into the scaffold, as well as for repairing tissue defects in animals. We report here the development of several peptide nanofiber scaffolds designed specifically for osteoblasts. We designed one of the pure self-assembling peptide scaffolds RADA16-I through direct coupling to short biologically active motifs. The motifs included osteogenic growth peptide ALK (ALKRQGRTLYGF) bone-cell secreted-signal peptide, osteopontin cell adhesion motif DGR (DGRGDSVAYG) and 2-unit RGD binding sequence PGR (PRGDSGYRGDS). We made the new peptide scaffolds by mixing the pure RAD16 and designer-peptide solutions, and we examined the molecular integration of the mixed nanofiber scaffolds using AFM. Compared to pure RAD16 scaffold, we found that these designer peptide scaffolds significantly promoted mouse pre-osteoblast MC3T3-E1 cell proliferation. Moreover, alkaline phosphatase (ALP) activity and osteocalcin secretion, which are early and late markers for osteoblastic differentiation, were also significantly increased. We demonstrated that the designer, self-assembling peptide scaffolds promoted the proliferation and osteogenic differentiation of MC3T3-E1. Under the identical culture medium condition, confocal images unequivocally demonstrated that the designer PRG peptide scaffold stimulated cell migration into the 3-D scaffold. Our results suggest that these designer peptide scaffolds may be very useful for promoting bone tissue regeneration

Does a Screening Trial for Spinal Cord Stimulation in Patients with Chronic Pain of Neuropathic Origin have Clinical Utility and Cost-Effectiveness? (TRIAL-STIM Study): study protocol for a randomised controlled trial

Abstract Background The TRIAL-STIM Study aims to assess the diagnostic performance, clinical outcomes and cost-effectiveness of a screening trial prior to full implantation of a spinal cord stimulation (SCS) device. Methods/design The TRIAL-STIM Study is a superiority, parallel-group, three-centre, randomised controlled trial in patients with chronic neuropathic pain with a nested qualitative study and economic evaluation. The study will take place in three UK centres: South Tees Hospitals NHS Foundation Trust (The James Cook University Hospital); Basildon and Thurrock University Hospitals NHS Foundation Trust; and Leeds Teaching Hospitals NHS Trust. A total of 100 adults undergoing SCS implantation for the treatment of neuropathy will be included. Subjects will be recruited from the outpatient clinics of the three participating sites and randomised to undergo a screening trial prior to SCS implant or an implantation-only strategy in a 1:1 ratio. Allocation will be stratified by centre and minimised on patient age (≥ 65 or < 65 years), gender, presence of failed back surgery syndrome (or not) and use of high frequency (HF10™) (or not). The primary outcome measure is the numerical rating scale (NRS) at 6 months compared between the screening trial and implantation strategy and the implantation-only strategy. Secondary outcome measures will include diagnostic accuracy, the proportion of patients achieving at least 50% and 30% pain relief at 6 months as measured on the NRS, health-related quality-of-life (EQ-5D), function (Oswestry Disability Index), patient satisfaction (Patients’ Global Impression of Change) and complication rates. A nested qualitative study will be carried out in parallel for a total of 30 of the patients recruited in each centre (10 at each centre) to explore their views of the screening trial, implantation and overall use of the SCS device. The economic evaluation will take the form of a cost–utility analysis. Discussion The TRIAL-STIM Study is a randomised controlled trial with a nested qualitative study and economic evaluation aiming to determine the clinical utility of screening trials of SCS as well as their cost-effectiveness. The nested qualitative study will seek to explore the patient’s view of the screening trials, implantation and overall use of SCS. Trial registration ISRCTN, ISRCTN60778781. Registered on 15 August 2017