Deciphering the mannose transfer mechanism of mycobacterial PimE by molecular dynamics simulations.

Phosphatidyl-myo-inositol mannosides (PIMs), Lipomannan (LM), and Lipoarabinomannan (LAM) are essential components of the cell envelopes of mycobacteria. At the beginning of the biosynthesis of these compounds, phosphatidylinositol (PI) is mannosylated and acylated by various enzymes to produce Ac1/2PIM4, which is used to synthesize either Ac1/2PIM6 or LM/LAM. The protein PimE, a membrane-bound glycosyltransferase (GT-C), catalyzes the addition of a mannose group to Ac1PIM4 to produce Ac1PIM5, using polyprenolphosphate mannose (PPM) as the mannose donor. PimE-deleted Mycobacterium smegmatis (Msmeg) showed structural deformity and increased antibiotic and copper sensitivity. Despite knowing that the mutation D58A caused inactivity in Msmeg, how PimE catalyzes the transfer of mannose from PPM to Ac1/2PIM4 remains unknown. In this study, analyzing the AlphaFold structure of PimE revealed the presence of a tunnel through the D58 residue with two differently charged gates. Molecular docking suggested PPM binds to the hydrophobic tunnel gate, whereas Ac1PIM4 binds to the positively charged tunnel gate. Molecular dynamics (MD) simulations further demonstrated the critical roles of the residues N55, F87, L89, Y163, Q165, K197, L198, R251, F277, W324, H326, and I375 in binding PPM and Ac1PIM4. The mutation D58A caused a faster release of PPM from the catalytic tunnel, explaining the loss of PimE activity. Along with a hypothetical mechanism of mannose transfer by PimE, we also observe the presence of tunnels through a negatively charged aspartate or glutamate with two differently-charged gates among most GT-C enzymes. Common hydrophobic gates of GT-C enzymes probably harbor sugar donors, whereas, differently-charged tunnel gates accommodate various sugar-acceptors.

Structural variations and roles of rhamnose-rich cell wall polysaccharides in Gram-positive bacteria.

Rhamnose-rich cell wall polysaccharides (Rha-CWPSs) have emerged as crucial cell wall components of numerous Gram-positive, ovoid-shaped bacteria-including streptococci, enterococci, and lactococci-of which many are of clinical or biotechnological importance. Rha-CWPS are composed of a conserved polyrhamnose backbone with side-chain substituents of variable size and structure. Because these substituents contain phosphate groups, Rha-CWPS can also be classified as polyanionic glycopolymers, similar to wall teichoic acids, of which they appear to be functional homologs. Recent advances have highlighted the critical role of these side-chain substituents in bacterial cell growth and division, as well as in specific interactions between bacteria and infecting bacteriophages or eukaryotic hosts. Here, we review the current state of knowledge on the structure and biosynthesis of Rha-CWPS in several ovoid-shaped bacterial species. We emphasize the role played by multicomponent transmembrane glycosylation systems in the addition of side-chain substituents of various sizes as extracytoplasmic modifications of the polyrhamnose backbone. We provide an overview of the contribution of Rha-CWPS to cell wall architecture and biogenesis and discuss current hypotheses regarding their importance in the cell division process. Finally, we sum up the critical roles that Rha-CWPS can play as bacteriophage receptors or in escaping host defenses, roles that are mediated mainly through their side-chain substituents. From an applied perspective, increased knowledge of Rha-CWPS can lead to advancements in strategies for preventing phage infection of lactococci and streptococci in food fermentation and for combating pathogenic streptococci and enterococci.

Recent Progress in Structural Studies on the GT-C Superfamily of Protein Glycosyltransferases.

Protein glycosylation is an essential covalent modification involved in protein secretion, stability, binding, folding, and activity. One or more sugars may be O-, N-, S-, or C-linked to specific amino acids by glycosyltransferases, which catalyze the transfer of these sugars from a phosphate-containing carrier molecule. Most glycosyltransferases are members of the GT-A, GT-B, or GT-C structural superfamilies. GT-C enzymes are integral membrane proteins that utilize a phospho-isoprenoid carrier for sugar transfer. To-date, two families of GT-Cs involved in protein glycosylation have been structurally characterized: the family represented by PglB, AglB, and Stt3, which catalyzes oligosaccharide transfer to Asn, and the family represented by Pmt1 and Pmt2, which catalyzes mannose transfer to Thr or Ser. This chapter reviews progress made over recent years on the structure and function of these two GT-C families.

Genetic characterization and phylogenetic variations of human adenovirus-F strains circulating in eastern India during 2017-2020.

Human adenovirus-F (HAdV-F) (genotype 40/41) is the second-most leading cause of pediatric gastroenteritis after rotavirus, worldwide, accounting for 2.8%-11.8% of infantile diarrheal cases. Earlier studies across eastern India revealed a shift in the predominance of genotypes from HAdV41 in 2007-09 to HAdV40 in 2013-14. Thus, the surveillance for HAdV-F genotypes in this geographical setting was undertaken over 2017-2020 to analyze the viral evolutionary dynamics. A total of 3882 stool samples collected from children (≤5 years) were screened for HAdV-F positivity by conventional PCR. The hypervariable regions of the hexon and the partial shaft region of long fiber genes were amplified, sequenced, and phylogenetically analyzed with respect to the prototype strains. A marginal decrease in enteric HAdV prevalence was observed (9.04%, n = 351/3882) compared to the previous report (11.8%) in this endemic setting. Children <2 years were found most vulnerable to enteric HAdV infection. Reduction in adenovirus-rotavirus co-infection was evident compared to the sole adenovirus infection. HAdV-F genotypes 40 and 41 were found to co-circulate, but HAdV41 was predominant. HAdV40 strains were genetically conserved, whereas HAdV41 strains accumulated new mutations. On the basis of a different set of mutations in their genome, HAdV41 strains segregated into 2 genome type clusters (GTCs). Circulating HAdV41 strains clustered with GTC1 of the fiber gene, for the first time during this study period. This study will provide much-needed baseline data on the emergence and circulation of HAdV40/41 strains for future vaccine development.

Magnetic particles for integrated nucleic acid purification, amplification and detection without pipetting.

Nucleic acid amplification based detection plays an important role in food safety, environmental monitoring and clinical diagnosis. However, traditional nucleic acid detection process involves transferring liquid from one tube to another by pipetting. It requires trained persons, equipped labs and consumes lots of time. The ideal nucleic acid detection is integrated, closed, simplified and automated. Magnetic particles actuated by magnetic fields can efficiently adsorb nucleic acids and promote integrated nucleic acid assays without pipetting driven by pumps and centrifuges. We will comprehensively review magnetic particles assisted integrated system for nucleic acid detection and hope it can inspire further related study.

Proteogenomic Analyses of Cellular Lysates Using a Phenol-Guanidinium Thiocyanate Reagent.

Protein and RNA profiles are highly informative when generating a comprehensive understanding of the dynamics of complex biological systems. Quantitative correlations between protein and RNA profiles are not always high, yet simultaneous acquisition of both profiles remains challenging, in part because of the limited availability of samples and the inconvenience of separately preparing protein and RNA fractions. In a previous study, protein, DNA, and RNA fractions were simultaneously prepared from the same sample using phenol-guanidinium isothiocyanate reagent (P/GTC), although the performance of P/GTC-extracts in proteogenomic analyses remains poorly understood. We therefore evaluated the performance of the P/GTC-extraction method in proteogenomic analyses using standard HEK293-F cells and human peripheral blood neutrophils. The latter cell type is renowned for its extreme vulnerability to protein/RNA degradation, reflecting high protease and RNase activities. Our data indicate that the P/GTC extraction method provides superior protein profiles from neutrophil and HEK293-F cell samples for simultaneous preparation of RNA and protein, as compared with those from conventional protein extraction methods. The P/GTC extraction method therefore provides a powerful and robust tool for a broad range of proteogenomic studies.

Time to response and patient visibility during tonic-clonic seizures in the epilepsy monitoring unit.

OBJECTIVE: There is a high cost associated with recording quality video and electroencephalography (EEG) data in National Association of Epilepsy Center (NAEC) level IV epilepsy monitoring units (EMU). This study considers potential quality measures in EMUs for generalized tonic-clonic (GTC) seizures: types of safety signals, response time, and visibility of patient's limbs for semiology. These quality measures have been summarized across 12 EMUs to estimate response times to GTC seizures and the quality of video data that is captured during admissions. METHODS: Video electroencephalographies (vEEGs) from two prospective regulatory studies for the Brain Sentinel device were reviewed. A total of 232 subjects with a history of GTC seizures underwent routine clinical EMU stays. Fifty-four of the study subjects had 96 GTC seizures. The vEEG of events were reviewed for safety signal used, response time, and visibility of patient's limbs. RESULTS: The average response time from members of the hospital team was 22 s from electrographic generalization (minimum -37 s, maximum 111 s, two no response). For caregivers, average response was 11 s (minimum -15 s, maximum 33 s, 45 not present/no response). In 73% of events, the patient visibility was limited at seizure onset. In 55% of events with limited limb visibility, the visibility was improved (by removing sheets or improving camera angle) >30 s after start of the event. The primary safety signals were as follows: an alert from outside the patient room (54%), button press (23%), hospital team present at seizure start (14%), caregiver vocal alert (6%), and no response (2%). SIGNIFICANCE: The average response time of caregivers was twice as fast as the hospital team, underscoring the importance of having a person in the room during onset of a GTC seizure. Diagnostic yield could be improved with more timely removal of patient coverings. It was observed that when patients experienced a GTC seizure, 40% were fully or partially obscured for more than 30 s during the event, compromising the ability of epileptologists to evaluate semiology during seizure onset. Automated seizure alarms may help staff get to patients more quickly and improve diagnostic characterization.

Outcome of radiotherapy for pituitary adenomas.

AIM: The aim of this study was to analyze the outcome and toxicities and its correlation to patient related and treatment related factors. BACKGROUND: Pituitary adenomas are treated by radiation therapy (RT) as one of the modalities along with surgery and medical therapy. RT to pituitary adenomas is a challenge due to adjacent dose limiting structures such as optic apparatus and hypothalamus. MATERIALS AND METHODS: Between January 2004 and December 2010, 94 patients treated for pituitary adenoma with RT who had hospital records of a minimum follow-up of 1 year were included in the analysis. Tests of correlation were done with regards to treatment factors. RESULTS: Male preponderance was noted in our patient population. Nonfunctioning and functioning tumors were equal in number in this series. Hypopituitarism was associated in 58.5% of patients prior to RT. Radiological tumor progression was seen in one patient (1/94) who had a nonfunctioning tumor. Among functioning tumors, biochemical remission was seen in 93.6% of patients at a median follow-up of 6 years. CONCLUSIONS: Visual complication was seen in 5.3% of patients and worsening or new onset hypopituitarism was seen in 6.4%. Conventional 3-field technique was associated with significantly more visual complication compared to Stereotactic Radiation Therapy (SRT) technique. Doses ≤50.4 Gy showed a trend of reduced rate of visual and endocrine complications with no compromise in efficacy.

Impaired development of intrinsic connectivity networks in children with medically intractable localization-related epilepsy.

Typical childhood development is characterized by the emergence of intrinsic connectivity networks (ICNs) by way of internetwork segregation and intranetwork integration. The impact of childhood epilepsy on the maturation of ICNs is, however, poorly understood. The developmental trajectory of ICNs in 26 children (8-17 years) with localization-related epilepsy and 28 propensity-score matched controls was evaluated using graph theoretical analysis of whole brain connectomes from resting-state functional magnetic resonance imaging (fMRI) data. Children with epilepsy demonstrated impaired development of regional hubs in nodes of the salience and default mode networks (DMN). Seed-based connectivity and hierarchical clustering analysis revealed significantly decreased intranetwork connections, and greater internetwork connectivity in children with epilepsy compared to controls. Significant interactions were identified between epilepsy duration and the expected developmental trajectory of ICNs, indicating that prolonged epilepsy may cause progressive alternations in large-scale networks throughout childhood. DMN integration was also associated with better working memory, whereas internetwork segregation was associated with higher full-scale intelligence quotient scores. Furthermore, subgroup analyses revealed the thalamus, hippocampus, and caudate were weaker hubs in children with secondarily generalized seizures, relative to other patient subgroups. Our findings underscore that epilepsy interferes with the developmental trajectory of brain networks underlying cognition, providing evidence supporting the early treatment of affected children.

Endoscopic submucosal dissection for gastric tube cancer after esophagectomy.

BACKGROUND: Recent improvements in the survival of patients after esophagectomy have led to an increasing occurrence of gastric tube cancer (GTC). Removal of the reconstructed gastric tube, however, can lead to high morbidity and mortality. OBJECTIVE: To assess the feasibility and effectiveness of endoscopic submucosal dissection (ESD) for GTC. DESIGN: Retrospective study. SETTING: National Cancer Center Hospital, Tokyo, Japan. PATIENTS: We investigated patients with GTC after esophagectomy undergoing ESD from 1998 to 2011. INTERVENTION ESD MAIN OUTCOME MEASUREMENTS: Patient characteristics, endoscopic findings, technical results, histopathology including curability and Helicobacter pylori gastritis, and long-term outcomes. RESULTS: There were 51 consecutive patients with 79 lesions including 38 lesions (48%) meeting the absolute indication, 31 (39%) satisfying the expanded indications, and 10 (13%) falling outside such indications. The median procedure time was 90 minutes. There were 73 en bloc resections (92%), 59 en bloc resections with tumor-free margins (R0 resections, 75%), and 51 curative resections (65%) based on the Japanese Gastric Cancer Association criteria. Fifty patients (98%) were assessed as H pylori gastritis positive. Adverse events included 3 perforations (3.8%) during ESD and 2 delayed perforations (2.5%) without any emergency surgery and 3 delayed bleeding (3.8%). Local recurrence was detected in 4 patients (7.8%), and metachronous GTCs were identified in 18 patients (35%). Five patients (10%) died of GTC including 3 metachronous lesions. The 5-year overall survival rate was 68.4%, and the disease-specific survival rate was 86.7% with 100% for curative and 72.7% for non-curative patients during a median follow-up period of 3.8 years (range, 0-12.1 years). LIMITATION: Single-center retrospective study. CONCLUSIONS: ESD for GTC was feasible and effective for curative patients; however, long-term outcomes for non-curative patients were less satisfactory.

Gastric transcatheter chemoembolization combined with systemic chemotherapy vs. systemic chemotherapy alone for patients with advanced gastric cardiac cancer presenting with dysphagia: A case control study.

The present study aimed to assess the effectiveness of gastric transcatheter chemoembolization (GTC) combined with systemic chemotherapy (SYS) compared with SYS alone in managing dysphagia, and improving the quality of life (QoL) and nutritional status of patients with advanced gastric cardiac cancer (AGCC). A retrospective review was performed using data from consecutive patients with AGCC who experienced dysphagia and underwent either SYS alone or SYS combined with GTC from January 2018 to December 2022. Propensity score matching (PSM) analysis was performed to address potential confounding factors. Ogilvie dysphagia scores were used to assess dysphagia, the Functional Assessment of Cancer Therapy-General 7 (FACT-G7) was used to assess QoL, and the Patient-Generated Subjective Global Assessment (PG-SGA) was used to evaluate nutritional status. After PSM, a total of 228 patients were included in the analysis, with 114 in each group. At 4 and 8 weeks after the initial treatment, the GTC + SYS group demonstrated significantly lower median Ogilvie scores compared with the SYS alone group (P<0.001). Similarly, the median PG-SGA score at 4 weeks after the initial treatment was 2.0 in the GTC + SYS group and 6.0 in the SYS alone group. The median FACT-G7 scores in the GTC + SYS group was 13.0, compared with 10.5 in the SYS alone group. These differences remained significant at 8 weeks (P<0.001). In conclusion, the addition of GTC to SYS may more effectively and promptly relieve dysphagia, improve nutritional status and enhance QoL compared with SYS alone in patients with AGCC presenting with dysphagia.

Quantifying Viable M. tuberculosis Safely Obviating the Need for High Containment Facilities.

Mycobacterium tuberculosis is an infectious pathogen that requires biosafety level-3 laboratory for handling. The risk of transmission is high to laboratory staff, and to manage the organism safely, it is necessary to construct high containment laboratory facilities at great expense. This limits the application of tuberculosis diagnostics to areas where there is insufficient capital to invest in laboratory infrastructure. In this method, we describe a process of inactivating sputum samples by either heat or guanidine thiocyanate (GTC) that renders them safe without affecting the quantification of viable bacteria. This method eliminates the need for level 3 containment laboratory for the tuberculosis molecular bacterial load assay (TB-MBLA) and is applicable in low- and middle-income countries.

The effect of epilepsy and antiseizure medications on cardiac autonomic functions in children with epilepsy.

BACKGROUND: Autonomic manifestations have been frequently studied in adults with epilepsy. Here, we evaluated cardiac autonomic (ANS) functions in children with epilepsy in the interictal period and determined the risks for their dysfunctions. RESEARCH DESIGN AND METHODS: This study included 60 patients (boys = 25; girls = 35 age: 14.53 ± 2.54 yrs) and 25 controls. Patients were well-controlled on antiseizure medications (ASMs). The battery of testing included measuring resting heart rate (HR) and blood pressure (BP), 30:15 ratio, HR variability (HRV) response to deep breathing, Valsalva ratio and BP changes in response to standing, isometric exercise and cold. RESULTS: Dizziness was reported in 25%. Autonomic dysfunctions were found in 45% (n = 27). Manifestations included high frequencies of abnormal 30:15 ratio (22%), HRV responses to deep breathing (45%), Valsalava ratio (45%), and BP responses to standing (35%), isometric exercise (27%) and cold (27%), indicating parasympathetic and sympathetic hypofunctions. There were positive correlations between parasympathetic and sympathetic dysfunctions. Logistic analysis showed that the durations of epilepsy and ASMs therapy were associated with ANS dysfunctions [95% CI: 0.895-4.719, p = 0.004]. CONCLUSIONS: Parasympathetic and sympathetic autonomic hypofunctions are common in children with epilepsy. This could be due to the depressant effect of sodium channel blocker ASMs on central and/or cardiac autonomic systems.

Structural and Dynamical Properties of Nucleic Acid Hairpins Implicated in Trinucleotide Repeat Expansion Diseases.

Dynamic mutations in some human genes containing trinucleotide repeats are associated with severe neurodegenerative and neuromuscular disorders-known as Trinucleotide (or Triplet) Repeat Expansion Diseases (TREDs)-which arise when the repeat number of triplets expands beyond a critical threshold. While the mechanisms causing the DNA triplet expansion are complex and remain largely unknown, it is now recognized that the expandable repeats lead to the formation of nucleotide configurations with atypical structural characteristics that play a crucial role in TREDs. These nonstandard nucleic acid forms include single-stranded hairpins, Z-DNA, triplex structures, G-quartets and slipped-stranded duplexes. Of these, hairpin structures are the most prolific and are associated with the largest number of TREDs and have therefore been the focus of recent single-molecule FRET experiments and molecular dynamics investigations. Here, we review the structural and dynamical properties of nucleic acid hairpins that have emerged from these studies and the implications for repeat expansion mechanisms. The focus will be on CAG, GAC, CTG and GTC hairpins and their stems, their atomistic structures, their stability, and the important role played by structural interrupts.

IoT based monitoring system for epileptic patients.

The unpredictable nature of epileptic seizures makes it challenging to detect and effectively treat this disorder. The seizures are random, and most epileptic patients experience dangerous physical symptoms during an attack that renders the patient uneasy when conducting their daily tasks. This paper focuses on the generalised type of epilepsy, namely "Grand mal epilepsy Tonic-Clonic (GTC) seizure. The research aims to monitor symptoms of epileptic disease behaviour signals in humans and prevent it at its early stage of illness. To achieve this objective, we used the Electrocardiogram (ECG), Electromyography (EMG), accelerometer 3-axes for fall detection, and Dallas sensor for body temperature signals monitoring for updating the IoT system. The fuzzy logic algorithm that has been used to assess specified data set of diseased patients' parameters allows the classification into diverse types of seizures such as heart rate, body temperature, muscles spasm and falls. These are used as inputs to obtain the seizure type as an output which is then illustrated graphically on the dashboard of an IoT platform (Think-Speak), where abnormal conditions have been used to notify the medical personnel by sending an SMS message through "If This Then That" (IFTTT) technology. A prototype of an epileptic monitoring system has been successfully built and tested. It has an average accuracy of 98.90%, 95.49%, 83.0%, and 87.21% for body temperature, heart rate monitoring, muscle spasm, and fall detection.

How does artificial intelligence affect green economic growth?-Evidence from China.

As the driving force behind the new wave of technological advancement, artificial intelligence (AI) paves the way for a new era of green economic growth. This paper uses the case of China and constructs a relevant mathematical model to propose the two-way impact of AI on green total factor productivity (GTFP) and systematically analyze the impact of AI on green economic growth. The main findings of this study are that AI has a significant "U-shaped" effect on GTFP, which was estimated using a nonlinear dynamic panel regression model. The analysis of regional heterogeneity shows that improving AI in resource-rich areas can boost GTFP and break the "resource curse". The "productivity paradox" arises, according to the industry heterogeneity analysis, because the current low level of intelligence in resource-intensive and labor-intensive industries fails to improve GTFP. This paper also breaks down GTFP into green technological progress and green efficiency improvement effects to figure out how AI affects green economic growth.

COVID-19 pandemic lesson learned- critical parameters and research needs for UVC inactivation of viral aerosols.

The COVID-19 pandemic highlighted public awareness of airborne disease transmission in indoor settings and emphasized the need for reliable air disinfection technologies. This increased awareness will carry in the post-pandemic era along with the ever-emerging SARS-CoV variants, necessitating effective and well-defined protocols, methods, and devices for air disinfection. Ultraviolet (UV)-based air disinfection demonstrated promising results in inactivating viral bioaerosols. However, the reported data diversity on the required UVC doses has hindered determining the best UVC practices and led to confusion among the public and regulators. This article reviews available information on critical parameters influencing the efficacy of a UVC air disinfection system and, consequently, the required dose including the system's components as well as operational and environmental factors. There is a consensus in the literature that the interrelation of humidity and air temperature has a significant impact on the UVC susceptibility, which translate to changing the UVC efficacy of commercialized devices in indoor settings under varying conditions. Sampling and aerosolization techniques reported to have major influence on the result interpretation and it is recommended to use several sampling methods simultaneously to generate comparable and conclusive data. We also considered the safety concerns and the potential safe alternative of UVC, far-UVC. Finally, the gaps in each critical parameter and the future research needs of the field are represented. This paper is the first step to consolidating literature towards developing a standard validation protocol for UVC air disinfection devices which is determined as the one of the research needs.

Development of nano-encapsulated green tea catechins: Studies on optimization, characterization, release dynamics, and in-vitro toxicity.

Green tea (Camelia sinesis) has been acknowledged for plethora of pharmacological activities attributed by green tea catechins (GTC), however, poor bioavailability, short half-life and stability issues hamper its use as a therapeutic agent. Chitosan and sodium -tripolyphosphate were used to encapsulate GTC, which reduced its degradation in gastro-intestinal tract. The average size, zeta potential, and encapsulation efficiency of nano-encapsulated epigallocatechin-3-gallate (EGCG) rich GTC were observed as 250 nm, +49.8 mV, and 87%, respectively. The morphological and physico-chemical characterizations affirmed the size, stability, and encapsulation efficacy of nano-encapsulated green tea catechins. The In-vitro simulated release model showed the release of GTC in the intestinal phase via zero order kinetics. Cell viability studies were conducted on PC12 cell line to validate safety efficacy of nanoencapsulated GTC. Moreover, the study concluded that stability, bioavailability and bioactivity of EGCG was improved by nanoencapsulation of GTC, thereby rendering it a potent nanoceutical for clinical implications. PRACTICAL APPLICATIONS: Green tea catechin has enormous health endorsing activities. One of the major potentials of GTC is its antioxidant activity that plays a promising role in the prevention of various lethal disorders. In the present study, nanoencapsulation is used as a potential approach to improve the low bioavailability of green tea catechin. The results enlightened that nanoencapsulation of green tea catechin could be useful for improving the stability of green tea catechin in the GI tract as well as its bioaccessibility. Henceforth, this strategy restores the stability and bioavailability of green tea catechin that could be practically implied as a nutraceutical in the food and pharmaceutical industry as it can enhance the biological activity of catechins in catechin rich green tea-related products.

Using sEMG to identify seizure semiology of motor seizures.

PURPOSE: Accurate characterization and quantification of seizure types are critical for optimal pharmacotherapy in epilepsy patients. Technological advances have made it possible to continuously monitor physiological signals within or outside the hospital setting. This study tested the utility of single-channel surface-electromyography (sEMG) for characterization of motor epileptic seizure semiology. METHODS: Seventy-one subjects were prospectively enrolled where vEEG and sEMG were simultaneously recorded. Three epileptologists independently identified and classified seizure events with upper-extremity (UE) motor activity by reviewing vEEG, serving as a clinical standard. Surface EMG recorded during the events identified by the clinical standard were evaluated using automated classification methods and expert review by a second group of three independent epileptologists (blinded to the vEEG data). Surface EMG classification categories included: tonic-clonic (TC), tonic only, clonic only, or other motor seizures. Both automated and expert review of sEMG was compared to the clinical standard. RESULTS: Twenty subjects experienced 47 motor seizures. Automated sEMG event classification methods accurately classified 72 % (95 % CI [0.57, 0.84]) of events (15/18 TC seizures, 5/9 tonic seizures, 1/3 clonic seizures, and 13/17 other seizures). Three independent reviewers' majority-rule analysis of sEMG correctly classified 81 % (95 % CI [0.67, 0.91]) of events (16/18 TC seizures, 8/9 tonic seizures, 1/3 clonic seizures, and 13/17 other manifestations). CONCLUSIONS: Continuous monitoring of sEMG data provides an objective measure to evaluate motor seizure activity. Using sEMG from a wearable monitor recorded from the biceps, automated and expert review may be used to characterize the semiology of events with UE motor activity, particularly TC and tonic seizures.

Seizure control after late introduction of anakinra in a patient with adult onset Rasmussen's encephalitis.

Neuroinflammation has been considered an important pathophysiological process involved in epileptogenesis and may provide possibilities for new treatment possibilities. We present the case of a 45-year-old female with drug resistant epilepsy and progressive right-sided cerebral hemiatrophy associated with adult onset Rasmussen's encephalitis. Over a period of 26 years, she was treated with 14 different antiseizure medications, intravenous immunoglobulins, glucocorticosteroids, underwent two operations with focal resection and subpial transections, and tried out trigeminal nerve stimulation. Extensive blood tests, including antibodies relevant for autoimmune encephalitis, and brain biopsy did not show any signs of neuroinflammation. Eventually, the patient received the interleukin-1 receptor antagonist, anakinra. Within 1-2 days after injection, seizure frequency decreased significantly, and, after one week, the seizures stopped completely. Anakinra treatment was continued for 2 months. Stopping medication led to a relapse of seizures after 2 weeks, with a frequency of up to 45 seizures per day. Reintroduction of anakinra led to rapid recovery. Treatment with anakinra was continued for 7 months. The treatment was discontinued in April 2020, and the patient has been completely seizure free since then. There have been no other changes in antiseizure medication.