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Nan Song,1,2,&ast; Xi-Sheng Shan,1,2,&ast; Yi Yang,3 Zhong Zheng,4 Wen-Cheng Shi,4 Xiao-Yan Yang,3 Yang Li,3 Ai-Ping Tan,3 Hong Liu,5 Ke Peng,1,2 Fu-Hai Ji1,2 1Department of Anesthesiology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 2Institute of Anesthesiology, Soochow University, Suzhou, Jiangsu, People’s Republic of China; 3Department of Anesthesiology, the People’s Hospital of SND, Suzhou, Jiangsu, People’s Republic of China; 4Department of Anesthesiology, Taicang First People’s Hospital, Taicang, Jiangsu, People’s Republic of China; 5Department of Anesthesiology and Pain Medicine, University of California Davis Health System, Sacramento, CA, USA&ast;These authors contributed equally to this workCorrespondence: Fu-Hai Ji, Chair and Professor, Department of Anesthesiology, First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, Jiangsu, 215006, People’s Republic of China, Tel +86-512-67780056, Email jifuhaisuda@163.com Ke Peng, Acting Vice Chair for Research and Associate Professor, Department of Anesthesiology, First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, Jiangsu, 215006, People’s Republic of China, Tel +86-512-67780055, Email pengke0422@163.comBackground: Same-visit bidirectional endoscopy (esophagogastroduodenoscopy and colonoscopy) is widely performed under sedation. At present, the optimal sedation regimen remains unclear. This study aims to test the hypothesis that a low-dose esketamine added to propofol sedation reduces hemodynamic and respiratory adverse events in these procedures.Methods: In this multicenter, randomized, double-blind, placebo-controlled trial, 660 adult patients scheduled for same-visit bidirectional endoscopy under sedation from 3 teaching hospitals in China will be recruited. Patients will be randomly allocated, in a 1:1 ratio, to an esketamine group or a normal saline group (n = 330 in each group), stratified by study center. All patients will receive intravenous propofol 0.5 mg/kg and sufentanil 0.1 μg/mL for induction of sedation, followed by intravenous esketamine 0.15 mg/kg or the same volume of normal saline. Propofol will be titrated to the target sedation levels during the procedures. The primary endpoint is a composite of desaturation (peripheral oxygen saturation < 90%) and hypotension (systolic blood pressure < 80 mmHg or decrease > 30% of baseline). Secondary endpoints include desaturation, hypotension, total dose of propofol, pain scores and fatigue scores on the 0– 10 numerical rating scale, dizziness or headache, hallucination or nightmare, nausea or vomiting, endoscopist satisfaction, and patient satisfaction. All analyses will be intention-to-treat.Discussion: We expect that a low-dose esketamine adjunct to propofol-based sedation will improve cardiorespiratory stability in patients undergoing same-visit bidirectional endoscopy, providing reference for clinical sedation practice during these procedures.Trial Registration: Chinese Clinical Trial Registry (Identifier: ChiCTR-ChiCTR2200055938).Keywords: esketamine, propofol, sedation, bidirectional endoscopy, desaturation, hypotension

Background: Harsh parenting in early childhood is related to offspring's adverse behavioral outcomes. Due to the scarcity of longitudinal neuroimaging data, few studies have explored the neurobiological underpinnings of this association, focusing on within-person variability. This study examined the temporal associations among harsh parenting, later behavioral problems, and the developmental trajectories of amygdala volume and amygdala resting-state functional connectivity (RSFC) profiles, using longitudinal neuroimaging data., Methods: The study was embedded in the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort. T1-weighted (296 children, 642 scans) and resting-state functional scans (256 children, 509 scans) were collected at ages 4.5, 6, 7.5, and 10.5 years. Amygdala volume and RSFC between the amygdala and six brain regions that have leading roles in emotional regulation were extracted. Harsh parenting at 4.5 years and child behavioral problems at 10.5 years were assessed via parent-report questionnaires. Linear regression and linear mixed models were applied., Results: Harsh parenting was associated with more severe externalizing problems in girls ( β = 0.24, 95% CI 0.08-0.40) but not boys ( p int = 0.07). In the overall sample, harsh parenting was associated with the developmental trajectories of amygdala-ACC, amygdala-OFC, and amygdala-DLPFC RSFC. In addition, the developmental trajectory of amygdala-ACC RSFC mediated the harsh parenting-externalizing problems association in girls (indirect effect = 0.06, 95% CI 0.01-0.14)., Conclusions: Harsh parenting in early childhood was associated with amygdala neurocircuitry development and behavioral problems. The developmental trajectory of amygdala-ACC RSFC is a potential neural mechanism linking harsh parenting and externalizing problems in girls.

Objective: Offspring of mothers with depression are at increased risk for executive function (EF) deficits and later depressive symptoms, but limited studies have examined EF as an intermediary pathway. This study examined the role of EF in mediating the association between maternal and child depressive symptoms., Method: Data were from a longitudinal birth cohort comprising 739 participants followed from the antenatal period for 12 years. Mothers completed the Edinburgh Perinatal Depression Scale at 26 to 28 weeks' gestation and at 3 and 24 months postpartum. At ages 8.5 to 10 years, children self-reported using the Children's Depression Inventory, Second Edition. Task-based and parent-reported EF measures were collected at 4 time points between 3.5 and 8.5 years. Latent growth curve models examined antenatal depressive symptoms and their trajectory in contributing to cold (ie, cognitive) and hot (ie, affective) EFs. The extent to which EF mediated this association was then assessed., Results: Maternal depressive symptoms did not directly predict depressive symptoms in late childhood. Antenatal depressive symptoms predicted lower cold EF (β = -.13, 95% CI [-0.25, -0.004]) and hot EF (β = -.26, 95% CI [-0.38, -0.15]). Deficits in cold EF (β = -.26, 95% CI [-0.41, -0.11]) acted as an intermediary path to depressive symptoms, whereas hot EF mediated the association between maternal and child depressive symptoms, forming an indirect path that accounted for 37.5% of the association., Conclusion: Deficits in hot EF may be a pathway in explaining the intergenerational transmission of depression. This finding suggests fostering EF skills as a potential strategy for at-risk children., Clinical Trial Registration Information: Growing Up in Singapore Towards Healthy Outcomes (GUSTO); https://clinicaltrials.gov/study/NCT01174875; NCT01174875., Diversity & Inclusion Statement: We worked to ensure that the study questionnaires were prepared in an inclusive way. We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. We actively worked to promote sex and gender balance in our author group. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. While citing references scientifically relevant for this work, we also actively worked to promote sex and gender balance in our reference list. While citing references scientifically relevant for this work, we also actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our reference list. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. One or more of the authors of this paper self-identifies as living with a disability., (Copyright © 2024 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: Maternal stress influences in utero brain development and is a modifiable risk factor for offspring psychopathologies. Reward circuitry dysfunction underlies various internalizing and externalizing psychopathologies. This study examined (1) the association between maternal stress and microstructural characteristics of the neonatal nucleus accumbens (NAcc), a major node of the reward circuitry, and (2) whether neonatal NAcc microstructure modulates individual susceptibility to maternal stress in relation to childhood behavioral problems., Method: K-means longitudinal cluster analysis was performed to determine trajectories of maternal stress measures (Perceived Stress Scale [PSS], hair cortisol) from preconception to the third trimester. Neonatal NAcc microstructural measures (orientation density index [ODI] and intracellular volume fraction [ICVF]) were compared across trajectories. We then examined the interaction between maternal stress and neonatal NAcc microstructure on child internalizing and externalizing behaviors, assessed between ages 3 and 4 years., Results: Two trajectories of maternal stress magnitude ("low"/"high") were identified for both PSS (n = 287) and hair cortisol (n = 336). Right neonatal NAcc ODI (rNAcc-ODI) was significantly lower in "low" relative to "high" PSS trajectories (n = 77, p = .04). PSS at preconception had the strongest association with rNAcc-ODI (r = 0.293, p = .029). No differences in NAcc microstructure were found between hair cortisol trajectories. A significant interaction between preconception PSS and rNAcc-ODI on externalizing behavior was observed (n = 47, p = .047)., Conclusion: Our study showed that the preconception period contributes to in utero NAcc development, and that NAcc microstructure modulates individual susceptibility to preconception maternal stress in relation to externalizing problems., Plain Language Summary: In the S-PRESTO population-based cohort study conducted in Singapore with 351 women and their children, higher levels of maternal perceived stress within the year before pregnancy were associated with increased dendritic complexity within offsprings' nucleus accumbens, indicative of a more advanced developmental profile. Variations in right nucleus accumbens microstructure significantly modulated the association between maternal perceived stress at preconception and externalizing behaviors in early childhood. Study findings suggest that maternal stress in the preconception period accelerates in-utero nucleus accumbens development, leading to differential risk to externalizing problems in later childhood., (Copyright © 2024 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Disorganized attachment is a risk for mental health problems, with increasing work focused on understanding biological mechanisms. Examining late childhood brain morphology may be informative - this stage coincides with the onset of many mental health problems. Past late childhood research reveals promising candidates, including frontal lobe cortical thickness and hippocampal volume. However, work has been limited to Western samples and has not investigated mediation or moderation by brain morphology. Furthermore, past cortical thickness research included only 33 participants. The current study utilized data from 166 children from the GUSTO Asian cohort, who participated in strange situations at 18 months and MRI brain imaging at 10.5 years, with 124 administered the Child Behaviour Checklist at 10.5 years. Results demonstrated disorganization liked to internalizing problems, but no mediation or moderation by brain morphology. The association to internalizing (but not externalizing) problems is discussed with reference to the comparatively higher prevalence of internalizing problems in Singapore.

The massage industry has been in the market for more than thousands of years. Consumers purchase massage services to treat illnesses, alleviate pain, or improve well-being. Despite the popularity of this industry and the benefits it entails, consumers' preferences vary and massage parlors' stakeholders have inconsistent market segmentation. Therefore, the purpose of this study was to investigate consumer preferences toward massage services offered by massage parlors in Indonesia through conjoint analysis. Conjoint analysis' orthogonal design concentrated on stimuli preferences and it was further supported by generating 1.000 consistency and reliability based on Kendall Tau's holdout. A total of 212 respondents answered the online questionnaire voluntarily. The results showed that the Google rating was the most important attribute (68.5%), followed by the gender of the massage therapist (12.4%), the type of massage (9.6%), the type of room (4.5%), the duration (3.6%) and the price (1.4%). Moreover, this research assessed 27 stimuli and found that the best combination was employing female massage therapists, IDR 100k-150k price every session, 90 minutes massage duration, couple room with two beds, acupuncture and cupping massage type, and massage parlors with greater than 4.6 Google review rating. This present research was one of the first studies that explored unique and holistic massage services through conjoint analysis. Unlike the previous studies that only focused on one massage service attribute or did not provide specific levels for evaluated attributes, the conjoint's orthogonal design delivered a new perception of prioritizing both consumers and the business side as some would only focus on one or the other. Also, the findings could be useful for massage parlors' stakeholders in developing marketing strategies, enhancing operational strategies, and promoting customer satisfaction. Marketing tactics such as promotional discounts would inspire customers to provide an optimistic Google review. Business owners were encouraged to focus on giving the best experience starting with a well-trained massage therapist, clean and hygienic rooms, and quality materials. These theoretical and practical implications aid in building the massage parlor's credibility that could be perceived positively by consumers., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Prasetyo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Patients with advanced non-small-cell lung cancer (NSCLC) with activating mutations in the epidermal growth factor receptor ( EGFR ) gene are a heterogeneous population who often develop brain metastases (BM). The optimal management of patients with asymptomatic brain metastases is unclear given the activity of newer-generation targeted therapies in the central nervous system. We present a protocol for an individual patient data (IPD) prospective meta-analysis to evaluate whether the addition of stereotactic radiosurgery (SRS) before osimertinib treatment will lead to better control of intracranial metastatic disease. This is a clinically relevant question that will inform practice., Methods: Randomised controlled trials will be eligible if they include participants with BM arising from EGFR- mutant NSCLC and suitable to receive osimertinib both in the first-line and second-line settings (P); comparisons of SRS followed by osimertinib versus osimertinib alone (I, C) and intracranial disease control included as an endpoint (O). Systematic searches of Medline (Ovid), Embase (Ovid), Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL (EBSCO), PsychInfo, ClinicalTrials.gov and the WHO's International Clinical Trials Registry Platform's Search Portal will be undertaken. An IPD meta-analysis will be performed using methodologies recommended by the Cochrane Collaboration. The primary outcome is intracranial progression-free survival, as determined by response assessment in neuro-oncology-BM criteria. Secondary outcomes include overall survival, time to whole brain radiotherapy, quality of life, and adverse events of special interest. Effect differences will be explored among prespecified subgroups., Ethics and Dissemination: Approved by each trial's ethics committee. Results will be relevant to clinicians, researchers, policymakers and patients, and will be disseminated via publications, presentations and media releases., Prospero Registration: CRD42022330532., Competing Interests: Competing interests: SL: research funding and honoraria from AstraZeneca. YYS: honoraria from AstraZeneca and Janssen. AGS: research grants (institution) from Elekta AB, Varian, Seagen and BrainLAB; consulting fees from Varian, Elekta (Gamma Knife Icon), BrainLAB, Merck, Abbvie and Roche; honoraria from AstraZeneca, Elekta AB, Varian, BrainLAB, Accuray and Seagen. MBP: speaker fees from AZ, BMS, MSD and Roche. AN: research grants from Varian Medical Systems. RAS: advisory board with Amgen, Astra-Zeneca, Bayer, BMS, Boehringer Ingelheim, Janssen, Lily, Merck, Merck Serono, Novartis, Pfizer, Puma Biotechnology, Roche, Taiho, Takeda, Thermo Fisher and Yuhan Corporation; research grant from Astra-Zeneca and Boehringer Ingelheim. FHJ: clinical trial funding, received honoraria and participated in advisory boards for Astra Zeneca; received payments and honoraria from BeiGene and MSD for lectures and presentations; supported by the Peter Mac Foundation and the Victorian Cancer Agency. BJS: advisory board/honoraria from AstraZeneca, Pfizer, Novartis, Roche, Takeda, Merck, Bristol Mysers Squibb, Janssen, Amgen and Eli Lilly. IWKT: honorarium from Elekta and MSD. CH: advisory boards with Abbvie, Amgen, AstraZeneca, Bayer, BMS, Eisai, EMD Serono, Janssen, Jazz, Merck, Novartis, Pfizer, Roche, Sanofi and Takeda; research grants from AstraZeneca, EMD Serono and Roche. CKL: advisory board with Amgen, Astra Zeneca, GSK, Merck KGA, Norvatis, Pfizer, Roche, Takeda, Boehringer-Ingelheim and Yuhan; research funding (institution) from Astra Zeneca, Roche, Merck KGA and Amgen. KPR, AP, MD, DBS, AGS, JT, CNL, WYK, YH, YLEA, JL, CY, MCL and APT have no competing interests. CH, SL, FHJ, CKL, YYS, RAS and IWKT are study chairs on the included trials., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Screen time in infancy is linked to changes in social-emotional development but the pathway underlying this association remains unknown. We aim to provide mechanistic insights into this association using brain network topology and to examine the potential role of parent-child reading in mitigating the effects of screen time., Methods: We examined the association of screen time on brain network topology using linear regression analysis and tested if the network topology mediated the association between screen time and later socio-emotional competence. Lastly, we tested if parent-child reading time was a moderator of the link between screen time and brain network topology., Results: Infant screen time was significantly associated with the emotion processing-cognitive control network integration ( p = 0.005). This network integration also significantly mediated the association between screen time and both measures of socio-emotional competence (BRIEF-2 Emotion Regulation Index, p = 0.04; SEARS total score, p = 0.04). Parent-child reading time significantly moderated the association between screen time and emotion processing-cognitive control network integration ( β = -0.640, p = 0.005)., Conclusion: Our study identified emotion processing-cognitive control network integration as a plausible biological pathway linking screen time in infancy and later socio-emotional competence. We also provided novel evidence for the role of parent-child reading in moderating the association between screen time and topological brain restructuring in early childhood.

There are inter-individual differences in susceptibility to the influence of early life experiences for which the underlying neurobiological mechanisms are poorly understood. Microglia play a role in environmental surveillance and may influence individual susceptibility to environmental factors. As an index of neurodevelopment, we estimated individual slopes of mean white matter fractional anisotropy (WM-FA) across three time-points (age 4.5, 6.0, and 7.5 years) for 351 participants. Individual variation in microglia reactivity was derived from an expression-based polygenic score(ePGS) comprised of Single Nucleotide Polymorphisms (SNPs) functionally related to the expression of microglia-enriched genes.A higher ePGS denotes an increased genetic capacity for the expression of microglia-related genes, and thus may confer a greater capacity to respond to the early environment and to influence brain development. We hypothesized that this ePGS would associate with the WM-FA index of neurodevelopment and moderate the influence of early environmental factors.Our findings show sex dependency, where a significant association between WM-FA and microglia ePGS was only obtained for females.We then examined associations with perinatal factors known to decrease (optimal birth outcomes and familial conditions) or increase (systemic inflammation) the risk for later mental health problems.In females, individuals with high microglia ePGS showed a negative association between systemic inflammation and WM-FA and a positive association between more advantageous environmental conditions and WM-FA. The microglia ePGS in females thus accounted for variations in the influence of the quality of the early environment on WM-FA.Finally, WM-FA slopes mediated the association of microglia ePGS with interpersonal problems and social hostility in females. Our findings suggest the genetic capacity for microglia function as a potential factor underlying differential susceptibility to early life exposuresthrough influences on neurodevelopment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

A balanced excitation-inhibition ratio (E/I ratio) is critical for healthy brain function. Normative development of cortex-wide E/I ratio remains unknown. Here, we noninvasively estimate a putative marker of whole-cortex E/I ratio by fitting a large-scale biophysically plausible circuit model to resting-state functional MRI (fMRI) data. We first confirm that our model generates realistic brain dynamics in the Human Connectome Project. Next, we show that the estimated E/I ratio marker is sensitive to the gamma-aminobutyric acid (GABA) agonist benzodiazepine alprazolam during fMRI. Alprazolam-induced E/I changes are spatially consistent with positron emission tomography measurement of benzodiazepine receptor density. We then investigate the relationship between the E/I ratio marker and neurodevelopment. We find that the E/I ratio marker declines heterogeneously across the cerebral cortex during youth, with the greatest reduction occurring in sensorimotor systems relative to association systems. Importantly, among children with the same chronological age, a lower E/I ratio marker (especially in the association cortex) is linked to better cognitive performance. This result is replicated across North American (8.2 to 23.0 y old) and Asian (7.2 to 7.9 y old) cohorts, suggesting that a more mature E/I ratio indexes improved cognition during normative development. Overall, our findings open the door to studying how disrupted E/I trajectories may lead to cognitive dysfunction in psychopathology that emerges during youth., Competing Interests: Competing interests statement:The authors declare no competing interest.

Early life adversity has been posited to influence the pace of structural neurodevelopment. Most research, however, has relied on cross-sectional data, which do not reveal whether the pace of neurodevelopmental change is accelerated or slowed following early exposures. In a birth cohort study that included neuroimaging data obtained at 4.5, 6, and 7.5 years of age (N = 784), we examined associations among a cumulative measure of perinatal adversity relative to resources, nonlinear trajectories of hippocampal and amygdala volume, and children's subsequent depressive symptoms at 8.5 years of age. Greater adversity was associated with reduced bilateral hippocampal body volume in early childhood, but also to faster growth in the right hippocampal body across childhood. Further, the association between adversity and childhood depressive symptoms was mediated by faster hippocampal body growth. These findings suggest that perinatal adversity is biologically embedded in hippocampal structure development, including an accelerated pace of change in the right hippocampal body that is implicated in children's psychopathology risk. In addition, our findings suggest that reduced hippocampal volume is not inconsistent with accelerated hippocampal change; these aspects of structural development may typically co-occur, as smaller regional volumes in early childhood were associated with faster growth across childhood., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: It is unclear how the functional brain hierarchy is organized in preschool-aged children, and whether alterations in the brain organization are linked to mental health in this age group. Here, we assessed whether preschool-aged children exhibit a brain organizational structure similar to that of older children, how this structure might change over time, and whether it might reflect mental health., Method: This study derived functional gradients using diffusion embedding from resting state functional magnetic resonance imaging data of 4.5-year-old children (N = 100, 42 male participants) and 6.0-year-old children (N = 133, 62 male participants) from the longitudinal Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort. We then conducted partial least-squares correlation analyses to identify the association between the impairment ratings of different mental disorders and network gradient values., Results: The main organizing axis of functional connectivity (ie, principal gradient) separated the visual and somatomotor regions (ie, unimodal) in preschool-aged children, whereas the second axis delineated the unimodal-transmodal gradient. This pattern of organization was stable from 4.5 to 6 years of age. The second gradient separating the high- and low-order networks exhibited a diverging pattern across mental health severity, differentiating dimensions related to attention-deficit/hyperactivity disorder and phobic disorders., Conclusion: This study characterized, for the first time, the functional brain hierarchy in preschool-aged children. A divergence in functional gradient pattern across different disease dimensions was found, highlighting how perturbations in functional brain organization can relate to the severity of different mental health disorders., (Copyright © 2023 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Importance: Propofol sedation is widely used for endoscopic procedures, but it poses risks of hemodynamic and respiratory depression. The addition of esketamine as an adjuvant may reduce propofol requirements and associated adverse events., Objective: To evaluate the effects of low-dose esketamine added to propofol-based sedation on desaturation and hypotension during same-visit bidirectional endoscopy., Design, Setting, and Participants: This multicenter, double-blind, placebo-controlled randomized clinical trial assessed patients from 3 teaching hospitals in China who were scheduled for same-visit bidirectional endoscopy between February 8 and November 30, 2022, and randomly assigned to receive esketamine or normal saline (placebo)., Interventions: After induction of sedation with 0.1 μg/kg of sufentanil and 0.5 mg/kg of propofol, patients in the esketamine group received 0.15 mg/kg of intravenous esketamine, whereas patients in the placebo group received an equivalent volume of saline. Sedation was achieved through propofol titration., Main Outcomes and Measures: The primary outcome was the composite of desaturation and hypotension during the procedures. Secondary outcomes included desaturation, hypotension, propofol requirements, postprocedure pain and fatigue, nausea or vomiting, dizziness or headache, hallucination or nightmare, endoscopist satisfaction, and patient satisfaction., Results: Among the 663 initially enrolled patients, 660 completed the study (median [IQR] age, 48 [36-57] years; 355 [53.8%] female), with 331 randomized to the esketamine group and 329 to the placebo group. The administration of esketamine compared with placebo significantly reduced the incidence of the composite outcome of desaturation and hypotension (8.2% vs 21.0%; difference, -12.8 percentage points; odds ratio [OR], 0.34; 95% CI, 0.21-0.54; P < .001). Additionally, esketamine led to significantly lower incidences of desaturation (OR, 0.36; 95% CI, 0.18-0.72; false discovery rate q = .01) and hypotension (OR, 0.33; 95% CI, 0.18-0.60; q < .001) and reduced propofol requirements (difference, -58.9 mg; 95% CI, -65.7 to -52.2 mg; q < .001), without significant effects on other secondary outcomes., Conclusions and Relevance: In this randomized clinical trial of patients undergoing same-visit bidirectional endoscopy, the administration of low-dose esketamine resulted in an approximately 61% reduction in the incidence of desaturation and hypotension, accompanied by decreased propofol requirements. These findings support the use of esketamine as an adjuvant to propofol-based sedation in endoscopic procedures., Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2200055938.

Lesions of the paediatric cranial vault are diverse both in their presentation and aetiology. As such, they pose a diagnostic challenge to the paediatric neurosurgeon and neuroradiologist. In this article, we delineate the spectrum of paediatric calvarial pathology into four distinct groups: (1) lytic lesion(s); (2) focal sclerotic lesion(s); (3) diffuse cranial vault sclerosis; and (4) abnormal shape of the cranial vault. It is our aim that this more pragmatic, algorithmic approach may mitigate diagnostic uncertainty and aid the more accurate diagnosis of paediatric calvarial lesions.

Background: Metabolic syndrome score in children assesses the risk of developing cardiovascular disease in future. We aim to probe the role of the caudate in relation to the metabolic syndrome score. Furthermore, using both functional and structural neuroimaging, we aim to examine the interplay between functional and structural measures., Methods: A longitudinal birth cohort study with functional and structural neuroimaging data obtained at 4.5, 6.0 and 7.5 years and metabolic syndrome scores at 8.0 years was used. Pearson correlation and linear regression was used to test for correlation fractional anisotropy (FA) and fractional amplitude of low frequency fluctuations (fALFF) of the caudate with metabolic syndrome scores. Mediation analysis was used to test if later brain measures mediated the relation between earlier brain measures and metabolic syndrome scores. Inhibitory control was also tested as a mediator of the relation between caudate brain measures and metabolic syndrome scores., Results: FA at 4.5 years and fALFF at 7.5 years of the left caudate was significantly correlated with metabolic syndrome scores. Post-hoc mediation analysis showed that fALFF at 7.5 years fully mediated the relation between FA at 4.5 years and metabolic syndrome scores. Inhibitory control was significantly correlated with fALFF at 7.5 years, but did not mediate the relation between fALFF at 7.5 years and metabolic syndrome scores., Conclusions: We found that variations in caudate microstructure at 4.5 years predict later variation in functional activity at 7.5 years. This later variation in functional activity fully mediates the relation between microstructural changes in early childhood and metabolic syndrome scores at 8.0 years., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yap-Seng Chong is part of an academic consortium that has received research funding from Abbott Nutrition, Nestec, and Danone. All other authors report no financial relationships with commercial interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Resting-state fMRI is commonly used to derive brain parcellations, which are widely used for dimensionality reduction and interpreting human neuroscience studies. We previously developed a model that integrates local and global approaches for estimating areal-level cortical parcellations. The resulting local-global parcellations are often referred to as the Schaefer parcellations. However, the lack of homotopic correspondence between left and right Schaefer parcels has limited their use for brain lateralization studies. Here, we extend our previous model to derive homotopic areal-level parcellations. Using resting-fMRI and task-fMRI across diverse scanners, acquisition protocols, preprocessing and demographics, we show that the resulting homotopic parcellations are as homogeneous as the Schaefer parcellations, while being more homogeneous than five publicly available parcellations. Furthermore, weaker correlations between homotopic parcels are associated with greater lateralization in resting network organization, as well as lateralization in language and motor task activation. Finally, the homotopic parcellations agree with the boundaries of a number of cortical areas estimated from histology and visuotopic fMRI, while capturing sub-areal (e.g., somatotopic and visuotopic) features. Overall, these results suggest that the homotopic local-global parcellations represent neurobiologically meaningful subdivisions of the human cerebral cortex and will be a useful resource for future studies. Multi-resolution parcellations estimated from 1479 participants are publicly available (https://github.com/ThomasYeoLab/CBIG/tree/master/stable&#95;projects/brain&#95;parcellation/Yan2023&#95;homotopic)., (Copyright © 2023. Published by Elsevier Inc.)

Aims: Glioneuronal tumours (GNTs) are poorly distinguished by their histology and lack robust diagnostic indicators. Previously, we showed that common GNTs comprise two molecularly distinct groups, correlating poorly with histology. To refine diagnosis, we constructed a methylation-based model for GNT classification, subsequently evaluating standards for molecular stratification by methylation, histology and radiology., Methods: We comprehensively analysed methylation, radiology and histology for 83 GNT samples: a training cohort of 49, previously classified into molecularly defined groups by genomic profiles, plus a validation cohort of 34. We identified histological and radiological correlates to molecular classification and constructed a methylation-based support vector machine (SVM) model for prediction. Subsequently, we contrasted methylation, radiological and histological classifications in validation GNTs., Results: By methylation clustering, all training and 23/34 validation GNTs segregated into two groups, the remaining 11 clustering alongside control cortex. Histological review identified prominent astrocytic/oligodendrocyte-like components, dysplastic neurons and a specific glioneuronal element as discriminators between groups. However, these were present in only a subset of tumours. Radiological review identified location, margin definition, enhancement and T2 FLAIR-rim sign as discriminators. When validation GNTs were classified by SVM, 22/23 classified correctly, comparing favourably against histology and radiology that resolved 17/22 and 15/21, respectively, where data were available for comparison., Conclusions: Diagnostic criteria inadequately reflect glioneuronal tumour biology, leaving a proportion unresolvable. In the largest cohort of molecularly defined glioneuronal tumours, we develop molecular, histological and radiological approaches for biologically meaningful classification and demonstrate almost all cases are resolvable, emphasising the importance of an integrated diagnostic approach., (© 2023 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society.)

Background: Experiences of early life adversity pose significant psychological and physical health risks to exposed individuals. Emerging evidence suggests that these health risks can be transmitted across generations; however, the mechanisms underlying the intergenerational impacts of maternal early-life trauma on child health remain unknown., Methods: The current study used a prospective longitudinal design to determine the unique and joint contributions of maternal childhood trauma (neglect and abuse) and maternal prenatal and postnatal mental health (anxiety and depressive symptoms) (N = 541) to children's resting frontoamygdala functional connectivity at 6 years (N = 89) and emotional health at 7-8 years, as indexed by parent-reported internalizing problems and child self-reported anxiety and depressive symptoms (N = 268-418)., Results: Greater maternal childhood neglect was indirectly associated with greater internalizing problems serially through a pathway of worse maternal prenatal and postnatal mental health (greater maternal anxiety and depressive symptoms). Worse maternal postnatal mental health was also uniquely associated with more negative child frontoamygdala resting-state functional connectivity, over and above maternal childhood trauma (both neglect and abuse) and prenatal mental health. More negative frontoamygdala functional connectivity was, in turn, associated with poorer child emotional health outcomes., Conclusions: Findings from the current study provide support for the existence of intergenerational influences of parental exposure to childhood trauma on childhood risk for psychopathology in the next generation and point to the importance of maternal factors proximal to the second generation (maternal prenatal and postnatal mental health) in determining the intergenerational impact of maternal early experiences., (© 2022 Association for Child and Adolescent Mental Health.)

Human brain development starts in the embryonic period. Maternal preconception nutrition and nutrient availability to the embryo may influence brain development at this critical period following conception and early cellular differentiation, thereby affecting offspring neurodevelopmental and behavioural disorder risk. However, studying this is challenging due to difficulties in characterizing preconception nutritional status and few studies have objective neurodevelopmental imaging measures in children. We investigated the associations of maternal preconception circulating blood nutrient-related biomarker mixtures (~15 weeks before conception) with child behavioural symptoms (Child Behaviour Checklist (CBCL), aged 3 years) within the Singapore Preconception Study of Long-Term Maternal and Child Outcomes (S-PRESTO) study. The CBCL preschool form evaluates child behaviours based on syndrome scales and Diagnostic and Statistical Manual of Mental Disorders (DSM) oriented scales. These scales consist of internalizing problems, externalizing problems, anxiety problems, pervasive developmental problems, oppositional defiant, etc. We applied data-driven clustering and a method for modelling mixtures (Bayesian kernel machine regression, BKMR) to account for complex, non-linear dependencies between 67 biomarkers. We used effect decomposition analyses to explore the potential mediating role of neonatal (week 1) brain microstructure, specifically orientation dispersion indices (ODI) of 49 cortical and subcortical grey matter regions. We found that higher levels of a nutrient cluster including thiamine, thiamine monophosphate (TMP), pyridoxal phosphate, pyridoxic acid, and pyridoxal were associated with a higher CBCL score for internalizing problems (posterior inclusion probability (PIP) = 0.768). Specifically, thiamine independently influenced CBCL (Conditional PIP = 0.775). Higher maternal preconception thiamine level was also associated with a lower right subthalamic nucleus ODI (P-value = 0.01) while a lower right subthalamic nucleus ODI was associated with higher CBCL scores for multiple domains (P-value < 0.05). One potential mechanism is the suboptimal metabolism of free thiamine to active vitamin B1, but additional follow-up and replication studies in other cohorts are needed., (© 2023. The Author(s).)

Background: Childhood depression is a highly distinct and prevalent condition with an unknown neurobiological basis. We wish to explore the resting state fMRI data in children for potential associations between neural connectivity and childhood depressive symptoms., Methods: A longitudinal birth cohort study with neuroimaging data obtained at 4.5, 6.0 and 7.5 years of age and the Children Depression Inventory 2 (CDI) administered between 8.5 and 10.5 years was used. The CDI score was used as the dependent variable and tested for correlation, both simple Pearson and network based statistic, with the functional connectivity values obtained from the resting state fMRI. Cross-validated permutation testing with a general linear model was used to validate that the identified functional connections were indeed implicated in childhood depression., Results: Ten functional connections and four brain regions (Somatomotor Area B, Temporoparietal Junction, Orbitofrontal Cortex and Insula) were identified as significantly associated with childhood depressive symptoms for girls at 6.0 and 7.5 years. No significant functional connections were found in girls at 4.5 years or for boys at any timepoint. Network based statistic and permutation testing confirmed these findings., Conclusions: This study revealed significant sex-dependent associations of neural connectivity and childhood depressive symptoms. The regions identified are implicated in speech/language, social cognition and information integration and suggest unique pathways to childhood depressive symptoms., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Competing Interests: Competing interests: None declared.

Early differences in reward behavior have been linked to executive functioning development. The nucleus accumbens (NAc) and orbitofrontal cortex (OFC) are activated by reward-related tasks and identified as key nodes of the brain circuit that underlie reward processing. We aimed to investigate the relation between NAc-OFC structural and functional connectivity in preschool children, as well as associations with future reward sensitivity and executive function. We showed that NAc-OFC structural and functional connectivity were not significantly associated in preschool children, but both independently predicted sensitivity to reward in males in a left-lateralized manner. Moreover, significant NAc-OFC structure-function coupling was only found in individuals who performed poorly on executive function tasks in later childhood, but not in the middle- and high-performing groups. As structure-function coupling is proposed to measure functional specialization, this finding suggests premature functional specialization within the reward network, which may impede dynamic communication with other regions, affects executive function development. Our study also highlights the utility of multimodal imaging data integration when studying the effects of reward network functional flexibility in the preschool age, a critical period in brain and executive function development., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Neonatal adiposity is associated with a higher risk of obesity and cardiometabolic risk factors in later life. It is however unknown if central food intake regulating networks in the ventral striatum are altered with in-utero abdominal growth, indexed by neonatal adiposity in our current study. We aim to examine the relationship between striatal microstructure and abdominal adipose tissue compartments (AATCs) in Asian neonates from the Growing Up in Singapore Toward healthy Outcomes mother-offspring cohort., Study Design: About 109 neonates were included in this study. Magnetic resonance imaging (MRI) was performed for the brain and abdominal regions between 5 to 17 days of life. Diffusion-weighted imaging of the brain was performed for the derivation of caudate and putamen fractional anisotropy (FA). Abdominal imaging was performed to quantify AATCs namely superficial subcutaneous adipose tissue (sSAT), deep subcutaneous adipose tissue (dSAT), and internal adipose tissue (IAT). Absolute and percentage adipose tissue of total abdominal volume (TAV) were calculated., Results: We showed that AATCs at birth were significantly associated with increased FA in bilateral ventral caudate heads which are part of the ventral striatum (sSAT: β left  = 0.56, p < 0.001; β right  = 0.65, p < 0.001, dSAT: β left  = 0.43, p < 0.001; β right  = 0.52, p < 0.001, IAT: β left  = 0.30, p = 0.005; β right  = 0.32, p = 0.002) in neonates with low birth weights adjusted for gestational age., Conclusions: Our study provides preliminary evidence of a potential relationship between neonatal adiposity and in-utero programming of the ventral striatum, a brain structure that governs feeding behavior., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

As a proinflammatory cytokine of the interleukin-1 (IL-1) family, IL-18 plays important roles in host protection against bacterial, viral, and fungal infection. We cloned the open reading frame of snakehead (Channa argus) IL-18 (shIL-18) and found that it contained 609 base pairs and encoded 202 amino acid residues. The shIL-18 included a conserved IL-1-like family signature and two potential IL-1β-converting enzyme cutting sites; one was conserved in all analyzed IL-18s, but the other was unique to shIL-18. Unlike other IL-18s, shIL-18 also contained a predicted signal peptide. In this study, shIL-18 was constitutively expressed in all tested tissues, and its expression was induced by Aeromonas schubertii and Nocardia seriolae in the head kidney and spleen in vivo and by lipoteichoic acid, lipopolysaccharides, and polyinosinic-polycytidylic acid in head kidney leukocytes in vitro. Moreover, recombinant shIL-18 upregulated the expression of interferon-γ, IL-1β, and tumor necrosis factor-α1 and -α2 and promoted the proliferation of leukocytes. Taken together, these results showed that IL-18 played crucial roles in host defense against bacterial infection in fish, as it does in mammals., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

For decades, CT has been the primary imaging modality for the diagnosis and surveillance of paediatric craniofacial disorders. However, the deleterious effects of ionising radiation in the paediatric population are well established and remain an ongoing concern. This is especially so in the head and neck region, which has relatively poor soft tissue shielding with many radiosensitive organs. The development of "black bone" imaging utilising low flip angles and short echo time (TE) has shown considerable promise in alleviating the use of ionising radiation in many cases of craniofacial disorders. In this review article, we share our experience of utilising "black bone" sequence in children with craniofacial pathologies, ranging from traumatic injuries to craniosynostosis and focal osseous/fibro-osseous lesions such as fibrous dysplasia and Langerhans cell histiocytosis (LCH). A detailed discussion on the technical aspects of "black bone" sequence, including its potential pitfalls and limitations, will also be included.

Gamma knife radiosurgery (GKS), a technique which involves delivery of a high dose of radiation to a precisely defined target, has become the predominant treatment option for brain metastases (BM) because of its high effectiveness and relatively minimal toxicity. Herein, we report a case of late-onset radiation-induced edema around an asymptomatic cyst, more than 20 years after salvage GKS, with 27 years of imaging follow-up, allowing the description of the evolutionary trajectory of these relatively rare complications. Our reported case also demonstrated the benign nature of delayed cyst formation (DCF), emphasizing that observation alone is reasonable for asymptomatic patients.

The complex interaction between brain and behaviour in language disorder is well established. Yet to date, the imaging literature in the language disorder field has continued to pursue heterogeneous and relatively small clinical cross-sectional samples, with emphasis on cortical structures and volumetric analyses of subcortical brain structures. In our current work, we aimed to go beyond this state of knowledge to focus on the microstructural features of subcortical brain structures (specifically the caudate nucleus) in a large cohort of neonates and study its association with emerging language skills at 24 months. Variations in neonatal brain microstructure could be interpreted as a proxy for in utero brain development. As language development is highly dependent on cognitive function and home literacy environment, we also examined their effect on the caudate-language function relationship utilizing a conditional process model. Our findings suggest that emerging language development at 24 months is influenced by the degree of left lateralization of neonatal caudate microstructure, indexed by diffusion tensor imaging (DTI)-derived fractional anisotropy (FA). FA is an indirect measure of neuronal and dendritic density within grey matter structures. We also found that the caudate-language function relationship is partially mediated by cognitive function. The conditional indirect effect of left caudate FA on language composite score through cognitive function was only statistically significant at low levels of home literacy score (-1 standard deviation [SD]). The authors proposed that this may be related to 'compensatory' development of cognitive skills in less favourable home literacy environments., (© 2021 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Physiologically based thermoregulatory models are useful for deriving predictions of heat strain for pragmatic applications such as planning of continuous exercise/work-rest protocols. The SCENARIO model is an example of a thermoregulatory model that predicts heat strain including body core temperature (Tc) from individual characteristics, physical activity, clothing properties and environmental conditions. This paper presents work to optimize and enhance the SCENARIO model for prediction of Tc during high intensity load carriage tasks under predominantly tropical climate conditions. Data for model optimization (in-sample analysis) and model external validation were derived from four and two load carriage studies respectively. A total of four parameters characterizing metabolic heat production, sweat evaporation and ice ingestion for hydration were identified for model optimization based on physiological reasoning. The accuracy of Tc estimates was evaluated based on bias, root mean square deviation (RMSD), RMSD based on mean values (RMSD-Mean), and standard deviation fall-in percentage (SDP). Under in-sample analysis, the optimized model achieved bias, RMSD, RMSD-Mean and SDP of 0.01°C, 0.39°C, 0.14°C and 99%, respectively. When externally validated against two sets of unseen data, the model achieved comparable bias, RMSD, RMSD-Mean and SDP values of 0.06°C, 0.32°C, 0.13°C, 92% and 0.08°C, 0.39°C, 0.19°C, 92%, respectively. Overall, the results indicate the robustness of the optimized SCENARIO model for predicting the Tc responses during prolonged, high-intensity physical tasks under hot and humid environments. Future work to further validate the model against data beyond the range of the present study's experimental data and enhancing it for more accurate simulations of other heat strain markers including heart rate is recommended., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: The advent of chimeric antigen receptor (CAR) T-cell therapy has created a paradigm shift in the management of patients with refractory B-cell acute lymphocytic leukaemia (ALL). The aim of this study is to correlate imaging findings of CAR T-cell therapy related neurotoxicity with clinical course and eventual clinical outcome, with the hope that it will bring us a step closer to the identification of potential imaging biomarkers that may allow more accurate prognostication and risk stratification of patients., Procedure: Our imaging database was queried from January 2018 to April 2020 to identify paediatric patients who fulfil the following criteria: (a) diagnosed with ALL, (b) underwent CAR T-cell therapy, and (c) had magnetic resonance imaging (MRI) brain studies performed before and after CAR T-cell therapy. A total of seven patients were included and all MRI studies were analysed by a paediatric neuroradiologist for the presence of acute neuroimaging findings post CAR T-cell infusion. Acute neuroimaging findings are defined as new imaging findings detected within 28 days of CAR T-cell infusion., Results: Three out of four patients with acute neuroimaging findings had sustained complete remission for more than 6 months, while all three patients without acute neuroimaging findings had positive minimal residual disease (MRD) within 1 month. Both patients with acute diffuse leptomeningeal enhancement showed clinical improvement within 1-2 days., Conclusions: Acute neuroimaging findings may be a potential imaging biomarker for peak neurotoxicity and treatment response, and it is not necessarily associated with poor outcome, as previously reported., (© 2020 Wiley Periodicals LLC.)

The emergence of CD19-targeted chimeric antigen receptor-T (CAR-T) cell therapy has created a new era in the management of pediatric patients with refractory B-cell malignancies such as B-cell acute lymphoblastic leukemia. Immune effector cell-associated neurotoxicity syndrome (ICANS) is frequently encountered in the postinfusion period of CD19-targeted chimeric antigen receptor-T cell therapy and in some cases may be fatal. Knowledge related to the spectrum of imaging findings of CD19-targeted CAR-T cell therapy-related ICANS is, however, still very much lacking, underscoring the need for continued research in this area. In this review, we hope to provide an overview of current knowledge and provide an in-depth literature review related to this topic. A brief discussion of possible imaging differential diagnoses, specifically in children with acute lymphoblastic leukemia, will also be included. Illustrative cases for each imaging phenotype will be provided to facilitate a better understanding. A greater level of insight of the spectrum of imaging findings related to ICANS will improve patients' management and enhance efforts to safely deliver CAR-T cell immunotherapy. It will also facilitate further studies to derive mechanistic insights of ICANS and potentially assist in the testing and monitoring of therapeutic interventions., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Tumor necrosis factor-α (TNF-α) is a pluripotent mediator of pro-inflammatory and antimicrobial defense mechanisms and a regulator of lymphoid organ development. Although two types of TNF-α have been identified in several teleost species, their functions in pathogen infection remain largely unexplored, especially in pathogen clearance. Herein, we cloned and characterized two types of TNF-α, termed shTNF-α1 and shTNF-α2, and their receptors, shTNFR1 and shTNFR2, from snakehead (Channa argus). These genes were constitutively expressed in all tested tissues, and were induced by Aeromonas schubertii and Nocardia seriolae in head kidney and spleen in vivo, and by lipoteichoic acid (LTA), lipopolysaccharides (LPS), and Polyinosinic-polycytidylic acid [Poly (I:C)] in head kidney leukocytes (HKLs) in vitro. Moreover, recombinant shTNF-α1 and shTNF-α2 upregulated the expression of endogenous shTNF-α1, shTNF-α2, shTNFR1, and shTNFR2, and enhanced intracellular bactericidal activity, with shTNF-α1 having a greater effect than shTNF-α2. These findings suggest important roles of fish TNFα1, TNFα2, and their receptors in bacterial infection and pathogen clearance, and provide a new insight into their function in antibacterial innate immunity., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Competing Interests: Declaration of competing interests The authors declare no conflict of interest.

Purpose/Aim: Acute movement disorder is an uncommon presenting symptom in patients with diabetes mellitus. We report a 20-year-old lady with poorly controlled type 1 diabetes, who presented with acute hemichorea and was found to have two rare diabetes-related central nervous complications of diabetic striatopathy and severe moyamoya disease (MMD). Materials and methods: She was treated with aggressive glycemic control; clonazepam and tetrabenazine as well as aspirin stroke prophylaxis for her MMD with resolution of her chorea 3 months later. She subsequently underwent cerebral revascularization surgery for her MMD. Results: This case highlights the possible differentials of acute chorea in diabetic patients and explores the pathophysiological mechanisms that may underlie both conditions in patients with type 1 diabetes. Conclusion: We recommend performing both magnetic resonance imaging (MRI) and magnetic resonance angiogram (MRA) brain for comprehensive evaluation of diabetic patients with new onset chorea. Prompt and accurate diagnosis is crucial as it guides prognostication and treatment strategies.

Background: Cerebral venous complications related to neurosurgical interventions are only rarely reported in the literature. Internal cerebral veins (ICVs) are vulnerable to injury during neurosurgical approaches to the pineal and thalamic regions. The occurrence of unilateral postoperative ICV thrombosis in children is extremely rare, with only 2 such cases reported thus far., Case Description: A 15-year-old child presented to the emergency department with headache, persistent vomiting, and pronounced lethargy for 3 days. Magnetic resonance imaging of the brain was performed and showed a large solid-cystic mass at the pineal region, resulting in upstream hydrocephalus. Serum beta-human chorionic gonadotropin was elevated, and a diagnosis of germ cell tumor was made. Patient was started on neoadjuvant chemotherapy, with partial response on repeat imaging after 3 courses of chemotherapy. Decision was made to proceed with surgical resection of the residual tumor. Magnetic resonance imaging of the brain performed on postoperative day 1 showed multiple foci of restricted diffusion in the right cerebral deep white matter, giving rise to a "string of pearls" appearance. There is also absence of enhancement of the right ICV, suspicious for deep cerebral venous thrombosis. This was confirmed on subsequent computed tomography venogram., Conclusions: Our reported case adds to the limited literature on postoperative ICV thrombosis in children and describes a unique imaging phenotype of venous watershed infarcts. Neurosurgeons and neuroradiologists should be aware of this unique imaging phenotype and have a high index of suspicion for deep cerebral venous thrombosis, especially in patients with prior neurosurgical intervention in the pineal or thalamic regions., (Copyright © 2020 Elsevier Inc. All rights reserved.)

As a central pro-inflammatory cytokine, interleukin-1β (IL-1β) plays critical roles in the inflammatory response, pathogen infection, and immunological challenges in mammals. Although fish IL-1β has been confirmed to participate in inflammatory response to pathogen infection, few studies have been performed to characterize the antibacterial and bactericidal functions of fish IL-1β. In this study, snakehead (Channa argus) IL-1β (shIL-1β) and its receptors, shIL-1R1 and shIL-1R2, were cloned and functionally characterized. ShIL-1β contained the IL-1 family signature domain, and a potential cutting site at Asp 96 that presented in all vertebrate IL-1β sequences. ShIL-1R1 had three extracellular IG-like domains and one intracellular signal TIR domain, while shIL-1R2 had three extracellular IG-like domain but lacked the intracellular signal TIR domain. ShIL-1β, shIL-1R1, and shIL-1R2 were constitutively expressed in all tested tissues, and their expressions could be induced by Aeromonas schubertii and Nocardia seriolae in the head kidney and spleen in vivo, and by LTA, LPS, and Poly (I:C) in head kidney leukocytes (HKLs) in vitro. Moreover, recombinant shIL-1β upregulated the expression of endogenous shIL-1β, shIL-R1, and shIL-R2 in snakehead HKLs, and enhanced intracellular bactericidal activity. Taken together, this study found that, like IL-1β and its receptors in mammals, shIL-1β and its receptors play crucial roles in antibacterial innate immunity. This provides new insight into the evolution of IL-1β function in vertebrates., Competing Interests: Declaration of competing interest The authors have no conflicting commercial or financial interest in publishing this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

A 14-year-old boy undergoing brain MRI had an incidental avidly enhancing lobulated lesion in the left superolateral orbital rim with associated cortical erosion. Apart from Contrast-enhanced Magnetic Resonance Imaging (MRI), and Computed Tomography (CT), Contrast-Enhanced Ultrasound (CEUS) was obtained prior to a biopsy. It provided additional information about the microvasculature and an orbital biopsy was subsequently performed through an upper eyelid crease incision with minimal blood loss and no postoperative complications. Histopathological examination revealed features which were compatible with the diagnosis of LCH. The authors propose that CEUS may be considered as an adjunct and possibly alternative imaging modality for the evaluation of craniofacial osseous lesions, especially in the orbital region (due to the known radio-sensitivity of the eyes) and in pediatric patients, to minimize the risk of ionizing-radiation exposure., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Inherited neurotransmitter disorders are rare neurometabolic conditions which encompass genetic disorders of neurotransmitter metabolism or transport. The clinical manifestations of these rare disorders are often nonspecific, ranging from encephalopathies and seizures to movement disorders. As a consequence, neurotransmitter disorders are underrecognized and often misdiagnosed. Accurate and timely diagnosis is, however, of utmost importance, given the availability of therapeutic strategies. A high index of clinical suspicion and familiarity with the neuroimaging phenotypes is therefore crucial. While the imaging features of various neurotransmitter disorders often overlap and are nonspecific, imaging can be helpful in providing useful clues to guide the diagnostic algorithm for uncommon conditions in a neonate presenting with nonspecific neurological symptoms. In this review paper, we aim to bring together current knowledge of neuroimaging phenotypes associated with inherited (primary) disorders of neurotransmitter biosynthesis. Magnetic resonance imaging phenotypes of disorders of monoamine biosynthesis, primary cerebral folate deficiency, disorders of pyridoxine metabolism, disorders of gamma-aminobutyric acid metabolism, nonketotic hyperglycinemia (glycine encephalopathy), disorders of serine biosynthesis, and cerebral creatine deficiency syndrome will be discussed and illustrated with case examples., Competing Interests: None., (Georg Thieme Verlag KG Stuttgart · New York.)

Pure bacterial cultures were isolated from different tissues of moribund Megalobrama terminalis from a high mortality event that occurred at a farm in Foshan, China. Two isolates (F2 and F3) were identified as Streptococcus dysgalactiae subsp. dysgalactiae based on morphological and biochemical detection as well as molecular analysis. In brain heart infusion broth, the best growth conditions of isolate F3 were 35ºC, salinity 5‰ and pH 7. Furthermore, infection with isolate F3 (1.2 × 10 6  CFU/fish) led to the death of M. terminalis and zebrafish (Danio rerio). However, isolate F3 had no obvious pathogenicity to tilapia (GIFT, Oreochromis niloticus). When the water temperature was 29ºC, the corresponding mortality rates for zebrafish infected by isolate F3 were higher than those at 23ºC. Culture for 24 and 72 hr with isolate F3 resulted in the same mortality rates for zebrafish. The antimicrobial susceptibility assay revealed that isolate F3 was susceptible to ampicillin, florfenicol and several other antibiotics but resistant to nalidixic acid, streptomycin, sulfamethoxazole/trimethoprim, neomycin and amikacin. To our knowledge, this is the first report that S. dysgalactiae infected the subtropical freshwater fish M. terminalis, which indicates that this bacterium is a potential threat to subtropical freshwater fish., (© 2019 John Wiley & Sons Ltd.)

Purpose: Conventional computed tomography (CT) exophthalmometry requires an intact lateral orbital wall and is therefore not feasible in patients who have undergone any form of lateral orbital wall surgery where the normal bony landmark may be lost or displaced. The purpose of our study is to validate an alternative method of CT exophthalmometry utilizing the posterior clinoid (PC) process as a new reference point that will allow for reproducible comparison of the anterior-posterior globe position in the preoperative and postoperative settings., Design: Cohort study., Methods: This is a retrospective study of 48 patients with clinically diagnosed thyroid eye disease who had undergone cross-sectional CT imaging in the pre- or postoperative settings. CT exophthalmometry was performed using both the conventional interzygomatic method and our proposed PC process method on all pre- and postoperative CT imaging by two independent observers. Interobserver variability analysis was performed with intraclass correlation coefficient. Correlation and agreement between the two methods were analyzed with Pearson correlation coefficient and linear regression method. All analyses were conducted at 5% level of significance with Stata MP V14., Results: Interobserver variability analysis showed an intraclass correlation coefficient of >0.9 for both interzygomatic and PC methods. There is good correlation between the two different measurements observed in both the pre- and postoperative groups (r = 0.68 and r = 0.72, respectively, P < 0.001). Linear regression showed good agreement between the two different measurements with most of the points lying within the 95% limits., Conclusions: Our new method agrees well with the conventional method and has the added benefit of being able to reliably assess the anterior-posterior globe position in patients who do not have intact lateral orbital walls after decompressive surgery.

The interpretation of cerebral venous pathologies in paediatric practice is challenging as there are several normal anatomical variants, and the pathologies are diverse, involving the venous system through direct and indirect mechanisms. This paper aims to provide a comprehensive review of these entities, as their awareness can avoid potential diagnostic pitfalls. We also propose a practical classification system of paediatric cerebral venous pathologies, which will enable more accurate reporting of the neuroimaging findings, as relevant to the underlying pathogenesis of these conditions. The proposed classification system comprises of the following main groups: arterio-venous shunting-related disorders, primary venous malformations and veno-occlusive disorders. A multimodal imaging approach has been included in the relevant subsections, with a brief overview of the modality-specific pitfalls that can also limit interpretation of the neuroimaging. The article also summarises the current literature and international practices in terms of management options and outcomes in specific disease entities.

OBJECTIVE. The purpose of this article is to describe my institution's experience using a black bone sequence (a 3D low flip angle gradient-echo MRI sequence) in children with craniosynostosis and present our MRI brain protocol for the imaging of craniosynostosis. CONCLUSION. The MRI protocol proposed in this article has the potential to replace CT for the diagnosis and surveillance of craniosynostosis. MRI has excellent soft-tissue resolution and hence is superior to CT in the detection of associated intracranial anomalies and potential complications.