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BACKGROUND: Despite medical advancements in neonatal survival rates, many children have poor neurological outcomes. Because the law in Korea restricts the withdrawal of life-sustaining treatment to only cases of imminent death, treatment discontinuation may not be an option, even in patients with poor neurological prognosis. This study investigated the opinions of the general population and clinicians regarding life-sustaining treatment withdrawal in such cases using hypothetical scenarios. METHODS: We conducted a cross-sectional study on the general population and clinicians using a web-based questionnaire. The sample of the general population from an online panel comprised 500 individuals aged 20-69 years selected by quota sampling. The clinician sample comprised 200 clinicians from a tertiary university hospital. We created hypothetical vignettes and questionnaire items to assess attitudes regarding mechanical ventilation withdrawal for an infant at risk of poor neurological prognosis due to birth asphyxia at 2 months and 3 years after the incidence. RESULTS: Overall, 73% of the general population and 74% of clinicians had positive attitudes toward mechanical ventilator withdrawal at 2 months after birth asphyxia. The proportion of positive attitudes toward mechanical ventilator withdrawal was increased in the general population (84%, P < 0.001) and clinicians (80.5%, P = 0.02) at 3 years after birth asphyxia. Religion, spirituality, the presence of a person with a disability in the household, and household income were associated with the attitudes of the general population. In the multivariable logistic regression analysis of the general population, respondents living with a person with a disability or having a disability were more likely to find the withdrawal of the ventilator at 2 months and 3 years after birth asphyxia not permissible. Regarding religion, respondents who identified as Christians were more likely to find the ventilator withdrawal at 2 months after birth asphyxia unacceptable. CONCLUSION: The general population and clinicians shared the perspective that the decision to withdraw life-sustaining treatment in infants with a poor neurological prognosis should be considered before the end of life. A societal discussion about making decisions centered around the best interest of pediatric patients is warranted.

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OBJECTIVE: We investigated how electroencephalography (EEG) quantitative measures and dysglycemia relate to neurodevelopmental outcomes following neonatal encephalopathy (NE). METHODS: This retrospective study included 90 neonates with encephalopathy who received therapeutic hypothermia. EEG absolute spectral power was calculated during post-rewarming and 2-month follow-up. Measures of dysglycemia (hypoglycemia, hyperglycemia, and glycemic lability) and glucose variability were computed for the first 48 h of life. We evaluated the ability of EEG and glucose measures to predict neurodevelopmental outcomes at ≥ 18 months, using logistic regressions (with area under the receiver operating characteristic [AUROC] curves). RESULTS: The post-rewarming global delta power (average all electrodes), hyperglycemia and glycemic lability predicted moderate/severe neurodevelopmental outcome separately (AUROC = 0.8, 95%CI [0.7,0.9], p < .001) and even more so when combined (AUROC = 0.9, 95%CI [0.8,0.9], p < .001). After adjusting for NE severity and magnetic resonance imaging (MRI) brain injury, only global delta power remained significantly associated with moderate/severe neurodevelopmental outcome (odds ratio [OR] = 0.9, 95%CI [0.8,1.0], p = .04), gross motor delay (OR = 0.9, 95%CI [0.8,1.0], p = .04), global developmental delay (OR = 0.9, 95%CI [0.8,1.0], p = .04), and auditory deficits (OR = 0.9, 95%CI [0.8,1.0], p = .03). CONCLUSIONS: In NE, global delta power post-rewarming was predictive of outcomes at ≥ 18 months. SIGNIFICANCE: EEG markers post-rewarming can aid prediction of neurodevelopmental outcomes following NE.

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The critical care management of patients after cardiac arrest is burdened by a lack of high-quality clinical studies and the resultant lack of high-certainty evidence. This results in limited practice guideline recommendations, which may lead to uncertainty and variability in management. Critical care management is crucial in patients after cardiac arrest and affects outcome. Although guidelines address some relevant topics (including temperature control and neurological prognostication of comatose survivors, 2 topics for which there are more robust clinical studies), many important subject areas have limited or nonexistent clinical studies, leading to the absence of guidelines or low-certainty evidence. The American Heart Association Emergency Cardiovascular Care Committee and the Neurocritical Care Society collaborated to address this gap by organizing an expert consensus panel and conference. Twenty-four experienced practitioners (including physicians, nurses, pharmacists, and a respiratory therapist) from multiple medical specialties, levels, institutions, and countries made up the panel. Topics were identified and prioritized by the panel and arranged by organ system to facilitate discussion, debate, and consensus building. Statements related to postarrest management were generated, and 80% agreement was required to approve a statement. Voting was anonymous and web based. Topics addressed include neurological, cardiac, pulmonary, hematological, infectious, gastrointestinal, endocrine, and general critical care management. Areas of uncertainty, areas for which no consensus was reached, and future research directions are also included. Until high-quality studies that inform practice guidelines in these areas are available, the expert panel consensus statements that are provided can advise clinicians on the critical care management of patients after cardiac arrest.

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The critical care management of patients after cardiac arrest is burdened by a lack of high-quality clinical studies and the resultant lack of high-certainty evidence. This results in limited practice guideline recommendations, which may lead to uncertainty and variability in management. Critical care management is crucial in patients after cardiac arrest and affects outcome. Although guidelines address some relevant topics (including temperature control and neurological prognostication of comatose survivors, 2 topics for which there are more robust clinical studies), many important subject areas have limited or nonexistent clinical studies, leading to the absence of guidelines or low-certainty evidence. The American Heart Association Emergency Cardiovascular Care Committee and the Neurocritical Care Society collaborated to address this gap by organizing an expert consensus panel and conference. Twenty-four experienced practitioners (including physicians, nurses, pharmacists, and a respiratory therapist) from multiple medical specialties, levels, institutions, and countries made up the panel. Topics were identified and prioritized by the panel and arranged by organ system to facilitate discussion, debate, and consensus building. Statements related to postarrest management were generated, and 80% agreement was required to approve a statement. Voting was anonymous and web based. Topics addressed include neurological, cardiac, pulmonary, hematological, infectious, gastrointestinal, endocrine, and general critical care management. Areas of uncertainty, areas for which no consensus was reached, and future research directions are also included. Until high-quality studies that inform practice guidelines in these areas are available, the expert panel consensus statements that are provided can advise clinicians on the critical care management of patients after cardiac arrest.

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BACKGROUND: The RNA m6A modification has been implicated in multiple neurological diseases as well as macrophage activation. However, whether it regulates microglial activation during hypoxic-ischemic brain damage (HIBD) in neonates remains unknown. Here, we aim to examine whether the m6A modification is involved in modulating microglial activation during HIBD. We employed an oxygen and glucose deprivation microglial model for in vitro studies and a neonatal mouse model of HIBD. The brain tissue was subjected to RNA-seq to screen for significant changes in the mRNA m6A regulator. Thereafter, we performed validation and bioinformatics analysis of the major m6A regulators. RESULTS: RNA-seq analysis revealed that, among 141 m6A regulators, 31 exhibited significant differential expression (FC (abs) ≥ 2) in HIBD mice. We then subjected the major m6A regulators Mettl3, Mettl14, Fto, Alkbh5, Ythdf1, and Ythdf2 to further validation, and the results showed that all were significantly downregulated in vitro and in vivo. GO analysis reveals that regulators are mainly involved in the regulation of cellular and metabolic processes. The KEGG results indicate the involvement of the signal transduction pathway. CONCLUSIONS: Our findings demonstrate that m6A modification of mRNA plays a crucial role in the regulation of microglial activation in HIBD, with m6A-associated regulators acting as key modulators of microglial activation.

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Extracorporeal membrane oxygenation (ECMO), in conjunction with its life-saving benefits, carries a significant risk of acute brain injury (ABI). Hypoxic-ischemic brain injury (HIBI) is one of the most common types of ABI in ECMO patients. Various risk factors, such as history of hypertension, high day 1 lactate level, low pH, cannulation technique, large peri-cannulation PaCO2 drop (∆PaCO2), and early low pulse pressure, have been associated with the development of HIBI in ECMO patients. The pathogenic mechanisms of HIBI in ECMO are complex and multifactorial, attributing to the underlying pathology requiring initiation of ECMO and the risk of HIBI associated with ECMO itself. HIBI is likely to occur in the peri-cannulation or peri-decannulation time secondary to underlying refractory cardiopulmonary failure before or after ECMO. Current therapeutics target pathological mechanisms, cerebral hypoxia and ischemia, by employing targeted temperature management in the case of extracorporeal cardiopulmonary resuscitation (eCPR), and optimizing cerebral O2 saturations and cerebral perfusion. This review describes the pathophysiology, neuromonitoring, and therapeutic techniques to improve neurological outcomes in ECMO patients in order to prevent and minimize the morbidity of HIBI. Further studies aimed at standardizing the most relevant neuromonitoring techniques, optimizing cerebral perfusion, and minimizing the severity of HIBI once it occurs will improve long-term neurological outcomes in ECMO patients.

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Brain injury due to intrauterine growth restriction (IUGR) is a thorny clinical problem that often leads to permanent neurological deficits such as cerebral palsy. Few practical therapies can treat an IUGR-associated brain injury. We employed acupuncture to treat a 6-month-old male patient with severe hypoxic-ischemic encephalopathy (HIE) due to IUGR, as confirmed by magnetic resonance imaging (MRI). Three courses of acupuncture treatment significantly improved some of the patient's clinical characteristics, such as his insensitive responsiveness and motor deficits, with remarkably reversed HIE features on MRI at 1-year of age. This case suggests that acupuncture is a potential treatment option for an IUGR-associated brain injury and warrants further investigation.

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Hypoxia-ischemia (HI) of the brain not only impairs neurodevelopment but also causes pineal gland dysfunction, which leads to circadian rhythm disruption. However, the underlying mechanism of circadian rhythm disruption associated with HI-induced pineal dysfunction remains unknown. The zinc finger protein repressor protein with a predicted molecular mass of 58 kDa (RP58) is involved in the development and differentiation of nerve cells. In this study, we established an HI model in neonatal rats to investigate the expression of RP58 and its role in pineal dysfunction and circadian rhythm disruption induced by HI. We demonstrated that RP58 was highly expressed in the pineal gland under normal conditions and significantly downregulated in the pineal gland and primary pinealocytes following HI. Knockdown of RP58 decreased the expression of enzymes in the melatonin (Mel) synthesis pathway (tryptophan hydroxylase 1 [TPH1], acetylserotonin O-methyltransferase [ASMT], and arylalkylamine N-acetyltransferase [AANAT]) and clock genes (circadian locomotor output cycles kaput [CLOCK] and brain and muscle ARNT-like 1 [BMAL1]), and it also reduced the production of Mel, caused pineal cell injury, and disrupted circadian rhythms in vivo and in vitro. Similarly, HI reduced the expression of Mel synthesis enzymes (TPH1, ASMT, and AANAT) and clock genes (CLOCK and BMAL1), and caused pineal injury and circadian rhythm disruption, which were exacerbated by RP58 knockdown. The detrimental effect of RP58 knockdown on pineal dysfunction and circadian rhythm disruption was reversed by the addition of exogenous Mel. Furthermore, exogenous Mel reversed HI-induced pineal dysfunction and circadian rhythm disruption, as reflected by improvements in Mel production, voluntary activity periods, and activity frequency, as well as a diminished decrease in the expression of Mel synthesis enzymes and clock genes. The present study suggests that RP58 is an endogenous source of protection against pineal dysfunction and circadian rhythm disruption after neonatal HI.

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Neonatal brain injury resulting from various intractable disorders including intraventricular hemorrhage and hypoxic ischemic encephalopathy still remains a major cause of mortality and morbidities with few effective treatments. Recent preclinical research results showing the pleiotropic neuroprotective effects of stem cell therapy, specifically mesenchymal stem cells (MSCs), suggest that MSCs transplantation might be a promising new therapeutic modality for neuroprotection against the currently intractable and devastating neonatal brain injury with complex multifactorial etiology. This review summarizes recent advances in preclinical stem cell research for treating neonatal brain injury with a focus on the important issues including the mechanism of neuroprotection, and determining the ideal cell source, route, timing and dose of MSCs transplantation.

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INTRODUCTION: Experimental evidence, as well as improved clinical studies of the reduction of brain injury and, improves the neurological outcome, in newborns with hypoxic-ischemic encephalopathy (HIE) occurring in therapeutic hypothermia (TH). OBJECTIVE: To verify the potential of hypothermic hypoxic-ischemic encephalopathy (HIE) therapy in neonatal asphyxia, based on literature data, comparing the benefits between selective head cooling (SHC) and whole-body cooling (WBC), see that the use of TH as a standard treatment in newborns with moderate or severe HIE has been adopted. METHODS: A search was performed in the PubMed and SciELO databases of human studies, using the keywords "Therapeutic Hypothermia", "Induced Hypothermia", and "Hypoxic-Ischemic Encephalopathy", "Selective cooling of the head", "Total body cooling" and its variables. RESULTS: Eleven articles were selected to compose the review, after detailed reading. There is a consensus, that the reduction of the risk of death or disability at 18 months of life in neonates with moderate to severe HIE, occurs to TH through the techniques of WBC or SHC. It was found in the studies that there is no difference in terms of adverse effects between the two methods. As for radiological changes, such as hypoxic-ischemic injuries and the incidence of seizures after cooling, they are more frequent with SHC. CONCLUSION: Both WBC and SHC demonstrated neuroprotective properties, although WBC provides a broader area of brain protection. However, no significant differences were found between the methods in terms of adverse effects and beneficial short or long-term results.

INTRODUÇÃO: Evidências experimentais, assim como estudos clínicos, sugerem a redução da lesão cerebral e melhora do desfecho neurológico, em recém-nascidos com encefalopatia isquêmica hipóxica (EHI) submetidos à hipotermia terapêutica (HT). OBJETIVO: Verificar a potencialidade da terapia hipotérmica de encefalopatia hipóxico-isquêmica (EHI) na asfixia neonatal, com base em dados da literatura, comparando os benefícios entre o resfriamento seletivo da cabeça (RSC) e o resfriamento de corpo inteiro (RCI), visto que o uso de hipotermia terapêutica (HT) como tratamento padrão em recém-nascidos com EHI moderada ou grave tem sido amplamente adotada. MÉTODOS: Foi realizada uma busca nas bases de dados PubMed e SciELO de estudos em humanos, utilizando-se as palavras-chave "Therapeutic Hypothermia", "Induced Hypothermia", "Hypoxic-Ischemic Encephalopathy", "selective head cooling", "whole body cooling" e suas respectivas variáveis. RESULTADOS: Foram selecionados 11 artigos para compor a revisão, após leitura detalhada. É consenso, a redução do risco de morte ou incapacidade aos 18 meses de vida nos neonatos com EHI moderado a grave, submetidos à HT através das técnicas de RCI ou RSC. Constatou-se diante dos estudos que não há diferença em termos de efeitos adversos entre os dois métodos. Quanto às alterações radiológicas, as lesões hipóxico-isquêmicas e incidência de convulsões após o resfriamento são mais frequentes com o RSC. CONCLUSÃO: Tanto RCI quanto o RSC demonstraram propriedades neuroprotetoras, embora o RCI proporcione uma área de proteção cerebral mais ampla. No entanto, não foram constatadas diferenças significativas entre os métodos quanto a efeitos adversos e a resultados benéficos em curto e longo prazo.

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Objective:To investigate the effect of Edaravone and dexborneol(Eda.B)on oxidative stress pathway in peripheral blood of elderly patients with acute ischemic stroke.Methods:A total of 87 elderly patients with acute ischemic stroke in the Department of Neurology, Qinghai University Affiliated Hospital from July 2021 to January 2022 were selected as the study subjects.According to the random number table, they were divided into control group(44 cases)and edaravone dexborneol group(43 cases). Each group was divided into <12 h group, 12-24 h group and 24-48 h group according to the time of onset.Peripheral blood was collected in each group at admission and discharge, respectively.The serum levels of reactive oxygen species(ROS), Kelch-like epichlorohydrin-associated protein 1(Keap1), nuclear factor-E2-associated factor 2(Nrf2), heme oxygenase-1(HO-1), NAD(P)H quinone oxidoreductase 1(NQO1), tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6), as well as superoxide dismutase(SOD)activity and malondialdehyde(MDA)content were detected.Results:Elderly patients with acute ischemic stroke receving Eda.B treatment after admission could reduce the serum concentration of ROS, TNF-α and IL-6, as well as MDA content, and increase the concentration of Keap1, Nrf2, HO-1 and NQO1 and SOD activity.Except for ROS concentration in <12 h group and SOD activity in <12 h and 12 h-24 h groups, the differences between the other groups were statistically significant( P<0.05 for all). Compared with the control group, the serum concentration of TNF-α and IL-6 of patients in the Eda.B group at discharge decreased, while the concentration of Nrf2(24-48 h group)and HO-1(24-48 h group), and SOD activity increased, the differences were statistically significant( P<0.05 for all). In the control group at discharge, the concentrations of ROS(24-48 h group), TNF-α(<12 h group, 24-48 h group)and IL-6, as well as MDA content decreased, while the concentrations of Keap1, Nrf2(<12 h group, 12-24 h group)and HO-1(<12 h group, 12-24 h group)increased, the differences were also statistically significant( P<0.05 for all). Compared with admission, the concentration of Keap1(24-48 h group)and HO-1(24-48 h group), the activity of SOD(<12 h group, 12-24 h group)increased and the content of MDA(12-24 h group)in the Eda.B group decreased at discharge( P<0.05 for all). Conclusions:Eda.B can reduce oxidative stress and inflammatory response in peripheral blood of elderly patients with acute ischemic stroke by acting on the Keap1/Nrf2 pathway.

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Objective:To evaluate the role of nuclear factor-erythroid 2-related factor 2 (Nrf2)/glutathione peroxidase-4 (GPX4) signaling pathway-mediated ferroptosis in midazolam-induced reduction of hypoxic-ischemic brain damage (HIBD) in neonatal rats.Methods:Ninety healthy 7-day-old neonatal rats, weighing 16-20 g, were divided into 6 groups ( n=15 each) using the random number table method: sham operation group (Sham group), HIBD group, low-dose midazolam (10 mg/kg) group (group L), medium-dose midazolam (20 mg/kg) group (group M), high-dose midazolam (40 mg/kg) group (group H), and Nrf2 inhibitor ML385 group (group I). The HIBD model was developed by ligating the left carotid artery and exposing to a hypoxic condition for 2 h in anesthetized animals. Starting from 2nd day after developing the model, the corresponding doses of midazolam were intraperitoneally injected in midazolam groups, the equal volume of normal saline was intraperitoneally injected in Sham and HIBD groups, midazolam 40 mg/kg and Nrf2 inhibitor ML385 30 mg/kg were intraperitoneally injected once a day for 8 consecutive days in group I. The rats were weighed and subjected to the Morris water maze test after the end of administration. Blood samples were taken from the abdominal aorta after the end of the Morris water maze test, and then the animals were sacrificed to remove the brain for determination of the concentrations of serum iron, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) (by enzyme-linked immunosorbent assay), contents of iron and GSH in hippocampal tissues (by ultraviolet spectrophotometry and micro method), the number of Nrf2/neuronal nuclear antigen (NeuN) and GPX4/NeuN positive cells (by immunofluorescent staining), and expression of Nrf2, GPX4, and 4-hydroxynonaenoic acid (4-HNE) in hippocampal tissues and for microscopic examination of the pathological changes of hippocampal neurons in brain tissues (after HE staining and Nissl staining). Results:Compared with Sham group, the first time to arrival at platform was significantly prolonged, the number of crossing the origional platform was reduced, and the time of staying at the target quadrant was shortened, the iron content in the hippocampal tissues was increased, the content of GSH and the number of Nrf2/NeuN and GPX4/NeuN positive cells were decreased, the expression of Nrf2 and GPX4 was down-regulated, the expression of 4-HNE was up-regulated, the concentrations of serum iron, IL-6 and TNF-α were increased, and the injury to hippocampal neurons was marked in HIBD group ( P<0.05). Compared with HIBD group, the first time to arrival at platform was significantly shortened, the number of crossing the origional platform was increased, and the time of staying at the target quadrant was prolonged, the iron content in the hippocampus tissues was decreased, the content of GSH and the number of Nrf2/NeuN and GPX4/NeuN positive cells were increased, the expression of Nrf2 and GPX4 was up-regulated, the expression of 4-HNE was down-regulated, the concentrations of serum iron, IL-6 and TNF-α were decreased ( P<0.05), and the injury to hippocampal neurons was significantly reduced in H, M and L groups. Compared with group H, the first time to arrival at platform was significantly prolonged, the number of crossing the origional platform was reduced, and the time of staying at the target quadrant was shortened, the iron content in the hippocampus tissue was increased, the content of GSH and the number of Nrf2/NeuN and GPX4/NeuN positive cells were decreased, the expression of Nrf2 and GPX4 was down-regulated, the expression of 4-HNE was up-regulated, the concentrations of serum iron, IL-6 and TNF-α were increased ( P<0.05), and the injury to hippocampal neurons was aggravated in group I. Conclusions:The mechanism by which midazolam reduces HIBD may be related to activation of the Nrf2/GPX4 signaling pathway and inhibition of hippocampal neuronal ferroptosis in neonatal rats.

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Neonatal hypoxic-ischemic encephalopathy often causes long-term adverse effect on neurological system or even death in near-term or full-term infants, but no effective treatment is available currently. Studies have shown that xenon can reduce brain injury caused by hypoxia-ischemia and is promising in clinical practice. The possible mechanisms include antagonism to glutamic acid receptors, anti-apoptosis, promotion of cell repair and xenon preconditioning. This article reviews the mechanism and research progress on neuroprotection effect of xenon in the treatment of neonatal hypoxic-ischemic encephalopathy.

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BACKGROUND: Delayed post-hypoxic leukoencephalopathy is a rare entity following hypoxia. Clinical and radiological signs of delayed post-hypoxic leukoencephalopathy have not previously been reported following acute ischemic stroke. CASE PRESENTATION: We report a case of an 81-year-old Central European man who presented with a dissection-related occlusion of the left carotid artery. He showed clinical improvement immediately after endovascular stroke therapy, followed by a significant clinical and especially cognitive deterioration thereafter and a clinical recovery after several weeks. The clinical course of the patient was accompanied by morphological changes on magnetic resonance imaging characteristic of delayed post-hypoxic leukoencephalopathy; that is, strictly limited and localized unilaterally to the left anterior circulation. CONCLUSION: This case demonstrates that clinical symptoms and morphological changes on magnetic resonance imaging compatible with delayed post-hypoxic leukoencephalopathy do not necessarily only occur with global hypoxia, but can also occur in patients with a large vessel occlusion in the corresponding vascular territories.

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OBJECTIVE: To improve perinatal outcomes and minimize provider error by increasing awareness of strategies to detect intrapartum maternal heart rate artefact and to respond when such artefact is suspected. TARGET POPULATION: All pregnant patients during labour. OPTIONS: Maternal heart rate artefact may be detected based on clinical features or through technology. Suspected maternal heart rate artefact may be assessed by applying a fetal scalp electrode (preferred) or through external fetal monitoring, augmented by point-of-care sonography (alternative). OUTCOMES: Unrecognized intrapartum maternal heart rate artefact increases the risk that abnormal/atypical fetal heart rate patterns will go undetected and, hence, the risk of adverse perinatal outcomes. BENEFITS, HARMS, AND COSTS: Unrecognized maternal heart rate artefact can lead to adverse perinatal outcomes (hypoxic-ischemic encephalopathy, fetal death, and neonatal death) and adverse maternal outcomes (unnecessary cesarean delivery or operative vaginal delivery). Timely recognition of such artefact may avoid these adverse outcomes. The costs of early recognition of maternal heart rate artefact are relatively small: increased use of fetal scalp electrodes and point-of-care sonography, as well as additional assessments by the health care provider. The cost savings are significant, as a result of lower risk of adverse perinatal outcomes. Potential harms are false-positive diagnoses of maternal heart rate artefact, expediting delivery unnecessarily when the fetal status cannot be reliably determined but is normal, and the rare complications associated with increased use of fetal scalp electrodes. EVIDENCE: Two PubMed searches were completed. The first was for articles published between January 1, 1970, and November 25, 2021, using the medical subject headings (MeSH) "fetal monitoring" and "artifacts" (38 articles). The second was for articles published during the same period using the MeSH "fetal monitoring" and "maternal heart rate" (841 articles). VALIDATION METHODS: The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and conditional [weak] recommendations). INTENDED AUDIENCE: All health care providers involved in obstetrical care. SUMMARY STATEMENTS: RECOMMENDATIONS.

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Perinatal hypoxia-ischemia (HI) is still a significant contributor to mortality and adverse neurodevelopmental outcomes in term and preterm infants. HI brain injury evolves over hours to days, and involves complex interactions between the endogenous protective and pathological processes. Understanding the timing of evolution of injury is vital to guide treatment. Post-HI recovery is associated with a typical neurophysiological profile, with stereotypic changes in cerebral perfusion and oxygenation. After the initial recovery, there is a delayed, prolonged reduction in cerebral perfusion related to metabolic suppression, followed by secondary deterioration with hyperperfusion and increased cerebral oxygenation, associated with altered neurovascular coupling and impaired cerebral autoregulation. These changes in cerebral perfusion are associated with the stages of evolution of injury and injury severity. Further, iatrogenic factors can also affect cerebral oxygenation during the early period of deranged metabolism, and improving clinical management may improve neuroprotection. We will review recent evidence that changes in cerebral oxygenation and metabolism after HI may be useful biomarkers of prognosis.

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Hypoxia-ischemia brain damage (HIBD) is a leading cause of neonatal death worldwide, which significantly influences the development of newborns; however, effective treatment strategies remain limited. Recent studies have discovered that microRNAs (miRNAs) play essential roles in the progression of HIBD. Our study was designed to explore whether miR-17-5p was involved in the pathological development of HIBD. In our study, HIBD mouse experimental model was established by carotid artery ligation combined with a hypoxic environment. RT-qPCR and western blot analyses found that Casp2 was high expressed while miR-17-5p was poorly expressed in the cerebral cortical tissue of HIBD mice. Knockdown of Casp2 significantly alleviated brain injury and cell apoptosis. Additionally, the luciferase reporter assay confirmed that miR-17-5p targeted the 3' UTR of Casp2 and negatively regulated Casp2 expression. The rescue experiment demonstrated that miR-17-5p mimic significantly relieved brain tissue damage and improved memory ability in the HIBD mouse model, while these functions of miR-17-5p were blocked by overexpression of Casp2. In summary, our results indicated that miR-17-5p exerted protective effects on HIBD by targeting Casp2.

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Objective:To study the regulatory effects of transforming growth factor beta-activated kinase 1 (TAK1) on microglia pyroptosis in hypoxic-ischemic brain damage (HIBD).Methods:Primary microglia cells were isolated from fetal mice and randomly assigned into 4 groups: the control group, 5z-7-oxozeaneol (5z-7) group, oxygen-glucose deprivation (OGD) group and OGD+5z-7 group. OGD models of microglia cells were established for the OGD groups and 5z-7 groups received a small molecule TAK1 inhibitor 5z-7. Expression of phosphorylated TAK1(P-TAK1), pyroptosis related proteins including NOD-like receptor pyrin domain containing 3 (NLRP-3), apoptosis-associated speck-like protein containing a CARD (ASC) oligomers, N terminal of Gasdermin D (GSDMD-N) and interleukin 1β (IL-1β) were examined using Western blot at 0 h, 6 h and 24 h after intervention. Lactate dehydrogenase (LDH) test and transmission electron microscope were used for pyroptosis evaluation.Results:(1) Compared with the control group, expressions of all proteins including P-TAK1, NLRP-3, ASC oligomers, GSDMD-N, IL-1β and LDH level showed no significant differences in the OGD group at 0 h ( P>0.05). P-TAK1 levels in OGD group at 6 h and 24 h were lower than the control group and the levels of NLRP-3, ASC oligomers, GSDMD-N, IL-1β and LDH were significantly higher ( P<0.05). Microglia pyroptosis (characterized by disruption of cell membrane, extravasation of cytoplasm and chromatin margin aggregation) was observed under electron microscope. (2) 5z-7 group and OGD+5z-7 group had lower P-TAK1 levels and higher NLRP-3, ASC oligomers, GSDMD-N, IL-1β and LDH levels than the control group and OGD group at 6 h and 24 h. Conclusions:The down-regulation of TAK1 phosphorylation level may promote microglia pyroptosis in HIBD. This regulatory effects is related to the up-regulation of NLRP-3 expression and the oligomerization of ASC.

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Objective:To investigate the efficacy of an adjustable anti-snoring device in improving brain oxygen supply and chronic cerebral circulation insufficiency in patients with obstructive sleep apnea syndrome (OSAS).Methods:Thirty-four patients with OSAS who received treatment in Huidong People's Hospital from January to September 2018 were included in the OSAS group. An additional 34 sex- and age-matched healthy volunteers who concurrently received physical examination were included in the control group. Apnea-hypopnea index score for each patient was determined by polysomnography. Cerebral blood flow velocity was measured by transcranial Doppler ultrasonography. Forearm blood flow was measured by venous occlusion plethysmography. Heart rate was obtained by electrocardiography. Arterial oxygen saturation (SaO 2) was obtained using pulse oximetry. Blood pressure was obtained by an automatic sphygmomanometer. Peripheral and cerebral hemodynamics of patients with OSAS were measured. Nighttime sleep quality of patients was assessed using polysomnography. Lateral projection of the skull was photographed using an X-ray machine for correcting measurement results. Results:There were no significant differences in sex and age between OSAS and control groups (both P > 0.05). Body mass index, Apnea-hypopnea index score and the percentage of time spent at SaO 2 below 90% in the OSAS group were significantly higher than those in the control group (all P < 0.05). The lowest SaO 2 value in the OSAS group was significantly lower than that in the control group ( P < 0.05). Heart rate and forearm blood flow in the OSAS group were (76.27 ± 9.34) beats/min and (7.24 ± 3.13) mL·100 mL -1·min -1, respectively, which were significantly higher than those in the control group [(65.42 ± 6.38) beats/min, (4.11 ± 1.25) mL·100 mL -1·min -1]. After treatment with an adjustable anti-snoring device, heart rate and forearm blood flow in the OSAS group were (66.17 ± 4.53) beats/min and (4.54 ± 3.26) mL·100 mL -1·min -1, respectively, which were significantly lower than those in the control group ( F = 2.66, 0.85, both P < 0.05). Peripheral oxygen saturation, tissue oxygen saturation, and total hemoglobin in the OSAS group were significantly lower than those in the control group. These indexes in the anti-snoring device treatment group were significantly higher than those in the OSAS group ( F = 12.33, 13.57, 14.22, all P < 0.05). The number of snorings and number of wake-ups from sleep in the anti-snoring device treatment group were significantly lower compared with those in the OSAS group ( χ2 = 13.14, 12.36, both P < 0.05).Palatopharyngeal diameter, glossopharyngeal diameter and laryngopharyngeal diameter in the anti-snoring device treatment group were significantly higher than those in the OSAS group, and they were almost close to the levels of healthy people ( t = 11.46, 15.13, 12.58, all P < 0.05). Conclusion:Adjustable anti-snoring device can improve brain oxygen supply and chronic cerebral circulation insufficiency in patients with OSAS, in particular with mild and moderate OSAS.