Seizure Detection, Seizure Prediction, and Closed-Loop Warning Systems in Epilepsy

Nearly one-third of patients with epilepsy continue to have seizures despite optimal medication management. Systems employed to detect seizures may have the potential to improve outcomes in these patients by allowing more tailored therapies and might, additionally, have a role in accident and SUDEP prevention. Automated seizure detection and prediction require algorithms which employ feature computation and subsequent classification. Over the last few decades, methods have been developed to detect seizures utilizing scalp and intracranial EEG, electrocardiography, accelerometry and motion sensors, electrodermal activity, and audio/video captures. To date, it is unclear which combination of detection technologies yields the best results, and approaches may ultimately need to be individualized. This review presents an overview of seizure detection and related prediction methods and discusses their potential uses in closed-loop warning systems in epilepsy

High-content screen in human pluripotent cells identifies miRNA-regulated pathways controlling pluripotency and differentiation

Background: By post-transcriptionally regulating multiple target transcripts, microRNAs (miRNAs or miR) play important biological functions. H1 embryonic stem cells (hESCs) and NTera-2 embryonal carcinoma cells (ECCs) are two of the most widely used human pluripotent model cell lines, sharing several characteristics, including the expression of miRNAs associated to the pluripotent state or with differentiation. However, how each of these miRNAs functionally impacts the biological properties of these cells has not been systematically evaluated. Methods: We investigated the effects of 31 miRNAs on NTera-2 and H1 hESCs, by transfecting miRNA mimics. Following 3-4 days of culture, cells were stained for the pluripotency marker OCT4 and the G2 cell-cycle marker Cyclin B1, and nuclei and cytoplasm were co-stained with Hoechst and Cell Mask Blue, respectively. By using automated quantitative fluorescence microscopy (i.e., high-content screening (HCS)), we obtained several morphological and marker intensity measurements, in both cell compartments, allowing the generation of a multiparametric miR-induced phenotypic profile describing changes related to proliferation, cell cycle, pluripotency, and differentiation. Results: Despite the overall similarities between both cell types, some miRNAs elicited cell-specific effects, while some related miRNAs induced contrasting effects in the same cell. By identifying transcripts predicted to be commonly targeted by miRNAs inducing similar effects (profiles grouped by hierarchical clustering), we were able to uncover potentially modulated signaling pathways and biological processes, likely mediating the effects of the microRNAs on the distinct groups identified. Specifically, we show that miR-363 contributes to pluripotency maintenance, at least in part, by targeting NOTCH1 and PSEN1 and inhibiting Notch-induced differentiation, a mechanism that could be implicated in na\uefve and primed pluripotent states. Conclusions: We present the first multiparametric high-content microRNA functional screening in human pluripotent cells. Integration of this type of data with similar data obtained from siRNA screenings (using the same HCS assay) could provide a large-scale functional approach to identify and validate microRNA-mediated regulatory mechanisms controlling pluripotency and differentiation

Effect of SGLT2 inhibitors on stroke and atrial fibrillation in diabetic kidney disease: Results from the CREDENCE trial and meta-analysis

BACKGROUND AND PURPOSE: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-Analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus. METHODS: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-Analysis. RESULTS: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55-1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61-1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19-1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20-1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53-1.10]; n=115). The overall effects in the 4 CVOTs combined were: Total stroke (HRpooled, 0.96 [95% CI, 0.82-1.12]), ischemic stroke (HRpooled, 1.01 [95% CI, 0.89-1.14]), hemorrhagic stroke (HRpooled, 0.50 [95% CI, 0.30-0.83]), undetermined stroke (HRpooled, 0.86 [95% CI, 0.49-1.51]), and AF/AFL (HRpooled, 0.81 [95% CI, 0.71-0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (P=0.01), with protection in the lowest estimated glomerular filtration rate (45 mL/min/1.73 m2]) subgroup (HRpooled, 0.50 [95% CI, 0.31-0.79]). CONCLUSIONS: Although we found no clear effect of SGLT2i on total stroke in CREDENCE or across trials combined, there was some evidence of benefit in preventing hemorrhagic stroke and AF/AFL, as well as total stroke for those with lowest estimated glomerular filtration rate. Future research should focus on confirming these data and exploring potential mechanisms

Pseudorapidity distribution of charged hadrons in proton-proton collisions at root s=13TeV

Peer reviewe

Canagliflozin and Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus and Chronic Kidney Disease in Primary and Secondary Cardiovascular Prevention Groups

Background: Canagliflozin reduces the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, but effects on specific cardiovascular outcomes are uncertain, as are effects in people without previous cardiovascular disease (primary prevention). Methods: In CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation), 4401 participants with type 2 diabetes mellitus and chronic kidney disease were randomly assigned to canagliflozin or placebo on a background of optimized standard of care. Results: Primary prevention participants (n=2181, 49.6%) were younger (61 versus 65 years), were more often female (37% versus 31%), and had shorter duration of diabetes mellitus (15 years versus 16 years) compared with secondary prevention participants (n=2220, 50.4%). Canagliflozin reduced the risk of major cardiovascular events overall (hazard ratio [HR], 0.80 [95% CI, 0.67-0.95]; P=0.01), with consistent reductions in both the primary (HR, 0.68 [95% CI, 0.49-0.94]) and secondary (HR, 0.85 [95% CI, 0.69-1.06]) prevention groups (P for interaction=0.25). Effects were also similar for the components of the composite including cardiovascular death (HR, 0.78 [95% CI, 0.61-1.00]), nonfatal myocardial infarction (HR, 0.81 [95% CI, 0.59-1.10]), and nonfatal stroke (HR, 0.80 [95% CI, 0.56-1.15]). The risk of the primary composite renal outcome and the composite of cardiovascular death or hospitalization for heart failure were also consistently reduced in both the primary and secondary prevention groups (P for interaction >0.5 for each outcome). Conclusions: Canagliflozin significantly reduced major cardiovascular events and kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, including in participants who did not have previous cardiovascular disease

Interictal EEG in temporal lobe epilepsy in childhood

The authors clarified the value of interictal discharges and verified which extratemporal regions may also show epileptiform activity in temporal lobe epilepsy (TLE) in childhood. Thirty consecutive patients aged 3 to 18 years (mean age = 12.16 years; 16 male) with TLE associated with hippocampal atrophy were studied. Each patient had I to 15 interictal EEG recordings (mean: 5.6; total = 192 EEGs). Video-EEG monitoring was performed in 20 patients. All patients had MRI. The findings were compared with a control group of 53 consecutive TLE adult outpatients with hippocampal atrophy. Each adult patient underwent 3 to 21 routine EEGs (mean: 10.67; total = 566). Interictal EEGs of children with TLE showed extratemporal epileptiform discharges more frequently than EEGs of adults with TLE. Frontal, parietal, and occipital discharges were more frequently seen in children (P < 0.05). These results suggest a close interaction between temporal and other cerebral regions in children with epilepsy and provide further evidence of the existence of neural networks.241111