A Narrative Review Illustrating the Clinical Utility of Electroencephalogram-Guided Anesthesia Care in Children.

The major therapeutic end points of general anesthesia include hypnosis, amnesia, and immobility. There is a complex relationship between general anesthesia, responsiveness, hemodynamic stability, and reaction to noxious stimuli. This complexity is compounded in pediatric anesthesia, where clinicians manage children from a wide range of ages, developmental stages, and body sizes, with their concomitant differences in physiology and pharmacology. This renders anesthetic requirements difficult to predict based solely on a child's age, body weight, and vital signs. Electroencephalogram (EEG) monitoring provides a window into children's brain states and may be useful in guiding clinical anesthesia management. However, many clinicians are unfamiliar with EEG monitoring in children. Young children's EEGs differ substantially from those of older children and adults, and there is a lack of evidence-based guidance on how and when to use the EEG for anesthesia care in children. This narrative review begins by summarizing what is known about EEG monitoring in pediatric anesthesia care. A key knowledge gap in the literature relates to a lack of practical information illustrating the utility of the EEG in clinical management. To address this gap, this narrative review illustrates how the EEG spectrogram can be used to visualize, in real time, brain responses to anesthetic drugs in relation to hemodynamic stability, surgical stimulation, and other interventions such as cardiopulmonary bypass. This review discusses anesthetic management principles in a variety of clinical scenarios, including infants, children with altered conscious levels, children with atypical neurodevelopment, children with hemodynamic instability, children undergoing total intravenous anesthesia, and those undergoing cardiopulmonary bypass. Each scenario is accompanied by practical illustrations of how the EEG can be visualized to help titrate anesthetic dosage to avoid undersedation or oversedation when patients experience hypotension or other physiological challenges, when surgical stimulation increases, and when a child's anesthetic requirements are otherwise less predictable. Overall, this review illustrates how well-established clinical management principles in children can be significantly complemented by the addition of EEG monitoring, thus enabling personalized anesthesia care to enhance patient safety and experience.

The effects of psychosocial interventions using generic photos on social interaction, mood and quality of life of persons with dementia: a systematic review.

BACKGROUND: Although family photos are often used in the psychosocial care for people with dementia, little is known about the use and effectiveness of generic photos. This systematic literature review explored psychosocial interventions using generic photos for people with dementia, and the effects they have on their social interaction and/or mood and/or quality of life. In addition, it was investigated whether these interventions made use of technology in its implementation. METHODS: A systematic search on the following databases was performed: PubMed, Embase, APA PsychInfo, Cinahl, Web of Science, Scopus and Cochrane Central. Inclusion and exclusion criteria were based on the PICO model (Population, Intervention, Comparison, Outcome), and quality assessment was undertaken using the Weight of Evidence Framework. Narrative synthesis was undertaken to summarize study characteristics- settings and designs, type of psychosocial interventions identified, type of photos and technology used, outcome measures, and results. RESULTS: A total of 2,035 results were found, however after title, abstract and full-text screening, a total of 8 studies were included. The most common psychosocial intervention using generic photos was found to be reminiscence therapy, followed by art-viewing activities. In studies that used technology, it was reported that viewing digitalized photos were either similar or better to conventional printed photos. Despite photos being generic, it was found that generic photos could still hold personal significance to the person with dementia. Some positive and significant effects were found for the outcomes social interaction, mood and quality of life, though no study evaluated all three outcomes. Two studies were rated as having high overall quality, 4 were rated as fair, and 2 studies had a low quality assessment rating. CONCLUSION: Studies found using generic photos were limited, showing varying outcomes and methodological quality. Firm conclusions on the effectiveness of interventions using generic photos are not possible. However, the use of generic photos in psychosocial interventions is a promising area for future research. Researchers should consider studies with better methodological quality and larger samples; and qualitative studies where the intention is to get better insight into successful implementation and impact mechanisms of such psychosocial interventions. TRIAL REGISTRATION: n/a.

Known in the nursing home: development and evaluation of a digital person-centered artistic photo-activity intervention to promote social interaction between residents with dementia, and their formal and informal carers.

BACKGROUND: To address the lack of social interaction and meaningful activities for persons with dementia (PWD) in nursing homes an artistic Photo-Activity was designed. The present study aims to develop a digital version of the Photo-Activity and to investigate its implementation and impact on nursing home residents with advanced dementia, and their (in)formal carers. METHODS: First, within a user-participatory design, a digital-app version of the Photo-Activity will be developed and pilot-tested, in co-creation with (in)formal carers and PWD. Next, the feasibility and effectiveness of the Photo-Activity versus a control activity will be explored in a randomized controlled trial with nursing home residents (N=90), and their (in)formal carers. Residents will be offered the Photo-Activity or the control activity by (in)formal carers during one month. Measurements will be conducted by independent assessors at baseline (T0), after one month (T1) and at follow up, two weeks after T1 (T2). Qualitative and quantitative methods will be used to investigate the effects of the intervention on mood, social interaction and quality of life of the PWD, sense of competence of informal carers, empathy and personal attitude of the formal carers, and quality of the relationship between the PWD, and their (in)formal carers. In addition, a process evaluation will be carried out by means of semi-structured interviews with the participating residents and (in)formal carers. Finally, an implementation package based on the process evaluation will be developed, allowing the scaling up of the intervention to other care institutions. DISCUSSION: Results of the trial will be available for dissemination by Spring 2023. The digital Photo-Activity is expected to promote meaningful connections between the resident with dementia, and their (in)formal carers through the facilitation of person-centered conversations. TRIAL REGISTRATION: Netherlands Trial Register: NL9219 ; registered (21 January 2021); NTR (trialregister.nl).

Deuterium MRS of early treatment-induced changes in tumour lactate in vitro.

Elevated production of lactate is a key characteristic of aberrant tumour cell metabolism and can be non-invasively measured as an early marker of tumour response using deuterium (2 H) MRS. Following treatment, changes in the 2 H-labelled lactate signal could identify tumour cell death or impaired metabolic function, which precede morphological changes conventionally used to assess tumour response. In this work, the association between apoptotic cell death, extracellular lactate concentration, and early treatment-induced changes in the 2 H-labelled lactate signal was established in an in vitro tumour model. Experiments were conducted at 7 T on acute myeloid leukaemia (AML) cells, which had been treated with 10 µg/mL of the chemotherapeutic agent cisplatin. At 24 and 48 h after cisplatin treatment the cells were supplied with 20 mM of [6,6'-2 H2 ]glucose and scanned over 2 h using a two-dimensional 2 H MR spectroscopic imaging sequence. The resulting signals from 2 H-labelled glucose, lactate, and water were quantified using a spectral fitting algorithm implemented on the Oxford Spectroscopy Analysis MATLAB toolbox. After scanning, the cells were processed for histological stains (terminal deoxynucleotidyl transferase UTP nick end labelling and haematoxylin and eosin) to assess apoptotic area fraction and cell morphology respectively, while a colorimetric assay was used to measure extracellular lactate concentrations in the supernatant. Significantly lower levels of 2 H-labelled lactate were observed in the 48 h treated cells compared with the untreated and 24 h treated cells, and these changes were significantly correlated with an increase in apoptotic fraction and a decrease in extracellular lactate. By establishing the biological processes associated with treatment-induced changes in the 2 H-labelled lactate signal, these findings suggest that 2 H MRS of lactate may be valuable in evaluating early tumour response.

Randomised controlled trial of dexmedetomidine sedation vs general anaesthesia for inguinal hernia surgery on perioperative outcomes in infants.

BACKGROUND: Neonates and infants undergoing general anaesthesia for hernia surgery are at risk of perioperative cardiorespiratory adverse events. The use of regional anaesthesia with dexmedetomidine preserves airway tone and may potentially avoid these complications. This study compares the perioperative conditions and adverse events between dexmedetomidine sedation with caudal block and general anaesthesia with caudal block for inguinal hernia surgery in infants. METHODS: A randomised controlled trial was conducted in a tertiary hospital in Singapore involving 104 infants younger than 3 months, who were randomised to receive either dexmedetomidine sedation (DEX) with caudal block or general sevoflurane anaesthesia with tracheal intubation and caudal block (GA) for inguinal hernia surgery. Perioperative conditions, haemodynamics and adverse events were compared between groups. RESULTS: Fifty-one infants received DEX and 48 infants received GA. In the DEX group, 46 infants (90.2%) had their operations completed solely under this technique, two (3.9%) were converted to general anaesthesia with intubation, and three (5.9%) required brief administration of nitrous oxide or low-dose sevoflurane. Overall, 96.1% of infants in the DEX group did not require intubation. Perioperative conditions were similar in both groups. The DEX group had significantly lower heart rates and higher mean arterial pressures intraoperatively. Two infants in the DEX group (3.9%) required postoperative intensive care admission compared with six infants (12.5%) in the GA group. CONCLUSIONS: Dexmedetomidine sedation with caudal block provides a feasible alternative to general anaesthesia in infants undergoing hernia surgery. This technique avoids the need for tracheal intubation, which may be beneficial in neonates. CLINICAL TRIAL REGISTRATION: NCT02559102.

History and Current Status of Cardiac Anesthesia in Singapore.

Singapore is a small Southeast Asian island city-state located at the tip of the Malay peninsula with a population of 5.61 million people. It was a former British colony that went on to become a part of Malaysia before gaining independence in 1965. Since then, Singapore has developed tremendously from a small fishing village into the region's medical hub. This article will explore the roots of cardiac anesthesia in Singapore and how it has developed into a subspecialty today.

Transtracheal jet oxygenation: Comparing the efficacy and safety of two self-made Y-connector devices with the ENK oxygen flow modulator™ in an infant animal model.

BACKGROUND: Self-made Y-connector jet-oxygenation devices with wide-bore expiratory port have been described but not evaluated in infant models. Little is known about the effect of oxygen flow rates on jet oxygenation via transtracheal cannula. AIMS: The aim of this study was to compare two self-made Y-connector jet-oxygenation devices against the ENK oxygen flow modulator™, and the effects of three different oxygen flow rates based on body weight, in both unobstructed and obstructed airways, on the time to re-oxygenate in a rabbit infant model. The aim was also to assess the effectiveness of an oxygen flow rate of 1 L/min, for re-oxygenation using ENK oxygen flow modulator™. METHODS: Nine rabbits were grouped in threes: Group 1 had a Y-connector attached to an intravenous infusion tubing, Group 2 the same Y-connector attached to a perfusion oxygenator tubing and Group 3, ENK oxygen flow modulator™. From oxygen saturations of 75%, the rabbits were jet oxygenated using their assigned device for 10 minutes at each flow rate of 1 L/kg/min, 1.5 L/kg/min and 2 L/kg/min with their airways unobstructed and later, obstructed. Group 3 had additional experiments involving an absolute oxygen flow rate of 1 L/min. RESULTS: All devices resulted in rapid re-oxygenation within 40 seconds at flow rates of 1 L/kg/min. Oxygen flow rates beyond 1 L/kg/min in obstructed airways resulted in high airway pressures. All rabbits in Group 3 with obstructed airways died from barotrauma when jet oxygenated at a flow rate of 1.5 L/kg/min. When an oxygen flow rate of 1 L/min was used in Group 3, there was a failure to re-oxygenate to SpO2 90% within 120 seconds in some rabbits. CONCLUSION: Our animal model results suggest that self-made Y-connector jet-oxygenation devices with wide-bore expiratory port are efficacious and perhaps safer than ENK oxygen flow modulator™ in obstructed airways, and jet oxygenation with minimal oxygen flow rates starting at 1 L/kg/min or (age [years] + 4) L/min, whichever lower, should be considered.

Haploid Mammalian Genetic Screen Identifies UBXD8 as a Key Determinant of HMGCR Degradation and Cholesterol Biosynthesis.

OBJECTIVE: The cellular demand for cholesterol requires control of its biosynthesis by the mevalonate pathway. Regulation of HMGCR (3-hydroxy-3-methylglutaryl coenzyme A reductase), a rate-limiting enzyme in this pathway and the target of statins, is a key control point herein. Accordingly, HMGCR is subject to negative and positive regulation. In particular, the ability of oxysterols and intermediates of the mevalonate pathway to stimulate its proteasomal degradation is an exquisite example of metabolically controlled feedback regulation. To define the genetic determinants that govern this process, we conducted an unbiased haploid mammalian genetic screen. APPROACH AND RESULTS: We generated human haploid cells with mNeon fused to endogenous HMGCR using CRISPR/Cas9 and used these cells to interrogate regulation of HMGCR abundance in live cells. This resulted in identification of known and new regulators of HMGCR, and among the latter, UBXD8 (ubiquitin regulatory X domain-containing protein 8), a gene that has not been previously implicated in this process. We demonstrate that UBXD8 is an essential determinant of metabolically stimulated degradation of HMGCR and of cholesterol biosynthesis in multiple cell types. Accordingly, UBXD8 ablation leads to aberrant cholesterol synthesis due to loss of feedback control. Mechanistically, we show that UBXD8 is necessary for sterol-stimulated dislocation of ubiquitylated HMGCR from the endoplasmic reticulum membrane en route to proteasomal degradation, a function dependent on its UBX domain. CONCLUSIONS: We establish UBXD8 as a previously unrecognized determinant that couples flux across the mevalonate pathway to control of cholesterol synthesis and demonstrate the feasibility of applying mammalian haploid genetics to study metabolic traits.

A pilot study of dexmedetomidine sedation and caudal anesthesia for inguinal hernia repair in infants.

BACKGROUND: Recent concerns regarding possible long-term effects of early anesthesia exposure on neurodevelopment in children have provided an impetus to explore alternative anesthetic techniques using potentially neuroprotective agents. Dexmedetomidine has not been implicated in anesthesia-induced neurotoxicity and has been shown to be neuroprotective in preclinical studies. We describe a case series of 50 neonates and infants who received dexmedetomidine sedation with caudal anesthesia instead of general endotracheal anesthesia for inguinal hernia surgery. METHODS: We conducted a retrospective chart review on all neonates and infants who underwent inguinal hernia surgery with dexemetomidine sedation and caudal anesthesia in our institution. We started exploring this technique since October 2011 and established a protocol of administering dexmedetomidine 2 mcg·kg(-1) over 10 min, followed by 1 mcg·kg(-1) over the next 10 min. This led to satisfactory conditions for caudal placement in 20 min, with minimal need for airway intervention during surgery. RESULTS: The median gestational age of the infants was 31.4 (28.7, 36.0) weeks and median postconceptual age was 39.7 weeks (IQR 37.8, 45.7) at time of surgery. Of patients, 86% had surgery successfully completed under this technique alone. Seven patients required sevoflurane or nitrous oxide due to failed caudal block (n = 1) or difficult or prolonged surgery (n = 6). After establishing the sedation protocol and excluding patients with large or complicated hernias, the success rate was 96%. Transient intra-operative apnea or hypoventilation occurred in five patients and postoperative apnea in two patients. All respiratory events were easily reversed and no patient developed significant bradycardia or required intubation. CONCLUSIONS: Dexmedetomidine sedation with caudal anesthesia is a feasible alternative to spinal or general anesthesia in selected infants undergoing uncomplicated hernia surgery. It avoids the need for endotracheal intubation and may be potentially beneficial in avoiding the unknown effects of general anesthesia on neurodevelopment.

Selective insensitivity to income held by the richest.

The misperception of income inequality is often touted as a critical barrier to more widespread support of redistributive policies. Here, we examine to what extent and why (mis)perceptions vary systematically across the income distribution. Drawing on data from four studies (N = 2,744)-including a representative sample and preregistered incentive-compatible experiments-we offer converging evidence that people specifically underestimate the amount of income held by the top of the income distribution. While this selective underestimation is likely driven by multiple mechanisms, including systemic factors, we find that cognitive biases contribute to the observed pattern of results. The rise of inequality in many developed countries has been documented before, and the fact that this growing inequality is largely driven by the outsized gains of the richest individuals may pose new challenges previously underappreciated: our theory and findings highlight that cognitive biases pose a key obstacle to people's recognition of the concentration of income among the richest individuals, and may potentially distort their preferences for redistribution. We conclude by discussing future directions for research and the importance of incorporating behavioral and cognitive limitations into the design of redistributive public policy.

Comparative biochemical analysis of full-length and truncated BaqA α-amylases from Bacillus aquimaris MKSC 6.2.

BaqA is a raw starch degrading α-amylase produced by the marine bacterium Bacillus aquimaris MKSC 6.2, associated with soft corals. This α-amylase belongs to a new subfamily Glycoside Hydrolases (GH) 13_45 which has several unique characteristics, namely, a pair of tryptophan residues Trp201 and Trp202, a distinct LPDIx signature in the Conserved Sequence Region-V (CSR-V), and an elongated C-terminus containing five aromatic residues. The research aims to investigate physicochemical, kinetics, and biochemical properties of BaqA. In this study, the full-length enzyme (BaqA) and a truncated form of BaqA (designated as BaqAΔC), lacking the C-terminal 34 amino acids were constructed and expressed in Escherichia coli ArcticExpress (DE3). BaqA formed inclusion bodies, while BaqAΔC was produced as a soluble protein. Purified and refolded BaqA exhibited a catalytic efficiency (k cat/K m) of 53.1 ± 6.3 mL mg-1 s-1 at 40 °C and pH 7.5, whereas the purified BaqAΔC displayed k cat/K m of 11.4 ± 1.3 mL mg-1 s-1 under the optimum condition of 50 °C and pH 6.5. Moreover, BaqAΔC showed a slight reduction in the binding affinity towards sago granules. Interestingly, BaqAΔC displayed robust stability and halotolerant properties compared to BaqA. BaqAΔC maintained 50 % amylolytic activity for up to 6 h, whereas BaqA lost over 50 % of its activity within 90 min. Furthermore, BaqAΔC showed a remarkable increase in amylolytic activity upon the addition of NaCl, with an optimum concentration of 0.5 M. Even at a high salt concentration (1.5 M NaCl), BaqAΔC retained over 50 % of its residual activity. Taken together, its solubility, amylolytic activity, stability, ability to degrade raw starch, and moderate halotolerance make BaqAΔC a promising candidate for various starch processing industries.

Peer-reviewed publications in orthopaedic surgery from lower income countries: A comparative analysis.

INTRODUCTION: Musculoskeletal (MSK) disease is a substantial global burden, especially in lower income countries. However, limited research has been published on MSK health by scholars from these countries. We aimed to study the distribution of authorships, including trends in peer-reviewed orthopaedic publications based on each author's affiliated institution's country income status. METHODS: Based on a bibliometric search, 119 orthopaedic-related journals were identified using the Journal Citation Reports database. Details of all scientific articles published in these journals between 2012 and 2021 were used to study trends and association between each of the author's affiliated institution's country income status, using the World Bank Classification. RESULTS: Of the 133,718 unique articles, 87.6% had at least one author affiliation from a high-income country (HIC), 7.0% from an upper-middle income country (UMIC), 5.2% from a lower-middle income country (LMIC), and 0.2% from a low-income country (LIC). Overall, these articles were cited 1,825,365 times, with 92.5% of citations from HIC-affiliated authors and < 0.1% from LIC-affiliated authors. Over the 10-year study period, HIC-affiliated articles demonstrated the largest increase in the number of publications (9107-14,619), compared to UMIC-affiliated (495-1214), LMIC-affiliated (406-874), and LIC-affiliated articles (4-28). CONCLUSIONS: There are large and persistent disparities in orthopaedic research publications based on the country income status of the author's affiliated institution, especially in the higher impact orthopaedic journals. Efforts should be made to increase opportunities for scholars from LICs and LMICs to publish their research in high-impact orthopaedic journals.

SPRING is a Dedicated Licensing Factor for SREBP-Specific Activation by S1P.

SREBP transcription factors are central regulators of lipid metabolism. Their proteolytic activation requires ER to the Golgi translocation and subsequent cleavage by site-1-protease (S1P). Produced as a proprotein, S1P undergoes autocatalytic cleavage from its precursor S1PA to mature S1PC form. Here, we report that SPRING (previously C12ORF29) and S1P interact through their ectodomains, and that this facilitates the autocatalytic cleavage of S1PA into its mature S1PC form. Reciprocally, we identified a S1P recognition-motif in SPRING and demonstrate that S1P-mediated cleavage leads to secretion of the SPRING ectodomain in cells, and in liver-specific Spring knockout (LKO) mice transduced with AAV-mSpring. By reconstituting SPRING variants into SPRINGKO cells we show that the SPRING ectodomain supports proteolytic maturation of S1P and SREBP signaling, but that S1P-mediated SPRING cleavage is not essential for these processes. Absence of SPRING modestly diminishes proteolytic maturation of S1PA→C and trafficking of S1PC to the Golgi. However, despite reaching the Golgi in SPRINGKO cells, S1PC fails to rescue SREBP signaling. Remarkably, whereas SREBP signaling was severely attenuated in SPRINGKO cells and LKO mice, that of ATF6, another S1P substrate, was unaffected in these models. Collectively, our study positions SPRING as a dedicated licensing factor for SREBP-specific activation by S1P.

2023 Society for Academic Emergency Medicine Consensus Conference on Precision Emergency Medicine: Development of a policy-relevant, patient-centered research agenda.

OBJECTIVES: Precision medicine is data-driven health care tailored to individual patients based on their unique attributes, including biologic profiles, disease expressions, local environments, and socioeconomic conditions. Emergency medicine (EM) has been peripheral to the precision medicine discourse, lacking both a unified definition of precision medicine and a clear research agenda. We convened a national consensus conference to build a shared mental model and develop a research agenda for precision EM. METHODS: We held a conference to (1) define precision EM, (2) develop an evidence-based research agenda, and (3) identify educational gaps for current and future EM clinicians. Nine preconference workgroups (biomedical ethics, data science, health professions education, health care delivery and access, informatics, omics, population health, sex and gender, and technology and digital tools), comprising 84 individuals, garnered expert opinion, reviewed relevant literature, engaged with patients, and developed key research questions. During the conference, each workgroup shared how they defined precision EM within their domain, presented relevant conceptual frameworks, and engaged a broad set of stakeholders to refine precision EM research questions using a multistage consensus-building process. RESULTS: A total of 217 individuals participated in this initiative, of whom 115 were conference-day attendees. Consensus-building activities yielded a definition of precision EM and key research questions that comprised a new 10-year precision EM research agenda. The consensus process revealed three themes: (1) preeminence of data, (2) interconnectedness of research questions across domains, and (3) promises and pitfalls of advances in health technology and data science/artificial intelligence. The Health Professions Education Workgroup identified educational gaps in precision EM and discussed a training roadmap for the specialty. CONCLUSIONS: A research agenda for precision EM, developed with extensive stakeholder input, recognizes the potential and challenges of precision EM. Comprehensive clinician training in this field is essential to advance EM in this domain.

Current practices in library/informatics instruction in academic libraries serving medical schools in the Western United States: a three-phase action research study.

BACKGROUND: To conduct a systematic assessment of library and informatics training at accredited Western U.S. medical schools. To provide a structured description of core practices, detect trends through comparisons across institutions, and to identify innovative training approaches at the medical schools. METHODS: Action research study pursued through three phases. The first phase used inductive analysis on reported library and informatics skills training via publicly-facing websites at accredited medical schools and the academic health sciences libraries serving those medical schools. Phase Two consisted of a survey of the librarians who provide this training to undergraduate medical education students at the Western U.S. medical schools. The survey revealed gaps in forming a complete picture of current practices, thereby generating additional questions that were answered through the Phase Three in-depth interviews. RESULTS: Publicly-facing websites reviewed in Phase One offered uneven information about library and informatics training at Western U.S. medical schools. The Phase Two survey resulted in a 77% response rate. The survey produced a clearer picture of current practices of library and informatics training. The survey also determined the readiness of medical students to pass certain aspects of the United States Medical Licensure Exam. Most librarians interacted with medical school curricular leaders through either curricula committees or through individual contacts. Librarians averaged three (3) interventions for training within the four-year curricula with greatest emphasis upon the first and third years. Library/informatics training was integrated fully into the respective curricula in almost all cases. Most training involved active learning approaches, specifically within Problem-Based Learning or Evidence-Based Medicine contexts. The Phase Three interviews revealed that librarians are engaged with the medical schools' curricular leaders, they are respected for their knowledge and teaching skills, and that they need to continually adapt to changes in curricula. CONCLUSIONS: This study offers a long overdue, systematic view of current practices of library/informatics training at Western U.S. medical schools. Medical educators, particularly curricular leaders, will find opportunities in this study's results for more productive collaborations with the librarians responsible for library and informatics training at their medical schools.

Control of murine brown adipocyte development by GATA6.

Brown adipose tissue (BAT) is a thermogenic organ that protects animals against hypothermia and obesity. BAT derives from the multipotent paraxial mesoderm; however, the identity of embryonic brown fat progenitor cells and regulators of adipogenic commitment are unclear. Here, we performed single-cell gene expression analyses of mesenchymal cells during mouse embryogenesis with a focus on BAT development. We identified cell populations associated with the development of BAT, including Dpp4+ cells that emerge at the onset of adipogenic commitment. Immunostaining and lineage-tracing studies show that Dpp4+ cells constitute the BAT fascia and contribute minorly as adipocyte progenitors. Additionally, we identified the transcription factor GATA6 as a marker of brown adipogenic progenitor cells. Deletion of Gata6 in the brown fat lineage resulted in a striking loss of BAT. Together, these results identify progenitor and transitional cells in the brown adipose lineage and define a crucial role for GATA6 in BAT development.

Early Neurodevelopmental Outcomes Following Exposure to General Anesthesia in Infancy: EGAIN, a Prospective Cohort Study.

BACKGROUND: General anesthesia (GA) is known to worsen neural outcomes in animals, but human research assessing early-life GA exposure and neurodevelopment show inconsistent findings. We investigated the effects of a single GA exposure for minor surgery on the neurodevelopment of healthy children at multiple time-points, using clinical assessments along with behavioral and neurophysiological measures rarely used in human research. METHODS: GA-exposed children were a prospective cohort of 250 full-term, healthy infants who underwent GA for minor surgery before 15 months. Nonexposed children were from a separate cohort of similar age, sex, ethnicity, and maternal education. In both cohorts, clinical measures (Bayley Scales of Infant and Toddler Development-III [BSID-III] and Child Behavior Checklist [CBCL1½-5]) were assessed at 24 months, and experimental tests (memory and attentional) and neurophysiology (event-related potentials) at 6 and 18 months. RESULTS: At 24 months, there were no differences between GA-exposed and nonexposed children in the cognitive, language, motor, and socioemotional domains of the BSDI-III; however, GA-exposed children had poorer parental-reported scores in BSID-III general adaptability (94.2 vs. 99.0 [mean difference, 4.77; 97.3% confidence interval, -9.29, -0.24]; P =0.020) and poorer internalizing behavior scores on CBCL1½-5 (52.8 vs. 49.4 [mean difference, 3.35; 97.3% confidence interval, 0.15-6.55]; P =0.021). For experimental measures, GA-exposed children showed differences in 4 tests at 6 and 18 months. CONCLUSIONS: GA-exposed children did not differ from unexposed children in cognitive, language or motor outcomes at 24 months, but exhibited poorer parent-reported behavior scores. Differences in infant behavior and neurophysiology were detected at 6 and 18 months. Neurophysiological assessments may complement clinically relevant assessments to provide greater insights into neurodevelopment following early GA exposure.

Interim Singapore guidelines for basic and advanced life support for paediatric patients with suspected or confirmed COVID-19.

The COVID-19 pandemic has resulted in significant challenges for the resuscitation of paediatric patients, especially for infants and children who are suspected or confirmed to be infected. Thus, the paediatric subcommittee of the Singapore Resuscitation and First Aid Council developed interim modifications to the current Singapore paediatric guidelines using extrapolated data from the available literature, local multidisciplinary expert consensus and institutional best practices. It is hoped that this it will provide a framework during the pandemic for improved outcomes in paediatric cardiac arrest patients in the local context, while taking into consideration the safety of all community first responders, medical frontline providers and healthcare workers.

High frequency ultrasound nonlinear scattering from porphyrin nanobubbles.

Emerging contrast imaging studies have highlighted the potential of nanobubbles for both intravascular and extravascular applications. Reports to date on nanobubbles have generally utilized low frequencies (<12 MHz), high concentrations (>109 mL-1), and B-mode or contrast-mode on preclinical and clinical systems. However, none of these studies directly examined nanobubble acoustic signatures systematically to implement nonlinear imaging schemes in a methodical manner based on nanobubble behaviour. Here, nanobubble nonlinear behaviour is investigated at high frequencies (12.5, 25, 30 MHz) and low concentration (106 mL-1) in a channel phantom, with different pulse types in single- and multi-pulse sequences to examine behaviour under conditions relevant to high frequency imaging. Porphyrin nanobubbles are demonstrated to initiate nonlinear scattering at high frequencies in a pressure-threshold dependent manner, as previously observed at low frequencies. This threshold behaviour was then utilized to demonstrate enhanced nanobubble imaging with pulse inversion, amplitude modulation, and a combination of the two, progressing towards the improved sensitivity and expanded utility of these ultrasound contrast agents.