Developmentally regulated subnuclear genome reorganization restricts neural progenitor competence in Drosophila.

Stem and/or progenitor cells often generate distinct cell types in a stereotyped birth order and over time lose competence to specify earlier-born fates by unknown mechanisms. In Drosophila, the Hunchback transcription factor acts in neural progenitors (neuroblasts) to specify early-born neurons, in part by indirectly inducing the neuronal transcription of its target genes, including the hunchback gene. We used in vivo immuno-DNA FISH and found that the hunchback gene moves to the neuroblast nuclear periphery, a repressive subnuclear compartment, precisely when competence to specify early-born fate is lost and several hours and cell divisions after termination of its transcription. hunchback movement to the lamina correlated with downregulation of the neuroblast nuclear protein, Distal antenna (Dan). Either prolonging Dan expression or disrupting lamina interfered with hunchback repositioning and extended neuroblast competence. We propose that neuroblasts undergo a developmentally regulated subnuclear genome reorganization to permanently silence Hunchback target genes that results in loss of progenitor competence.

Mosaic analysis with double markers reveals tumor cell of origin in glioma.

Cancer cell of origin is difficult to identify by analyzing cells within terminal stage tumors, whose identity could be concealed by the acquired plasticity. Thus, an ideal approach to identify the cell of origin is to analyze proliferative abnormalities in distinct lineages prior to malignancy. Here, we use mosaic analysis with double markers (MADM) in mice to model gliomagenesis by initiating concurrent p53/Nf1 mutations sporadically in neural stem cells (NSCs). Surprisingly, MADM-based lineage tracing revealed significant aberrant growth prior to malignancy only in oligodendrocyte precursor cells (OPCs), but not in any other NSC-derived lineages or NSCs themselves. Upon tumor formation, phenotypic and transcriptome analyses of tumor cells revealed salient OPC features. Finally, introducing the same p53/Nf1 mutations directly into OPCs consistently led to gliomagenesis. Our findings suggest OPCs as the cell of origin in this model, even when initial mutations occur in NSCs, and highlight the importance of analyzing premalignant stages to identify the cancer cell of origin.

Single generation epigenetic change in captivity and reinforcement in subsequent generations in a delta smelt (Hypomesus transpacificus) conservation hatchery.

A refugial population of the endangered delta smelt (Hypomesus transpacificus) has been maintained at the Fish Conservation and Culture Laboratory (FCCL) at UC Davis since 2008. Despite intense genetic management, fitness differences between wild and cultured fish have been observed at the FCCL. To investigate the molecular underpinnings of hatchery domestication, we used whole-genome bisulfite sequencing to quantify epigenetic differences between wild and hatchery-origin delta smelt. Differentially methylated regions (DMRs) were identified from 104 individuals by comparing the methylation patterns in different generations of hatchery fish (G1, G2, G3) with their wild parents (G0). We discovered a total of 132 significant DMRs (p < .05) between G0 and G1, 132 significant DMRs between G0 and G2, and 201 significant DMRs between G0 and G3. Our results demonstrate substantial differences in methylation patterns emerged between the wild and hatchery-reared fish in the early generations in the hatchery, with a higher proportion of hypermethylated DMRs in hatchery-reared fish. The rearing environment was found to be a stronger predictor of individual clustering based on methylation patterns than family, sex or generation. Our study indicates a reinforcement of the epigenetic status with successive generations in the hatchery environment, as evidenced by an increase in methylation in hypermethylated DMRs and a decrease in methylation in hypomethylated DMRs over time. Lastly, our results demonstrated heterogeneity in inherited methylation pattern in families across generations. These insights highlight the long-term consequences of hatchery practices on the epigenetic landscape, potentially impacting wild fish populations.

LRRC8A anion channels modulate vascular reactivity via association with myosin phosphatase rho interacting protein.

Leucine-rich repeat containing 8A (LRRC8A) volume regulated anion channels (VRACs) are activated by inflammatory and pro-contractile stimuli including tumor necrosis factor alpha (TNFα), angiotensin II and stretch. LRRC8A associates with NADPH oxidase 1 (Nox1) and supports extracellular superoxide production. We tested the hypothesis that VRACs modulate TNFα signaling and vasomotor function in mice lacking LRRC8A exclusively in vascular smooth muscle cells (VSMCs, Sm22α-Cre, Knockout). Knockout (KO) mesenteric vessels contracted normally but relaxation to acetylcholine (ACh) and sodium nitroprusside (SNP) was enhanced compared to wild type (WT). Forty-eight hours of ex vivo exposure to TNFα (10 ng/mL) enhanced contraction to norepinephrine (NE) and markedly impaired dilation to ACh and SNP in WT but not KO vessels. VRAC blockade (carbenoxolone, CBX, 100 µM, 20 min) enhanced dilation of control rings and restored impaired dilation following TNFα exposure. Myogenic tone was absent in KO rings. LRRC8A immunoprecipitation followed by mass spectroscopy identified 33 proteins that interacted with LRRC8A. Among them, the myosin phosphatase rho-interacting protein (MPRIP) links RhoA, MYPT1 and actin. LRRC8A-MPRIP co-localization was confirmed by confocal imaging of tagged proteins, Proximity Ligation Assays, and IP/western blots. siLRRC8A or CBX treatment decreased RhoA activity in VSMCs, and MYPT1 phosphorylation was reduced in KO mesenteries suggesting that reduced ROCK activity contributes to enhanced relaxation. MPRIP was a target of redox modification, becoming oxidized (sulfenylated) after TNFα exposure. Interaction of LRRC8A with MPRIP may allow redox regulation of the cytoskeleton by linking Nox1 activation to impaired vasodilation. This identifies VRACs as potential targets for treatment or prevention of vascular disease.

Home-based fecal calprotectin utilization in a general pediatric gastroenterology clinic.

OBJECTIVE: Remote investigation and monitoring have gained importance in ambulatory practice. A home-based fecal calprotectin (FC) test has been developed where the sample is processed and analyzed at home through a smartphone application. We aimed to assess the use of standard ELISA (sFC) versus home-based (hFC) FC testing in a general pediatric gastroenterology clinic. METHODS: Ambulatory pediatric patients with hFC or sFC performed between August 2019 and November 2020 were included. Data regarding demographics, clinical characteristics, medication use, investigations, and final diagnosis, categorized as inflammatory bowel disease (IBD), functional gastrointestinal (GI) disorders, organic non-IBD (ONI) GI disorders, non-GI disorders, and undetermined after 6 months of investigation, were recorded. RESULTS: A total of 453 FC tests from 453 unique patients were included. Of those, 249 (55%) were hFC. FC levels (median) were higher in children with IBD compared to non-IBD diagnosis (sFC 795 vs. 57 µg/g, hFC 595 vs. 47 µg/g, p < 0.001), and in ONI compared to functional GI disorders (sFC 85 vs. 54 µg/g, p = 0.003, hFC 57 vs. 40 µg/g, p < 0.001). No significant difference was observed between different ONI GI disorders or subtypes of functional disorders. Age did not significantly influence levels. CONCLUSIONS: Overall, hFC and sFC provide similar results in the general pediatric GI ambulatory setting. FC is a sensitive but not disease-specific marker to identify patients with IBD. Values appear to be higher in ONI GI disorders over functional disorders, although cut-off values have yet to be determined.

Paediatric obesity and Crohn's disease: a descriptive review of disease phenotype and clinical course.

Objectives: In an era of increasing paediatric obesity and inflammatory bowel disease (IBD), this study evaluates the disease phenotype and clinical course of Crohn's disease (CD) in paediatric patients who are obese or overweight. Methods: This is a retrospective, single-center, descriptive observational study from January 2010 to May 2020. Participants were included if they were: aged 2 to 18 years at the time of diagnosis, had a confirmed diagnosis of CD, and met WHO criteria for overweight or obesity at the time of diagnosis or within one year before diagnosis. Results: A total of 345 patient charts with CD were screened during the study period, with 16 patients meeting inclusion criteria. Median age of patients was 15.5 years (IQR = 13.6, 16.1). Of the 15 patients over 10 years of age, median anthropometrics at diagnosis included body mass index (BMI) of 27.2 (IQR = 24.9, 29.4) and BMI for age z-score of 1.82 (IQR = 1.58, 2.19). Presenting symptoms included abdominal pain (80.0%), diarrhea (66.7%), hematochezia (66.7%), and weight loss (26.7%). Five patients (33.3%) had obesity-related complications. Median time from symptom onset to diagnosis was 146 days (IQR = 31, 367), and median time from diagnosis to remission was 229 days (IQR = 101.8, 496.3). Conclusions: Patients with elevated BMI and CD present with typical symptoms of IBD, although weight loss was a less common presenting symptom. Time to disease remission is delayed, and obesity-related complications are common. Primary care providers must have a high degree of clinical suspicion in patients to prevent delays to gastroenterology referral and to improve time to disease remission.

Predictors of Developing Heart Failure in Adults with Congenital Heart Defects.

Background: The population of adults with congenital heart defects (ACHD) is growing. The leading cause of premature death in these patients is heart failure (HF). However, there is still limited information on the predictive factors for HF in ACHD patients. Objectives: This study re-examined a group of patients with repaired or palliated congenital heart defects (CHD) that were initially studied in 2003. A follow-up period of 15 years has allowed us to identify and evaluate predictors for the development of HF in ACHD. Methods: All patients with repaired or palliated CHD who participated in the initial study (n = 364) were invited for a follow-up examination. The effects of maximum oxygen uptake ( VO 2max ) during exercise stress testing, the cardiac biomarker N-terminal pro brain natriuretic peptide (NT-proBNP), and QRS complex on the development of HF during the follow-up period were investigated. Results: From May 2017 to April 2019, 249 of the initial 364 (68%) patients participated in the follow-up study. Of these, 21% were found to have mild CHD, 60% had moderate CHD, and 19% had complex CHD. Significant predictors for the development of HF were: NT-proBNP level > 1.7 times the upper normal limit, VO 2max < 73% of predicted values, and QRS complex duration > 120 ms. Combination of these three parameters resulted in the highest area-under-the-curve of 0.75, with a sensitivity of 75% and specificity of 63% for predicting the development of HF. Conclusions: In this cohort of ACHD patients, the combination of VO 2max% , NT-proBNP, and QRS duration was predictive of HF development over a 15-year follow-up period. Enhanced surveillance of these parameters in patients with ACHD may be beneficial for the prevention of HF and early intervention.

Emergency department visits and hospital admissions for suicidal ideation, self-poisoning and self-harm among adolescents in Canada during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic had profound effects on the mental wellbeing of adolescents. We sought to evaluate pandemic-related changes in health care use for suicidal ideation, self-poisoning and self-harm. METHODS: We obtained data from the Canadian Institute for Health Information on emergency department visits and hospital admissions from April 2015 to March 2022 among adolescents aged 10-18 years in Canada. We calculated the quarterly percentage of emergency department visits and hospital admissions for a composite outcome comprising suicidal ideation, self-poisoning and self-harm relative to all-cause emergency department visits and hospital admissions. We used interrupted time-series methods to compare changes in levels and trends of these outcomes between the prepandemic (Apr. 1, 2015-Mar. 1, 2020) and pandemic (Apr. 1, 2020-Mar. 31, 2022) periods. RESULTS: The average quarterly percentage of emergency department visits for suicidal ideation, self-poisoning and self-harm relative to all-cause emergency department visits was 2.30% during the prepandemic period and 3.52% during the pandemic period. The level (0.08%, 95% confidence interval [CI] -0.79% to 0.95%) or trend (0.07% per quarter, 95% CI -0.14% to 0.28%) of this percentage did not change significantly between periods. The average quarterly percentage of hospital admissions for the composite outcome relative to all-cause admissions was 7.18% during the prepandemic period and 8.96% during the pandemic period. This percentage showed no significant change in level (-0.70%, 95% CI -1.90% to 0.50%), but did show a significantly increasing trend (0.36% per quarter; 95% 0.07% to 0.65%) during the pandemic versus prepandemic periods, specifically among females aged 10-14 years (0.76% per quarter, 95% CI 0.22% to 1.30%) and females aged 15-18 years (0.56% per quarter, 95% CI 0.31% to 0.81%). INTERPRETATION: The quarterly change in the percentage of hospital admissions for suicidal ideation, self-poisoning and self-harm increased among adolescent females in Canada during the first 2 years of the COVID-19 pandemic. This underscores the need to promote public health policies that mitigate the impact of the pandemic on adolescent mental health.

Impact of Targeted Neonatal Echocardiography on Patent Ductus Arteriosus Management in a Canadian Tertiary Care Neonatal Unit: A Retrospective Cohort Study.

OBJECTIVE: Comprehensive assessment of hemodynamic significance of a patent ductus arteriosus (PDA) is a common indication to perform targeted neonatal echocardiography (TNE). Impact of implementation of such an assessment on PDA management decisions remains to be reported. The objective of this study is to compare PDA-related hemodynamic information and PDA treatment decisions before and after introduction of TNE service. STUDY DESIGN: This was a retrospective cohort study at a tertiary level neonatal intensive care unit in Southwestern Ontario. We investigated two time periods: Epoch-1 (non-TNE 2013-2016) versus Epoch-2 (TNE 2018-2021). We included neonates < 32 weeks with PDA. Data on baseline clinical characteristics, PDA-related echocardiographic parameters, PDA treatment details, and relevant long-term outcomes were collected. Primary outcome was defined as PDA treatment rates and need for multiple courses. Secondary outcomes included availability of PDA hemodynamic data and neonatal mortality/morbidity (PDA-related) RESULTS: A total of 275 neonates were included. A total of 162 were assessed by conventional echocardiography in Epoch-1, whereas 113 were assessed by TNE in Epoch-2. Baseline clinical characteristics were similar. Epoch-2 had more echocardiographic assessments per patient of 2.7 (±1.8) versus 1.9 (± 1.3), p < 0.001 in Epoch1. The mean postnatal age at first echocardiographic assessment was higher in Epoch-2 (12.7 days [ ± 14.6]) than in Epoch-1 (7.9 days [ ± 10.4]), p < 0.001. Comprehensive hemodynamic assessment of PDA-related echocardiographic parameters such as PDA size, shunt pattern, effect on systemic circulation, and pulmonary circulation were higher in Epoch-2. Overall, PDA treatment rates were comparable in the two time periods. The use of multiple courses of treatment was higher in Epoch-1 than in Epoch-2 (47.8 vs. 31.7%, p = 0.047). In Epoch-1, neonates received PDA treatment earlier than in Epoch-2. CONCLUSION: With the implementation of the TNE service, increased echocardiographic evaluations per patient were completed with availability of more comprehensive hemodynamic information about PDA. PDA treatment rates were similar in the two epochs, but need for multiple courses were less in TNE era. KEY POINTS: · TNE allows comprehensive hemodynamic assessment of PDA.. · Implementation of dedicated TNE service led to increased use of echocardiography to assess PDA.. · Standardized hemodynamic assessment of PDA may allow improved individualization of treatment need..

Paediatricians' awareness of Canadian screen time guidelines, perception of screen time use, and counselling during the COVID-19 pandemic.

Objectives: Paediatricians are essential in guiding families on screen time use as digital media becomes increasingly prevalent. While this has been highlighted through the COVID-19 pandemic there is no literature on paediatricians' awareness of Canadian screen time guidelines, or perception of these guidelines during this time. The aim of this study was to assess pediatricians' knowledge, attitudes, and comfort with the Canadian Paediatric Society's (CPS) screen time guidelines, specifically during the COVID-19 pandemic. Methods: Our survey was developed by a paediatric resident and paediatric endocrinologist, reviewed by local experts, and sent electronically to members of the CPS Community and Developmental Paediatrics sections. Results: All 53 respondents were aware of current CPS screen time guidelines, and the majority self-reported fair to excellent knowledge of guidelines for both age groups (<5 years and school-aged children/adolescents). Over 80% noticed increased screen use during the pandemic, and 98% were somewhat or very concerned about screen use and their patients' health and well-being. Pediatricians reported concerns about associations between increased screen time with worsening behaviour, mental health concerns, obesity, and sedentary lifestyle. The greatest barrier to reducing screen time was perceived insufficient motivation or support from caregivers/families. Conclusions: Responding Canadian paediatricians are knowledgeable and comfortable with current screen time guidelines in Canada. Despite this, there is increasing concern with health outcomes associated with screen use. These results highlight paediatricians' important role in counselling patients and may encourage further local advocacy and public education around screen use and associated health risks in children.

Purpose Built Catheters for Minimally Invasive Surfactant Therapy: Experience from a Canadian Tertiary Level Neonatal Intensive Care Unit.

Background: Minimally invasive surfactant therapy (MIST), a method of surfactant delivery via a thin catheter during spontaneous breathing, is an increasingly popular alternative to intubation and surfactant administration. Recently, purpose-built catheters for MIST received regulatory approval in Canada and became available for use. However, procedural success and user experience with such catheters have not been described. Methods: This retrospective cohort study included neonates who received MIST using purpose-built catheters between January 1, 2021, and March 31, 2022. Two types of purpose-built catheters were used in this period - SurfCath™ and BLEScath™. Procedural success, number of attempts, and adverse events in neonates receiving MIST via the two catheters were compared using chi-square or Fisher's tests. User experience was described using an ease-of-use scale. Results: Thirty-seven neonates met eligibility criteria; 22 received MIST via SurfCath™, whereas 15 received MIST via BLEScath™. Success rates were 91% in SurfCath™ and 93% in BLEScath™ (P> 0.994). Failed attempts were lower in SurfCath™ (23%) in comparison to BLEScath™ (33%), but the difference was not statistically significant (P=0.708). Among operators, 90% found SurfCath™ very easy/relatively easy to use compared to 43% of users reflecting the same degree of use with BLEScath™ (P=.021). There was no difference in adverse events. Conclusion: This is the first study in Canada to report MIST with purpose-built catheters. Overall, the success rate was equally high with both catheters. Users subjectively reported higher ease of use with SurfCath™. Commercially available purpose-built catheters should facilitate universal adaptation of the MIST method.

Population genetics of a recent range expansion and subsequent loss of migration in monarch butterflies.

Range expansions-whether permanent or transient-strongly influence the distribution of genetic variation in space. Monarch butterflies are best known for long-distance seasonal migration within North America but are also established as nonmigratory populations around the world, including on Pacific Islands. Previous research has highlighted stepwise expansion across the Pacific, though questions remain about expansion timing and the population genetic consequences of migration loss. Here, we present reduced-representation sequencing data for 275 monarchs from North America (n = 85), 12 Pacific Islands (n = 136) and three locations in Australia (n = 54), with the goal of understanding (i) how the monarch's Pacific expansion has shaped patterns of population genetic variation and (ii) how loss of migration has influenced spatial patterns of differentiation. We find support for previously described stepwise dispersal across the Pacific and document an additional expansion from Hawaii into the Mariana Islands. Nonmigratory monarchs within the Mariana Islands show strong patterns of differentiation, despite their proximity; by contrast, migratory North American samples form a single genetically panmictic population across the continent. Estimates of Pacific establishment timing are highly uncertain (~100-1,000,000 years ago) but overlap with historical records that indicate a recent expansion. Our data support (i) a recent expansion across the Pacific whose timing overlaps with available historical records of establishment and (ii) a strong role for seasonal migration in determining patterns of spatial genetic variation. Our results are noteworthy because they demonstrate how the evolution of partial migration can drive population differentiation over contemporary timescales.

Novel plasma protein biomarkers from critically ill sepsis patients.

BACKGROUND: Despite the high morbidity and mortality associated with sepsis, the relationship between the plasma proteome and clinical outcome is poorly understood. In this study, we used targeted plasma proteomics to identify novel biomarkers of sepsis in critically ill patients. METHODS: Blood was obtained from 15 critically ill patients with suspected/confirmed sepsis (Sepsis-3.0 criteria) on intensive care unit (ICU) Day-1 and Day-3, as well as age- and sex-matched 15 healthy control subjects. A total of 1161 plasma proteins were measured with proximal extension assays. Promising sepsis biomarkers were narrowed with machine learning and then correlated with relevant clinical and laboratory variables. RESULTS: The median age for critically ill sepsis patients was 56 (IQR 51-61) years. The median MODS and SOFA values were 7 (IQR 5.0-8.0) and 7 (IQR 5.0-9.0) on ICU Day-1, and 4 (IQR 3.5-7.0) and 6 (IQR 3.5-7.0) on ICU Day-3, respectively. Targeted proteomics, together with feature selection, identified the leading proteins that distinguished sepsis patients from healthy control subjects with ≥ 90% classification accuracy; 25 proteins on ICU Day-1 and 26 proteins on ICU Day-3 (6 proteins overlapped both ICU days; PRTN3, UPAR, GDF8, NTRK3, WFDC2 and CXCL13). Only 7 of the leading proteins changed significantly between ICU Day-1 and Day-3 (IL10, CCL23, TGFα1, ST2, VSIG4, CNTN5, and ITGAV; P < 0.01). Significant correlations were observed between a variety of patient clinical/laboratory variables and the expression of 15 proteins on ICU Day-1 and 14 proteins on ICU Day-3 (P < 0.05). CONCLUSIONS: Targeted proteomics with feature selection identified proteins altered in critically ill sepsis patients relative to healthy control subjects. Correlations between protein expression and clinical/laboratory variables were identified, each providing pathophysiological insight. Our exploratory data provide a rationale for further hypothesis-driven sepsis research.

Harnessing the power of RADseq for ecological and evolutionary genomics.

High-throughput techniques based on restriction site-associated DNA sequencing (RADseq) are enabling the low-cost discovery and genotyping of thousands of genetic markers for any species, including non-model organisms, which is revolutionizing ecological, evolutionary and conservation genetics. Technical differences among these methods lead to important considerations for all steps of genomics studies, from the specific scientific questions that can be addressed, and the costs of library preparation and sequencing, to the types of bias and error inherent in the resulting data. In this Review, we provide a comprehensive discussion of RADseq methods to aid researchers in choosing among the many different approaches and avoiding erroneous scientific conclusions from RADseq data, a problem that has plagued other genetic marker types in the past.

Implications of Large-Effect Loci for Conservation: A Review and Case Study with Pacific Salmon.

The increasing feasibility of assembling large genomic datasets for non-model species presents both opportunities and challenges for applied conservation and management. A popular theme in recent studies is the search for large-effect loci that explain substantial portions of phenotypic variance for a key trait(s). If such loci can be linked to adaptations, 2 important questions arise: 1) Should information from these loci be used to reconfigure conservation units (CUs), even if this conflicts with overall patterns of genetic differentiation? 2) How should this information be used in viability assessments of populations and larger CUs? In this review, we address these questions in the context of recent studies of Chinook salmon and steelhead (anadromous form of rainbow trout) that show strong associations between adult migration timing and specific alleles in one small genomic region. Based on the polygenic paradigm (most traits are controlled by many genes of small effect) and genetic data available at the time showing that early-migrating populations are most closely related to nearby late-migrating populations, adult migration differences in Pacific salmon and steelhead were considered to reflect diversity within CUs rather than separate CUs. Recent data, however, suggest that specific alleles are required for early migration, and that these alleles are lost in populations where conditions do not support early-migrating phenotypes. Contrasting determinations under the US Endangered Species Act and the State of California's equivalent legislation illustrate the complexities of incorporating genomics data into CU configuration decisions. Regardless how CUs are defined, viability assessments should consider that 1) early-migrating phenotypes experience disproportionate risks across large geographic areas, so it becomes important to identify early-migrating populations that can serve as reliable sources for these valuable genetic resources; and 2) genetic architecture, especially the existence of large-effect loci, can affect evolutionary potential and adaptability.

Anthropogenic habitat alteration leads to rapid loss of adaptive variation and restoration potential in wild salmon populations.

Phenotypic variation is critical for the long-term persistence of species and populations. Anthropogenic activities have caused substantial shifts and reductions in phenotypic variation across diverse taxa, but the underlying mechanism(s) (i.e., phenotypic plasticity and/or genetic evolution) and long-term consequences (e.g., ability to recover phenotypic variation) are unclear. Here we investigate the widespread and dramatic changes in adult migration characteristics of wild Chinook salmon caused by dam construction and other anthropogenic activities. Strikingly, we find an extremely robust association between migration phenotype (i.e., spring-run or fall-run) and a single locus, and that the rapid phenotypic shift observed after a recent dam construction is explained by dramatic allele frequency change at this locus. Furthermore, modeling demonstrates that continued selection against the spring-run phenotype could rapidly lead to complete loss of the spring-run allele, and an empirical analysis of populations that have already lost the spring-run phenotype reveals they are not acting as sustainable reservoirs of the allele. Finally, ancient DNA analysis suggests the spring-run allele was abundant in historical habitat that will soon become accessible through a large-scale restoration (i.e., dam removal) project, but our findings suggest that widespread declines and extirpation of the spring-run phenotype and allele will challenge reestablishment of the spring-run phenotype in this and future restoration projects. These results reveal the mechanisms and consequences of human-induced phenotypic change and highlight the need to conserve and restore critical adaptive variation before the potential for recovery is lost.

Quantitative EEG-Based Seizure Estimation in Super-Refractory Status Epilepticus.

BACKGROUND: The objective of this study was to evaluate the accuracy of seizure burden in patients with super-refractory status epilepticus (SRSE) by using quantitative electroencephalography (qEEG). METHODS: EEG recordings from 69 patients with SRSE (2009-2019) were reviewed and annotated for seizures by three groups of reviewers: two board-certified neurophysiologists using only raw EEG (gold standard), two neurocritical care providers with substantial experience in qEEG analysis (qEEG experts), and two inexperienced qEEG readers (qEEG novices) using only a qEEG trend panel. RESULTS: Raw EEG experts identified 35 (51%) patients with seizures, accounting for 2950 seizures (3,126 min). qEEG experts had a sensitivity of 93%, a specificity of 61%, a false positive rate of 6.5 per day, and good agreement (κ = 0.64) between both qEEG experts. qEEG novices had a sensitivity of 98.5%, a specificity of 13%, a false positive rate of 15 per day, and fair agreement (κ = 0.4) between both qEEG novices. Seizure burden was not different between the qEEG experts and the gold standard (3,257 vs. 3,126 min), whereas qEEG novices reported higher burden (6066 vs. 3126 min). CONCLUSIONS: Both qEEG experts and novices had a high sensitivity but a low specificity for seizure detection in patients with SRSE. qEEG could be a useful tool for qEEG experts to estimate seizure burden in patients with SRSE.

Laryngeal Mask Airway for Surfactant Administration Versus Standard Treatment Methods in Preterm Neonates with Respiratory Distress Syndrome: A Systematic Review and Meta-analysis.

OBJECTIVE: Laryngeal mask airway (LMA) has emerged as an alternative surfactant delivery method. The effectiveness of this method for the delivery of surfactant is uncertain. A meta-analysis of randomized control trials (RCTs) comparing LMA with standard methods of surfactant delivery for the outcomes of surfactant dose repetition, oxygen requirement, mechanical ventilation, intubation, mortality, bronchopulmonary dysplasia (BPD), and pneumothorax. STUDY DESIGN: Systematic review and meta-analysis of RCTs. Homogeneity between studies was analyzed by using I2 statistics. Risk ratio or mean difference of outcomes was assessed from random effects models. Subgroup analyses were conducted when necessary. Data sources are as follows: Ovid Medline, Embase, and the Cochrane Central Register of Controlled trials from inception till December 2018, bibliographies of identified reviews and trial registries for ongoing studies. RCTs comparing short-term respiratory outcomes in neonates with respiratory distress syndrome who were administered surfactant through an LMA versus standard method of care. RESULTS: Six RCTs were identified, enrolling a total of 357 infants. Administering surfactant via LMA was associated with decreased FiO2 requirement (mean difference = 1.82 (95% confidence interval [CI]: -6.01-9.66), decreased intubation (risk ratio [RR] = 0.17; 95% CI: 0.05-0.57), and decreased mechanical ventilation (RR = 0.44; 95% CI: 0.31-0.61). There were no significant differences between groups for death, BPD, or pneumothorax. CONCLUSION: LMA might be an effective alternative method of surfactant delivery; however, further high-quality RCTs with larger sample size and including extreme preterm infants are needed to establish LMA as an alternative technique for surfactant delivery. KEY POINTS: · Pulmonary surfactants reduce mortality and pulmonary air leaks in newborns with respiratory distress syndrome.. · Preterm lungs are at risk of volutrauma by mechanical ventilation; laryngoscopy is still traumatic.. · Surfactant administration via LMA to avoid mechanical ventilation and intubation might be feasible..

Pediatric Transport Safety Collaborative: Adverse Events With Parental Presence During Pediatric Critical Care Transport.

OBJECTIVES: In Canada, critically ill pediatric patients require transfer to a tertiary care center for definitive medical and surgical management. Some studies suggest that family accompaniment could compromise care; currently, limited research has examined patient safety and outcomes during pediatric critical care transport with family presence, and no Canada-specific data currently exists. The primary objective of this study was to compare the rate of adverse events during the transport of pediatric patients by a specialized pediatric critical care transport team with parental accompaniment to those without parental accompaniment. Secondary objectives included whether geographic or patient-specific factors affected rates of parental accompaniment and if parental presence during transport was related to patient outcomes. METHODS: Retrospective cohort study in a pediatric critical care unit convenience sample at an academic children's hospital. Inclusion criteria constituted all patients younger than 18 years who were admitted to the pediatric critical care unit after interfacility transport by the London Health Sciences Center Neonatal Pediatric Transport Team between April 1, 2018, and April 30, 2020, inclusive. Adverse event rates, patient characteristics, and clinical outcomes were compared. RESULTS: There were 357 transports eligible for analysis. Of these, there were 180 transports with, and 177 without, parental accompaniment. The primary outcome was adverse event occurrence using the composite definition of adverse events, previously defined by a Canadian consensus process, which included patient-, transport provider-, laboratory-, and system/vehicle-related safety factors. The occurrence of adverse events was not significantly different between transports with and without parental accompaniment, 49.4% and 54.8%, respectively (odds ratio, 0.80; P = 0.311). CONCLUSIONS: This is the first study to compare the effect on adverse event rate and clinically relevant outcomes between transports with and without parental presence during interfacility pediatric critical care transport. Our study found no significant difference in the adverse event rate between transports with and without parental presence.

Use of Unsafe Teething Remedies: A Survey.

OBJECTIVE: Various teething remedies have been widely marketed to caregivers. Unsafe remedies, including teething necklaces and topical anesthetics, have been implicated in adverse events, such as suffocation injuries and death. However, little is known about the extent of their use. Our primary objective was to assess the prevalence of teething remedy use among caregivers. A secondary objective was to determine whether the use of unsafe teething remedies is related to socioeconomic status (SES) or maternal education. METHODS: Children aged 12-18 months visiting primary care providers for routine checkups were included. Children outside that age group and those with chronic medical conditions were excluded. Caregivers completed a questionnaire about their children's teething symptoms and remedies used to relieve them. Unsafe remedies were defined on the basis of American Academy of Pediatrics and Canadian Paediatric Society recommendations and included topical anesthetics, teething necklaces and liquid-filled teething rings. RESULTS: Of the 130 questionnaires, 123 were complete and included in statistical analysis: 98% of families used teething remedies and 67% were unsafe. Of these families, 27% used amber teething necklaces; 28% used more than 1 unsafe remedy. Apart from topical anesthetic use, no significant correlations were found between overall unsafe remedy use and SES or maternal education. CONCLUSION: Unsafe teething remedies are commonly used despite recommendations against them. Use of unsafe teething remedies transcends SES and education level.