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The emerging concept of psychobiotics—live microorganisms with a potential mental health benefit—represents a novel approach for the management of stress-related conditions. The majority of studies have focused on animal models. Recent preclinical studies have identified the B. longum 1714 strain as a putative psychobiotic with an impact on stress-related behaviors, physiology and cognitive performance. Whether such preclinical effects could be translated to healthy human volunteers remains unknown. We tested whether psychobiotic consumption could affect the stress response, cognition and brain activity patterns. In a within-participants design, healthy volunteers ( N= 22) completed cognitive assessments, resting electroencephalography and were exposed to a socially evaluated cold pressor test at baseline, post-placebo and post-psychobiotic. Increases in cortisol output and subjective anxiety in response to the socially evaluated cold pressor test were attenuated. Furthermore, daily reported stress was reduced by psychobiotic consumption. We also observed subtle improvements in hippocampus-dependent visuospatial memory performance, as well as enhanced frontal midline electroencephalographic mobility following psychobiotic consumption. These subtle but clear benefits are in line with the predicted impact from preclinical screening platforms. Our results indicate that consumption of B. longum 1714 is associated with reduced stress and improved memory. Further studies are warranted to evaluate the benefits of this putative psychobiotic in relevant stress-related conditions and to unravel the mechanisms underlying such effects.

Background:Neonatal seizures are often subclinical, making accurate diagnosis difficult.Objective:To describe the clinical manifestations of electrographic seizures recorded on continuous video-EEG, and to compare this description with the recognition of clinical seizures by experienced neonatal staff.Methods:Term infants, at risk of seizures, were monitored by continuous 12-channel video-EEG from <6 hours of birth for up to 72 hours. All clinical seizures were recorded by experienced neonatal staff on individual seizure charts. Video-EEG recordings were subsequently analysed. The number, duration and clinical expression of electrographic seizures were calculated (in seconds), and compared with the seizures clinically suspected by the neonatal staff.Results:Of 51 infants enrolled, nine had electrographic seizures. A further three had clinically suspected seizures, without associated electrographic abnormality. Of the total 526 electrographic seizures, 179 (34%) had clinical manifestations evident on the simultaneous video recording. The clinical seizure activity corresponded to 18.8% of the total electrographic seizure burden. Overdiagnosis also occurred frequently. Of the 177 clinically suspected seizure episodes documented by staff, 48 (27%) had corresponding electrographic evidence of seizure activity Thus, only 9% (48/526) of electrographic seizures were accompanied by clinical manifestations, which were identified and documented by neonatal staff.Conclusion:Only one-third of neonatal EEG seizures displays clinical signs on simultaneous video recordings. Moreover, two-thirds of these clinical manifestations are unrecognised, or misinterpreted by experienced neonatal staff. In the recognition and management of neonatal seizures clinical diagnosis alone is not enough.

Background: The cerebral function monitor (CFM) is widely used to detect neonatal seizures, but there are very few studies comparing it with simultaneous electroencephalography (EEG). Objective: To determine the accuracy of non-expert use of the CFM and to assess interobserver agreement of CFM seizure detection. Patients: Babies admitted to the neonatal intensive care unit at King’s College Hospital who were at high risk of seizure and had video-EEG monitoring. Methods: Video-EEG was used to detect seizures. Each baby had CFM recordings at speeds of 6, 15, and 30 cm/h during the EEG. Four neonatologists, trained in CFM seizure recognition, independently rated one hour CFM samples at three speeds from each baby. Interobserver agreement was quantified using Cohen’s κ. Results: CFM traces from 19 babies with EEG seizures and 21 babies without EEG seizures were analysed. Overall non-expert interpretation of the CFM performed poorly as a seizure detector compared with simultaneous EEG (sensitivities 38% at 6 cm/h; 54% at 15 cm/h; 55% at 30 cm/h). Although babies with seizures were more likely to be correctly classified at higher speeds (p = 0.02), babies without seizures were also more likely to be misclassified (p < 0.001). Agreement between observers was not good at any speed (κ values from 0.01 to 0.39). The observers usually detected generalised seizures but often missed seizures that were focal, low amplitude, or lasted less than one minute. Conclusion: Approximately half of all neonatal seizures may be missed using CFM alone. Neonatal seizures need to be diagnosed, characterised, and quantified first using EEG. The CFM may then be useful for long term monitoring.

Aims: To evaluate the effectiveness of phenobarbitone as an anticonvulsant in neonates. Methods: An observational study using video-EEG telemetry. Video-EEG was obtained before treatment was started, for an hour after treatment was given, two hours after treatment was given, and again between 12 and 24 hours after treatment was given. Patients were recruited from all babies who required phenobarbitone (20–40 mg/kg intravenously over 20 minutes) for suspected clinical seizures and had EEG monitoring one hour before and up to 24 hours after the initial dose. An EEG seizure discharge was defined as a sudden repetitive stereotyped discharge lasting for at least 10 seconds. Neonatal status epilepticus was defined as continuous seizure activity for at least 30 minutes. Seizures were categorised as EEG seizure discharges only (electrographic), or as EEG seizure discharges with accompanying clinical manifestations (electroclinical). Surviving babies were assessed at one year using the Griffiths neurodevelopmental score. Results: Fourteen babies were studied. Four responded to phenobarbitone; these had normal or moderately abnormal EEG background abnormalities and outcome was good. In the other 10 babies electrographic seizures increased after treatment, whereas electroclinical seizures reduced. Three babies were treated with second line anticonvulsants, of whom two responded. One of these had a normal neurodevelopmental score at one year, but the outcome for the remainder of the whole group was poor. Conclusion: Phenobarbitone is often ineffective as a first line anticonvulsant in neonates with seizures in whom the background EEG is significantly abnormal.

Automated analysis of the neonatal EEG has the potential to assist clinical decision making for neonates with hypoxic-ischaemic encephalopathy. This paper proposes a method of automatically grading the degree of abnormality in an hour long epoch of neonatal EEG. The automated grading system (AGS) was based on a multi-class linear classifier grading of short-term epochs of EEG which were converted into a long-term grading of EEG using a majority vote operation. The features used in the AGS were summary measurements of two sub-signals extracted from a quadratic time-frequency distribution: the amplitude modulation and instantaneous frequency. These sub-signals were based on a model of EEG as a multiplication of a coloured random process with a slowly varying pseudo-periodic waveform and may be related to macroscopic neurophysiological function. The 4 grade AGS had a classification accuracy of 83% compared to human annotation of the EEG (level of agreement, κ  = 0.76). Features estimated on the developed sub-signals proved more effective at grading the EEG than measures based solely on the EEG and the incorporation of additional sub-grades based on EEG states into the AGS also improved performance.

Hypoxic-ischaemic encephalopathy (HIE) remains one of the leading causes of neurological disability worldwide. No blood biomarker capable of early detection and classification of injury severity in HIE has been identified. This study aimed to investigate the potential of miRNA-181b (miR-181b) and its downstream target, ubiquitin C-terminal hydrolase-L1 (UCH-L1), to predict the severity of HIE. Full-term infants with perinatal asphyxia were recruited at birth and observed for the development of HIE, along with healthy controls. Levels of miR-181b and messenger UCH-L1 (mUCH-L1) in umbilical cord blood were determined using qRT-PCR. In total, 131 infants; 40 control, 50 perinatal asphyxia without HIE (PA) and 41 HIE, recruited across two separate cohorts (discovery and validation) were included in this study. Significant and consistent downregulation of miR-181b was observed in infants with moderate/severe HIE compared to all other groups in both cohorts: discovery 0.25 (0.16–0.32) vs 0.61 (0.26–1.39), p  = 0.027 and validation 0.33 (0.15–1.78) vs 1.2 (0.071–2.09), p  = 0.035. mUCH-L1 showed increased expression in infants with HIE in both cohorts. The expression ratio of miR-181b to mUCH-L1 was reduced in those infants with moderate/severe HIE in both cohorts: discovery cohort 0.23 (0.06–0.44) vs 1.59 (0.46–2.54), p  = 0.01 and validation cohort 0.41 (0.10–0.81) vs 1.38 (0.59–2.56) in all other infants, p  = 0.009. We have validated consistent patterns of altered expression in miR-181b/mUCH-L1 in moderate/severe neonatal HIE which may have the potential to guide therapeutic intervention in HIE.

IntroductionCerebral oxygenation (rcSO2) monitoring in preterm infants may identify periods of cerebral hypoxia or hyperoxia. We hypothesised that there was a relationship between rcSO2 values and short term outcome in infants of GA < 32weeks.MethodsRcSO2 values were recorded for the first 48 h of life using an INVOS monitor with a neonatal sensor. The association between cranial ultrasound scan measured brain injury and rcSO2 was assessed.Results120 infants were included. Sixty-nine percent (83) of infants had a normal outcome (no IVH, no PVL, and survival at 1 month); less than one-quarter, 22% (26), had low grade IVH 1 or 2 (moderate outcome); and 9% (11) of infants had a severe outcome (IVH ≥ 3, PVL or died before 1 month age). rcSO2 values were lower for infants GA < 28weeks when compared with those GA 28–32, p < 0.001. There was no difference in absolute rcSO2 values between the three outcome groups but a greater degree of cerebral hypoxia was associated with preterm infants who had low grade 1 or 2 IVH.ConclusionInfants of GA < 28 weeks have lower cerebral oxygenation in the first 2 days of life. A greater degree of hypoxia was seen in infants with grade 1 or 2 haemorrhage. Normative ranges need to be gestation specific.

Human microRNA miR-374a is downregulated in the umbilical cord blood (UCB) of infants with hypoxic-ischaemic encephalopathy (HIE). The downstream targets of this microRNA (miRNA) are unclear, but one putative target is the activin-A receptor type IIb (ACVR2B). ACVR2B is required for activin-A function and previous reports have shown alterations of activin-A levels in neonatal HIE. Our aim was to investigate the expression of the potential downstream targets of miR-374a, activin-A and ACVR2B, at birth in a cohort of full-term infants with perinatal asphyxia (PA) only, and those with PA who developed clinical and electrographic HIE. UCB was drawn and processed immediately after delivery. Levels of serum activin-A were measured using ELISA. mRNA levels of ACVR2B in whole blood were quantified using qRT-PCR. Outcome was assessed at 3 years of age using standardised developmental assessment. In total, 171 infants were enrolled: 88 healthy controls, 56 PA and 27 HIE. A statistically significant elevation of median (IQR) ACVR2B was detected in infants with severe HIE compared to moderate/mild HIE, PA and control groups (3.3 (2.94–3.67) vs. 0.91 (0.55–1.21) vs. 0.88 (0.57–1.38) vs. 0.84 (0.74–1.24), p values = 0.04, 0.027 and 0.025, respectively). Although serum activin-A levels were elevated in infants with severe HIE, this elevation did not reach significance. ACVR2B may be a potential novel marker of HIE severity. This is the first study to examine the relationship between activin-A, its receptor AVCR2B and potentially upstream miRNA miR-374a in a cohort of carefully categorised and phenotyped infants. We have shown that miRNA analysis, combined with downstream target exploration, may yield novel biomarkers for the prediction of HIE severity.

Newborn EEG is a complex multiple channel signal that displays nonstationary and nonlinear characteristics. Recent studies have focussed on characterizing the manifestation of seizure on the EEG for the purpose of automated seizure detection. This paper describes a novel model of newborn EEG that can be used to improve seizure detection algorithms. The new model is based on a nonlinear dynamic system; the Duffing oscillator. The Duffing oscillator is driven by a nonstationary impulse train to simulate newborn EEG seizure and white Gaussian noise to simulate newborn EEG background. The use of a nonlinear dynamic system reduces the number of parameters required in the model and produces more realistic, life-like EEG compared with existing models. This model was shown to account for 54% of the linear variation in the time domain, for seizure, and 85% of the linear variation in the frequency domain, for background. This constitutes an improvement in combined performance of 6%, with a reduction from 48 to 4 model parameters, compared to an optimized implementation of the best performing existing model.

Robotic-assisted laparoscopic surgery (RALS) is making an increasingly significant contribution to the field of gynaecological surgery. RALS offers similar patient benefits to standard laparoscopic surgery (SLS) with a potentially more ergonomically friendly and less stressful environment for the surgeon. However, our understanding of how RALS may potentially reduce physiological stress on the surgeon is currently limited. To assess how performing surgical tasks using RALS in comparison to SLS impacts on hypothalamic pituitary adrenal (HPA) axis function and sympathetic nervous system (SNS) activity, two key indicators of the physiological stress response. This study is an analytical, within subjects, crossover design study. Sixteen surgically inexperienced medical students performed tasks with both SLS and RALS instrumentation. Blood pressure (BP) was taken before and after task performance. Skin conductance level (SCL), heart rate (HR) and HR variability (HRV) were measured continuously during task performance. Pre- and post-task saliva samples were collected to determine cortisol levels using ELISA. SCL was significantly lower during RALS in comparison to SLS task performance ( p  < 0.05). HR was significantly lower during RALS vs. SLS tasks ( p  < 0.01). Both HRV measures were significantly higher during RALS vs. SLS tasks ( p  < 0.01). Cortisol levels and BP were lower during RALS vs. SLS but did not reach statistical significance ( p  = 0.73 and p  = 0.22, respectively). Stress can impair surgeon’s technical and nontechnical skills. These results indicate that the improved ergonomic setup of RALS has a beneficial impact on physiological indicators of stress. This also demonstrates the potential of RALS to reduce the negative effects of long-term stress exposure on the surgeon.