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Endogenous reprogramming of pancreas-derived non-beta cells into insulin-producing cells is a promising approach to treat type 1 diabetes (T1D). One strategy that has yet to be explored is the specific delivery of insulin-producing essential genes, Pdx1 and MafA, to pancreatic alpha cells to reprogram the cells into insulin-producing cells in an adult pancreas. In this study, we utilized an alpha cell-specific glucagon (GCG) promoter to drive Pdx1 and MafA transcription factors to reprogram alpha cells to insulin-producing cells in chemically induced and autoimmune diabetic mice. Our results showed that a combination of a short glucagon-specific promoter with AAV serotype 8 can be used to successfully deliver Pdx1 and MafA into alpha cells in the mouse pancreas. Pdx1 and MafA expression specifically in alpha cells was also able to correct hyperglycemia in both induced and autoimmune diabetic mice. With this technology, targeted gene specificity and reprogramming were accomplished with an alpha-specific promotor combined with an AAV-specific serotype and provide an initial basis to develop a novel therapy for the treatment of T1D.

Introduction Alpha-gal syndrome is a potentially severe food allergy caused by the presence of alpha-gal-specific IgE. The aim of this study is to describe our series of 13 patients. Material and methods This work is a retrospective study of patients diagnosed in 2016 and 2017. Skin tests were performed with commercial extract and gelaspan as well as specific IgE determination for alpha-gal and different types of meat. Results Thirteen patients diagnosed with alpha-gal syndrome were analyzed; 9 of them had anaphylaxis, 6 of whom had been diagnosed with idiopathic anaphylaxis. All had a positive skin test with gelaspan, though this was not true with the commercial extracts, whose results were less conclusive. Conclusions We believe that a diagnosis of idiopathic anaphylaxis may prevent the identification of patients with alpha-gal syndrome. The gelaspan skin test is more useful than commercial extracts.

Previous research established that rhythmic sensory stimulation can affect subsequent stimulus perception, possibly through 'entrainment' of oscillations in the brain. Alpha frequency is a natural target for visual entrainment, because fluctuations in posterior alpha oscillations have been linked to visual target detection or discrimination. On the other hand, alpha oscillations also relate to attentional mechanisms, such as attentional orienting or selection. Previous visual alpha entrainment studies focused on differential processing of targets presented in-phase with the preceding rhythmic stimulation relative to out-of-phase targets (an 'SOA effect'), putatively related to the phase of entrained neuronal alpha oscillations. Fewer studies probed the consequences of rhythmic alpha stimulation for attention mechanisms related to alpha power. Here, we asked whether alpha stimulation of one hemifield has similar effects on reaction times as we see for increased alpha synchronization in magneto/electroencephalography (M/EEG) studies (i.e., more alpha means impaired processing and functional inhibition). We implemented a task inspired by attention studies, assessing reaction times to ipsilateral vs. contralateral visual targets, with and without concurrent presentation of distractors. Yet, in place of any attention cues, we presented a rhythmic, vs. arrhythmic, alpha-frequency train of visual flashes to one hemifield, in a large sample size (N = 115) in an online experiment. We found clear evidence that flash train rhythmicity did not impact task performance. We also found that the spatial congruence between the unilateral flash train and the subsequent visual target did impact response times but only in the presence of contralateral distractor stimuli. We discuss implications, limitations and future directions.

Perceptual decisions depend both on the features of the incoming stimulus and on the ongoing brain activity at the moment the stimulus is received. Specifically, trial-to-trial fluctuations in cortical excitability have been linked to fluctuations in the amplitude of pre-stimulus alpha oscillations (≈8-13 Hz), which are in turn are associated with fluctuations in subjects’ tendency to report the detection of a stimulus. It is currently unknown whether alpha oscillations bias post-perceptual decision making, or even bias subjective perception itself. To answer this question, we used a contrast discrimination task in which subjects reported which of two gratings – one in each hemifield – was perceived as having a stronger contrast. Our EEG analysis showed that subjective contrast was reduced for the stimulus in the hemifield represented in the hemisphere with relatively stronger pre-stimulus alpha amplitude, reflecting reduced cortical excitability. Furthermore, the strength of this spontaneous hemispheric lateralization was strongly correlated with the magnitude of individual subjects’ biases, suggesting that the spontaneous patterns of alpha lateralization play a role in explaining the intersubject variability in contrast perception. These results indicate that spontaneous fluctuations in cortical excitability, indicted by patterns of pre-stimulus alpha amplitude, affect perceptual decisions by altering the phenomenological perception of the visual world.Significance StatementOur moment to moment perception of the world is shaped by the features of the environment surrounding us, as much as by the constantly evolving states that characterize our brain activity. Previous research showed how the ongoing electrical activity of the brain can influence whether a stimulus has accessed conscious perception. However, evidence is currently missing on whether these electrical brain states can be associated to the subjective experience of a sensory input. Here we show that local changes in patterns of electrical brain activity preceding visual stimulation can bias our phenomenological perception. Importantly, we show that the strength of these variations can help explaining the great inter-individual variability in how we perceive the visual environment surrounding us.

One of the most rapidly growing options in the management of cancer therapy is Targeted Alpha Therapy (TAT) through which lethal α-emitting radionuclides conjugated to tumor-targeting vectors selectively deliver high amount of radiation to cancer cells.225Ac, 212Bi, 211At, 213Bi, and 223Ra have been investigated by plenty of clinical trials and preclinical researches for the treatment of smaller tumor burdens, micro-metastatic disease, and post-surgery residual disease. In order to send maximum radiation to tumor cells while minimizing toxicity in normal cells, a high affinity of targeting vectors to cancer tissue is essential. Besides that, the stable and specific complex between chelating agent and α-emitters was found as a crucial parameter. The present review was planned to highlight recent achievements about TAT-based targeting vectors and chelating agents and provide further insight for future researches.

Transcranial direct and alternating current stimulation (tDCS and tACS, respectively) can modulate human brain dynamics and cognition. However, these modalities have not been compared using multiple imaging techniques concurrently. In this study, 15 participants participated in an experiment involving two sessions with a gap of 10 days. In the first and second sessions, tACS and tDCS were administered to the participants. The anode for tDCS was positioned at point FpZ, and four cathodes were positioned over the left and right prefrontal cortices (PFCs) to target the frontal regions simultaneously. tDCS was administered with 1 mA current. tACS was supplied with a current of 1 mA (zero-to-peak value) at 10 Hz frequency. Stimulation was applied concomitantly with functional near-infrared spectroscopy and electroencephalography acquisitions in the resting-state. The statistical test showed significant alteration (p0.001) in the mean hemodynamic responses during and after tDCS and tACS periods. Between-group comparison revealed a significantly less (p0.001) change in the mean hemodynamic response caused by tACS compared with tDCS. As hypothesized, we successfully increased the hemodynamics in both left and right PFCs using tDCS and tACS. Moreover, a significant increase in alpha-band power (p0.01) and low beta band power (p0.05) due to tACS was observed after the stimulation period. Although tDCS is not frequency-specific, it increased but not significantly (p0.05) the powers of most bands including delta, theta, alpha, low beta, high beta, and gamma. These findings suggest that both hemispheres can be targeted and that both tACS and tDCS are equally effective in high-definition configurations, which may be of clinical relevance.

Objective To investigate whether regional white matter hyperintensities (WMHs) relate to alpha oscillations (AO) in a large population-based sample of elderly individuals. Methods We associated voxel-wise WMHs from high-resolution 3-Tesla MRI with neuronal alpha oscillations (AO) from resting-state multichannel EEG at sensor (N=907) and source space (N=855) in older participants of the LIFE-Adult study (60–80 years). In EEG, we computed relative alpha power (AP), individual alpha peak frequency (IAPF), as well as long-range temporal correlations (LRTC) that represent dynamic properties of the signal. We implemented whole-brain voxel-wise regression models to identify regions where parameters of AO were linked to probability of WMH occurrence. We further used mediation analyses to examine whether WMH volume mediated the relationship between age and AO. Results Higher prevalence of WMHs in the superior and posterior corona radiata was related to elevated relative AP, with strongest correlations in the bilateral occipital cortex, even after controlling for potential confounding factors. The age-related increase of relative AP in the right temporal brain region was shown to be mediated by total WMH volume. Conclusion A high relative AP corresponding to increased regional WMHs was not associated with age per se, in fact, this relationship was mediated by WMHs. We argue that the WMH-associated increase of AP reflects a generalized and likely compensatory spread of AO leading to a larger number of synchronously recruited neurons. Our findings thus suggest that longitudinal EEG recordings might be sensitive to detect functional changes due to WMHs.

Increasing life expectancy is prompting the need to understand how the brain changes during healthy aging. Research utilizing Electroencephalography (EEG) has found that the power of alpha oscillations decrease from adulthood on. However, non-oscillatory (aperiodic) components in the data may confound results and thus require re-investigation of these findings. The present report aims at analyzing a pilot and two additional independent samples (total N = 533) of resting-state EEG from healthy young and elderly individuals. A newly developed algorithm will be utilized that allows the decomposition of the measured signal into aperiodic and aperiodic-adjusted signal components. By using multivariate sequential Bayesian updating of the age effect in each signal component, evidence across the datasets will be accumulated. It is hypothesized that previously reported age-related alpha power differences will disappear when absolute power is adjusted for the aperiodic signal component. Consequently, age-related differences in the intercept and slope of the aperiodic signal component are expected. Importantly, using a battery of neuropsychological tests, we will assess how the previously reported relationship between cognitive functions and alpha oscillations changes when taking the aperiodic signal into account; this will be done on data of the young and aged individuals separately. The aperiodic signal components and adjusted alpha parameters could potentially offer a promising biomarker for cognitive decline, thus finally the test–retest reliability of the aperiodic and aperiodic-adjusted signal components will be assessed.

BACKGROUND: Left frontal alpha oscillations are associated with decreased approach motivation and have been proposed as a target for non-invasive brain stimulation for the treatment of depression and anhedonia. Indeed, transcranial alternating current stimulation (tACS) at the alpha frequency reduced left frontal alpha power and was associated with a higher response rate than placebo stimulation in patients with major depressive disorder (MDD) in a recent double-blind placebo controlled clinical trial. METHODS: In this current study, we aimed to replicate successful target engagement by delineating the effects of a single session of bifrontal tACS at the individualized alpha frequency (IAF-tACS) on alpha oscillations in patients with MDD. 84 participants were randomized to receive verum or sham IAF-tACS. Electrical brain activity was recorded during rest and while viewing emotionally-salient images before and after stimulation to investigate if the modulation of alpha oscillation by tACS exhibited specificity with regards to valence. RESULTS: In agreement with the previous study of tACS in MDD, we found that a single session of bifrontal IAF-tACS reduced left frontal alpha power during the resting state when compared to placebo. Furthermore, the reduction of left frontal alpha oscillation by tACS was specific for stimuli with positive valence. In contrast, these effects on left frontal alpha power were not found in healthy control participants. CONCLUSION: Together these results support an important role of tACS in reducing left frontal alpha oscillations as a future treatment for MDD. NATIONAL CLINICAL TRIAL: NCT03449979, “Single Session of tACS in a Depressive Episode (SSDE)” https://www.clinicaltrials.gov/ct2/show/NCT03449979

The apparent total tract digestibility and retention of calcium (Ca) and phosphorus (P) and concentrations of digestible energy and metabolizable energy in diets fed to late-gestating sows were not affected by Ca and P levels, but they were increased by dietary supplementation with 1-alpha-hydroxycholecalciferol. There was no interaction between dietary Ca and P and supplementation with 1-alpha-hydroxycholecalciferol.

In this study we quantified performance variations of motor imagery (MI)-based brain-computer interface (BCI) systems induced by practice. Two experimental sessions were recorded from ten healthy subjects while playing a BCI-oriented videogame for two weeks. The analysis focused on the exploration of electroencephalographic changes during mental preparation between novice and practiced subjects. EEG changes were quantified using global field power (GFP), dynamic time warping (TW) and mutual information (MutInf): GFP represents the strength of the electric field, TW measures signal similarities and MutInf signals inter-dependency. Each metric was selected to relate insights extracted from mental preparation to the three experimental hypotheses associating practice with BCI performance. Significant results were identified in lower alpha for GFP and upper alpha for TW and MutInf. GFP in lower alpha during mental preparation assessed not only novice vs practiced variations but also “intra-session” differences. Findings suggest that EEG changes during mental preparation provide a quantitative measure of practice level. These metrics extracted before motor intention could be applied to BCI models targeting MI to monitor a user’s degree of training.

Owing to the rising concern of global warming, lithium-ion batteries have gained immense attention over the past few years for the development of highly efficient electrochemical energy conversion and storage systems. In this study, alpha-phase VOPO4·2H2O with nanosheet morphology was prepared via a facile hydrothermal method for application in high-performance lithium-ion batteries. The X-ray diffraction and scanning electron microscopy (SEM) analyses indicated that the obtained sample had an alpha-2 (αII) phase, and the nanosheet morphology of the sample was confirmed using SEM. The lithium-ion battery with VOPO4·2H2O as the anode exhibited excellent long-term cycle life and a high capacity of 256.7 mAh g−1 at room temperature. Prelithiation effectively improved the specific capacity of pristine VOPO4·2H2O. The underlying electrochemical mechanisms were investigated by carrying out AC impedance, rate capability, and other instrumental analyses.

SARS-CoV-2 infection has been associated with increased morbidity and mortality in organ transplant recipients, and data are limited on 2-dose or 3-dose vaccine immunogenicity against SARS-CoV-2 variants in this population. In this secondary analysis of a randomized trial of a third dose of mRNA-1273 vaccine versus placebo, the authors assessed neutralizing antibody responses against SARS-CoV-2 variants in transplant recipients after 2 and 3 vaccine doses., Visual Abstract. SARS-CoV-2 Variant Neutralization After Vaccine in Transplant Recipients. SARS-CoV-2 infection has been associated with increased morbidity and mortality in organ transplant recipients, and data are limited on 2-dose or 3-dose vaccine immunogenicity against SARS-CoV-2 variants in this population. In this secondary analysis of a randomized trial of a third dose of mRNA-1273 vaccine versus placebo, the authors assessed neutralizing antibody responses against SARS-CoV-2 variants in transplant recipients after 2 and 3 vaccine doses. Visual Abstract. SARS-CoV-2 Variant Neutralization After Vaccine in Transplant Recipients. SARS-CoV-2 infection has been associated with increased morbidity and mortality in organ transplant recipients, and data are limited on 2-dose or 3-dose vaccine immunogenicity against SARS-CoV-2 variants in this population. In this secondary analysis of a randomized trial of a third dose of mRNA-1273 vaccine versus placebo, the authors assessed neutralizing antibody responses against SARS-CoV-2 variants in transplant recipients after 2 and 3 vaccine doses., Background: COVID-19 is more severe in transplant recipients. Variants of concern have supplanted wild-type virus. In transplant recipients, data are limited on 2-dose or 3-dose vaccine immunogenicity against variant viruses. Objective: To assess neutralizing antibody responses against SARS-CoV-2 variants in transplant recipients after 2 and 3 vaccine doses. Design: Secondary analysis of a randomized, double-blind, controlled trial of a third dose of mRNA-1273 vaccine versus placebo. (ClinicalTrials.gov: NCT04885907) Setting: Single-center transplant program. Patients: Organ transplant recipients. Intervention: Third dose of mRNA-1273 vaccine versus placebo. Measurements: Sera were analyzed for neutralization against wild-type virus and the Alpha, Beta, and Delta variants using a surrogate virus neutralization assay and a spike-pseudotyped lentivirus assay. Results: A total of 117 transplant recipients were analyzed (60 in the mRNA-1273 group and 57 in the placebo group). Sera were obtained before and 4 to 6 weeks after the third dose. After 2 doses, the proportion of patients with positive neutralization for all 3 variants was small compared with wild-type virus. After the third dose of mRNA-1273 vaccine, the proportion with a positive neutralization response versus placebo was improved for all 3 variants as measured by both assays. Based on the pseudovirus neutralization assay against the Delta variant, 33 of 60 (55%) patients were positive in the mRNA-1273 group versus 10 of 57 (18%) in the placebo group (difference, 37 [95% CI, 19 to 53] percentage points). The differences were 36 (CI, 17 to 51) percentage points for the Alpha variant and 31 (CI, 15 to 46) percentage points for the Beta variant. In the mRNA-1273 group, lower neutralization values were observed for variants compared with wild-type virus, especially the Beta variant. Limitations: There is no clear correlate of protection for neutralizing antibody. This was a secondary analysis. Conclusion: In organ transplant recipients, a third dose of mRNA vaccine increases neutralizing antibody response against SARS-CoV-2 variants compared with placebo. Primary Funding Source: Ajmera Transplant Centre.

Spontaneous neural oscillations are key predictors of perceptual decisions to bind multisensory signals into a unified percept. Research links decreased alpha power in the posterior cortices to attention and audiovisual binding in the sound-induced flash illusion (SIFI) paradigm. This suggests that controlling alpha oscillations would be a way of controlling audiovisual binding. In the present feasibility study we used MEG-neurofeedback to train one group of subjects to increase left/right and another to increase right/left alpha power ratios in the parietal cortex. We tested for changes in audiovisual binding in a SIFI paradigm where flashes appeared in both hemifields. Results showed that the neurofeedback induced a significant asymmetry in alpha power for the left/right group, not seen for the right/left group. Corresponding asymmetry changes in audiovisual binding in illusion trials (with 2, 3, and 4 beeps paired with 1 flash) were not apparent. Exploratory analyses showed that neurofeedback training effects were present for illusion trials with the lowest numeric disparity (i.e., 2 beeps and 1 flash trials) only if the previous trial had high congruency (2 beeps and 2 flashes). Our data suggest that the relation between parietal alpha power (an index of attention) and its effect on audiovisual binding is dependent on the learned causal structure in the previous stimulus. The present results suggests that low alpha power biases observers towards audiovisual binding when they have learned that audiovisual signals originate from a common origin, consistent with a Bayesian causal inference account of multisensory perception.

Introduction Phaeochromocytomas/paraganglioma (PPGL) surgery was historically associated with significant risks of perioperative complications. The decreased mortality (Methods A retrospective study using data from our institutional database was conducted. All patients undergoing adrenalectomy for PPGL from October 2011 to September 2020 were included. All patients were routinely alpha-blocked. Intraoperative cardiovascular instability (ICI) was assessed through number of systolic blood pressure (SBP) episodes >160mmHg, SBP Results A total of 100 consecutive patients undergoing surgery were identified of whom 53 patients had complete anaesthetic records available for analysis. Thirty-two patients (60%) had at least one episode with an SBP >160mmHg. Nine (17%) cases had no intraoperative hypotensive episodes, while 3 (6%) patients had >10 intraoperative episodes of an SBP Conclusions Cardiac instability remained significant in PPGL surgery despite optimal alpha- and beta-blockade. While omitting blockade would appear empirically questionable, a randomised controlled trial (RCT) of surgery with and without alpha-blockade will provide an answer.

The article presents the main approaches to the treatment and prevention of acute respiratory viral infections in sickly children. The analysis of our own researches on the efficacy of recombinant interferon alpha (Nazoferon) in the treatment of acute respiratory viral infections in these children has been carried out. The feasibility of adding this drug in the therapeutic complex has been proved.

OBJECTIVE. To test the hypothesis that an altered gut microbiota (dysbiosis) plays a role in obesity-associated osteoarthritis (OA). METHODS. Stool and blood samples were collected from 92 participants with BMI ≥ 30 kg/m(2) recruited from the Johnston County Osteoarthritis Project. OA cases (n=50) had hand plus knee OA (Kellgren-Lawrence [KL] grade ≥2 or arthroplasty). Controls (N=42) had no hand OA and KL grade 0–1 knees. Compositional analysis of stool samples was carried out by 16S rRNA amplicon sequencing. Alpha and beta diversity and differences in taxa relative abundances were determined. Blood samples were used for multiplex cytokine analysis and measures of lipopolysaccharide (LPS) and LPS binding protein. Germ-free mice were gavaged with case or control pooled fecal samples and placed on a 40% fat, high sucrose diet for 40 weeks. Knee OA was evaluated histologically. RESULTS. OA cases were slightly older with more females and higher BMI, WOMAC pain and KL grades than controls. There were no significant differences in alpha or beta diversity or genus level composition between cases and controls. Cases had higher plasma levels of osteopontin (p=0.01) and serum LPS (p

Objective Patients with schizophrenia are characterized by compromised working memory (WM) performance and increased distractibility. Theta synchronization (especially over the frontal midline areas) is related to cognitive control and executive processes during WM encoding and retention. Alpha event-related desynchronization (ERD) is associated with information processing and attention. Methods Participants (35 patients and 39 matched controls) performed a modified Sternberg WM task, containing salient and non-salient distractor items in the retention period. A high-density 128 channel EEG was recorded during the task. Theta (4-7 Hz) and fast alpha (10-13 Hz) event-related spectral perturbation (ERSP) were analyzed during the retention and encoding period. Results Patients with schizophrenia showed worse WM performance and increased attentional distractibility in terms of lower hit rates and increased distractor-related commission errors compared to healthy controls. Theta synchronization was modulated by condition (learning vs. distractor) in both groups but it was modulated by salience only in controls. Furthermore, salience of distractors modulated less the fast alpha ERD in patients. Conclusions Our results suggest that patients with schizophrenia process salient and non-salient distracting information less efficiently and show weaker cognitive control compared to controls. Significance These differences may partly account for diminished WM performance and increased distractibility in schizophrenia.

Although most studies describing coronavirus disease 2019 vaccine responses have focused on antibodies, there is increasing evidence that T cells play a critical role. Here the authors evaluated T-cell responses in seronegative donors before and after vaccination to define responses to the severe acute respiratory syndrome coronavirus 2 reference strain as well as to mutations in the variant strains Alpha/B.1.1.7 and Beta/B.1.351. The authors observed enhanced T-cell responses to reference and variant spike strains post-vaccination.

Background Nocturnal wakefulness has emerged as a potential predictor of short-term suicide risk. This analysis used dynamic temporal patterns in alpha and beta power and global sleep metrics to explore the possible link between next-day suicidal ideation (NDSI) and wakefulness measures in unmedicated participants with treatment-resistant depression. Methods Thirty-three medication-free participants with treatment-resistant depression completed overnight polysomnography. Alpha and beta spectral power as functions over time were used to represent arousal-related components of the dynamic sleep process. A functional data analytic approach (multilevel functional principal component analysis [MFPCA]) was used to preserve the oscillatory nature of the data; MFPCA PC scores were then associated with NDSI. Associations between NDSI and polysomnography-defined wakefulness after sleep onset, sleep efficiency, and total sleep time were also evaluated. Results NDSI had the strongest relationship with the second beta PC score (slope = 0.09 [90% credible interval, 0.03 to 0.14]), which represented an oscillating pattern that reflected disturbed sleep. The first PCs from both alpha and beta MFPCAs represented the overall magnitude of power and were most closely associated with traditional polysomnography metrics but were not related to NDSI. Results were equivocal for wakefulness after sleep onset with NDSI and did not support a relationship between NDSI and either sleep efficiency or total sleep time, highlighting the value of information contained in oscillating electroencephalogram patterns for identifying physiological links between nocturnal wakefulness and NDSI. Conclusions This study leveraged the dynamic nature of wakefulness-related electroencephalogram frequencies and provides a potential electrophysiological link between suicidal ideation and wakefulness during sleep in individuals with treatment-resistant depression.

Background Autoantibodies (AAbs) against immunoglobulin E (IgE) antibodies (Abs) and their high-affinity receptor alpha subunits (FceRIα) are key factors in the elicitation of type IIb autoimmune chronic spontaneous urticaria (type IIb aiCSU). In this study, we aimed to develop a new method to detect functional anti-FceRIα and anti-IgE AAbs, which can crosslink the plural FceRІα molecules and IgE Abs on the surface of mast cells and basophils, in sera from aiCSU patients using the amplified luminescence proximity homogeneous assay (Alpha). Methods Sera were obtained from 14 aiCSU patients, as diagnosed by recurrent chronic spontaneous urticaria episodes and positive results for the autologous serum skin test and/or histamine release test (HRT). The AAbs to FceRIα and IgE Abs were determined in sera from aiCSU patients using enzyme-linked immunosorbent assay (ELISA) and Alpha by cross-linking (AlphaCL) of IgE Abs and/or FceRІα. Results Serum anti-FceRIα and anti-IgE AAb levels were not significantly different between aiCSU patients and healthy subjects in ELISA. Anti-FceRIα AAbs were detected in 10 of 14 aiCSU patients who displayed positive (5/5) and negative (5/9) results in the HRT for anti-FceRIα AAbs by AlphaCL, whereas no signals were observed in healthy subjects. Additionally, anti-IgE AAbs were detected in two of four aiCSU patients who displayed positive results in the HRT for anti-IgE AAbs. Conclusions A new assay method using AlphaCL can detect anti-FceRIα and anti-IgE AAbs with FceRIα- and IgE-crosslinking abilities in sera from aiCSU patients. This simple and practical assay method may be available as a diagnostic tool for urticaria patients.

Tuberous sclerosis complex (TSC) is a genetic disorder caused by mutations on the TSC1/TSC2 genes, which result in alterations in molecular signalling pathways involved in neurogenesis and hamartomas in the brain and other organs. TSC carries a high risk for autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), although the reasons for this are unclear. One proposal is that TSC-related alterations in molecular signalling during neurogenesis lead to atypical development of neural networks, which are involved in the occurrence of ASD and ADHD in TSC. We investigated this proposal in young people with TSC who have been studied longitudinally since their diagnosis in childhood. Electroencephalography (EEG) was used to examine oscillatory connectivity in functional neural networks and local and global network organisation during three tasks (resting-state, attentional and inhibitory control Go/Nogo task, upright and inverted face processing task) in participants with TSC (n = 48) compared to an age- and sex-matched group of typically developing Controls (n = 20). Compared to Controls, the TSC group showed hypoconnected neural networks in the alpha frequency during the resting-state and in the theta and alpha frequencies during the Go/Nogo task (P ≤ .008), as well as reduced local network organisation in the theta and alpha frequencies during the Go/Nogo task (F = 3.95, P = .010). There were no significant group differences in network metrics during the face processing task. Increased connectivity in the hypoconnected alpha-range resting-state network was associated with greater ASD and inattentive ADHD symptoms (rho≥.40, P ≤ .036). Reduced local network organisation in the theta-range during the Go/Nogo task was significantly associated with higher hyperactive/impulsive ADHD symptoms (rho = −.43, P = .041). These findings suggest that TSC is associated with widespread hypoconnectivity in neural networks and support the proposal that altered network function may be involved in the co-occurrence of ASD and ADHD in TSC.

Granulocyte colony-stimulating factor (G-CSF) has been reported to exert a protective effect against secondary brain damage, but the underlying mechanisms remain unknown. We explored the ability of G-CSF to protect the brain from injury in a rat autologous blood-induced model of intracerebral hemorrhage (ICH), with a special focus on the anti-inflammation effect. An ICH was induced in 8-week-old male rats by an infusion of autologous blood, and the rats were then randomly assigned to five treatment groups: sham, ICH, and ICH+ low-dose (25 µg/kg), middle-dose (50 µg/kg), and high-dose (75 µg/kg) G-CSF. We then evaluated the levels of brain inflammation-related genes and proteins. The levels of tumor-necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) mRNA increased between days 1 and 14 post-ICH, with the highest expression on day 3. These changes were rectified by G-CSF in a dose-dependent manner. At day 3 post-injury, an elevation of the nuclear factor-kappa B (NF-κB) p65 protein level and a reduction of the inhibitor of NF-κB alpha (IκBα) protein level were observed; G-CSF treatment exerted a beneficial effect on both protein expressions. The expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins were increased; these changes were rectified by the highest dose of G-CSF. The brain-protecting effects of G-CSF are likely to be attributable, at least in part, to attenuation of the TNF-α, IL-6, iNOS, and COX-2 expressions induced by NF-κB activation in the brain tissues of this autologous blood-induced ICH rat model.

Field experiments were carried out at Shandaweel Agricultural Research Station, Sohag, Egypt to study the effects of deficit irrigation and harvesting date chemical composition of three sugar beet varieties. A split block design with three replications was used. Main blokes were assigned to three irrigation water regimes (100%, 85%, and 70% of water requirement). The sub blot was occupied by three harvesting dates (180, 195 and 210 days). Sub- sub plots comprised three sugar beet varieties namely (RAVEL, SV1841and SA1686). Results indicated that reducing water supply reduced alpha - amino N present in the second season, Na present in the second season, and K present and sugar lost to molasses, but increased sucrose present, extractable present, QZ present, purity present, extractability present. Increasing harvesting date increased K present, sucrose present, extractable present, QZ present, purity present, extractability present but reduced alpha - amino N present, Na present and sugar lost to molasses in the second season. Sucrose present, extractable present, QZ present purity present and extractability present of RAVEL and SA1686 varieties were almost comparable but higher than those of SV1841 variety.

Delta’s spike Understanding the molecular mechanisms of the increased transmissibility and immune evasion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants is critical to guiding current and future intervention strategies. Zhang et al . determined cryo–electron microscopy structures of the full-length spike protein trimers of the Delta, Kappa, and Gamma variants of SARS-CoV-2 and studied their function and antigenic properties. The Delta spike protein fused membranes more efficiently at low levels of the cellular receptor ACE2, and its pseudotyped viruses infected target cells substantially more rapidly than all other variants tested, possibly at least partly accounting for its heightened transmissibility. Mutations of each variant rearranged the antigenic surface of the N-terminal domain of the spike protein but only caused local changes in the receptor-binding domain, consistent with greater resistance to neutralizing antibodies. These findings elucidate the molecular events that have led these viruses to adapt in human communities and to evade host immunity. —VV

The emergence of SARS-CoV-2 variants that are more resistant to antibody-mediated neutralization pose a new hurdle in combating the COVID-19 pandemic. Although vaccines based on the original Wuhan sequence have been shown to be effective at preventing COVID-19, their efficacy is likely to be decreased against more neutralization-resistant variants-of-concern (VOC), in particular, the Beta variant originating in South Africa. We assessed, in mice, rabbits, and non-human primates, whether a third vaccination with experimental Wuhan-based Spike vaccines could alleviate this problem. Our data show that a third immunization improves neutralizing antibody titers against the variants-of-concern, Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), and Delta (B.1.617.2). After three vaccinations, the level of neutralization against Beta was similar to the level of neutralization against the original strain after two vaccinations, suggesting that simply providing a third immunization could nullify the reduced activity of current vaccines against VOC.

Background People with schizophrenia (SZ) exhibit impaired episodic memory when relating objects to each other in time and space. Empirical studies and computational models suggest that low-frequency neural oscillations may be a mechanism by which the brain keeps track of temporal relationships during encoding and retrieval, with modulation of oscillatory power as sequences are learned. It is unclear whether sequence memory deficits in SZ are associated with altered neural oscillations. Methods Using electroencephalography, this study examined neural oscillations in 51 healthy control subjects and 37 people with SZ during a temporal sequence learning task. Multiple 5-object picture sequences were presented across 4 study-test blocks in either fixed or random order. Participants answered semantic questions for each object (e.g., living/nonliving), and sequence memory was operationalized as faster responses for fixed versus random sequences. Differences in oscillatory power between fixed versus random sequences provided a neural index of temporal sequence memory. Results Although both groups showed reaction time differences in late blocks (blocks 3 and 4), this evidence of sequence memory was reduced in people with SZ relative to healthy control subjects. Decreases in globally distributed prestimulus alpha (8–12 Hz) and beta 1 (13–20 Hz) power for fixed versus random sequences in late blocks were also attenuated in people with SZ relative to healthy control subjects. Moreover, changes in oscillatory power predicted individual reaction time differences and fully mediated the relationship between group and sequence memory. Conclusions Disrupted modulation of alpha and beta 1 electroencephalography oscillations is a candidate mechanism of temporal sequence memory deficits in people with SZ.

MicroRNA-199a-5p (miR-199a-5p) and -3p are enriched in the myocardium, but it is unknown whether miR-199a-5p and -3p are co-expressed in cardiac remodeling and what roles they have in cardiac hypertrophy and fibrosis. We show that miR-199a-5p and -3p are co-upregulated in the mouse and human myocardium with cardiac remodeling and in Ang-II-treated neonatal mouse ventricular cardiomyocytes (NMVCs) and cardiac fibroblasts (CFs). miR-199a-5p and -3p could aggravate cardiac hypertrophy and fibrosis in vivo and in vitro. PPAR gamma coactivator 1 alpha (Ppargc1a) and sirtuin 1 (Sirt1) were identified as target genes to mediate miR-199a-5p in promoting both cardiac hypertrophy and fibrosis. However, miR-199a-3p aggravated cardiac hypertrophy and fibrosis through targeting RB transcriptional corepressor 1 (Rb1) and Smad1, respectively. Serum response factor and nuclear factor κB p65 participated in the upregulation of miR-199a-5p and -3p in Ang-II-treated NMVCs and mouse CFs, and could be conversely elevated by miR-199a-5p and -3p. Together, Ppargc1a and Sirt1, Rb1 and Smad1 mediated the pathological effect of miR-199a-5p and -3p by promoting cardiac hypertrophy and fibrosis, respectively. This study suggests a possible new strategy for cardiac remodeling therapy by inhibiting miR-199a-5p and -3p., Graphical abstract, Transcription factor SRF and NF-κB p65 regulate the co-expression of miR-199a-5p and -3p by positive feedback in the pathological cardiac remodeling. Ppargc1a and Sirt1, Rb1 and Smad1 mediate the pathological role of miR-199a-5p and -3p by promoting cardiac hypertrophy and fibrosis, respectively.

Introduction: Obesity is a strong promoter of cardiometabolic risk factors and is associated with several chronic comorbidities. Recently, the role of α-melanocyte stimulating hormone (α-MSH) and agouti related peptide (Ag-RP) in regulation of energy balance has attracted much attention. In current study, we evaluated the association between α-MSH and Ag-RP with cardiometabolic factors among obese individuals with different adherence to Diet Quality Index-International (DQI-I) values. Methods: In this research, 188 obese adults aged between 20 and 50 years old and body mass index (BMI) between 30 and 40 kg/m2 were recruited. Dietary intakes of participants and DQI-I calculation was performed using a semi-quantitative food frequency questionnaire (FFQ) with 132 food items. Serum glucose, lipids, insulin, and plasma α-MSH and Ag-RP levels were measured using ELISA kits. Homeostasis model assessment for insulin resistance index (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI) were also calculated. Results: Among those with the lowest adherence to DQI-I, Ag-RP was positively associated with systolic blood pressure (SBP) (P = 0.03) among males, which was associated with waist circumference (WC) (P = 0.01) and diastolic blood pressure (DBP) (P = 0.01). Moreover, among males with low and moderate adherence to DQI-I, α-MSH was positively associated with insulin (P = 0.04), weight (P = 0.03), WC (P < 0.01), SDP (P = 0.02) and DBP (P = 0.01). Also, Ag-RP showed a positive association with BMI values (R2 = 0.03; P = 0.03). Conclusion: According to our findings, in obese subjects with poor to moderate adherence to DQI-I, Ag-RP and α-MSH were in positive correlation with cardiometabolic risk factors. These findings further clarify the clinical importance of these parameters as prognostic factors of cardiometabolic abnormalities.

Objective Ketamine is an anesthetic drug associated with dissociation. Decreased electroencephalogram alpha (8–13 Hz) and low-beta (13–20 Hz) oscillation power have been associated with ketamine-induced dissociation. We aimed to characterize surface electroencephalogram signatures that may serve as biomarkers for dissociation. Methods We analyzed data from a single-site, open-label, high-density surface electroencephalogram study of ketamine anesthesia (2 mg/kg, n = 15). We assessed dissociation longitudinally using the Clinician Administered Dissociation States Scale (CADSS) and administered midazolam to attenuate dissociation and enable causal inference. We analyzed electroencephalogram power and global coherence with multitaper spectral methods. Mixed effects models were used to assess whether power and global coherence signatures of ketamine could be developed into dissociation-specific biomarkers. Results Compared to baseline, ketamine unresponsiveness was associated with increased frontal power between 0.5 to 9.3 Hz, 12.2 to 16.6 Hz, and 24.4 to 50 Hz. As subjects transitioned into a responsive but dissociated state (mean CADSS ± SD, 22.1 ± 17), there was a decrease in power between 0.5 to 10.3 Hz and 11.7 to 50 Hz. Midazolam reduced dissociation scores (14.3 ± 11.6), decreased power between 4.4 to 11.7 Hz and increased power between 14.2 to 50 Hz. Our mixed-effects model demonstrated a quadratic relationship between time and CADSS scores. When models (frontal power, occipital power, global coherence) were reanalyzed with midazolam and electroencephalogram features as covariates, only midazolam was retained. Conclusions Ketamine is associated with structured electroencephalogram power and global coherence signatures that may enable principled anesthetic state but not dissociation monitoring. Significance A neurophysiological biomarker for dissociation may lead to a better understanding of neuropsychiatric disorders.

The majority of Streptococcus agalactiae strains express one or more surface-anchored proteins that vary by strain. These proteins, which are characteristic for S. agalactiae, and are able to induce protective antibodies, include the alpha C, Rib proteins, alpha-like protein 2, and alpha-like protein 3. In this study was developed multiplex PCR method for detection of genes encoding these proteins, and its occurrence within a various S. agalactiae isolates of bovine origin. Also are reported two new genes from bovine isolates of S. agalactiae amplified by PCR, encoding other putative members of the family, alphalike protein 6, and alpha-like protein 7. They contain an overall genetic organization highly similar to that of the alpha C and Rib proteins.

BACKGROUND AND AIMS Globally, NAFLD is one of the most common liver disorders, with an estimated prevalence rate of more than 30% in men and 15% in women and an even higher prevalence in people with type 2 diabetes mellitus. Optimal pharmacologic therapeutic approaches for NAFLD are an urgent necessity. APPROACH AND RESULTS In this study, we showed that compared with healthy controls, hepatic ACSL4 levels in patients with NAFLD were found to be elevated. Suppression of ACSL4 expression promoted mitochondrial respiration, thereby enhancing the capacity of hepatocytes to mediate β-oxidation of fatty acids and to minimize lipid accumulation by up-regulating peroxisome proliferator-activated receptor coactivator-1 alpha. Moreover, we found that abemaciclib is a potent and selective ACSL4 inhibitor, and low dose of abemaciclib significantly ameliorated most of the NAFLD symptoms in multiple NAFLD mice models. CONCLUSIONS Therefore, inhibition of ACSL4 is a potential alternative therapeutic approach for NAFLD.

Summary Beginning in the summer of 2020, a variant of SARS-CoV-2, the cause of the COVID-19 pandemic, emerged in the United Kingdom (UK). This B.1.1.7 variant increased rapidly in prevalence among sequenced strains, attributed to an increase in infection and/or transmission efficiency. The UK variant has 19 nonsynonymous mutations across its viral genome including 8 substitutions or deletions in the spike protein, which interacts with cellular receptors to mediate infection and tropism. Here, using a reverse genetics approach, we show that, of the 8 individual spike protein substitutions, only N501Y exhibited consistent fitness gains for replication in the upper airway in the hamster model as well as primary human airway epithelial cells. The N501Y substitution recapitulated the phenotype of enhanced viral transmission seen with the combined 8 UK spike mutations, suggesting it is a major determinant responsible for increased transmission of this variant. Mechanistically, the N501Y substitution improved the affinity of the viral spike protein for cellular receptors. As suggested by its convergent evolution in Brazil and South Africa, our results indicate that N501Y substitution is a major adaptive spike mutation of major concern.

Individuals with schizophrenia use twice as much caffeine on average when compared to healthy controls. Knowing the high rates of consumption, and the potential negative effects of such, it is important we understand the cortical mechanisms that underlie caffeine use, and the consequences of caffeine use on neural circuits in this population. Using a randomized, placebo controlled, double-blind, repeated measures design, the current study examines caffeine's effects on resting electroencephalography (EEG) power in those who have been recently diagnosed with schizophrenia (SZ) compared to regular-using healthy controls (HC). Correlations between average caffeine consumption, withdrawal symptoms, drug related symptoms and clinical psychosis symptoms were measured and significant correlations with neurophysiological data were examined. Results showed caffeine had no effect on alpha asymmetry in the SZ group, although caffeine produced a more global effect on the reduction of alpha2 power in the SZ group. Further, those with more positive symptoms were found to have a greater reduction in alpha2 power following caffeine administration. Caffeine also reduced beta power during eyes closed and eyes open resting in HC, but only during eyes closed resting conditions in the SZ group. These findings provide a descriptive profile of the resting EEG state following caffeine administration in individuals with schizophrenia. The findings ultimately suggest caffeine does not affect alpha or beta power as readily in this population and a higher dose may be needed to achieve the desired effects, which may elucidate motivational factors for high caffeine use.

Background. Electroencephalography is the main technique for assessing the functional state of the brain. Indications for EEG are diagnosis of paroxysmal states, prediction of the outcome of a pathological state, evaluation of bioelectrical activity if brain death is suspected. Up to 90 % of the native EEG in calm wakefulness in healthy individuals is occupied by “alpha activity”. In children in active wakefulness, the EEG pattern depends to a great extent on their age.Objective. The aim of the work was to assess EEG parameters in children aged 3–4 years in eyes-open resting state. Design and methods. 31 healthy participants aged 3–4 years were enrolled. EEG was registered for 30 minutes in a state of passive wakefulness in the supine position with open eyes. Average values of the power of the spectra for the alpha-rhythm, delta-rhythm and theta-rhythm in the frontal and temporal leads, as well as the ratio of the average power of alpha/theta and alpha/delta rhythms in the frontal and temporal leads were calculated.Results. Average power of the alpha-rhythm was significantly higher over the right frontal lobe than over the right frontal-temporal area, as well as average amplitude of it was significantly higher in F3-A1 than F7-A1, F4-A2 than F8-A2, which is associated with the articulatory praxis. Average alpha-rhythm power was significantly higher in T5-A1 than T3-A1 and T6-A2 than T4-A2, which corresponds to the recognition and naming of objects optically. Significant differences according to the total average power of the alpha- and theta-rhythms above the frontal and frontal-temporal regions reflect the relationship between the frontal cortex temporal lobes and the premotor zones, i.e. arcuate bundle, responsible for the “speech system”.Conclusion. The identified patterns can reflect the characteristics of the state of active wakefulness in a 3–4-year-old child and can be used for comparison in the future (both in the course of behavioral experiments and observation of patients with certain pathological processes).

Interruptions lead to a deterioration of primary task performance. Applied research usually describes a delay in primary task resumption as an essential component of this performance deficit. Here, we investigate this approach using electrophysiological correlates of the focusing of attention within working memory, a process that is fundamental to switching between different tasks. A lateralized working memory task was frequently interrupted by either a high- or low-demanding arithmetic task and a subsequent retrospective cue indicated the working memory item required for later report. The detrimental effect of interruptions on primary task performance was most pronounced for high-demanding interruptions. After retro-cue presentation, fronto-central theta power (4–7 Hz) was lowest following high-demanding interruptions and posterior alpha power (8–14 Hz) was less suppressed in the two interruption conditions. These effects might be related to a deficit in attentional control processes following the retrospective cue. Furthermore, we introduce the suppression of posterior alpha power contralateral to the remembered primary task stimuli during the interruption phase as a temporal marker for primary task resumption. Especially for cognitively demanding interruption tasks, this effect seems to overlap in time with the processing of the interruption, which should contribute to the primary task performance deficit.

Pfizer-BioNTech and Moderna developed in record time mRNA vaccines against COVID-19 of high efficacy. The modest protection achieved with a similarly designed mRNA from CureVac underlines the importance of biotechnological details in formulation such as replacement of uridine by pseudouridine in the mRNA encoding the SARS-CoV-2 spike protein or the lipid composition of the nanoparticle coating the mRNA. Phase 3 vaccine trials and vaccine studies in special subject groups as well observational studies in whole populations confirmed the real-world vaccine efficacy against symptomatic disease, particularly against severe COVID-19 cases and to a lesser extent against mild SARS-CoV-2 infections. mRNA vaccine protection extended also to the alpha and beta variant viruses. The surge of delta variants led to an increase of infections and cases even in populations which achieved high vaccine coverage. This efficacy decline resulted to a lesser extent from a weaker neutralization of the delta variant but mostly from a waning vaccine protection over time. Data from Israel documented the efficacy of a third 'booster' injection 5 months after the second injection in older segments of the population. Adverse reactions consisted of transient injection site pain, headache, muscle pain, fatigue, fever and chills. Extensive surveillance studies documented a good safety profile revealing only a non-significant increase in transient facial nerve paralysis and a significant, but modest increase in myocarditis in vaccinated young males that was lower than the myocarditis risk induced by SARS-CoV-2 infection. ispartof: MICROBIAL BIOTECHNOLOGY vol:15 issue:1 pages:135-148 ispartof: location:United States status: published

The aim of this study is to evaluate the risk of alpha emitter’s concentrations and measure it in human blood. The current study was done in the central laboratory and archaeologist employees of the Iraqi museum; likewise, the study also involved employees in State board of antiquities and heritage and Abd al-karim qasim museum that are located in Baghdad, Iraq. CR-39 Detector was used to measure alpha emitters track density. 60 participants Blood samples were collected in total (30 people in workers and 30 people in controls that were collected from general population). The maximum obtained values of alpha track density were (213.16±7.58 tracks/ mm2) and minimum obtained values (32.61±3.70 tracks/ mm2) in workers group with average of (81.36±3.78 No. of tracks/mm2) and the maximum obtained values of alpha track density were (219.37±6.75 tracks/ mm2) and minimum obtained values (3.02±0.37 tracks/ mm2) in control group with average of (28.45± 2.10 tracks/mm2). The result showed higher alpha emitter concentration in workers compared to the control group. Based on these results, high alpha concentrations to museum workers and archaeologists may have increased risk to DNA damage and cancer compared to non-occupational workers.

Different studies have suggested that language and developmental disorders such as dyslexia are associated with a disturbance of auditory entrainment and of the functional hemispheric asymmetries during speech processing. These disorders typically result from an issue in the phonological component of language that causes problems to represent and manipulate the phonological structure of words at the syllable and/or phoneme level. We used Auditory Steady-State Responses (ASSRs) in EEG recordings to investigate the brain activation and hemisphere asymmetry of theta, alpha, beta and low-gamma range oscillations in typical readers and readers with dyslexia. The aim was to analyse whether the group differences found in previous electrode level studies were caused by a different source activation pattern or conversely was an effect that could be found on the active brain sources. We could not find differences in the brain locations of the main active brain sources. However, we observed differences in the extracted waveforms. The group average of the first DSS component of all signal-to-noise ratios of ASSR at source level were higher than the group averages at the electrode level. These analyses included a lower alpha synchronisation in adolescents with dyslexia and the possibility of compensatory mechanisms in theta, beta and low-gamma frequency bands. The main brain auditory sources were located in cortical regions around the auditory cortex. Thus, the differences observed in auditory EEG experiments would, according to our findings, have their origin in the intrinsic oscillatory mechanisms of the brain cortical sources related to speech perception.

Background Behcet’s syndrome (BS) is a systemic vasculitic disorder. This study aimed to investigate the levels of serum IL-36α and IL-36Ra in patients with BS. Material and Methods A total of 80 subjects (60 BS patients and 20 healthy controls [HC]) were included. Results The median IL-36α level was 0.11 ng/ml in the BS group and 0.09 ng/ml in the HC group (p=0.058). The mean IL-36Ra level was 13.62 pg/ml in the BS group and 13.26 pg/ml in the HC group (p=0.348). Serum IL-36Ra levels of the active group were significantly higher (p=0.037). Patients with oral ulcers and central nervous system involvement had higher serum IL36Ra levels. In the BS group, a positive correlation was found between serum IL-36Ra and CRP. In a multivariate analysis, the IL-36Ra level (OR=1.067; 95% CI=1.001–1.137; p=0.045) was independently associated with disease activity. Conclusion According to these findings, it is not clear whether such a slight difference is clinically significant, but they suggest that the IL-36 cytokine family may play a role in the course of the disease.

The mirror neuron system (MNS) has been theorized to play a neurobiological role in a number of social cognitive abilities and is commonly indexed putatively in humans via interpersonal motor resonance (IMR) and mu suppression. Although both indices are thought to measure similar neuronal populations (i.e., "mirror neurons"), it has been suggested that these methods are unrelated, and therefore, incompatible. However, prior studies reporting no relationships were typically conducted in small and underpowered samples. Thus, we aimed to investigate this potential association in a large sample of neurotypical adults (N = 116; 72 females). Participants underwent transcranial magnetic stimulation (TMS), electromyography (EMG), and electroencephalography (EEG) during the observation of videos of actors performing grasping actions in order to index IMR and mu suppression (in beta, lower alpha, and upper alpha bandwidths). A series of linear regressions revealed no associations between IMR and each of the mu suppression bandwidths. Supplementary Bayesian analyses provided further evidence in favor of the null (B01 = 8.85-8.93), providing further support for no association between the two indices of MNS activity. Our findings suggest that these two measures may indeed be unrelated indices that perhaps assess different neurophysiological aspects of the MNS. These results have important implications for future studies examining the MNS.