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Purpose: Vagus nerve stimulators (VNS) have emerged as an effective treatment modality for pediatric patients suffering from intractable, drug-resistant epilepsy. Newer devices, AspireSR™ Model 106 and the SenTiva™ Model 1000 (VNS TherapyⓇ, LivaNova™), contain an "auto-stimulation" feature that detects ictal tachycardia and transmits pulsations to attenuate seizures. However, the exact benefits of auto-stimulation compared to its risks still merit further exploration. This study evaluates the utility of these specific devices in a heterogeneous population of pediatric and young adult patients with intractable epilepsy., Methods: This is a retrospective chart review of 55 patients who underwent either VNS insertion with or without an auto-stimulation-enabled VNS device at a single level four epilepsy center. Seizure frequency, seizure subtype, side effects, and change in anti-seizure medication load both before and after VNS implantations were collected from patient self-reporting at the time of VNS insertion and 12 months following implantation. Information regarding output current, auto-stimulation current, duty cycling, and auto-stimulation threshold of the device was obtained from documented VNS interrogation for patients with auto-stimulation-enabled VNS devices., Results: Patients with auto-stimulation-enabled VNS devices had a mean 56.0% (SD = 0.414) seizure frequency reduction 12 months post-VNS insertion, while patients without auto-stimulation-enabled VNS devices had a mean 41.6% (SD = 0.456) seizure frequency reduction during the same interval. The mean seizure frequency reduction 12 months post-VNS insertion for patients with a SenTiva™ 1000 model was 66.0% (SD = 0.426). For patients with auto-stimulation-enabled VNS devices, post-treatment seizure reduction was significantly correlated with daily auto-stimulation activation (R = 0.432, p = 0.025)., Conclusion: This study supports the clinical safety and utility of auto-stimulation-enabled VNS models, specifically the SenTiva™ 1000, in treating pediatric patients with intractable epilepsy of various subtypes and etiologies. Further research is needed to evaluate the sustained impact of auto-stimulation on long-term outcomes (≥ 2 years follow-up post-VNS)., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: We describe a detailed evaluation of predictors associated with individual lead placement efficiency and accuracy for 261 stereoelectroencephalography (sEEG) electrodes placed for epilepsy monitoring in twenty-three children at our institution., Methods: Intra- and post-operative data was used to generate a linear mixed model to investigate predictors associated with three outcomes (lead placement time, lead entry error, lead target error) while accounting for correlated observations from the same patients. Lead placement time was measured using electronic time-stamp records stored by the ROSA software for each individual electrode; entry and target site accuracy was measured using postoperative stereotactic CT images fused with preoperative electrode trajectory planning images on the ROSA computer software. Predictors were selected from a list of variables that included patient demographics, laterality of leads, anatomic location of lead, skull thickness, bolt cap device used, and lead sequence number., Results: Twenty-three patients (11 female, 48%) of mean age 11.7 (± 6.1) years underwent placement of intracranial sEEG electrodes (median 11 electrodes) at our institution over a period of 1 year. There were no associated infections, hemorrhages, or other adverse events, and successful seizure capture was obtained in all monitored patients. The mean placement time for individual electrodes across all patients was 6.56 (± 3.5) min; mean target accuracy was 4.5 (± 3.5) mm. Lesional electrodes were associated with 25.7% (95% CI: 6.7-40.9%, p = 0.02) smaller target point errors. Larger skull thickness was associated with larger error: for every 1-mm increase in skull thickness, there was a 4.3% (95% CI: 1.2-7.5%, p = 0.007) increase in target error. Bilateral lead placement was associated with 26.0% (95% CI: 9.9-44.5%, p = 0.002) longer lead placement time. The relationship between placement time and lead sequence number was nonlinear: it decreased consistently for the first 4 electrodes, and became less pronounced thereafter., Conclusions: Variation in sEEG electrode placement efficiency and accuracy can be explained by phenomena both within and outside of operator control. It is important to keep in mind the factors that can lead to better or worse lead placement efficiency and/or accuracy in order to maximize patient safety while maintaining the standard of care.

DNA gyrase is a type II topoisomerase that can introduce negative supercoils into DNA at the expense of ATP hydrolysis. It is essential in all bacteria but absent from higher eukaryotes, making it an attractive target for antibacterials. The fluoroquinolones are examples of very successful gyrase-targeted drugs, but the rise in bacterial resistance to these agents means that we not only need to seek new compounds, but also new modes of inhibition of this enzyme. We review known gyrase-specific drugs and toxins and assess the prospects for developing new antibacterials targeted to this enzyme.

Nucleic acid analogs and mimics are commonly the modifications of native nucleic acids at the nucleobase, the sugar ring, or the phosphodiester backbone. Many forms of promising nucleic acid analogs and mimics are available, such as locked nucleic acids (LNAs), peptide nucleic acids (PNAs), and morpholinos. LNAs, PNAs, and morpholinos can form both duplexes and triplexes and have improved biostability. They have become a general and versatile tool for DNA and RNA recognition. LNA is a general and versatile tool for specific, high-affinity recognition of single-stranded DNA (ssDNA) and single-stranded RNA (ssRNA). LNA can be used for designing LNA oligoes for hybridization studies or as real time polymerase chain reaction probes in the form of Taqman probes. LNA also has therapeutic and diagnostic applications. PNA is another type of DNA analog with neutral charge. The extreme stability of PNA makes it an ideal candidate for the antisense and antigene application. PNA is used as probe for gene cloning, mutation detection, and in homologous recombination studies. It was also used to design transcription factor decoy molecules for target gene induction. Morpholino, another structural type, was devised to circumvent cost problems associated with DNA analogs. It has become the premier knockdown tool in developmental biology due to its cytosolic delivery in the embryos by microinjection. Thus, the nucleic acid analogs provide an advantage to design and implementation, therapies, and research assays, which were not implemented due to limitations associated with standard nucleic acids chemistry.