Notes

[Experimental analysis with the security associated with terahertz the radiation in corneal moisture assessment].
The nuclear receptor (NR) superfamily is one of the major druggable gene families, representing targets of approximately 13.5% of approved drugs. Certain NRs, such as estrogen receptor and androgen receptor, have been well demonstrated to be functionally involved in cancer and serve as informative biomarkers and therapeutic targets in oncology. However, the spectrum of NR dysregulation across cancers remains to be comprehensively characterized. Through computational integration of genetic, genomic, and pharmacologic profiles, we characterized the expression, recurrent genomic alterations, and cancer dependency of NRs at a large scale across primary tumor specimens and cancer cell lines. Expression levels of NRs were highly cancer-type specific and globally downregulated in tumors compared to corresponding normal tissue. Although the majority of NRs showed copy number losses in cancer, both recurrent focal gains and losses were identified in select NRs. Recurrent mutations and transcript fusions of NRs were observed in a small portion of cancers, serving as actionable genomic alterations. Analysis of large-scale CRISPR and RNAi screening datasets identified 10 NRs as strongly selective essential genes for cancer cell growth. In a subpopulation of tumor cells, growth dependencies correlated significantly with expression or genomic alterations. Overall, our comprehensive characterization of NRs across cancers may facilitate the identification and prioritization of potential biomarkers and therapeutic targets, as well as the selection of patients for precision cancer treatment.We aimed to study the ictal EEG patterns in patients with non-convulsive seizures (NCS) and their relationship with underlying etiology and patient outcome. We conducted a retrospective review of EEG studies from patients undergoing continuous EEG (cEEG) monitoring for indication of altered mental status with a suspicion of NCS. Ictal EEG findings of NCS were categorized as three patterns focal or generalized epileptiform discharges (EDs) at frequencies >2.5 Hz (Pattern 1); EDs at frequencies of ≤2.5 Hz or rhythmic activity >0.5 Hz with spatiotemporal evolution (Pattern 2); and EDs with ≤2.5 Hz with subtle clinical correlate during the ictal EEG or clinical and EEG improvement after a trial of IV anti-seizure drugs (Pattern 3). Patients with anoxic brain injury were excluded from the study. Associations between ictal EEG patterns and underlying etiology and their impact on in-hospital mortality was measured. Of 487 patients included in the study, NCS was recorded on cEEG monitoring in 57 (12%). The ictal EEG Pattern 2 was the most commonly seen ictal EEG finding in our cohort of patients with NCS (70%, n=40/57), followed by Pattern 3 (15%, n=9/57) and Pattern 1(14%, n=8/57). In patients with acute brain injury, Pattern 2 (67%, n=27/40) was a commonly seen ictal EEG finding, whereas Pattern 1 (62% n=5/8) was seen in patients with underlying acute medical illness. No statistically significant difference was found between ictal EEG patterns and underlying neurological versus medical etiologies (p=0.27) or in-hospital mortality (p=0.5). Spatiotemporal evolution of epileptiform discharges at a lower frequency was the most commonly recorded ictal EEG pattern in our cohort. Further prospective studies with a larger sample size of patients with NCS may provide valuable clinical data that could be used to evaluate the etiologic correlate of the various ictal EEG patterns and their effect on outcome.
Focal cortical dysplasia (FCD) is a malformation of cortical development and is associated with drug-resistant epilepsy. Standard indication for epilepsy surgery is drug resistance (as defined by the ILAE). Given the high incidence of drug resistance in these children, this delay may not be warranted. The aim of the study was to determine the proportion of patients with a presumed FCD who develop drug resistance, and evaluate post-operative outcomes.

This study incorporated a survey within a regional paediatric epilepsy network and a retrospective database review of a paediatric epilepsy centre serving the network to identify children with epilepsy and a presumed FCD on MRI.

The survey revealed that 86% of the patients with epilepsy and presumed FCD on MRI within the network were referred to our centre. Of 139 paediatric patients included in the study, 131 (94.2%) had drug-resistant epilepsy. One hundred and ten (83.9%) patients were referred to epilepsy surgery, of whom 97 underwent surgery. Of 92 withl develop drug-resistant epilepsy and are candidates for epilepsy surgery. The main outcome predictors are the correlation between MRI and ictal EEG localization and age at onset. This suggests that patients with FCD and epilepsy may be considered for surgery before traditional criteria of drug resistance are met. This change in practice has the potential to improve quality of life and cognitive function, and reduce burden on epilepsy services.This seminar in epileptology addresses Learning Objective 6.1.4 of the International League against Epilepsy Curriculum Demonstrate the ability to recognize and manage the special needs of persons with epilepsy (and Neurodevelopmental Disorders [NDDs]). The review identifies the essential competencies for neurologists working with people with epilepsy and NDDs, and these competencies are discussed alongside clinical examples. Furthermore, the seminar explores the opportunities offered by integrated service provision between neurology and services for NDD. The epileptic encephalopathies are not a subject of this seminar paper as they are circumscribed by other ILAE learning objectives. This seminar frames the complexity of seizures in association with NDD with a focus on major NDDs; intellectual disability, autism spectrum disorder, and attention deficit hyperactivity disorder. The evidence presented considers epidemiology, co-morbidities, risk factors, mortality, and the diagnostic and treatment challenges. selleck products P case studies and a video to highlight what can go wrong and how it can be avoided.Limb loss experience is a type of body illusion characterized by the sensation of a missing limb or body part. We aimed to investigate the brain areas involved in this unusual somatosensory experience evoked by electric cortical stimulation with stereo-electroencephalography electrodes. We retrospectively reviewed the data of patients with medical intractable epilepsy, from October 2015 to December 2020, who underwent stereo-electroencephalography implantation and electric cortical stimulation in order to locate the epileptogenic zone and obtain a functional map. We included patients who reported experiences of limb loss during the process of electric cortical stimulation for functional mapping. Three patients reported experiences of limb loss in the process of electric cortical stimulation. Limb loss experience (including the right hand, right upper limb and right side of the body) occurred when the cortex of the left posterior insula, posterior dorsal cingulate and parietal operculum were stimulated. Limb loss experience can be evoked by electric cortical stimulation of the posterior insula, parietal operculum, and posterior cingulate cortex, and provides additional evidence that these cortices play a role in the integration of body sensory perception.Population-based studies of epilepsy risk factors are rare. We aimed to evaluate the prevalence of various risk factors associated with new-onset epilepsy after the age of 50 years. We included all incident cases in North Macedonia between 2015 and 2018. Study participants were ascertained from the national healthcare platform. We performed a retrospective analysis of Electronic Health Records of 2,367 patients (1,017 females and 1,350 males) whose epileptic seizures started after the age of 50 years. Patients were stratified into 10-year age groups. The most common risk factor for new-onset epilepsy in our cohort was stroke, which was associated with new-onset epilepsy in 20% of patients aged 50-59 years and almost 50% of patients aged 70-79 years. The second most frequent risk factor was neoplasm in patients aged 50-69 years and dementia in patients older than 70 years. The other pre-existing conditions included metabolic disorders, traumatic brain injury, and postencephalitic and inflammatory diseases. Chronic alcoholism was the most common metabolic risk factor associated with new-onset epilepsy and accounted for 84% of cases in this subgroup. Only metabolic disorders were significantly more frequent in males than in females (p less then 0.00001). We did not identify any epilepsy risk factor in 967 patients (41%). Systemic vascular risk factors were frequent in our cohort 1,574 patients had hypertension (66%) and 449 patients had diabetes (19%), and 339 had both conditions (14%). We found that structural lesions were the most prevalent risk factor associated with new-onset epilepsy in middle-aged and elderly patients. Recognition of possibly modifiable factors associated with late-onset epilepsy could have a positive impact on reducing the risk of developing epilepsy.Different sleep stages exert differential effects on interictal discharges, neural synchrony and seizure threshold. We sought to assess the relationship between localization of the epileptogenic focus and seizure distribution in sleep versus wakefulness among patients with refractory epilepsy. We conducted a retrospective chart review-based study. Video-electroencephalography of patients with refractory epilepsy, planned for resective surgery, were reviewed for seizure localisation and occurrence relative to stage of sleep/wakefulness. Demographic/clinical data, including details of surgery, were also recorded. Bivariate analysis was conducted using the chi-square test for proportions and unpaired t-test/ANOVA to compare the means within groups. We enrolled 175 patients (107 males) with a mean age of 26.1 + 9.8 years (range 4-53 years). We analysed 1,282 seizures, of which 916 (71.5%) were temporal, 95 (7.4%) frontal, 144 (11.2 %) central/ parietal and 19 (1.5%) arose from the occipital lobe. Temporal lobe onset seizures were more frequent during wakefulness (77.7%) compared to extra-temporal localization (65%) (p less then 0.0001). Amongst temporal lobe onset seizures, those during wakefulness arose more frequently from the lateral temporal (88.6%) compared to the mesial temporal lobe (75.5%) (p=0.0003). A higher proportion of seizures evolved into secondary generalisation during sleep (23.5%) versus 8.7% during wakefulness (p less then 0.0001). Our study demonstrates that lobar location of epileptogenic foci is associated with a predilection of seizures to occur, as well as secondarily generalise, during sleep/wakefulness. Seizures with lateral temporal lobe as well as extratemporal lobe onset were more likely to occur during wakefulness. Overall, sleep related seizures were more likely to be of extratemporal lobe onset, though.Plants and associated microorganisms are essential sources of natural products against human cancer diseases, partly exemplified by plant-derived anticancer drugs such as Taxol (paclitaxel). Natural products provide diverse mechanisms of action and can be used directly or as prodrugs for further anticancer optimization. Despite the success, major bottlenecks can delay anticancer lead discovery and implementation. Recent advances in sequencing and omics-related technology have provided a mine of information for developing new therapeutics from natural products. Artificial intelligence (AI), including machine learning (ML), has offered powerful techniques for extensive data analysis and prediction-making in anticancer leads discovery. This review presents an overview of current AI-guided solutions to discover anticancer lead compounds, focusing on natural products from plants and associated microorganisms.
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