Systematic analysis of circadian disrupting substances with a high-throughput zebrafish circadian behavior screening approach.

Circadian rhythm aligns numerous biological functions in majority of animals. Aside from well-known external factors such as the light-dark cycle and temperature, circadian rhythm can also be regulated by rarely explored factors such as synthetic substances. Here, we established a circadian behavior screening approach utilizing zebrafish larvae model, which integrated high-throughput capabilities with automated batch processing. With this approach, we systematically analyzed the circadian disruptive effects of >60 synthetic substances commonly detected in aquatic environment by assessing both the circadian period length and amplitude of circadian behavior, with an exposure concentration set at 100 µg/L. Among tested substances, a series of circadian disrupting compounds (circadian disruptors) were identified. Several categories of the hit compounds can be recognized, such as phthalate (diisopentyl phthalate (DIPP), with 10.1 % and 49.6 % increases for circadian period length and amplitude, respectively), neuroactive substance (mirtazapine, with 10.6 % and 63.1 % increases, respectively), and biocides (thiamethoxam, with 100.3 % increase for amplitude). Among these compounds, DIPP increased circadian period length and amplitude with a high degree. Aside from DIPP, we further examined eleven other phthalates and demonstrated that benzyl butyl phthalate, diisobutyl phthalate and diisohexyl phthalate could also significantly increase the zebrafish circadian period length by 7.9 %, 3.7 % and 8.5 %, respectively. Collectively, the present findings substantiated the feasibility of this high throughput screening strategy for circadian disruptor's discovery and provided novel insights into understanding of the potential risks of synthetic substances.

Comparative developmental toxicities of zebrafish towards structurally diverse per- and polyfluoroalkyl substances.

Structurally diverse per- and polyfluoroalkyl substances (PFASs) are increasingly detected in ecosystems and humans. Therefore, the clarification of their ecological and health risks is urgently required. In the present study, the toxicity of a series of PFASs, including PFOS, PFBS, Nafion BP1, Nafion BP2, F53B, OBS, PFOA, PFUnDA, PFO5DoDA, HFPO-TA was investigated. Similarities and differences in the developmental toxicity potentials were revealed. Our results demonstrated that PFUnDA exhibited the highest toxicity with the lowest EC50 value of 4.36 mg/L (for morphological abnormality); this was followed by F53B (5.58 mg/L), PFOS (6.15 mg/L), and OBS (10.65 mg/L). Positive correlations with volatility/solubility and chemotypes related to specific biological activity, including the bioconcentration factor (LogBCF), and negative correlations with lipid solubility and carbon chain component-related chemotypes, including the number of carbon and fluorine atoms, provided a reasonable explanation in the view of molecular structures. Furthermore, comparative transcriptome analysis provided molecular evidence for the relationship between PFASs exposure and malformations. Common differentially expressed genes (DEGs) involved in spine curve development, pericardial edema, and cell/organism growth-related pathways presented common targets, leading to toxic effects. Therefore, the present results provide novel insights into the potential environmental risks of structurally diverse PFASs and contribute to the selection of safer PFAS replacements.

Postoperative Serotonin Syndrome Following Administration of Preoperative Intrapulmonary Methylene Blue and Intraoperative Granisetron: A Case Report.

BACKGROUND Methylene blue (MB), which is often used perioperatively, is a potent monoamine oxidase inhibitor that can strongly block the clearance of extracellular serotonin. Granisetron, a serotonin receptor subtype 3 (5-HT3) antagonist, is an antiemetic used to prevent or treat postoperative nausea and vomiting (PONV). Through its antagonism, granisetron can increase the extracellular serotonin concentration. Serotonin syndrome is a potentially life-threatening condition resulting from a drug reaction that affects serotonin levels. This report is of a 50-year-old woman with postoperative serotonin syndrome following co-administration of preoperative intrapulmonary methylene blue and intraoperative granisetron. CASE REPORT A 50-year-old woman with well-controlled gastroesophageal regurgitation disease presented under impression of lung cancer. She received a computed tomography (CT)-guided localization followed by video-assisted thoracic surgery under endotracheal general anesthesia. The surgery was completed uneventfully. Her postoperative course was significant for serotonin syndrome, likely triggered by co-administration of preoperative intrapulmonary MB for tumor localization and intraoperative granisetron. Other differential diagnoses were ruled out. Her management was primarily supportive, using benzodiazepine administration, and resulted in full neurologic recovery. CONCLUSIONS Intrapulmonary MB can lead to serotonin syndrome in combination with 5HT-3 antagonists when used for preoperative tumor localization. Because both MB and 5-HT3 antagonists are being widely used clinically at present, this report has highlighted that physicians, surgeons, and anesthesiologists should be aware of serotonin syndrome, its presenting features, and management, and its association with the use of methylene blue and 5-HT3 receptor antagonists, including granisetron.

Case report: The art of anesthesiology-Approaching a minor procedure in a child with MPI-CDG.

Background: Protein glycosylation plays an important role in post-translational modification, which defines a broad spectrum of protein functions. Accordingly, infants with a congenital disorder of glycosylation (CDG) can have N-glycosylation, O-glycosylation, or combined N- and O-glycosylation defects, resulting in similar but different multisystem involvement. CDGs can present notable gastrointestinal and neurologic symptoms. Both protein-losing enteropathy and hypotonia affect the decision of using anesthetics. We reported a case of MPI-CDG with protein-losing enteropathy and muscular hypotonia that underwent different anesthesia approach strategies of vascular access. Here, we highlight why intubation with sevoflurane anesthesia and sparing use of muscle relaxants is the optimal strategy for such a condition. Case presentation: A 25-month-old girl, weighing 6.6 kg and 64 cm tall, suffered chronic diarrhea, hypoalbuminemia, and hypotonia since birth. Protein-losing enteropathy due to MPI-CDG was documented by whole-exome sequencing. She underwent three sedated surgical procedures in our hospital. The sedation was administered twice by pediatricians with oral chloral hydrate, intravenous midazolam, and ketamine, to which the patient showed moderate to late recovery from sedation and irritability the following night. The most recent one was administered by an anesthesiologist, where endotracheal intubation was performed with sevoflurane as the main anesthetic. The patient regained consciousness immediately after the operation. She had no complications after all three sedation/anesthesia interventions and was discharged 7 days later, uneventful after the third general anesthesia procedure. Conclusion: We performed safe anesthetic management in a 25-month-old girl with MPI-CDG using sevoflurane under controlled ventilation. She awoke immediately after the procedure. Due to the disease entity, we suggested bypassing the intravenous route to avoid excess volume for drug administration and that muscle relaxant may not be necessary for endotracheal intubation and patient immobilization when performing procedures under general anesthesia in CDG patients.

Assisted therapeutic system based on reinforcement learning for children with autism.

Assisted therapy is increasingly used in autism spectrum disorders (ASD) for improving social interaction and communication skills in recent years. A lot of studies have proven that the form of interactive games for therapy has a good effect on children with autism. Thus, our study provided an assisted therapeutic system based on Reinforcement Learning (RL) for children with ASD, which has five interactive subgames. As is well known, it is necessary to establish and maintain compelling interactions in therapeutic process. Therefore, we aim to adjust the interactive content according to the emotions of children with autism. However, due to the atypical and unusually differences in children with autism, most systems are based on off-line training of small samples of individuals and online recognition, so the existing assisted systems are limited in their ability to automatically update system parameters of new mappings. The integration of RL and Convolutional Neural Network (CNN)-Support Vector Regression (SVR) was used to deal with the updating online of prediction model's weights. The normalized emotion labels were evaluated by the therapists. Eleven children with autism as subjects were invited in this experiment and captured facial video images. The experiment lasted for five weeks of intermittent assisted therapy, and the results were evaluated for the system and the therapy effect. Finally, we achieved a general reduction in the root mean square error of the model prediction results and labels. Although there is no significant difference in Social Responsiveness Scale (SRS) scores before and after assisted therapy (p value = 0.60), in individual subjects (Sub. 1, Sub. 2 and Sub.3), the SRS total score is significantly reduced (Average drop of 19 points). These results demonstrate the effectiveness of prediction model based on RL and show the feasibility of assisted therapeutic system in children with autism.

Reinforcement Emotion-Cognition System: A Teaching Words Task.

The goal of this paper is to suggest a system for intelligent learning environments with robots modeling of emotion regulation and cognition based on quantitative motivation. A detailed interactive situation for teaching words is proposed. In this study, we introduce one bottom-up collaboration method for emotion-cognition interplay and behaviour decision-making. Integration with gross emotion regulation theory lets the proposed system adapt to natural interactions between students and the robot in emotional interaction. Four key ideas are advocated, and they jointly set up a reinforcement emotion-cognition system (RECS). First, the quantitative motivation is grounded on external interactive sensory detection, which is affected by memory and preference. Second, the emotion generation triggered by an initial motivation such as external stimulus is also influenced by the state in the previous time. Third, the competitive and cooperative relationship between emotion and motivation intervenes to make the decision of emotional expression and teaching actions. Finally, cognitive reappraisal, the emotion regulation strategy, is introduced for the establishment of emotion transition combined with personalized cognition. We display that this RECS increases the robot emotional interactive performance and makes corresponding teaching decision through behavioural and statistical analysis.

A Transductive Model-based Stress Recognition Method Using Peripheral Physiological Signals.

Existing research on stress recognition focuses on the extraction of physiological features and uses a classifier that is based on global optimization. There are still challenges relating to the differences in individual physiological signals for stress recognition, including dispersed distribution and sample imbalance. In this work, we proposed a framework for real-time stress recognition using peripheral physiological signals, which aimed to reduce the errors caused by individual differences and to improve the regressive performance of stress recognition. The proposed framework was presented as a transductive model based on transductive learning, which considered local learning as a virtue of the neighborhood knowledge of training examples. The degree of dispersion of the continuous labels in the y space was also one of the influencing factors of the transductive model. For prediction, we selected the epsilon-support vector regression (e-SVR) to construct the transductive model. The non-linear real-time features were extracted using a combination of wavelet packet decomposition and bi-spectrum analysis. The performance of the proposed approach was evaluated using the DEAP dataset and Stroop training. The results indicated the effectiveness of the transductive model, which had a better prediction performance compared to traditional methods. Furthermore, the real-time interactive experiment was conducted in field studies to explore the usability of the proposed framework.

Perioperative transient ischemic attack caused by the cessation of warfarin.

This paper describes the circumstances of a patient who had been receiving long-term warfarin treatment, but ceased it prior to surgical operation, sustained a transient ischemic heart attack post-operatively, which eventuated in delayed extubation and locked-in syndrome. For patients at low risk of perioperative bleeding, anticoagulation with oral vitamin K antagonist can probably be able to maintain the therapeutic range (INR ≤ 2.0) extreme. For patients with a high risk of bleeding, the international normalized ratio (INR) should be kept ≤ 1.5. Within this range, patients at low risk of thrombosis can discontinue warfarin treatment for 2-5 days pre-operatively; patients at high risk for thrombosis can stop warfarin but should probably be treated with intravenous or subcutaneous heparin when the INR is subtherapeutic.