Central Spike Research Articles

Efficacy and tolerability of sulthiame in the treatment of epilepsy: a literature review

This review aims to summarize the available evidence on the efficacy and tolerability of sulthiame for different forms of epilepsy. The analysis of international publications suggests that sulthiame is considered as a first-line drug for the treatment of age-dependent epilepsy with central temporal spikes (rolandic epilepsy). Sulthiame is highly effective in children with epileptic encephalopathies manifesting with spike-and-wave activity during sleep, including Landau-Kleffner syndrome, as well as in patients with myoclonic seizures. The drug might be also effective in patients with other forms of focal epilepsy, including those resistant to therapy. The tolerability of sulthiame is higher that that of old antiepileptic drugs and even levetiracetam; thus, it is associated with a lower risk of treatment interruptions due to adverse events. Moreover, sulthiame can be used for behavioral disorders (such as hyperkinetic behavior, aggressiveness) and cognitive impairments. Sulthiame can be effective in patients with epilepsy and sleep apnea.

New Onset Seizures in a Child Taking 0.01% Atropine Drops

Introduction: Myopia is a refractive disorder commonly diagnosed in childhood that follows a progressive course. It is considered a global epidemic with nearly 23% of the world’s population being diagnosed with this condition. Moreover, myopia is increasing in prevalence worldwide, demonstrated by studies in Asian and Western populations. This has important implications as myopic progression to high myopia is associated with significant morbidity and visual disability if left untreated. Of these treatments, the pharmacologic agent atropine has demonstrated the greatest efficacy in reducing myopia progression. Case report: This is a case report of an 11-year-old male treated with 0.01% atropine drops for myopia progression that developed new-onset seizures. The seizures were characterized as benign epilepsy with central temporal spikes and ceased when drops were discontinued. Discussion: Atropine 1% drops have previously been associated with new or increased seizure activity in a handful of case reports, however, it is our knowledge that this is the first report associated with 0.01% drops. This is important given the growing use of 0.01% drops as well as higher concentrations such as 0.025 % and 0.05% for the treatment of pediatric myopia. Conclusion: While it cannot be proven that the drops were causative in the seizure events, it is important to consider prior seizures as a relative contraindication to the use of these drops. Atropine has the potential to exacerbate seizure activity, so it is possible that the 0.01% atropine drops played a role in the patient’s seizures. Also, any diagnosis of new-onset seizures in pediatric patients should prompt discontinuation of drops at seizure onset.

A novel Queuovirinae lineage of Pseudomonas aeruginosa phages encode dPreQ0 DNA modifications with a single GA motif that provide restriction and CRISPR Cas9 protection in vitro.

Deazaguanine DNA modifications are widespread in phages, particularly in those with pathogenic hosts. Pseudomonas phage iggy substitutes ∼16.5% of its genomic 2'-deoxyguanosine (G) with dPreQ0, and the iggy deazaguanine transglycosylase (DpdA) is unique in having a strict GA target motif, not observed previously. The iggy PreQ0 modification is shown to provide protection against both restriction endonucleases and Cas9 (when present in PAM), thus expanding our understanding of the deazaguanine modification system, its potential, and diversity. Phage iggy represents a new genus of Pseudomonas phages within the Queuovirinae subfamily; which have very little in common with other published phage genomes in terms of nucleotide similarity (<10%) and common proteins (<2%). Interestingly, shared similarity is concentrated in dpdA and preQ0 biosynthesis genes. TEM imaging confirmed a siphovirus morphology with a prolate icosahedral head and a non-contractile flexible tail with one long central tail spike. The observed protective effect of the deazaguanine modification on the iggy DNA may contribute to its broad within-species host range. Phage iggy was isolated on Pseudomonas aeruginosa PAO1, but also infects PDO300, PAK, PA14, as well as 10 of 27 tested environmental isolates and 13 of 20 tested clinical isolates of P. aeruginosa from patients with cystic fibrosis.

Outcomes In Patients with Traumatic Acute Subdural Hematoma with Non-Convulsive Status Epilepticus (N3.002)

<h3>Objective:</h3> To evaluate the factors contributing to poor outcomes in patients with acute traumatic subdural hematoma (aSDH) who developed nonconvulsive status epilepticus (NCSE). <h3>Background:</h3> NCSE in patients with aSDH is an underdiagnosed yet fatal complication that requires prompt diagnosis and treatment. A high degree of clinical suspicion and evaluation with continuous EEG is required for prompt diagnosis and treatment. <h3>Design/Methods:</h3> This is a single-institution retrospective study approved by the local IRB. Patients with traumatic brain injury (TBI) with aSDH diagnosed with status epilepticus between the years 2016–2020 were included. Demographic, clinical, imaging, treatment, and EEG details were reviewed and collected in a HIPPA-compliant format. Logistic regression analysis was used to evaluate factors contributing to poor outcomes. <h3>Results:</h3> Out of a total of 540 patients, who had presented with traumatic acute intra-cerebral hemorrhage between the years 2016–2022, 28 patients with traumatic aSDH who had presented with status epileptics during the same hospitalization were included in the present study. NCSE was the most common form of status epilepticus (27/28). The mean age was 67 (range 20–92) years and 17(60%) were male. 12(48%) of the patients had an initial presenting GCS of 7 or less. The mean length of stay in the hospital was 16 (5–44) days. Overall mortality was 19(64%). Logistic regression analysis identified the presence of central spikes on EEG (p:0.43, OR:12.72; 95% CI 1.083–149.35) and thickness of aSDH&gt; 1cm (p: 0.025; OR: 16.545; 95%CI: 1.426–191.95) as predictors of mortality in both univariate and multivariate analysis. Good functional outcomes with mRS&lt;2 were seen in rarely 10(35%) of these patients. <h3>Conclusions:</h3> Nonconvulsive status epilepticus (NCSE) is a common form of presentation of status epilepticus in patients with acute traumatic SDH. The presence of epileptiform activity in the central leads in EEG often leads to resistant seizures. NCSE carries a poor prognosis with high mortality. <b>Disclosure:</b> Dr. Mohammed has nothing to disclose. Miss Stebbins has nothing to disclose. The institution of Dr. Shah has received research support from Eisai pharma .

The Unfinished Business of Unsettled Things: Art from an African American South

The Unfinished Business of Unsettled Things: Art from an African American South

SARS-CoV-2 Spike Protein Induces Hemagglutination: Implications for COVID-19 Morbidities and Therapeutics and for Vaccine Adverse Effects

Experimental findings for SARS-CoV-2 related to the glycan biochemistry of coronaviruses indicate that attachments from spike protein to glycoconjugates on the surfaces of red blood cells (RBCs), other blood cells and endothelial cells are key to the infectivity and morbidity of COVID-19. To provide further insight into these glycan attachments and their potential clinical relevance, the classic hemagglutination (HA) assay was applied using spike protein from the Wuhan, Alpha, Delta and Omicron B.1.1.529 lineages of SARS-CoV-2 mixed with human RBCs. The electrostatic potential of the central region of spike protein from these four lineages was studied through molecular modeling simulations. Inhibition of spike protein-induced HA was tested using the macrocyclic lactone ivermectin (IVM), which is indicated to bind strongly to SARS-CoV-2 spike protein glycan sites. The results of these experiments were, first, that spike protein from these four lineages of SARS-CoV-2 induced HA. Omicron induced HA at a significantly lower threshold concentration of spike protein than the three prior lineages and was much more electropositive on its central spike protein region. IVM blocked HA when added to RBCs prior to spike protein and reversed HA when added afterward. These results validate and extend prior findings on the role of glycan bindings of viral spike protein in COVID-19. They furthermore suggest therapeutic options using competitive glycan-binding agents such as IVM and may help elucidate rare serious adverse effects (AEs) associated with COVID-19 mRNA vaccines, which use spike protein as the generated antigen.

Right Peri-insular Hemispherotomy: 2-dimensional operative video

This is a surgical technique video of a right peri-insular hemispherotomy in a child with Rasmussen’s encephalitis. The patient is a 5-year-old boy with focal onset impaired awareness seizures started 6 months before surgery, developing different subtypes of focal seizures and evolving to drug-resistant epilepsy. In neurological examination, he already had a left-sided hemiparesis with pyramidal signs. Magnetic resonance imaging showed right-sided cortical atrophy and fronto-insular subcortical hyperintensity signal areas. The preoperative electroencephalogram revealed frequent right-sided central mid temporal spikes. The history and complementary exams raised a hypothesis of Rasmussen’s encephalitis, a rare neurological condition, characterized by unilateral chronic inflammation of the cerebral cortex, causing drug-resistant epilepsy, and evolving to progressive neurological decline1. The hemispherotomy is an effective procedure aimed to isolate the entire hemisphere functionally with minimal removal of brain tissue, and remains the only cure for seizures caused by Rasmussen’s encephalitis2,3. Long-term seizure freedom may be achieved in around 80% of patients and improves quality of life4. It’s already accepted that briefer duration of epilepsy preceding the surgery is associated to better adaptive functioning postoperatively due to the high neuroplasticity of young patients4. Three years after surgery, the patient remains seizure free, walking without help.

Percentage of luminosity and sandpaper bean in the firing of cocoa grafting in Puerto Bermúdez

The influence of the percentages of luminosity and number of sandpaper grains in the grasping of the central spike type graft of Theobroma cacao L., which was carried out in the San Pedro Native Community, of the District of Puerto Bermúdez, Province of Oxapampa, was studied. Pasco Department. Three nurseries were built with a Raschel mesh roof, with shade percentages of 40%, 60% and 80%. The seeds for the patterns came from the CCN-51 clone, which were sown in 6 x 8-inch bags containing substrate and placed in a nursery. The rods for grafting corresponded to clone CCN 51, which were extracted the same day as grafting. Three grafting blades were sharpened using three sizes of water sandpaper grains (400-A, 600-A and 1000-A) respectively, executing the central spike grafting procedure, to later condition the grafted seedlings in the three built nurseries. , evaluating at 30 and 60 days after grafting. The Completely Random Design (DCA) was used with a 3 x 3 factorial arrangement, concluding that the percentage of luminosity has no influence on the percentage of seizure, being the number of sandpaper grit 1000-A which achieved 100% of seizure. Likewise, the interaction 60% of luminosity plus the number of sandpaper grain 1000-A showed greater averages of shoot length and number of leaves, however, the interaction 80% of luminosity plus the number of sandpaper 1000-A achieved greater averages of number of shoots, and the interaction 60% of luminosity plus the number of sandpaper grit 400-A achieved higher averages of bud diameter, finally, 60% and 40% of luminosity achieved the best averages of pattern diameter.

The CFD modeling of bund overtopping phenomena and prediction of dynamic pressure on the bund

The storage tank of hazardous materials is usually equipped with bund system for hazard mitigation in case of a release incident. The catastrophic release incident requires an effective bund system to control overtopping and withstand the liquid dynamic pressure. This work developed three-dimensional (3D) Computational Fluid Dynamic (CFD) models based on RNG k-ε and Large Eddy Simulation (LES) model, respectively. These two CFD models were compared in terms of overtopping fraction and flow behavior, and both were validated against the experimental results. The validated 3D RNG k-ε model was used to investigate the flow behavior and dynamic pressure of the circular and square bund. Based on the results, the 3D RNG k-ε model is slightly better than the 3D LES model in terms of predicting the overtopping fraction and the height of central spike in this study; the 3D RNG k-ε model predicts the height of central spike better than the 2D model, and has the advantage to simulate complex bund design; the findings on flow behavior and dynamic pressure of the circular and square bund will help provide a scientific basis to design the bund system for minimizing the overtopping fraction and withstanding the liquid dynamic pressure.

Characterization of Photorhabdus Virulence Cassette as a causative agent in the emerging pathogen Photorhabdus asymbiotica.

The extracellular contractile injection systems (eCISs) are encoded in the genomes of a large number of bacteria and archaea. We have previously characterized the overall structure of Photorhabdus Virulence Cassette (PVC), a typical member of the eCIS family. PVC resembles the contractile tail of bacteriophages and exerts its action by the contraction of outer sheath and injection of inner tube plus central spike. Nevertheless, the biological function of PVC effectors and the mechanism of effector translocation are still lacking. By combining cryo-electron microscopy and functional experiments, here we show that the PVC effectors Pdp1 (a new family of widespread dNTP pyrophosphatase effector in eCIS) and Pnf (a deamidase effector) are loaded inside the inner tube lumen in a "Peas in the Pod" mode. Moreover, we observe that Pdp1 and Pnf can be directly injected into J774A.1 murine macrophage and kill the target cells by disrupting the dNTP pools and actin cytoskeleton formation, respectively. Our results provide direct evidence of how PVC cargoes are loaded and delivered directly into mammalian macrophages.

Use of cluster analysis and analysis of the main components for evaluation of triticale samples

The study was conducted in the period 2015-2017 in the experimental field of IRGR "K. Malkov” Sadovo. The elements of productivity of 24 varieties and lines of triticale (X. Triticosecale Wittmacks) were studied. The degree of variation of each of the indicators of productivity is determined by calculating a coefficient of variation. The results obtained show that the most variable indicator is the weight of grains in the central spike whereas the slightest variation is observed in the parameters of test weight and 1000 grains weight. Hierarchical cluster analysis and analysis of the main components (PC-analysis) are applied to assess the genetic similarity and distance between the different varieties. As a result of the clustering the studied samples were divided into six groups. The varieties Trit 32/6 and KS 60 are characterized with the greatest genetic proximity, followed by line BGR 30071 with the Bulgarian variety Rozhen. The largest genetic difference was reported between line BGR 30816 and variety KT 81. The applied analysis of the main components shows that the components PC 1, PC 2 and PC 3 explain 70.6% of the total variation of all traits by genotypes. The largest numbers of samples (9) belong to component 3, as four of them are located in the negative values of PC 3, and the other five genotypes are in the positive values of PC 3. Component 1 is represented by eight samples, and component 2 includes seven triticale genotypes.

Genetic divergence in maize regarding grain yield and tassel traits

Maize tassels with a longer length and higher number of branches prevent the passage of solar radiation into the upper plant canopy and act as a drain for photoassimilates that could be used for grain production. This study aimed to verify if there is genetic divergence regarding grain yield and tassel traits among maize cultivars in three agricultural years. Twenty maize cultivars were evaluated and 11 tassel traits and grain yield were measured. Individual and joint analyses of variance were performed for each trait. Principal component analysis was performed, the generalized Mahalanobis distance matrix between cultivars was determined, and the genetic divergence analysis was performed, using the unweighted pair group method with arithmetic mean (UPGMA), which allowed constructing the dendrogram. The cophenetic correlation coeffi cient was calculated to validate the cluster. There is genetic divergence among maize cultivars and six groups of cultivars were formed. Tassel length, total branches number, central spike dry matter, and grain yield are the traits that most contribute to the genetic divergence among maize cultivars.

The Central Spike Complex of Bacteriophage T4 Contacts PpiD in the Periplasm of Escherichia coli.

Infecting bacteriophage T4 uses a contractile tail structure to breach the envelope of the Escherichia coli host cell. During contraction, the tail tube headed with the “central spike complex” is thought to mechanically puncture the outer membrane. We show here that a purified tip fragment of the central spike complex interacts with periplasmic chaperone PpiD, which is anchored to the cytoplasmic membrane. PpiD may be involved in the penetration of the inner membrane by the T4 injection machinery, resulting in a DNA-conducting channel to translocate the phage DNA into the interior of the cell. Host cells with the ppiD gene deleted showed partial reduction in the plating efficiency of T4, suggesting a supporting role of PpiD to improve the efficiency of the infection process.

Phytopathological Assessment of Lines of Common Winter Wheat to the Cause of Brown Leaf Rust (Puccinia recondita f. sp. tritici)

The study was conducted in the period 2017-2019 in the experimental fields of the Institute of Plant Genetic Resources K. Malkov” in Sadovo, near Plovdiv, Bulgaria. At the infectious area, the immune responses of twenty-two genotypes of common winter wheat to the causative agent of brown leaf rust - Puccinia recondita f. sp. Tritici were tested The line MX 289/2048 has shown high resistance to the pathogen, and seven samples are characterized by a stable reaction. The biggest share of the studied breeding materials showed average resistance to the phytopathogen. A comparison of the indicators of grain weight in the central spike and 1000 kernel weight was made for samples grown on an infectious site and under natural field conditions. The obtained results showed an exceeding the values of the trait in favor of the samples grown under natural field conditions. It was found that the greatest influence on the traits grainsweight in the central spike and 1000 kernels weight has the year of cultivation. To assess the genetic diversity, a cluster analysis was applied, in which the selection materials were grouped into five main cluster groups. The lines MX 286/1777 and MX 270/3461 are characterized by the greatest genetic proximity, and the line MX 285/1058 is genetically the most distant compared to the samples from the first cluster group.

Mayahuelin, a Type I Ribosome Inactivating Protein: Characterization, Evolution, and Utilization in Phylogenetic Analyses of Agave.

Agaves resist extreme heat and drought. In A. tequilana var. azul, the central spike of the rosette -containing the shoot apical meristem and folded leaves in early stages of development- is remarkably heat tolerant. We found that the most abundant protein in this organ is a 27 kDa protein. This protein was named mayahuelin to honor Mayáhuel, the agave goddess in the Aztec pantheon. LC-MS/MS analyses identified mayahuelin as a type I RIP (Ribosome Inactivating Protein). In addition to the spike, mayahuelin was expressed in the peduncle and in seeds, whereas in mature leaves, anthers, filaments, pistils, and tepals was absent. Anti-mayahuelin antibody raised against the A. tequilana var. azul protein revealed strong signals in spike leaves of A. angustifolia, A. bracteosa, A. rhodacantha, and A. vilmoriniana, and moderate signals in A. isthmensis, A. kerchovei, A. striata ssp. falcata, and A. titanota, indicating conservation at the protein level throughout the Agave genus. As in charybdin, a type I RIP characterized in Drimia maritima, mayahuelin from A. tequilana var. azul contains a natural aa substitution (Y76D) in one out of four aa comprising the active site. The RIP gene family in A. tequilana var. azul consists of at least 12 genes and Mayahuelin is the only member encoding active site substitutions. Unlike canonical plant RIPs, expression of Mayahuelin gene in S. cerevisiae did not compromise growth. The inhibitory activity of the purified protein on a wheat germ in vitro translation system was moderate. Mayahuelin orthologs from other Agave species displayed one of six alleles at Y76: (Y/Y, D/D, S/S, Y/D, Y/S, D/S) and proved to be useful markers for phylogenetic analysis. Homozygous alleles were more frequent in wild accessions whereas heterozygous alleles were more frequent in cultivars. Mayahuelin sequences from different wild populations of A. angustifolia and A. rhodacantha allowed the identification of accessions closely related to azul, manso, sigüín, mano larga, and bermejo varieties of A. tequilana and var. espadín of A. angustifolia. Four A. rhodacantha accessions and A. angustifolia var. espadín were closer relatives of A. tequilana var. azul than A. angustifolia wild accessions or other A. tequilana varieties.

Dark matter around primordial black hole at the radiation-dominated stage

The accumulation of dark matter particles near the primordial black holes starts at the radiation-dominated cosmological stage and produces the central density spikes. The spikes can be the bright gamma-ray sources due to dark matter annihilation. We present the self-consistent derivation of the equation of motion of particle in the metrics of primordial black hole immersed into cosmological background. By numerical solution of this equation we find the central dark matter density profile. The density growth is suppressed in the central part of the profile compared with previous calculations.

Similar shot profile morphology of fast variability in a cataclysmic variable, X-ray binary, and blazar: The MV Lyrae case

Context. The cataclysmic variable MV Lyr has been found to be present in the Kepler field, yielding a light curve with the duration of almost 1500 days with 60 s cadence. Such high quality data of this nova-like system with obvious fast optical variability reveal multi-component power density spectra, as shown by previous works. Aims. Our goal is to study the light curve from a different point of view and perform a shot profile analysis. We search for characteristics that have not been discovered with standard methods based on power density spectrum. Methods. The shot profile method identifies individual shots in the light curve and averages these shots to reveal all substructures with typical timescales. We also tested the robustness of our analysis using a simple shot noise model. Although the principle of this method is not completely physically correct, we used it as a purely phenomenological approach. Results. We obtain mean profiles with multi-component features. The shot profile method distinguishes substructures with similar timescales which appear as a single degenerate feature in power density spectra. Furthermore, this method yields the identification of another high frequency component in the power density spectra of Kepler and XMM-Newton data that have not been detected so far. Moreover, we found side lobes accompanied with the central spike, making the profile very similar to the Kepler data of blazar W2R 1926+42 and the Ginga data of Cyg X-1. All three objects show similar timescale ratios of the rising versus declining part of the central spikes, while the two binaries also have similar rising profiles of the shots described by a power-law function. Conclusions. The similarity of both binary shot profiles suggests that the shots originate from the same origin, namely, aperiodic mass accretion in the accretion disc. Moreover, the similarity with the blazar may imply that the ejection fluctuations in the blazar jet are connected to accretion fluctuations driving the variability in binaries. This points out the connection between the jet and the accretion disc.

Atomic Structure of the Francisella T6SS Central Spike Reveals a Unique α-Helical Lid and a Putative Cargo

Francisella bacteria rely on a phylogenetically distinct type VI secretion system (T6SS) to escape host phagosomes and cause the fatal disease tularemia, but the structural and molecular mechanisms involved are unknown. Here we report the atomic structure of the Francisella T6SS central spike complex, obtained by cryo-electron microscopy. Our structural and functional studies demonstrate that, unlike the single-protein spike composition of other T6SS subtypes, Francisella T6SS's central spike is formed by two proteins, PdpA and VgrG, akin to T4-bacteriophage gp27 and gp5, respectively, and that PdpA has unique characteristics, including a putative cargo within its cavity and an N-terminal helical lid. Structure-guided mutagenesis demonstrates that the PdpA N-terminal lid and C-terminal spike are essential to Francisella T6SS function. PdpA isthus both an adaptor, connecting VgrG to the tube, and a likely carrier of secreted cargo. These findings are important to understanding Francisella pathogenicity and designing therapeutics to combat tularemia.

Benign epileptiform discharges of childhood may correspond with the period of rapid brain development

There were over 70 children (3-12 y.o.; 74.3% boys) with delayed speech functions and atypical autism spectrum disorder under medical supervision. Children have been receiving complex treatment for 3 years (every 3-6 months). During the rehabilitation course and according to the Protocol EEG sleep monitoring was carried out at the beginning and at the end of the treatment. We did not identify specific EEG patterns that may characterize the specifics of behavior. We have got a way to assess the EEG dynamics of children duaring 3 years (with 3-6 months intervals). Within the next three years 15 children have had a period of obvious progress in mental functions (not necessarily associated with the rehabilitation course) and during this period another EEG examination was conducted. Progress of mental functions have been evaluated by the Scale of General Impressions (CGI-S Scale). As a result, we noted the patterns of occurrence of benign childhood epileptic central temporal spike (BCECTS) on children EEG during the progress of mental functions. If initially BCECTS were registered in 3 children out of 70 (4,3%), but during the period of progress of mental functions in 15 children, BCECTS were registered in 8 (53,3%) (p

Clinical Significance of Incidental Rolandic Spikes in Children With Absence Epilepsy.

Absence epilepsy and benign epilepsy of childhood with central temporal spikes are common childhood epilepsy syndromes. Although 3-Hz generalized spike-wave discharges are almost always associated with absence seizures, rolandic spikes can be present in individuals without rolandic seizures. The co-occurrence of 3-Hz generalized spike-wave and rolandic spikes is very rare. Our objective was to compare clinical features of patients with absence epilepsy with and without rolandic spikes, to determine if the additional feature of rolandic spikes has any clinical significance. Clinical information of 17 children with absence epilepsy and rolandic spikes was compared to an age-matched control group of 90 children with absence epilepsy. Although most patients had excellent seizure control at follow-up, epilepsy comorbidities (cognitive and emotional problems) were observed. Comparing study vs control groups, there was no difference with anxiety (2 [11.8%] vs 8 [9%]), behavioral issues (4 [23.5%] vs 10 [11%]), mood disorders (0 vs 2 [2%]), and attention-deficit hyperactivity disorder (4 [24%] vs 10 [11%]). Significant differences were also observed: more global-developmental (5 [29%] vs 5 [6%], P < .009) and expressive-language (4 [24%] vs 5 [6%], P < .034) delay and more difficulties with school performance (11 [65%] vs 32 [36%], P < .025), especially with language-related tasks (6 [35%] vs 5 [6%], P < .001). Our results confirm the presence of additional epilepsy comorbidities in patients with absence epilepsy when rolandic spikes are present. Rolandic spikes in patients with absence epilepsy may be a marker of additional cognitive challenges that physicians should be aware of.