Beta Delta Research Articles

Suppressed ORAI1-STIM1-dependent Ca2+ entry by protein kinase C isoforms regulating platelet procoagulant activity

Agonist-induced rises in cytosolic Ca2+ control most platelet responses in thrombosis and hemostasis. In human platelets we earlier demonstrated that the ORAI1-STIM1 pathway is a major component of extracellular Ca2+ entry, in particular when induced via the ITAM-linked collagen receptor, glycoprotein VI (GPVI). In the present paper, using functionally defective platelets from patients with a loss-of-function mutation in ORAI1 or STIM1, we show that Ca2+ entry induced by the endoplasmic reticulum ATPase inhibitor, thapsigargin, fully relies on this pathway. We demonstrate that both the GPVI-induced and thapsigargin-induced Ca2+ entry is strongly suppressed by protein kinase C (PKC) activation, while leaving intracellular Ca2+ mobilization unchanged. Comparing effects of a PKC inhibitory panel pointed to redundant roles of beta and theta PKC isoforms in Ca2+-entry suppression. In contrast, tyrosine kinases positively regulated GPVI-induced Ca2+ entry and mobilization. Label-free and stable isotope phosphoproteome analysis of GPVI-stimulated platelets suggested a regulatory role of bridging integrator-2 (BIN2), known as important mediator of the ORAI1-STIM1 pathway in mouse platelets. Identified were 25-45 regulated phospho- sites in BIN2 and 16-18 in STIM1. Five of these were characterized as direct substrates of the expressed PKC isoforms alpha, beta delta and theta. Functional platelet testing indicated that the downregulation of Ca2+ entry by PKC resulted in suppressed phosphatidylserine exposure and plasmatic thrombin generation. Conclusively, our results indicate that in platelets multiple PKC isoforms constrain the store-regulated Ca2+ entry via ORAI1-BIN2-STIM1, and hence downregulate platelet-dependent coagulation.

Excessive hydrogen sulfide-induced activation of NMDA receptors in the colon participates in anxiety- and compulsive-like behaviors in a rodent model of hemorrhagic shock and resuscitation

ObjectiveHemorrhagic shock and resuscitation (HSR) cause inflammatory responses in the gastrointestinal tract and is associated with substantial morbidity and mortality rates. Hydrogen sulfide (H2S), a gasotransmitter with pleiotropic activity, exhibits anti-inflammatory benefits at physiological levels. However, deleterious effects are observed when its concentration increases. In this investigation, we employed a mouse model of HSR to examine the effects of an H2S scavenger on the gastrointestinal tract and brain, with emphasis on N-Methyl-d-Aspartate (NMDA) receptor function. MethodsMice were immediately administered dl-propargylglycine (PAG) intragastrically as an H2S scavenger after HSR exposure. The O-maze and buried beads tests were used to assess compulsive- and anxiety-like behaviors. Pathological changes in the intestine were evaluated at 24 and 30 days after HSR. Subsequently, at 30 days after HSR, we examined electrophysiological and pathological changes in the amygdala. ResultsWithin 24 h of HSR exposure, animals treated with PAG showed significantly lower colonic injury. Additionally, compared to the HSR-treated mice 30 days after HSR, the PAG-treated mice displayed reduced buried beads, increased open-arm time, lower blood levels of Diamine Oxidase (DAO) and considerably improved ZO-1 intensity, a stronger association between the delta rhythm phase and beta activity amplitude, and lower neuroinflammatory response in the amygdala. MK-801, an NMDA receptor inhibitor, significantly reversed H2S-induced intestinal and cerebral injury. ConclusionThis experimental data suggests that H2S-induced excessive activation of NMDA receptors contributes to anxiety- and compulsive-like behaviors caused by HSR.

Alpha band oscillations in common synaptic input are explanatory of the complexity of isometric knee extensor muscle torque signals.

We investigated whether the strength of oscillations in common synaptic input was explanatory of knee extensor (KE) torque signal complexity during fresh and fatigued submaximal isometric contractions, in adults aged from 18 to 90years. The discharge times of motor units were derived from the vastus lateralis muscle of 60 participants using high-density surface EMG, during 20s isometric KE contractions at 20% of maximal voluntary contraction, performed before and after a fatiguing repeated isometric KE contraction protocol at 60% of maximal voluntary contraction. Within-muscle coherence Z-scores were estimated using frequency-domain coherence analysis, and muscle torque complexity was assessed using multiscale entropy analysis and detrended fluctuation analysis. Alpha band (5-15Hz) coherence was found to predict 23.1% and 31.4% of the variance in the complexity index under 28-scales (CI-28) and detrended fluctuation analysis α complexity metrics, respectively, during the fresh contractions. Delta, alpha and low beta band coherence were significantly increased due to fatigue. Fatigue-related changes in alpha coherence were significantly predictive of the fatigue-related changes in CI-28 and detrended fluctuation analysis α. The fatigue-related increase in sample entropy from scales 11 to 28 of the multiscale entropy analysis curves was significantly predicted by the increase in the alpha band coherence. Age was not a contributory factor to the fatigue-related changes in within-muscle coherence and torque signal complexity. These findings indicate that the strength of alpha band oscillations in common synaptic input can explain, in part, isometric KE torque signal complexity and the fatigue-related changes in torque signal complexity.

Electrophysiological Markers Predicting Antipsychotic Treatment Response in Patients with Schizophrenia: A Retrospective Study.

This study aimed to provide an objective means of predicting treatment responses in patients with schizophrenia using quantitative electroencephalography (qEEG) as an electrophysiological indicator. We obtained qEEG recordings from patients with schizophrenia and explored them for patterns indicative of treatment responsiveness. The study included 68 patients had been diagnosed with schizophrenia spectrum disorder. After retrospectively gathering demographic information, clinical data such as qEEG, Positive and Negative Syndrome Scale (PANSS), a multiple regression analysis was performed. This analysis employed baseline qEEG findings as independent variables and PANSS score changes as dependent variables to discern causal relationships. The mean age of the participants was 38.4 years(SD =13.73). The mean PANSS score on admission was 92.97, decreasing to 67.41 at discharge. Multiple regression analysis revealed that delta waves in T4 (β=0.346, t=3.165, p=0.002), and high-beta waves in Fp2 (β=0.231, t=2.361, p=0.021) were associated with PANSS changes in absolute power. In addition, the delta waves of O2 (β=0.250, t=3.288, p=0.002); beta waves of T3 (β=-1.463, t=-5.423, p<0.001) and O2 (β=0.551, t=3.366, p=0.001); high beta waves of Fp1 (β=0.307, t=4.026, p<0.001), T3 (β=0.855, t=4.414, p<0.001) and T6 (β=-0.838, t=-4.559, p<0.001) of absolute power using the Z-score were also related to PANSS changes. Pearson's correlation analysis showed that only delta waves at Cz (r= 0.246, p=0.043) in absolute power correlated with changes in the PANSS. We found that certain qEEG wave patterns in patients with schizophrenia prior to antipsychotic treatment were linked to PANSS changes before and after treatment. Delta waves and beta waves, primarily in the frontal and temporal regions, were found to be significantly associated with changes in PANSS scores. In the future, the qEEG indicators identified in this study could serve as electrophysiological markers for predicting antipsychotic treatment responses in patients with schizophrenia.

EEG Correlates of Moral Decision-Making: Effect of Choices and Offers Types

Background Moral decision-making consists of a complex process requiring individuals to evaluate potential consequences of personal and social decisions, including applied organizational contexts. Methods This research aims to investigate the behavioral (offer responses and reaction times, RTs) and electrophysiological (EEG) correlates underlying moral decision-making during three different choice conditions (professional fit, company fit, and social fit) and offers (fair, unfair, and neutral). Results An increase of delta and theta frontal activity (related to emotional behavior and processes) and beta frontal and central activity (linked to cognitive and attentional processes) was found. A left beta, delta, and theta frontal activity was observed for fair offers in professional fit conditions, while increased right frontal delta and theta activity was found in response to unfair offers in company fit conditions. Also, an increase of left delta and theta parietal activity for unfair offers in social fit condition was detected. Finally, higher accepted responses were found for fair and neutral offers in professional and social fit conditions, with increased RTs for unfair offers suggesting decisions’ cognitive load and complexity. Conclusions By revealing a greater involvement of left and right frontal areas in decision-making processes based on choices and offers, personal interest evaluations and emotional values, and of parietal areas in more prosocial and altruistic moral behavior, current findings provide information about the neural and behavioral correlates underlying company moral behavior.

Examining the Changes in Coagulation Parameters in Patients Infected with SARS-CoV-2 Variants (Alpha, Beta, Delta, and Omicron)

Background: It is known that the change in coagulation parameters has an effect on mortality and prognosis in COVID-19 patients. The SARS-CoV-2 virus has changed with mutations in the genome of the virus since the beginning of the pandemic, and the resulting variants have been recorded by the World Health Organization. With these variations, the clinical severity of the disease and laboratory parameters have also changed. Objectives: In this study, we examined the changes in D-dimer levels, fibrinogen levels, platelet count (PLT), and mean platelet volume (MPV) between SARS-CoV-2 Alpha (B.1.1.7), Beta (B.1.351) Delta (B.1.617.2), and Omicron (B.1.1.529) variants. Methods: The study was conducted retrospectively on 28 195 adult patients with SARS-CoV-2 infection. At the time of application, data on age, gender, SARS-CoV-2 variant status, D-dimer levels (n = 7090), fibrinogen (n = 5709), PLT (n = 7066), and MPV (n = 8330) were collected. Patients were divided according to alpha, beta, delta, and omicron variants. The changes in variants were examined statistically. Results: The incidence of the delta variant in women was higher than the other variants, followed by alpha and omicron (P = 0.001). The Beta variant was detected at a higher rate in males. The ages of the cases with the Omicron variant were higher than the cases with Alpha, Beta, and Delta variants (P = 0.001, P = 0.001, P = 0.001, and P &lt; 0.01, respectively). In laboratory parameters, D-dimer and fibrinogen levels were detected to be significantly higher in Delta and Omicron variants. PLT and MPV were determined to be lower in delta and omicron than in alpha and beta variants. Conclusions: Examination of the changes in laboratory coagulation parameters according to variants shows that the tendency to clot increases from alpha to omicron.

Electric activity of the brain at early and late clinical stages of experimental modeling of Parkinson's disease, an impact of hemantane

S. To study an influence of the adamantane derivative hemantane on the electrical activity of the brain structures of mice at the early and late (severe) stages of experimental modeling of Parkinson's disease (PD). For experimental modeling of PD in C57BL/6J mice, 30 male C57BL/6J mice weighing 25-32 g were systemically (intraperitoneally) administered proneurotoxin MPTP in two modes corresponding to different clinical stages of the disease: 1-methyl-4-phenyl-1.2.3.6-tetrahydropyridine (MPTP) at a dose of 12 mg/kg, 4 times and 20 mg/kg, 4 times with an interval of 2 hours, respectively. At the early and late clinical stages of experimental modeling of PD in the brain structures of mice (sensorimotor cortex, substantia nigra, caudate nucleus), EEG desynchronization, an increase in wave amplitude, and an increase in the power spectrum in the range of delta frequencies and beta frequencies are observed at the late symptomatic stage experimental model of PD along with a decrease in electrical activity in the range of 4-12 Hz. Preliminary application of the adamantane derivative hemantane at a dose of 20 mg/kg, both in the early and late clinical stages of PD, prevented an excessive increase in the amplitudes of all groups of waves, normalized theta activity in the range of 4-12 Hz, reduced pathological slowing and dysregulation activity in the ranges delta and beta waves, with the prevalence of these effects in the substantia nigra of the brain of animals. The effect of hemantane is more pronounced at the early clinical stage of experimental modeling of PD than at the later (full-scale) stage.

The nudging effect of AIGC labeling on users' perceptions of automated news: evidence from EEG.

In the context of generative AI intervention in news production, this study primarily focuses on the impact of AI-generated content (AIGC) labeling cues on users' perceptions of automated news based on nudge theory. A 2 (authorship disclosure nudge cues: with vs. without AIGC label) × 2 (automated news type: descriptive vs. evaluative news) within-subject experiment was carried out. Thirty-two participants were recruited to read automated news, evaluate the perceived content trustworthiness, and record with an EEG device. The results demonstrated that disclosure of AIGC labeling significantly reduced the trustworthiness perception of both fact-based descriptive and opinion-based evaluative news. In EEG, the delta PSD, theta PSD, alpha PSD, and beta PSD with disclosure of AIGC labeling were significantly higher than those without AIGC labeling. Meanwhile, in descriptive news conditions, TAR with AIGC labeling was higher than without AIGC labeling. These results suggested that AIGC labeling significantly improves the degree of attention concentration in reading and deepens the degree of cognitive processing. Users are nudged by AIGC labeling to shift their limited attention and cognitive resources to re-evaluate the information quality to obtain more prudent judgment results. This helps to supplement the theoretical perspective on transparent disclosure nudging in the Internet content governance research field, and it can offer practical guidance to use content labeling to regulate the media industry landscape in the face of AI's pervasive presence.

Evening prolonged relatively low melanopic equivalent daylight illuminance light exposure increases arousal before and during sleep without altering sleep structure

SummaryLight can influence many psychophysiological functions beyond vision, including alertness, circadian rhythm, and sleep, namely the non‐image forming (NIF) effects of light. Melanopic equivalent daylight illuminance (mel‐EDI) is currently recommended as the predictor of the NIF effects of light. Although light dose is also critical for entraining and regulating circadian cycle, it is still unknown whether relatively low mel‐EDI light exposure for prolonged duration in the evening would affect pre‐sleep arousal and subsequent sleep. In all, 18 healthy college students (10 females, mean [standard deviation] age 21.67 [2.03] years) underwent 2 experimental nights with a 1 week interval in a simulated bedroom environment. During experimental nights, participants were either exposed to high or low mel‐EDI light (73 versus 38 lx mel‐EDI, 90 versus 87 photopic lx at eye level, 150 photopic lx at table level) for 3.5 h before regular bedtime, and their sleep was monitored by polysomnography. Subjective sleepiness, mood, and resting‐state electroencephalography during light exposure were also investigated. Results showed no significant differences in sleep structure and sleep quality between the two light conditions, whereas 3.5 h of exposure to high versus low mel‐EDI light induced marginally higher physiological arousal in terms of a lower delta but higher beta power density before sleep, as well as a lower delta power density during sleep. Moreover, participants felt happier before sleep under exposure to high versus low mel‐EDI light. These findings together with the current literature suggest that evening prolonged relatively low mel‐EDI light exposure may mildly increase arousal before and during sleep but affected sleep structure less.

Sars-Cov-2 and Chronic Myeloid Leukemia: A Systematic Review

Introduction Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus causing the coronavirus disease of 2019. Numerous mutations had developed in SARS-CoV-2 virus that resulted in strains (Alfa Beta Delta Omicron) with varying degrees of virulence disease severity. In coronavirus disease of 2019 (COVID-19) patients with chronic myeloid leukemia (CML), there is a controversy regarding the effect of tyrosine kinase inhibitors (TKI) on SARS-CoV-2 infection and patients' outcomes. Some studies showed that CML patients with COVID-19 had better outcomes; other reports showed no significant difference. Method Following the PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines, PubMed, Scopus, and Google Scholar databases were searched for published articles through 20 April 2023 for qualified studies. The search included retrospective, prospective studies, reviews, case series, and case reports. The inclusion criteria were English literature with CML patients above 18 years who had SARS-CoV-2 infection. Articles in languages other than English and articles with non-sufficient information were excluded, and patients with bone marrow transplants were excluded. Search terms were (chronic myeloid leukemia) OR (chronic myelogenous leukemia) AND (SARS-CoV-2) OR (COVID-19). Two eligibility checks were done on the included studies. Title and abstract screening was completed first, and the full text of articles that met the requirements for inclusion was subsequently obtained. The search included all articles published up to 20 April 2023. The review is registered in PROSPERO (registration number is: CRD42022326674). Results We reviewed 36 articles of published literature up to April 2023 and collected data for a total of 686 CML patients with COVID-19. The vast majority of patients were in the chronic phase; seven patients were in the accelerated phase, and eight patients were in the blast phase. Disease severity was classified according to WHO criteria. Twenty-seven patients were managed at home, and 21 patients were in ICU (intensive care unit) during the hospital course. Twenty-six patients required oxygen therapy; among them, seven patients required intubation and mechanical ventilation, and six patients required non-invasive ventilation. Mortality was seen in 47 patients, and there were no reports of thrombotic events, but some patients developed AKI, autoimmune hemolytic anemia, rhabdomyolysis, and DKA during COVID-19. Limitations The major limitation is the lack of details about the use or hold of TKIs during SARS-CoV-2 infection in the majority of the reports. Also, the specific or predominant strain of SARS-CoV-2 was not mentioned. Few studies mentioned the variant of the virus, which make it difficult to compare the outcome of the different variant of the SARS-CoV-2 virus in patients with CML. Discussion/Conclusions Hematological cancers are associated with an increased risk of thrombosis. Thrombosis risk is expected to increase in patients with COVID-19; interestingly, patients with CML have not been reported to have a significant increase in the risk of thrombosis during COVID-19. The crucial point is, does TKI continuation during COVID-19 beneficial or harmful? Few patients continued TKIs during Covid-19 without serious adverse events. For patients who had the TKI continued, there were no mortality or serious adverse events. In vitro, TKIs were found to have a significant effect on inhibiting viral replication, which might be the reason behind the better outcome in CML patients infected with SARS-CoV-2 virus. On the other hand, there is a theoretical risk of increased severe infection in CML patients taking TKI due to targeted inhibition of kinases involved in immune cell function. This might result in suppressed cellular immune response that facilitates viral replication. Despite that, CML patients with COVID-19 have no significant increase in mortality or ICU admission compared to other hematological malignancies. in fact, our review showed that the mortality of CML patients with COVID-19 has significantly improved from 0.12% in the pre-vaccination period to 0.04% in the post-vaccination era. The available data indicates that, COVID-19's effect on patients with chronic myeloid leukemia (CML) still needs to be better understood due to the limited data.

Quantitative electroencephalography as a potential biomarker in migraine.

The aim of this study was to investigate the utility of quantitative electroencephalography (QEEG) as a diagnostic tool for migraine and as an indicator of treatment response by comparing QEEG characteristics between migraine patients and controls, and monitoring changes in these characteristics alongside clinical symptoms in response to treatment BACKGROUND: We hypothesized that patients with migraine exhibit distinctive characteristics in QEEG measurements, which could be used as potential diagnostic biomarkers and as a tool for monitoring treatment response. A total of 720 patients were included in the study, comprising 619 patients with migraine and 101 subjects as a control group. QEEG measurements were analyzed for absolute power across specific frequency bands: delta wave (0.5-4Hz), theta wave (4-8Hz), alpha wave (8-12Hz), beta wave (12-25Hz), and high beta wave (25-30Hz). The absolute power was normalized against a normative dataset from NeuroGuide, with electrodes being highlighted for significance if they exceeded 1.96. Clinical symptoms were also monitored for correlation with QEEG changes. Our analysis showed that patients with migraine exhibited significantly higher absolute power across all frequencies, most markedly within the high beta frequency range. When considering electrodes with z-scores exceeding the threshold of 1.96 in the high beta range, a significant association with migraine diagnosis was observed (per 1 electrode increase, OR 1.06; 95% CI 1.01-1.11; p=.012). Moreover, pre- and posttreatment changes in QEEG measurements corresponded with changes in clinical symptoms. Patients with migraine have distinctive QEEG measurements, particularly regarding absolute power and the number of electrodes that surpassed the z-score threshold in high beta wave activity. These findings suggest the potential of QEEG as a diagnostic biomarker and as a tool for monitoring treatment response in migraine patients, warranting further large-scale studies for confirmation and expansion.

Subjective cognitive decline exhibits alterations of resting-state phase-amplitude coupling in precuneus

ObjectiveSubjective cognitive decline (SCD) is associated with increased risks for progressing to Alzheimer’s disease (AD). This study aimed to investigate phase-amplitude coupling (PAC) in individuals with SCD and healthy controls (HCs) in the baseline year and determined the predictability of cognitive changes in the clinical follow-up. MethodsResting-state magnetoencephalographic signals in 29 HCs and 23 SCD subjects were recorded in the baseline year. The parahippocampal gyrus, posterior cingulate cortex and precuneus were selected as regions of interest (ROIs). Based on the grand-averaged comodulograms, delta–beta, delta–gamma and theta–gamma PAC values were extracted from each ROI. ResultsCompared with the HCs, the SCD group showed decreased theta–gamma PAC in the precuneus. Theta–gamma PAC of the left precuneus was associated with SCD severity and performance of immediate recall in the baseline year. The SCD group was followed for 3 years and divided into SCD-Stable and SCD-Decline groups based on scores of Mini-Mental State Examination. No significant differences in PAC of the baseline year were found between SCD-Stable and SCD-Decline groups. ConclusionsThe SCD group demonstrated reduced theta–gamma PAC in the precuneus. SignificanceSubjective perception of cognitive decline is reflected by objective alterations of brain function.

Homozygous delta beta-thalassemia: A rare case report

Delta Beta (δβ) thalassemia is a rare autosomal recessive hemoglobinopathy. This is caused by either reduced production of δ and β genes (heterozygous state) or complete absence (homozygous state). High-performance liquid chromatography (HPLC) is an important screening and diagnostic tool, to be supported by molecular data and parental studies. A 40-year-old male (propositus), with mild anemia presented in the outpatient department. There were no other definitive causes of anemia with adequate nutritional status and no response after the treatment with nutritional supplements. HPLC was advised to look for any qualitative/quantitative defects. HPLC findings reveal 96% fetal hemoglobin (HbF), a very small quantity of adult hemoglobin (HbA), and an absent HbA2. In view of this data, followed up with parental studies. Both parents had elevated HbF and similar grades of anemia. These supported the presence of a heterozygous state of δβ-thalassemia in parents and homozygous δβ thalassemia in propositus. In δβ-thalassemia, there is a deletion of the δ and β genes on Chromosome 11. Expression of the gamma gene increases to compensate, causing increased production of gamma globulin for HbF (α2 β2). On HPLC or electrophoresis, heterozygosity shows as normal HbA2 and elevated HbF, and as absent HbA2 with almost 100% HbF for homozygous individuals. Screening of hemoglobinopathies by HPLC is that can be further subjected to parental screening for a more definitive diagnosis and narrow down the differentials as compared to molecular testing considering the cost, limited availability, and higher turnaround time.

Electroencephlographic predictors of epileptiphorm activity in children with lymphoid tumors under therapy

Objective. To identify electroencephalographic predictors of symptomatic seizure in children and adolescent with lymphoid tumors during chemotherapy.Material and methods. EEG results of a study in 20 children aged 7 to 15 years with lymphoid tumors during chemotherapy under the В-NHLBFM-90/95 и ALL IC-BFM 2002 program are presented. Depending on the presence of clinical manifestations, patients were divided into groups: 1st group (n = 10 without epileptiform signs), 2nd group (n = 10 with epileptiform signs).Results. In patients of group 1, who did not have clinical manifestations (seizures), the EEG recorded a signifiantly better, compared with patients of group 2, spectral dencity in band alpha rhythm and sensorimotor rhythm (p &lt; 0.001) and signifiantly less delta activity and beta frequencies (p &lt; 0.001). It was found that, despite the absence of epileptiform signs in the EEG, these patients had fewer EEG correlates of the ‘spike-wave’ complexes, and signifiantly less power levels of delta and beta-2 frequency bands (p &lt; 0.001).Conclusions. The use of comparative EEG mapping made it possible to identify predictors of epileptiform activity in children and adolescents with lymphoid tumors during chemotherapy.

1748-P: Assessing the Presence of Delta-Cell–Mediated Electrical Coupling in the Islet

Somatostatin-producing delta cells play an important role in the regulation of paracrine cross talk in the islet through inhibition of insulin and glucagon secretion by beta and alpha cells, respectively. However, recent studies have suggested the presence of electrical coupling via gap junctions between delta and beta cells. Electrical coupling mediated cross-talk would support the correlation between pulsatile insulin and somatostatin release and reveal a structural source of cell-cell communication within the islet. To test whether beta and delta cells are gap junction coupled, we measured the permeability of cell to cell connections and the relative dynamics of Ca2+. Islets of Sst-Cre;Rosa-LSL-tdTomato mice were used which show delta-cell specific labelling. They were then loaded with the cationic dye rhodamine-123 at 5mM glucose to measure performance of fluorescence recovery after photobleaching to assess gap junction coupling of delta cells and non-delta cells. Calcium dynamics were assessed using calcium dye Fluo-4 upon stimulating the islet from low glucose (2mM or 5 mM) to high glucose(11mM). No significant differences between recovery rate were observed when comparing delta cells and beta cells (p&amp;gt;0.05), which indicates some level of gap junction permeability among delta cells exists. The calcium activity of a population of delta cells was similar to those of neighboring beta cells, indicating a functional connection exists between these cell types. Furthermore, first-responder beta cells showed a preferential proximity to delta cells suggesting an impact of delta cells on functional sub-populations of nearby beta-cells. These results suggest a possible feedback system exists in the islet that is governed by electrical coupling of delta cells, which is important for both the function of beta cells and insulin secretion, and may also impact secretion of other islet hormones. Disclosure C.H.Levitt: None. R.K.Benninger: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (P30DK116073, R01DK102950, R01DK106412)

DNA methylation differences in monozygotic twins with Van der Woude syndrome.

Van der Woude Syndrome (VWS) is an autosomal dominant disorder responsible for 2% of all syndromic orofacial clefts (OFCs) with IRF6 being the primary causal gene (70%). Cases may present with lip pits and either cleft lip, cleft lip with cleft palate, or cleft palate, with marked phenotypic discordance even among individuals carrying the same mutation. This suggests that genetic or epigenetic modifiers may play additional roles in the syndrome's etiology and variability in expression. We report the first DNA methylation profiling of 2 pairs of monozygotic twins with VWS. Our goal is to explore epigenetic contributions to VWS etiology and variable phenotypic expressivity by comparing DNAm profiles in both twin pairs. While the mutations that cause VWS in these twins are known, the additional mechanism behind their phenotypic risk and variability in expression remains unclear. We generated whole genome DNAm data for both twin pairs. Differentially methylated positions (DMPs) were selected based on: (1) a coefficient of variation in DNAm levels in unaffected individuals < 20%, and (2) intra-twin pair absolute difference in DNAm levels >5% (delta beta > | 0.05|). We then divided the DMPs in two subgroups for each twin pair for further analysis: (1) higher methylation levels in twin A (Twin A > Twin B); and (2) higher methylation levels in twin B (Twin B >Twin A). Gene ontology analysis revealed a list of enriched genes that showed significant differential DNAm, including clef-associated genes. Among the cleft-associated genes, TP63 was the most significant hit (p=7.82E-12). Both twin pairs presented differential DNAm levels in CpG sites in/near TP63 (Twin 1A > Twin 1B and Twin 2A < Twin 2B). The genes TP63 and IRF6 function in a biological regulatory loop to coordinate epithelial proliferation and differentiation in a process that is critical for palatal fusion. The effects of the causal mutations in IRF6 can be further impacted by epigenetic dysregulation of IRF6 itself, or genes in its pathway. Our data shows evidence that changes in DNAm is a plausible mechanism that can lead to markedly distinct phenotypes, even among individuals carrying the same mutation.

The effect of musk incense stick aroma inhalation on different features of electroencephalogram signals and working memory for use in neurofeedback training

Susceptibility of brain activity to the inhalation of different aromas established the idea of inhaling an aroma as an auxiliary factor in neurofeedback training. The present study has focused on investigating the effect of musk incense stick aroma inhalation on various features of EEG signals (power of different frequency bands along with Katz fractal dimension (Katz’s FD), approximate entropy (ApEn) and scaling exponent) and working memory for use in neurofeedback training. To raise this aim, the EEG signals were recorded under eyes-open (EO) and eyes-closed (EC) conditions for 22 healthy subjects before and during the musk incense stick aroma inhalation, followed by performing Wechsler Memory Scale (WMS). The results showed that musk incense stick aroma inhalation under EO condition increased the relative power of delta, theta, sensorimotor rhythm (SMR) and low beta frequency bands along with ApEn and Katz’s FD in most channels, whereas decreased the relative power of alpha, high beta and gamma bands. A decrease was found in the relative power of delta, theta, SMR, low beta, high beta and gamma frequency bands in some channels under EC conditions. ApEn and Katz’s FD values also increased in most channels under EC conditions following musk incense stick aroma inhalation. The scaling exponent also decreased under the same conditions in most channels. However, these changes were not significant in all channels. The WMS score also increased after inhaling aroma, but not significantly. The findings of this research suggest the use of musk incense stick aroma inhalation during neurofeedback training to increase training efficiency.

Neural Markers of shootig performance: An explore of EEG frequency features during aiming

The frequency-domain characteristics of electroencephalogram (EEG) during shooting used to evaluate and improve shooting performance has become a research hotspot in recent years. However, neural markers that can be effectively and stably used to characterize various shooting performances remain unclear. In this study, a real shooting experiment was designed to study the effective EEG neural markers for different shooting performances. EEG data were obtained during the aiming period,the frequency domain characteristics such as spectrum, power spectrum, and differential entropy corresponding to Delta wave, Theta wave, Alpha wave, Beta wave, and Gamma wave were extracted respectively. Classical statistical analysis and machine learning methods were used to investigate the effectiveness of the characteristics. The results revealed that the overall energy of the EEG signals was low and stable for the participants with excellent shooting performance. The differential entropy feature of the gamma band as a effective neural marker had achieved the best classification accuracy of 74.91% throughout the aiming period. The results verified that the brain state of shooters is stable and their brains exhibit higher cognitive information processing efficiency during accurate shootings. The feasibility of using EEG neural markers to evaluate shooting performance is a novel avenue for the selection and performance evaluation of high-performance shooters.

Abstract WP39: Subhairline Electroencephalography For Detection Of Large Vessel Occlusion Stroke

Introduction: Endovascular thrombectomy (EVT) for large vessel occlusion stroke of the anterior circulation (LVO-a) can only be performed in selected hospitals. A prehospital triage instrument with which paramedics can reliably identify patients with an LVO-a stroke would enable direct routing of these patients to the right hospital and would consequently improve patient outcome. Electroencephalography (EEG) has previously shown to discriminate between patients with and without an LVO-a stroke. In this study, the diagnostic accuracy of subhairline EEG for LVO-a stroke was evaluated. Methods: A 3-minute EEG recording was performed in 35 patients who were presented to the emergency room with a suspected stroke or known LVO-a stroke, as soon as possible after presentation, and prior to potential EVT. Recordings were performed using 9 self-adhesive electrodes placed on the forehead and behind the ears. We evaluated the diagnostic accuracies of EEG features quantifying frequency band power (relative delta, theta, alpha and lower beta powers and power ratios), brain symmetry (pairwise derived Brain Symmetry Index [pdBSI]) and connectivity (Magnitude Squared Coherence [MSC] and Weighted Phase Lag Index) for LVO-a stroke using receiver operating characteristic analysis. Optimal cut-off points were determined as the maximum sensitivity at a specificity of ≥ 80% for LVO-a stroke. Results: Median age was 75 (IQR 67-81) years and 20/35 (57%) patients were male. 13/35 (37%) patients had an LVO-a stroke, 12/35 (34%) a non-LVO-a ischemic stroke, 4/35 (11%) a transient ischemic attack and 6/35 (17%) a stroke mimic. Median onset-to-EEG-time was 250 (IQR 118-535) minutes. Recordings of all patients were of sufficient quality to calculate frequency band power and brain symmetry measures. The connectivity measures could not be calculated for 3 LVO-a stroke patients. The highest diagnostic accuracy for LVO-a stroke was reached by the MSC in the delta frequency band (AUC 0.80; sensitivity 80%; specificity 82%) and the pdBSI in the theta frequency band (AUC 0.78; sensitivity 77%; specificity 82%). Conclusions: Subhairline EEG is a promising instrument for detection of LVO-a stroke, but validation in a larger study population and in the prehospital setting is necessary.

One-Step Method for Material Quantitation Using In-Line Tomography With Single Scanning.

Quantitative technique based on In-line phase-contrast computed tomography with single scanning attracts more attention in application due to the flexibility of the implementation. However, the quantitative results usually suffer from artifacts and noise since the phase retrieval and reconstruction are independent ("two-step") without feedback from the original data. The work aims to investigate a method for material quantitation to improve the image quality of In-line tomography within single scanning. An iterative method based Fresnel diffraction imaging model is developed in this work, which directly reconstructs the refractive index decrement δ and imaginary β of the object from observed data ("one-step"). Moreover, high-quality material decomposition results are obtained by using a linear approximation in the iterative process. Compared with the existing methods, Our method shows a higher peak signal-to-noise ratio and structural similarity in numerical experimental results. Additionally, the quantitation accuracy of the proposed method is greater than 97.2 % by calculating the equivalent atomic number of the decomposed basic material in the real experiment. We demonstrate that this one-step method greatly reduces noise and improves quantitative reconstruction and decomposition results. This algorithm has the potential for quantitative imaging research using In-line tomography in future biomedical applications.