A predictive model combining connectomics and entropy biomarkers to discriminate long-term vagus nerve stimulation efficacy for pediatric patients with drug-resistant epilepsy.

AIMS: To predict the vagus nerve stimulation (VNS) efficacy for pediatric drug-resistant epilepsy (DRE) patients, we aim to identify preimplantation biomarkers through clinical features and electroencephalogram (EEG) signals and thus establish a predictive model from a multi-modal feature set with high prediction accuracy. METHODS: Sixty-five pediatric DRE patients implanted with VNS were included and followed up. We explored the topological network and entropy features of preimplantation EEG signals to identify the biomarkers for VNS efficacy. A Support Vector Machine (SVM) integrated these biomarkers to distinguish the efficacy groups. RESULTS: The proportion of VNS responders was 58.5% (38/65) at the last follow-up. In the analysis of parieto-occipital α band activity, higher synchronization level and nodal efficiency were found in responders. The central-frontal θ band activity showed significantly lower entropy in responders. The prediction model reached an accuracy of 81.5%, a precision of 80.1%, and an AUC (area under the receiver operating characteristic curve) of 0.838. CONCLUSION: Our results revealed that, compared to nonresponders, VNS responders had a more efficient α band brain network, especially in the parieto-occipital region, and less spectral complexity of θ brain activities in the central-frontal region. We established a predictive model integrating both preimplantation clinical and EEG features and exhibited great potential for discriminating the VNS responders. This study contributed to the understanding of the VNS mechanism and improved the performance of the current predictive model.

Neurophysiological features of STN LFP underlying sleep fragmentation in Parkinson's disease.

BACKGROUND: Sleep fragmentation is a persistent problem throughout the course of Parkinson's disease (PD). However, the related neurophysiological patterns and the underlying mechanisms remained unclear. METHOD: We recorded subthalamic nucleus (STN) local field potentials (LFPs) using deep brain stimulation (DBS) with real-time wireless recording capacity from 13 patients with PD undergoing a one-night polysomnography recording, 1 month after DBS surgery before initial programming and when the patients were off-medication. The STN LFP features that characterised different sleep stages, correlated with arousal and sleep fragmentation index, and preceded stage transitions during N2 and REM sleep were analysed. RESULTS: Both beta and low gamma oscillations in non-rapid eye movement (NREM) sleep increased with the severity of sleep disturbance (arousal index (ArI)-betaNREM: r=0.9, p=0.0001, sleep fragmentation index (SFI)-betaNREM: r=0.6, p=0.0301; SFI-gammaNREM: r=0.6, p=0.0324). We next examined the low-to-high power ratio (LHPR), which was the power ratio of theta oscillations to beta and low gamma oscillations, and found it to be an indicator of sleep fragmentation (ArI-LHPRNREM: r=-0.8, p=0.0053; ArI-LHPRREM: r=-0.6, p=0.0373; SFI-LHPRNREM: r=-0.7, p=0.0204; SFI-LHPRREM: r=-0.6, p=0.0428). In addition, long beta bursts (>0.25 s) during NREM stage 2 were found preceding the completion of transition to stages with more cortical activities (towards Wake/N1/REM compared with towards N3 (p<0.01)) and negatively correlated with STN spindles, which were detected in STN LFPs with peak frequency distinguishable from long beta bursts (STN spindle: 11.5 Hz, STN long beta bursts: 23.8 Hz), in occupation during NREM sleep (ß=-0.24, p<0.001). CONCLUSION: Features of STN LFPs help explain neurophysiological mechanisms underlying sleep fragmentations in PD, which can inform new intervention for sleep dysfunction. TRIAL REGISTRATION NUMBER: NCT02937727.

Alteration of Excitation/Inhibition Imbalance in the Hippocampus and Amygdala of Drug-Resistant Epilepsy Patients Treated with Acute Vagus Nerve Stimulation.

An imbalance between excitation (E) and inhibition (I) in the brain has been identified as a key pathophysiology of epilepsy over the years. The hippocampus and amygdala in the limbic system play a crucial role in the initiation and conduction of epileptic seizures and are often referred to as the transfer station and amplifier of seizure activities. Existing animal and imaging studies reveal that the hippocampus and amygdala, which are significant parts of the vagal afferent network, can be modulated in order to generate an antiepileptic effect. Using stereo-electroencephalography (SEEG) data, we examined the E/I imbalance in the hippocampus and amygdala of ten drug-resistant epilepsy children treated with acute vagus nerve stimulation (VNS) by estimating the 1/f power slope of hippocampal and amygdala signals in the range of 1-80 Hz. While the change in the 1/f power slope from VNS-BASE varied between different stimulation amplitudes and brain regions, it was more prominent in the hippocampal region. In the hippocampal region, we found a flatter 1/f power slope during VNS-ON in patients with good responsiveness to VNS under the optimal stimulation amplitude, indicating that the E/I imbalance in the region was improved. There was no obvious change in 1/f power slope for VNS poor responders. For VNS non-responders, the 1/f power slope slightly increased when the stimulation was applied. Overall, this study implies that the regulation of E/I imbalance in the epileptic brain, especially in the hippocampal region, may be an acute intracranial effect of VNS.

Safety and precision of frontal trajectory of lateral habenula deep brain stimulation surgery in treatment-resistant depression.

Introduction: The lateral habenula (LHb) is a promising deep brain stimulation (DBS) target for treatment-resistant depression (TRD). However, the optimal surgical trajectory and its safety of LHb DBS are lacking. Methods: We reported surgical trajectories for the LHb in six TRD patients treated with DBS at the General Hospital of the Chinese People's Liberation Army between April 2021 and May 2022. Pre-operative fusions of magnetic resonance imaging (MRI) and computed tomography (CT) were conducted to design the implantation trajectory of DBS electrodes. Fusions of MRI and CT were conducted to assess the safety or precision of LHb DBS surgery or implantable electrodes locations. Results: Results showed that the optimal entry point was the posterior middle frontal gyrus. The target coordinates (electrode tips) were 3.25 ± 0.82 mm and 3.25 ± 0.82 mm laterally, 12.75 ± 0.42 mm and 13.00 ± 0.71 mm posterior to the midpoint of the anterior commissure-posterior commissure (AC-PC) line, and 1.83 ± 0.68 mm and 1.17 ± 0.75 mm inferior to the AC-PC line in the left and right LHb, respectively. The "Ring" angles (relative to the AC-PC level on the sagittal section plane) of the trajectories to the left and right LHb were 51.87° ± 6.67° and 52.00° ± 7.18°, respectively. The "Arc" angles (relative to the midline of the sagittal plane) were 33.82° ± 3.39° and 33.55° ± 3.72°, respectively. Moreover, there was small deviation of actual from planned target coordinates. No patient had surgery-, disease- or device-related adverse events during the perioperative period. Conclusion: Our results suggested that LHb-DBS surgery via frontal trajectory is safe, accurate, and feasible. This is an applicable work to report in detail the target coordinates and surgical path of human LHb-DBS. It has of great clinical reference value to treat more cases of LHb-DBS for TRD.

Progress in the development of a fully implantable brain-computer interface: the potential of sensing-enabled neurostimulators.

This perspective article investigates the performance of using a sensing-enabled neurostimulator as a motor brain-computer interface.

A prediction model integrating synchronization biomarkers and clinical features to identify responders to vagus nerve stimulation among pediatric patients with drug-resistant epilepsy.

AIMS: Vagus nerve stimulation (VNS) is a neuromodulation therapy for children with drug-resistant epilepsy (DRE). The efficacy of VNS is heterogeneous. A prediction model is needed to predict the efficacy before implantation. METHODS: We collected data from children with DRE who underwent VNS implantation and received regular programming for at least 1 year. Preoperative clinical information and scalp video electroencephalography (EEG) were available in 88 children. Synchronization features, including phase lag index (PLI), weighted phase lag index (wPLI), and phase-locking value (PLV), were compared between responders and non-responders. We further adapted a support vector machine (SVM) classifier selected from 25 clinical and 18 synchronization features to build a prediction model for efficacy in a discovery cohort (n = 70) and was tested in an independent validation cohort (n = 18). RESULTS: In the discovery cohort, the average interictal awake PLI in the high beta band was significantly higher in responders than non-responders (p < 0.05). The SVM classifier generated from integrating both clinical and synchronization features had the best prediction efficacy, demonstrating an accuracy of 75.7%, precision of 80.8% and area under the receiver operating characteristic (AUC) of 0.766 on 10-fold cross-validation. In the validation cohort, the prediction model demonstrated an accuracy of 61.1%. CONCLUSION: This study established the first prediction model integrating clinical and baseline synchronization features for preoperative VNS responder screening among children with DRE. With further optimization of the model, we hope to provide an effective and convenient method for identifying responders before VNS implantation.

Effects of Stable Vagus Nerve Stimulation Efficacy on Autistic Behaviors in Ten Pediatric Patients With Drug Resistant Epilepsy: An Observational Study.

Vagus nerve stimulation (VNS) is a safe and effective therapy for pediatric patients with drug-resistant epilepsy (DRE). However, in children with DRE, the effects of VNS on autistic behaviors remain controversial. We retrospectively collected data from 10 children with DRE who underwent VNS implantation and regular parameter regulation in three pediatric epilepsy centers, and completed the behavioral assessments, including the autistic behavior checklist and the child behavior checklist, at follow-ups 1 (mean 2.16 years) and 2 (mean 2.98 years). The 10 children maintained stable seizure control between the two follow-ups. Their autistic behaviors, especially in language, social and self-help, were reduced at follow-up 2 compared to follow-up 1 (p = 0.01, p = 0.01, respectively). Moreover, these improvements were not associated with their seizure control, whether it was positive or negative. These results suggested that the VNS had a positive effect on autistic behaviors, which provided a preliminary clinical basis that VNS may benefit to younger children with DRE comorbidity autism spectrum disorder (ASD).

Probiotic Properties of a Spaceflight-induced Mutant Lactobacillus Plant- arum SS18-50 in Mice.

BACKGROUND: Probiotics are a group of bacteria that play a critical role in intestinal microbiota homeostasis and may help adjunctively treat certain diseases like metabolic and immune disorders. OBJECTIVE: We recently generated a space-flight mutated Lactobacillus plantarum SS18-50 with good in vitro probiotic characteristics. In the current research, we designed two in vivo experiments to evaluate whether L. plantarum SS18-50 had the ability to increase beneficial gut bacteria, regulate oxidative status and ameliorate inflammation in mice. METHODS: Experiments I: the ICR mice were gavaged with L. plantarum SS18-50 or its wild type L. plantarum GS18 at 107 or 109 CFU/kg BW daily for one month, during which the body weight was recorded weekly. The feces were collected to determine the abundance of two main beneficial bacterial groups including Lactobacillus and Bifidobacterium by selective culturing, while the total triglycerides and cholesterols in sera were determined using commercial kits. Experiment II: the mice were gavaged with loperamide hydrochloride (Lop) to develop oxidative stress and inflammation phenotypes. At the same time, the experimental mice were gavaged with L. plantarum SS18-50 or wild type L. plantarum GS18 at 107 or 109 CFU/kg BW daily for one month. At the end of the experiment, oxidative indicators (SOD and MDA) and inflammatory cytokines (IL-17A and IL-10) were measured by commercial kits. RESULTS: Results showed that L. plantarum SS18-50 increased the abundance of Lactobacillus and Bifidobacterium in mice after one month's administration. L. plantarum SS18-50 also showed the anti-oxidant activity by increasing SOD and decreasing MDA and exerted the anti-inflammatory effect by increasing IL-10 and decreasing IL-17A in Lop treated mice. Both the wild type stain and the space mutant had such biomedical effects, but L. plantarum SS18-50 was better in increasing gut beneficial bacteria and oxidative regulation than the wild type (P<0.05). CONCLUSION: We conclude that L. plantarum SS18-50 has a great potential to serve as a dietary functional probiotic supplement and/or adjunctive treatment strategy.

Cause of Subharmonics in Local Field Potentials Recorded by Sensing-Enabled Neurostimulator.

Sensing-enabled neurostimulators have become an essential technology for recording local field potentials (LFPs) during neurostimulation. However, subharmonics from indeterminate sources make interpreting LFP recordings a challenge. In this study, we investigated the characteristics and the cause of the subharmonics recorded by sensing-enabled neurostimulators. We found that the amplitudes and frequencies of the subharmonics in clinical LFPs varied with stimulation parameters. Using simulated solutions, we demonstrated that these subharmonics were device-generated noise. The cause of the subharmonics was the ripples in the stimulation pulses residual in the final LFP recordings. Our results provided a method to discriminate the subharmonic artifacts and suggested that interpretation of the subharmonics at a fractional frequency of stimulations in LFP recordings should be performed carefully.Clinical Relevance- This study reveals the cause of subharmonics in LFP recordings for clinical neuroscience research.

[Identification of phosphatidic acid interacting proteins in Ganoderma lingzhi].

Ganoderma lingzhi is widely recognized as a medicinal basidiomycetes. Triterpene acids (TAs) are the key bioactive medicinal components of G. lingzhi. Our previous studies have shown that phospholipid acid (PA) produced by phospholipase D (PLD) plays a regulatory role in TA synthesis. In order to further elucidate the molecular mechanism how PA regulates TA synthesis in G. lingzhi, PA beads enrichment combined with LC-MS/MS technology was used to identify PA interacting proteins in G. lingzhi. A total of 19 PA interacting proteins were identified, including cytochrome P450 monooxygenase (GL22084), specific protein kinase MAPK (GL23765), catalase and cell surface hydrophobicity-associated protein. GST tagged GL22084 and GL23765 proteins were obtained through gene cloning, heterologous expression, and purification. The interactions between GL22084/GL23765 and PA were verified by GST pull down assay. The identification of PA interacting proteins provides a basis for further understanding the molecular mechanism how PLD-mediated PA signaling molecules regulates the TA synthesis in G. lingzhi. Moreover, the PA interacting proteins identified in this study can also provide clues for the research of PLD/PA signaling pathway in other species.

Hypoglycemic effects of space-induced Lactobacillus plantarum SS18-5 on type 2 diabetes in a rat model.

Probiotics can improve dyslipidemia and promote metabolic control as a therapeutic approach for type 2 diabetes mellitus (T2DM). The hypoglycemic effects of space-induced Lactobacillus plantarum SS18-5 on T2DM were explored in 4-week-old male Sprague Dawley rats. The normal (N) group was fed a basal diet, while the other groups received a high glucose fat diet. T2DM was established by streptozotocin injection and the T2DM rats were randomly divided into three groups, a diabetic (D) group (T2DM rats treated with saline only), GS18 group (T2DM rats treated with 109  CFU/ml of L. plantarum GS18), and SS18-5 group (T2DM rats treated with 109  CFU/ml of L. plantarum SS18-5). After continuous gavage for 6 weeks, blood biochemical indices were measured and livers were collected for histopathological examination. The colon contents were collected for counting of Escherichia coli, Clostridium perfringens, and Lactobacillus sp. The results showed that L. plantarum SS18-5 effectively controlled the weight of rats, reduced levels of fasting blood glucose, glycosylated hemoglobin, and insulin, increased liver glycogen levels, improved abnormal metabolism of blood lipids, enhanced the effect of anti-lipid peroxidation, alleviated chronic inflammation and fatty liver disease, and regulated the intestinal microbiota by reducing the numbers of E. coli and C. perfringens, and increasing the numbers of Lactobacillus sp. From these results, we conclude that space-induced L. plantarum SS18-5 has the potential to improve T2DM by alleviating hypoglycemia and regulating the intestinal microbiota. PRACTICAL APPLICATIONS: With the exploration of the universe, a large number of studies have observed the changes of microorganisms in space flight, which provided a new method for high-quality microbial pharmaceuticals in the space environment. In this study, the space environment mutated. Lactobacillus plantarum SS18-5 can effectively improve the blood glucose of rats with type 2 diabetes, relieve oxidative stress, reduce blood lipid content, enhance immune capacity, and regulate intestinal microflora, which has potential use in the treatment of type 2 diabetes.

Preoperative Heart Rate Variability During Sleep Predicts Vagus Nerve Stimulation Outcome Better in Patients With Drug-Resistant Epilepsy.

Objective: Vagus nerve stimulation (VNS) is an adjunctive and well-established treatment for patients with drug-resistant epilepsy (DRE). However, it is still difficult to identify patients who may benefit from VNS surgery. Our study aims to propose a VNS outcome prediction model based on machine learning with multidimensional preoperative heart rate variability (HRV) indices. Methods: The preoperative electrocardiography (ECG) of 59 patients with DRE and of 50 healthy controls were analyzed. Responders were defined as having at least 50% average monthly seizure frequency reduction at 1-year follow-up. Time domain, frequency domain, and non-linear indices of HRV were compared between 30 responders and 29 non-responders in awake and sleep states, respectively. For feature selection, univariate filter and recursive feature elimination (RFE) algorithms were performed to assess the importance of different HRV indices to VNS outcome prediction and improve the classification performance. Random forest (RF) was used to train the classifier, and leave-one-out (LOO) cross-validation was performed to evaluate the prediction model. Results: Among 52 HRV indices, 49 showed significant differences between DRE patients and healthy controls. In sleep state, 35 HRV indices of responders were significantly higher than those of non-responders, while 16 of them showed the same differences in awake state. Low-frequency power (LF) ranked first in the importance ranking results by univariate filter and RFE methods, respectively. With HRV indices in sleep state, our model achieved 74.6% accuracy, 80% precision, 70.6% recall, and 75% F1 for VNS outcome prediction, which was better than the optimal performance in awake state (65.3% accuracy, 66.4% precision, 70.5% recall, and 68.4% F1). Significance: With the ECG during sleep state and machine learning techniques, the statistical model based on preoperative HRV could achieve a better performance of VNS outcome prediction and, therefore, help patients who are not suitable for VNS to avoid the high cost of surgery and possible risks of long-term stimulation.

Impairment of Cardiac Autonomic Nerve Function in Pre-school Children With Intractable Epilepsy.

Objective: Intractable epilepsy and uncontrolled seizures could affect cardiac function and the autonomic nerve system with a negative impact on children's growth. The aim of this study was to investigate the variability and complexity of cardiac autonomic function in pre-school children with pediatric intractable epilepsy (PIE). Methods: Twenty four-hour Holter electrocardiograms (ECGs) from 93 patients and 46 healthy control subjects aged 3-6 years were analyzed by the methods of traditional heart rate variability (HRV), multiscale entropy (MSE), and Kurths-Wessel symbolization entropy (KWSE). Receiver operating characteristic (ROC) curve analysis was used to estimate the overall discrimination ability. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) models were also analyzed. Results: Pre-school children with PIE had significantly lower HRV measurements than healthy controls in time (Mean_RR, SDRR, RMSSD, pNN50) and frequency (VLF, LF, HF, LF/HF, TP) domains. For the MSE analysis, area 1_5 in awake state was lower, and areas 6_15 and 6_20 in sleep state were higher in PIE with a significant statistical difference. KWSE in the PIE group was also inferior to that in healthy controls. In ROC curve analysis, pNN50 had the greatest discriminatory power for PIE. Based on both NRI and IDI models, the combination of MSE indices (wake: area1_5 and sleep: area6_20) and KWSE (m = 2, τ = 1, α = 0.16) with traditional HRV measures had greater discriminatory power than any of the single HRV measures. Significance: Impaired HRV and complexity were found in pre-school children with PIE. HRV, MSE, and KWSE could discriminate patients with PIE from subjects with normal cardiac complexity. These findings suggested that the MSE and KWSE methods may be helpful for assessing and understanding heart rate dynamics in younger children with epilepsy.

Removal of Electrocardiogram Artifacts From Local Field Potentials Recorded by Sensing-Enabled Neurostimulator.

Sensing-enabled neurostimulators are an advanced technology for chronic observation of brain activities, and show great potential for closed-loop neuromodulation and as implantable brain-computer interfaces. However, local field potentials (LFPs) recorded by sensing-enabled neurostimulators can be contaminated by electrocardiogram (ECG) signals due to complex recording conditions and limited common-mode-rejection-ratio (CMRR). In this study, we propose a solution for removing such ECG artifacts from local field potentials (LFPs) recorded by a sensing-enabled neurostimulator. A synchronized monopolar channel was added as an ECG reference, and two pre-existing methods, i.e., template subtraction and adaptive filtering, were then applied. ECG artifacts were successfully removed and the performance of the method was insensitive to residual stimulation artifacts. This approach to removal of ECG artifacts broadens the range of applications of sensing-enabled neurostimulators.

In vitro probiotic screening and evaluation of space-induced mutant Lactobacillus plantarum.

Space mutation is an efficient tool in microbial breeding. The aim of the present study was to screen out space-induced mutants of Lactobacillus plantarum with potent probiotic properties. The wild-type Lactobacillus plantarum GS18 was subjected to 31 days and 18.5 hr of space flight, in which 13 isolates were selected for analysis. These mutants were assayed for milk fermentation performance, low pH resistance, bile salt tolerance, hydrophobicity, and antimicrobial activity. The 16S rDNA sequencing was applied to identify the stain and compare it with the wild type. Results showed that the isolate L. plantarum SS18-50 had the strongest probiotic properties with no mutation in 16S rRNA sequence compared to the wild type. Specifically, L. plantarum SS18-50 had good milk fermentation performance. The viscosity of fermented milk, acid tolerance, and bile salt tolerance were increased by approximately 10%, 8%, and 9%, respectively (p < .05). The antibacterial activity (Escherichia Coli, Salmonella Typhimurium, and Listeria Monocytogenes) was also increased significantly compared to the wild type (p < .05). This study indicates that L. plantarum SS18-50 has the great potential to serve as a probiotic for dairy products.

Neuromodulation effects of deep brain stimulation on beta rhythm: A longitudinal local field potential study.

BACKGROUND: Deep brain stimulation (DBS) holds great promise in treating various brain diseases but its chronic therapeutic mechanisms are unclear. OBJECTIVE: To explore the immediate and chronic effects of DBS on brain oscillations, and understand how different sub-bands of oscillations may be related to symptom improvement in Parkinson's patients. METHODS: We carried out a longitudinal study to examine the effects of DBS on local field potentials recorded by sensing-enabled neurostimulators in the subthalamic nuclei of Parkinson's patients, using a novel block-design stimulation paradigm. RESULTS: DBS significantly suppressed beta activity (13-35Hz) but the suppression effect appeared to gradually attenuate during a 6-month follow-up period after surgery (p = 0.002). However, beta suppression did not attenuate after repeated stimulation over several minutes (p > 0.110), suggesting that the changes in beta suppression may reflect a slow reconfiguration of neural pathways instead of habituation. Suppression of beta was also associated with clinical symptom improvement across subjects. Importantly, symptom-relevant features fell within the high beta band at month 1 but shifted to the low beta band at month 6, indicating that the high beta and the low beta oscillations may play different functional roles and respond differently to stimulation over the long-term treatment. CONCLUSION: These data may advance understanding of chronic DBS effects on beta oscillations and their association with clinical improvement, offering novel insights to the therapeutic mechanisms of DBS.

Automatic Sleep Stage Classification Based on Subthalamic Local Field Potentials.

Deep brain stimulation (DBS) is an established treatment for patients with Parkinson's disease (PD). Sleep disorders are common complications of PD and affected by subthalamic DBS treatment. To achieve more precise neuromodulation, chronicsleepmonitoringand closed-loop DBS toward sleep-wake cycles could potentially be utilized. Local field potential (LFP) signals that are sensed by the DBS electrode could be processed as primary feedback signals. This is the first study to systematically investigate the sleep-stage classification based on LFPs in subthalamic nucleus (STN). With our newly developed recording and transmission system, STN-LFPs were collected from 12 PD patients during wakefulness and nocturnal polysomnography sleep monitoring at one month after DBS implantation. Automatic sleep-stage classificationmodels were built with robust and interpretable machine learning methods (support vector machine and decision tree). The accuracy, sensitivity, selectivity, and specificity of the classification reached high values (above90% at most measures) at group and individual levels. Features extracted in alpha (8-13 Hz), beta (13-35 Hz), and gamma (35-50 Hz) bandswere found to contribute the most to the classification. These results will directly guide the engineering development of implantable sleepmonitoring and closed-loopDBS and pave the way for a better understanding of the STN-LFP sleep patterns.

Deceleration and acceleration capacities of heart rate in patients with drug-resistant epilepsy.

OBJECTIVE: Epilepsy and seizures can have dramatic effects on cardiac function. The aim of the present study was to investigate deceleration capacity, acceleration capacity and their 24-h fluctuations of heart rate variability in patients with drug-resistant epilepsy. METHODS: Deceleration capacity, acceleration capacity of heart rate and their 24-h dynamics derived from the phase rectified signal averaging method as well as traditional measures were analyzed in 39 patients with drug-resistant epilepsy and 33 healthy control subjects using 24-h electrocardiogram recordings. The discriminatory power of heart rate variability measures were validated by assessment of the area under the receiver operating characteristic curve. Net reclassification improvement and integrated discrimination improvement models were also estimated. RESULTS: Both deceleration capacity and absolute values of acceleration capacity were significantly lower in patients with drug-resistant epilepsy. The abnormal suppression of absolute deceleration capacity and acceleration capacity values were observed throughout the 24-h recording time (peaked at about 3 to 5 A.M.). Deceleration capacity had the greatest discriminatory power to differentiate the patients from the healthy controls. Moreover, in both net reclassification improvement and integrated discrimination improvement models, the combination of acceleration capacity or deceleration capacity with traditional heart rate variability measures has greater discriminatory power than any of the single heart rate variability features. INTERPRETATION: Drug-resistant epilepsy was associated with a significant inhibition of vagal modulation of heart rate, which was more pronounced during the night than during the day. These findings indicate that phase rectified signal averaging method may serve as a complementary approach for characterizing and understanding the neuro-pathophysiology in epilepsy, and may provide a new clue to sudden unexpected death in epilepsy.

Pretreatment with Lactobacillus reuteri F-9-35 attenuates ethanol-induced gastric injury in rats.

BACKGROUND: Previous studies suggested that probiotics intervention may be one of the methods for preventing and/or treating gastric ulcer. OBJECTIVE: The aim of the study was to compare the preventive effects of a spaceflight mutant Lactobacillus reuteri F-9-35 and its wild type on ethanol-induced gastric injury in rats. DESIGN: Forty rats were randomly allocated into five groups: a normal group (NOR), ethanol group (EtOH), skim milk group (MILK), L. reuteri F-9-35 group (F935) and wild-type group (WT). The NOR and EtOH groups received 1 ml of distilled water by daily gavage for 14 days. The MILK group received 1 ml of skim milk alone, while the F935 and WT groups were administered 1 ml of skim milk containing the mutant and wild type (1 × 1010 colony-forming unit/ml) by daily gavage for 14 days, respectively. Acute gastric injury was induced by absolute alcohol 1 h after the final administration of different treatments, except for the NOR group. RESULTS: Pretreatment with L. reuteri F-9-35, but not milk alone or milk with the L. reuteri wild type, showed significant reduction of ethanol-induced gastric injury, as evidenced by lowering of ulcer index, ulcer area (%), and histological lesion. F-9-35 decreased the levels of lipid peroxidation and myeloperoxidase and increased mucus, glutathione, and nitric oxide levels in gastric tissue. Moreover, F-9-35 inhibited the expression of proinflammatory genes including gastric tumor necrosis factor-α, interleukin-1ß, and cyclooxygenase-2 and decreased the activity of nuclear factor kappa B (NF-κB). CONCLUSION: These findings indicated that L. reuteri F-9-35 pretreatment can attenuate ethanol-induced gastric injury in rats by inhibiting oxidative stress and inflammatory response. Together, L. reuteri F-9-35 has potential preventive efficacy on gastric ulcer.