Role of visual brainwave entrainment on the resting state brainwaves of children with and without attention-deficit/hyperactivity disorder.

The relationship between brainwave oscillations and Attention-Deficit/Hyperactivity Disorder (ADHD)-related cognitive challenges is a trending proposition in the field of Cognitive Neuroscience. Studies suggest the role of brainwave oscillations in the symptom expressions of ADHD-diagnosed children. Intervention studies have further suggested the scope of brain stimulation techniques in improving cognition. The current manuscript explored the effect of changes in the brainwaves post-sensory entrainment on cognitive performance of children. We calculated each participant's brainwave difference and ratios of theta, alpha, and beta power after the entrainment sessions. Further, we explored possible correlations between these values and the psychometric scores. The beta resting state showed the strongest association with selective attention performance of all participants. Theta-beta ratio (TBR) showed an inverse correlation with selective attention and working memory performances. The theta frequency was associated with decreased working performance in children without ADHD. Our findings also suggest a predominant role of TBR than the theta-alpha ratio in determining the cognitive performance of children with ADHD. The individual differences in the entrainment reception were attributed to the participant's age, IQ, and their innate baseline frequencies. The implications of our findings can initiate substantiating brainwave-based entrainment sessions as a therapeutic modality to improve cognition among children.

A retrospective study of the yield of next-generation sequencing in the diagnosis of developmental and epileptic encephalopathies and epileptic encephalopathies in 0-12 years aged children at a single tertiary care hospital in South India.

OBJECTIVE: Studies on the genetic yield of developmental and epileptic encephalopathy and Epileptic encephalopathies using next-generation sequencing techniques are sparse from the Indian subcontinent. Hence, the study was conducted to assess the yield of genetic testing and the proportion of children where a positive genetic yield influenced treatment decisions. METHODS: In this retrospective observational study, electronic medical records of children (0-12 years) with suspected genetic epilepsy who underwent genetic testing using whole exome sequencing, focused exome sequencing and epilepsy gene panels were retrieved. Genetic yield was ascertained based on the detection of pathogenic and likely pathogenic variants. RESULTS: A total of 100 patients with epilepsy underwent genetic testing. A yield of 53.8% (42/78) was obtained. Pathogenic variants were identified in 18 (42.8%) cases and likely pathogenic variants in 24 (57.1%) cases. Yield was 66.6% each through whole exome sequencing, focused exome sequencing and 40% through Epilepsy gene panels (p = .07). Yield was not statistically significant across different age groups (p = .2). It was however found to significantly vary across different epilepsy syndromes with maximum yield in Epilepsy in infancy with migrating focal seizures in 2 (100%), followed by developmental and epileptic encephalopathy unspecified in 14 (77.7%), Dravet syndrome in 14 (60.8%), early infantile developmental and epileptic encephalopathy in 3 (60%), infantile epileptic spasm syndrome in 5 (35.7%), and other epileptic encephalopathies in 4 (30.7%) cases (p = .04). After genetic diagnosis and drug optimization, drug-refractory proportion reduced from 73.8% to 45.3%. About half of the cases achieved seizure control. SIGNIFICANCE: A reasonably high yield of 53.8% was obtained irrespective of the choice of panel or exome or age group using next-generation sequencing-based techniques. Yield was however higher in certain epilepsy syndromes and low in Infantile epileptic spasms syndrome. A specific genetic diagnosis facilitated tailored treatment leading to seizure freedom in 28.6% and marked seizure reduction in 54.7% cases.

Clinico-radiologic Spectrum and Outcome of Pediatric Acquired Demyelinating Disorders of Central Nervous System: A Retrospective Indian Tertiary Care Hospital Cohort.

BACKGROUND: Pediatric acquired demyelinating syndrome (ADS) constitutes a group of treatable disorders with acute neurologic dysfunction. Neuroimaging has played a significant role in diagnosis of ADS. We describe clinico-radiologic spectrum, outcomes, and comparison of the groups: acute disseminated encephalomyelitis (ADEM), neuromyelitis optica spectrum disorder (NMOSD), clinically isolated syndrome (CIS), multiple sclerosis (MS), and myelin oligodendrocyte glycoprotein antibody-associated disorders (MOGAD). METHODS: Retrospective review of 70 children with ADS at a tertiary care hospital over 15 years (2008-2023) was performed. Diagnosis was assigned as per International Pediatric Multiple Sclerosis Study Group criteria 2016. Fisher's exact and chi-square tests were applied. RESULTS: Thirty-nine boys and 31 girls aged 8.2 ± 4.0 years with CIS (n = 27), ADEM (n = 16), NMOSD (n = 13), MS (n = 1), and MOGAD (n = 13) were included. Clinical syndromes with positive significant association included polyfocal symptoms, encephalopathy in ADEM, optic neuritis (ON) in MOGAD, brainstem, area postrema syndrome in NMOSD. MOGAD presented with atypical presentations like prolonged fever (PF; 76.9%) and aseptic meningitis (23%). Seropositivity for myelin oligodendrocyte glycoprotein immunoglobulin-G was 62% and for NMO-IgG 2.6%. Neuroimaging of MOGAD showed lesions predominantly in basal ganglia/thalami (69.2%), optic nerve (46.2%), and cerebellum (46.2%). Imaging patterns between ADEM and MOGAD were comparable except for more ON (p = 0.004), spinal cord (p = 0.01), and cerebellar lesions (p = 0.03) in MOGAD. Area postrema lesion was unique to NMOSD. All patients received immunotherapy, of whom 91.4% (n = 64) had good recovery, 8.6% (n = 6) had functional limitation on modified Rankin scale at discharge, and 12 (17.1%) relapsed. CONCLUSION: The largest group was CIS. Seropositivity of MOG was high with atypical presentations like PF and aseptic meningitis. Specific neuroimaging patterns correlated with ADS categories. Short-term outcome with immunotherapy was favorable in spite of relapses.

Acute Encephalopathy with Biphasic Seizures and Late Reduced Diffusion following SARS-CoV-2 Infection-A Rare Case Report.

Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is a clinicoradiological syndrome first recognized during the influenza pandemic in Japanese population in the late twentieth century. 1 In this article, we presented a rare case report of AESD in a young child due to severe acute respiratory syndrome coronavirus 2 infection (SARS-CoV-2) who presented with febrile status epilepticus, persistent encephalopathy, and had recurrence of seizures on day 4 of illness with characteristic magnetic resonance imaging findings and a relatively fair outcome.

Potential of binaural beats intervention for improving memory and attention: insights from meta-analysis and systematic review.

Binaural beats (BB) entrainment is an auditory perceptual occurrence that exists when two tones of separate frequencies are simultaneously presented to each ear. Research on BB entrainment has gained attention due to its ability to treat various conditions like anxiety, attention-deficit/hyperactivity (ADHD), etc. Even though research on BB entrainment suggests its efficiency in improving cognition among individuals, existing literature indicates mixed results in the cognitive domains of attention and memory. Thus, we conducted meta-analysis to examine the effect of BB intervention on memory and attention, respectively, in the current paper. We further performed a systematic review on the selected studies to report their variables, demographic characteristics of the participants, and outcomes to comprehensively position the research on BB intervention exclusively in the areas of memory and attention. Fifteen studies met our inclusion criteria. Based on 31 effect sizes, the results indicated an overall medium and significant effect size (g = 0.40). Findings from systematic review reveal conflicting results, especially concerning theta and beta's efficacy on memory (recall and recognition tasks) and attention-related tasks. The findings of the current paper add to the growing evidence that BB intervention improves attention and memory in humans. Since the findings suggest a near-moderate effect of BB interventions and mixed results in the systematic review, more research with robust study designs must explore its guiding principle and the expanding role of brainwaves in improving memory and attention in individuals. Such an intervention has important implications in both clinical and non-clinical settings.

Eukaryotic initiation factor (eIF) 4F binding to barley yellow dwarf virus (BYDV) 3'-untranslated region correlates with translation efficiency.

Eukaryotic initiation factor (eIF) 4F binding to mRNA is the first committed step in cap-dependent protein synthesis. Barley yellow dwarf virus (BYDV) employs a cap-independent mechanism of translation initiation that is mediated by a structural BYDV translation element (BTE) located in the 3'-UTR of its mRNA. eIF4F bound the BTE and a translationally inactive mutant with high affinity, thus questioning the role of eIF4F in translation of BYDV. To examine the effects of eIF4F in BYDV translation initiation, BTE mutants with widely different in vitro translation efficiencies ranging from 5 to 164% compared with WT were studied. Using fluorescence anisotropy to obtain quantitative data, we show 1) the equilibrium binding affinity (complex stability) correlated well with translation efficiency, whereas the "on" rate of binding did not; 2) other unidentified proteins or small molecules in wheat germ extract prevented eIF4F binding to mutant BTE but not WT BTE; 3) BTE mutant-eIF4F interactions were found to be both enthalpically and entropically favorable with an enthalpic contribution of 52-90% to ΔG° at 25 °C, suggesting that hydrogen bonding contributes to stability; and 4) in contrast to cap-dependent and tobacco etch virus internal ribosome entry site interaction with eIF4F, poly(A)-binding protein did not increase eIF4F binding. Further, the eIF4F bound to the 3' BTE with higher affinity than for either m(7)G cap or tobacco etch virus internal ribosome entry site, suggesting that the 3' BTE may play a role in sequestering host cell initiation factors and possibly regulating the switch from replication to translation.

Effect of creatine monohydrate in improving cellular energetics and muscle strength in ambulatory Duchenne muscular dystrophy patients: a randomized, placebo-controlled 31P MRS study.

Randomized, placebo-controlled single blinded study was carried out to evaluate the effect of oral creatine supplementation on cellular energetics, manual muscle test (MMT) score and functional status in steroid-naive, ambulatory boys suffering with Duchenne muscular dystrophy (DMD; n=33). Eighteen patients received creatine monohydrate (Cr; 5 g/day for 8 weeks), while 15 received placebo (500 mg of vitamin C). Phosphorus metabolite ratios were determined from the right calf muscle of patients using phosphorus magnetic resonance spectroscopy ((31)P MRS) both prior to (baseline) and after supplementation of Cr or placebo. In addition, metabolite ratios were determined in normal calf muscle of age and sex matched controls (n=8). Significant differences in several metabolite ratios were observed between controls and DMD patients indicating a lower energy state in these patients. Analysis using analysis of covariance adjusted for age and stature showed that the mean phosphocreatine (PCr)/inorganic phosphate (Pi) ratio in patients treated with Cr (4.7; 95% CI; 3.9-5.6) was significantly higher (P=.03) compared to the placebo group (3.3; 95% CI; 2.5-4.2). The mean percentage increase in PCr/Pi ratio was also more in patients <7 years of age compared to older patients after Cr supplementation indicating variation in therapeutic effect with the age. In the placebo group, significant reduction in PCr/Pi (P=.0009), PCr/t-ATP (P=.05) and an increase in phosphodiester (PDE)/PCr ratios was observed after supplementation. Further, in the placebo group, patients <7 years showed reduction of PCr/t-ATP and Pi/t-ATP compared to older patients (>7 years), after supplementation. These results imply that the significant difference observed in PCr/Pi ratio between the Cr and the placebo groups after supplementation may be attributed to a decrease of PCr in the placebo group and an increase in PCr in the Cr group. Changes in MMT score between the two groups was significant (P=.04); however, no change in functional scale (P=.19) was observed. Parents reported subjective improvement on Cr supplementation versus worsening in placebo (P=.02). Our results indicated that Cr was well tolerated and oral Cr significantly improved the muscle PCr/Pi ratio and preserved the muscle strength in short term. However, this study provides no evidence that creatine will prove beneficial after long-term treatment, or have any positive effect on patient lifespan.

Midbrain and spinal cord magnetic resonance imaging (MRI) changes in poliomyelitis.

Poliomyelitis, though eradicated from most parts of the world, continues to occur in India. There is paucity of data on the magnetic resonance imaging (MRI) changes in poliomyelitis. We report a 3(1/2)-year-old boy who presented with subacute onset flaccid paralysis and altered sensorium. Stool culture was positive for wild polio virus type 3. Magnetic resonance imaging revealed signal changes in bilateral substantia nigra and anterior horns of the spinal cord. These MRI changes may be of potential diagnostic significance in a child with poliomyelitis.

Probing the dynamic organization of transcription compartments and gene loci within the nucleus of living cells.

The three-dimensional organization of nuclear compartments within living cells determines genome function and yet their underlying self-organizing principles are unclear. We visualize in real-time transcriptionally active compartments (TCs) by the transient enrichment of fluorescently-labeled uridine 5'-triphosphate molecules within living cells. These TCs partially colocalize with active RNA-Pol II in the cell nucleus. Fluorescence anisotropy maps of chromatin compaction evidences a more open chromatin structure at the TCs. Using live-cell timelapse imaging, heterogeneity in the dynamic behavior of TCs has been revealed which falls into three distinct classes: subdiffusive, super-diffusive, and normal diffusive behavior. In contrast, the mobility of a candidate gene locus, either in the repressed or activated state, undergoes a differential restricted motion that is coupled to TC movement. Further TC dynamics is directly affected by small molecule chromatin structure modulators and adenosine triphosphate depletion. This heterogeneous behavior in TC dynamics within living cells could provide an interesting paradigm to explore the spatiotemporal dimension to gene transcription control.

Trichostatin-A induces differential changes in histone protein dynamics and expression in HeLa cells.

Trichostatin-A (TSA), a histone deacetylase (HDAC) inhibitor, results in enhanced acetylation of core histones thereby disrupting chromatin organization within living cells. We report on changes in chromatin organization and the resultant alteration in nuclear architecture following treatment with TSA using fluorescence imaging. TSA triggers an expected increase in the euchromatin fraction which is accompanied by a significant increase in nuclear volume and alterations in chromatin compaction mapped using fluorescence anisotropy imaging. We observe differential changes in the mobility of core and linker histones as measured by fluorescence recovery after photo-bleaching (FRAP) and fluorescence correlation spectroscopy (FCS) methods. Further TSA induces a differential increase in linker histone transcription and increased phosphorylation of linker histone proteins accompanying an expected increase in core histone acetylation patterns. Thus subtle feedback responses triggered by changes in chromatin configurations impinge selectively on linker histone mobility and its expression. These observations have implications for understanding the role of HDAC in the dynamic maintenance of chromatin organization.

Chromatin structure exhibits spatio-temporal heterogeneity within the cell nucleus.

Local chromatin compaction undergoes dynamic perturbations to regulate genetic processes. To address this, the direct measurement of the fluidity of chromatin structure is carried out in single live cells using steady-state anisotropy imaging and polarization modulation microscopy. Fluorescently tagged core and linker histones are used to probe different structural aspects of chromatin compaction. A graded spatial heterogeneity in compaction is observed for the chromatin besides the distinct positional ordering of core and linker histones. These spatio-temporal features are maintained by active processes and perturbed during death. With cell cycle, the distribution in compaction heterogeneity continually changes maximizing during M-G1 transition where it displays bimodal behavior. Such measurements of spatio-temporal chromatin fluidity could have broader implications in understanding chromatin remodeling within living cells.

Stochastic simulations of the origins and implications of long-tailed distributions in gene expression.

Gene expression noise results in protein number distributions ranging from long-tailed to Gaussian. We show how long-tailed distributions arise from a stochastic model of the constituent chemical reactions and suggest that, in conjunction with cooperative switches, they lead to more sensitive selection of a subpopulation of cells with high protein number than is possible with Gaussian distributions. Single-cell-tracking experiments are presented to validate some of the assumptions of the stochastic simulations. We also examine the effect of DNA looping on the shape of protein distributions. We further show that when switches are incorporated in the regulation of a gene via a feedback loop, the distributions can become bimodal. This might explain the bimodal distribution of certain morphogens during early embryogenesis.