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Burn injury can have profound detrimental effects on the quality of life and mental health of children. We collected demographics, burn etiology, burn date, and home zip code for pediatric patients admitted to our burn unit from 2016 to 2023. Age, burn date, and etiology of burn were used to assess temporal and mechanistic patterns of injury for preschool-age and school-age children. Home zip code was used to determine each child's home Childhood Opportunity Index (COI) score, which is composed of subdomains for Education, Health and Environment, and Social and Economic. We calculated the odds ratio for odds of pediatric burn admission for each COI subdomain quintile, using very high opportunity neighborhoods as the reference. Scald was the prevailing burn etiology (64%). In school-age children, July was the month with the most burn injuries (19%), attributable to firework injuries. School-age children were also more likely to be injured in a week without classroom instruction (P < .001). There was a dose-response relationship between COI and odds of burn admission, with the greatest odds of burn admission observed for children from very low educational opportunity areas (OR 5.21, 95% CI 3.67-7.39). These findings support interventions for burn prevention such as increased education about the dangers of fireworks, addressing inequities in access to childcare and extracurricular activities, and reducing the default water heater temperatures in multi-unit dwellings., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Nutrition is paramount for wound healing after burn injury. With rising food prices and time off work due to burn injuries, access to adequate nutrition may be a significant financial stressor. We asked patients at an outpatient burn clinic to complete the Household Food Security Module, which queries about food security over the preceding 12 months. Demographics and burn characteristics were abstracted from the medical record. We assessed the overall prevalence of food insecurity, risk factors for food insecurity, and potential effects of food insecurity on nutritional status and wound healing time. Wound healing time was assessed via Cox regression while adjusting for burn depth, total body surface area burned, and diabetes. Over 40% of participants reported experiencing food insecurity; it was more common in patients who preferred Spanish language (P = 0014) or were unemployed (P = .049). Just over half of participants experiencing food insecurity were using any food assistance resources. Among patients more than 30 days from burn injury, patients who were food insecure had larger burns (P = .01). Experience of food insecurity was not associated presence of malnutrition on nutrition-focused physical exam (P = .47). Wound healing time for burns managed in the outpatient setting was associated with burn depth (P < .001), but not food insecurity (P = .95), burn size (P = .17), or diabetes (P = .14). Although food insecurity did not result in malnutrition or negatively impact wound healing time, it is important for providers to routinely screen for food insecurity due to increased nutritional requirements and loss of wages after burn injury., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

People experiencing homelessness are at increased risk for serious burn injuries and face additional barriers to care such as inability to perform wound care and difficulty with follow-up. Although not burn-specific, street medicine programs provide direct medical care to people experiencing unsheltered homelessness in their own environment and may be well positioned to bridge this gap in burn care for this population. We conducted a cross-sectional survey to characterize the burn care experience of street medicine teams with providing burn care for people experiencing homelessness. The 60 respondents included 18 (30%) physicians, 15 (25%) nurse practitioners or physician assistants, 15 (25%) registered nurses, and 6 (10%) medical students, and 6 (10%) other team members. The most common reported barriers to care were prior negative experiences with emergency departments, and transportation to burn centers. There was regional variability in frequency of providing burn care, which was reflected in respondent comfort with assessing and treating burns. Burns were most often dressed with daily dressings such as a non-adherent dressing over silver sulfadiazine or bacitracin. Silver-based contact dressings were rarely used. Street medicine teams in the United States are treating burn injuries among people experiencing homelessness, though management practices and experience treating burns was variable. As street medicine programs continue to grow, burn-related education, training, and connections to local burn centers for team members is important. Through strengthened partnerships between burn centers and street medicine teams, these programs may be well positioned to bridge the gap in burn care for people experiencing homelessness., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) is an autoimmune process resulting in painful epidermal sloughing that can involve the vulva and vagina. Current guideline recommendations are based on expert opinion and may not reflect modern management of SJS/TEN in burn centers. We performed a retrospective chart review of 34 female patients treated for SJS/TEN at our burn center from 2015 to 2023. Cases frequently involved the vulva (83.3%) and vagina (56.0%), though pelvic examination often was limited. For eight patients with confirmed vulvovaginal lesions, there were no direct sequelae of SJS/TEN requiring intervention. In the modern era of SJS/TEN management in burn centers, interventions such as steroids may not be needed., Competing Interests: Financial Disclosure The authors did not report any potential conflicts of interest., (Copyright © 2024 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: Cervical spine (c-spine) evaluation is a critical component in trauma evaluation, and although several pediatric c-spine evaluation algorithms have been developed, none have been widely implemented. Here, we assess rates of c-spine imaging use across children's hospitals, specifically temporal trends in imaging use, variation across hospitals in imaging used, and timing of magnetic resonance imaging in admitted patients., Methods: Data from the Children's Hospital Associations Pediatric Health Information System were abstracted from 2015 to 2020. Patients younger than 18 years seen in the emergency department with an International Classification of Diseases, Tenth Revision , code indicative of trauma and c-spine plain radiograph or computed tomography (CT) in the emergency department were included. Data visualization and descriptive statistics were used to assess rates of imaging use by age, year, hospital, injury severity, and day of service. Changes in rates of imaging use over time were evaluated via simple linear regression., Results: Across 25,238 patient encounters at 35 children's hospitals, there was an increase in use of c-spine CT from 2015 to 2020 (28.5-36.5%). There was substantial interinstitutional variation in rates of use of plain radiographs versus CT for initial evaluation of the c-spine across all age groups. Magnetic resonance imaging was obtained more than 3 days after admission in 31.5% of intensive care patients who received this imaging., Conclusion: Increasing use of CT, substantial interinstitutional variation in rates of use of plain radiographs versus CT, and heterogenous timing of magnetic resonance imaging for evaluation of the pediatric c-spine demonstrate the growing need for development and implementation of an age-specific c-spine evaluation algorithm to guide judicious use of diagnostic resources., Level of Evidence: Prognostic and Epidemiological; Level III., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Clinical clearance of a child's cervical spine after trauma is often challenging because of impaired mental status or an unreliable neurologic examination. Magnetic resonance imaging (MRI) is the criterion standard for excluding ligamentous injury in children but is constrained by long image acquisition times and frequent need for anesthesia. Limited-sequence magnetic resonance imaging (LSMRI) is used in evaluating the evolution of traumatic brain injury and may also be useful for cervical spine clearance while potentially avoiding the need for anesthesia. The purpose of this study was to assess the sensitivity and negative predictive value of LSMRI as compared with criterion standard full-sequence MRI as a screening tool to rule out clinically significant ligamentous cervical spine injury., Methods: We conducted a 10-center, 5-year retrospective cohort study (2017-2021) of all children (0-18 years) with a cervical spine MRI after blunt trauma. Magnetic resonance imaging images were rereviewed by a study pediatric radiologist at each site to determine if the presence of an injury could be identified on limited sequences alone. Unstable cervical spine injury was determined by study neurosurgeon review at each site., Results: We identified 2,663 children younger than 18 years who underwent an MRI of the cervical spine with 1,008 injuries detected on full-sequence studies. The sensitivity and negative predictive value of LSMRI were both >99% for detecting any injury and 100% for detecting any unstable injury. Young children (younger than 5 years) were more likely to be electively intubated or sedated for cervical spine MRI., Conclusion: Limited-sequence magnetic resonance imaging is reliably detects clinically significant ligamentous injury in children after blunt trauma. To decrease anesthesia use and minimize MRI time, trauma centers should develop LSMRI screening protocols for children without a reliable neurologic examination., Level of Evidence: Diagnostic Test/Criteria; Level III., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To determine if the elastic chain premaxillary retraction (ECPR) appliance increases inter-medial and inter-lateral canthal dimension in patients with bilateral complete cleft lip and palate (BCLP)., Design: Retrospective cohort study., Setting: Specialized tertiary care facility., Patients, Participants: 126 patients with BCLP; 75 had ECPR, 51 had no pre-surgical manipulation., Interventions: Three-dimensional facial photographs were obtained prior to insertion of appliance (T0), post-appliance therapy prior to appliance removal/labial repair (T1), and several months after labial repair (T2) for a longitudinal ECPR group, and were obtained after age 4 years (T3) for a non-longitudinal ECPR group and for the non-ECPR group., Main Outcome Measures: Inter-medial and inter-lateral canthal dimension (en-en, ex-ex) was determined for all groups/time-points. Measurements were compared between groups and to norms., Results: The mean en-en and ex-ex was 32.6 ± 3.2 mm and 84.4 ± 6.3 mm for the ECPR group and 33.5 ± 3.1 mm and 86.7 ± 7.2 mm for the non-ECPR group at T3. Inter-medial and inter-lateral canthal dimensions were significantly greater than normal ( P  < .05) in both groups; there was no significant difference between groups ( P  > .05). The mean en-en and ex-ex for the Longitudinal ECPR group was 27.5 ± 2.4 mm and 66.7 ± 3.7 mm at T0, 29.6 ± 2.4 mm and 70.4 ± 2.9 mm at T1, and 29.2 ± 2.3 mm and 72.3 ± 3.8 mm at T2. en-en and ex-ex increased significantly from T0-T1 ( P  < .05), decreased at T2 ( P  > .05) and was significantly larger than normal at all time-points ( P  < .05)., Conclusions: Inter-medial and inter-lateral canthal dimension increased after ECPR but returned to baseline growth trajectory. These dimensions were above normal at all time-points. There was no difference between those that did and did not have dentofacial orthopedic manipulation., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Unhoused patients are an overrepresented group in burn injury, and are a uniquely vulnerable population. Current research focuses on the consequences of homelessness on burn outcomes, with little known about the specific circumstances and behaviors leading to burn injury that may represent specific targets for injury prevention efforts. The burn registry at an urban regional burn center was queried for burn admissions in unhoused adults from 2019 to 2022. Registry data pulled included demographics, urine toxicology, mechanism of injury, and injury subjective history. Subjective injury history was reviewed to determine more specific injury circumstances and activities during which accidental burns occurred. Demographic and mechanistic trends in burn admissions were explored via descriptive statistics. Among 254 admissions for burns from the unhoused community, 58.1% of patients were positive for stimulants on admission. Among accidental injuries (69.7%), common circumstances included preparing food or beverages, cooking or using methamphetamine, smoking cannabis or tobacco, bonfires, and candles. A specific common circumstance was lighting a cigarette while handling accelerants (6.7%). Interventions for stimulant abuse, as well as outreach efforts to educate unhoused patients about situational awareness, safe handling of accelerants, safe smoking practices, and safe cooking practices, may be effective tools in reducing burn admissions in this vulnerable population., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

There has been conflicting data on the relationship between burn severity and psychological outcomes. The present study aims to characterize the baseline psychosocial disposition of adults attending outpatient burn clinic at a large urban safety net hospital, as well as the impact of clinical course on self-reported psychosocial well-being. Adult patients attending outpatient burn clinic completed survey questions from the National Institutes of Health Patient-Reported Outcomes Measurement Information System Managing Chronic Conditions: Self-Efficacy for Managing Social Interactions (SEMSI-4) and Managing Emotions (SEME). Sociodemographic variables were collected from surveys and retrospective chart review. Clinical variables included total body surface area burned, initial hospital length of stay, surgical history, and days since injury. Poverty level was estimated by U.S. census data using patient's home ZIP code. Scores on SEME-4 and SEMSI-4 were compared to the population mean by one-sample T-test, and independent variables evaluated for associations with managing emotions and social interactions by Tobit regression while adjusting for demographic variables. The 71 burn patients surveyed had lower scores in SEMSI-4 (mean = 48.0, P = .041) but not SEME-4 (mean = 50.9, P = .394) versus the general population. Marital status and neighborhood poverty level were associated with SEMSI-4, while length of stay and % total body surface area burned were associated with SEME-4. Patients who are single or from poorer neighborhoods may have difficulty interacting with their environment after burn injury and need extra social support. Prolonged hospitalization and increased severity of burn injury may have more impact on emotional regulation; these patients may benefit from psychotherapy during recovery., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Previous research has demonstrated mixed relationships between individual neighborhood socioeconomic factors and incidences of violence, such as poverty level, population density, and income inequality. We used the Childhood Opportunity Index and Area Disadvantage Index to evaluate the relationship between neighborhood characteristics and the number of incidents of violence among children across the zip codes of Los Angeles (LA) County., Methods: We performed a retrospective cross-sectional study of children younger than 18 years from 2017 to 2019 who were entered in the LA County Trauma and Emergency Medicine Information System registry with violent mechanisms of injury, including gunshot, stabbing, or assault. Mechanisms classified as self-inflicted injuries were excluded from the study. The number of incidences of violent mechanism per 100,000 persons younger than 18 years for each zip code was calculated using population data from the US Census American Community Survey 5-Year estimates from 2019. The incidences of violence per capita younger than 18 years for each zip code was compared with the zip code Area Deprivation Index and Childhood Opportunity Index using logistic regression models., Results: There were 6,791 trauma activations in LA County over the study period, 12.8% (n = 866) of which were due to violence. The mean prevalence of pediatric violent mechanism of injury per zip code was 4 cases per 100,000 persons younger than 18 years. Most injuries were the result of firearms (n = 345 [60.4%]) and occurred among Hispanic/Latino children (n = 362 [57.1%]). There were significantly greater rates of violent injury among children from highest disadvantage (odds ratio, 8.84) and lowest opportunity (odds ratio, 42.48) zip codes., Conclusion: Children living in high disadvantage or low opportunity zip codes had greater rates of violent injury. Further study of neighborhood factors is needed to develop targeted effective interventions to reduce violent injuries among children living in low opportunity areas., Level of Evidence: Prognostic and Epidemiological; Level IV., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Self-limited epilepsy with centrotemporal spikes is a transient developmental epilepsy with a seizure onset zone localized to the centrotemporal cortex that commonly impacts aspects of language function. To better understand the relationship between these anatomical findings and symptoms, we characterized the language profile and white matter microstructural and macrostructural features in a cohort of children with SeLECTS., Methods: Children with active SeLECTS (n = 13), resolved SeLECTS (n = 12), and controls (n = 17) underwent high-resolution MRIs including diffusion tensor imaging sequences and multiple standardized neuropsychological measures of language function. We identified the superficial white matter abutting the inferior rolandic cortex and superior temporal gyrus using a cortical parcellation atlas and derived the arcuate fasciculus connecting them using probabilistic tractography. We compared white matter microstructural characteristics (axial, radial and mean diffusivity, and fractional anisotropy) between groups in each region, and tested for linear relationships between diffusivity metrics in these regions and language scores on neuropsychological testing., Results: We found significant differences in several language modalities in children with SeLECTS compared to controls. Children with SeLECTS performed worse on assessments of phonological awareness (p = 0.045) and verbal comprehension (p = 0.050). Reduced performance was more pronounced in children with active SeLECTS compared to controls, namely, phonological awareness (p = 0.028), verbal comprehension (p = 0.028), and verbal category fluency (p = 0.031), with trends toward worse performance also observed in verbal letter fluency (p = 0.052), and the expressive one-word picture vocabulary test (p = 0.068). Children with active SeLECTS perform worse than children with SeLECTS in remission on tests of verbal category fluency (p = 0.009), verbal letter fluency (p = 0.006), and the expressive one-word picture vocabulary test (p = 0.045). We also found abnormal superficial white matter microstructure in centrotemporal ROIs in children with SeLECTS, characterized by increased diffusivity and fractional anisotropy compared to controls (AD p = 0.014, RD p = 0.028, MD p = 0.020, and FA p = 0.024). Structural connectivity of the arcuate fasciculus connecting perisylvian cortical regions was lower in children with SeLECTS (p = 0.045), and in the arcuate fasciculus children with SeLECTS had increased diffusivity (AD p = 0.007, RD p = 0.006, MD p = 0.016), with no difference in fractional anisotropy (p = 0.22). However, linear tests comparing white matter microstructure in areas constituting language networks and language performance did not withstand correction for multiple comparisons in this sample, although a trend was seen between FA in the arcuate fasciculus and verbal category fluency (p = 0.047) and the expressive one-word picture vocabulary test (p = 0.036)., Conclusion: We found impaired language development in children with SeLECTS, particularly in those with active SeLECTS, as well as abnormalities in the superficial centrotemporal white matter as well as the fibers connecting these regions, the arcuate fasciculus. Although relationships between language performance and white matter abnormalities did not pass correction for multiple comparisons, taken together, these results provide evidence of atypical white matter maturation in fibers involved in language processing, which may contribute to the aspects of language function that are commonly affected by the disorder., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Disparities in psychosocial outcomes after burn injury exist in patients from racial or ethnic minority groups in the United States. Peer support groups can help patients with many psychosocial aspects of recovery from burns; however, access to such support among patients of racial and ethnic minority or low socioeconomic groups are unknown. The present study examined participation rates in outpatient peer support within this patient population. Patients attending outpatient clinic at an urban safety-net hospital and regional burn center with a majority minority patient population were asked about participation in burn survivor group, interest in joining a group, and given validated survey questions about managing emotions and social interactions since injury. Current or past participation in peer support was low (4.2%), and 30.3% of patients not already in support group were interested in joining. Interest in future participation in peer support was highest among Hispanic patients (37.0%) and lowest among Black patients (0%). Logistic regression models demonstrated that increased total body surface area burned, hospital length of stay, and need for surgical intervention were associated with interest in joining or having joined a peer support group. Effectiveness of management of emotions and social interactions were not associated with interest in joining peer support in the future. These findings demonstrate a considerable difference between levels of interest and participation in peer support within this population. Improving access to and education about benefits of peer support in underresourced communities may help to address the variation in psychosocial outcomes of patients across racial or ethnic minority groups recovering from burns., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Our institution saw three cases of moderate to severe injury in children under 7 years of age caused by falls from mechanical bulls at private parties. Injuries sustained included long bone fracture, skull fracture and intracranial haemorrhage. The circumstances of these injuries led our institution's injury prevention team to investigate the safety protocols of local vendors, revealing limited regulation of safety equipment, rider age or height minimums and training for the operation of mechanical bulls. This information was reported to the US Consumer Product Safety Commission in order to reduce instances of these serious injuries in young children., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Despite the widespread institution of modern massive transfusion protocols with balanced blood product ratios, survival for patients with traumatic hemorrhage receiving ultramassive transfusion (UMT) (defined as ≥20 U of packed red blood cells [RBCs]) in 24 hours) remains low and resource consumption remains high. Therefore, we aimed to identify factors associated with mortality in trauma patients receiving UMT in the modern resuscitation era., Methods: An Eastern Association for the Surgery of Trauma multicenter retrospective study of 461 trauma patients from 17 trauma centers who received ≥20 U of RBCs in 24 hours was performed (2014-2019). Multivariable logistic regression and Classification and Regression Tree analysis were used to identify clinical characteristics associated with mortality., Results: The 461 patients were young (median age, 35 years), male (82%), severely injured (median Injury Severity Score, 33), in shock (median shock index, 1.2; base excess, -9), and transfused a median of 29 U of RBCs, 22 U of fresh frozen plasma (FFP), and 24 U of platelets (PLT). Mortality was 46% at 24 hours and 65% at discharge. Transfusion of RBC/FFP ≥1.5:1 or RBC/PLT ≥1.5:1 was significantly associated with mortality, most pronounced for the 18% of patients who received both RBC/PLT and RBC/FFP ≥1.5:1 (odds ratios, 3.11 and 2.81 for mortality at 24 hours and discharge; both p < 0.01). Classification and Regression Tree identified that age older than 50 years, low initial Glasgow Coma Scale, thrombocytopenia, and resuscitative thoracotomy were associated with low likelihood of survival (14-26%), while absence of these factors was associated with the highest survival (71%)., Conclusion: Despite modern massive transfusion protocols, one half of trauma patients receiving UMT are transfused with either RBC/FFP or RBC/PLT in unbalanced ratios ≥1.5:1, with increased associated mortality. Maintaining focus on balanced ratios during UMT is critical, and consideration of advanced age, poor initial mental status, thrombocytopenia, and resuscitative thoracotomy can aid in prognostication., Level of Evidence: Prognostic, level III., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Childhood epilepsy with centrotemporal spikes (CECTS) (formally benign epilepsy with centrotemporal spikes, BECTS) is a common childhood epilepsy syndrome characterized by psychiatric, behavioral, and cognitive abnormalities and self-limited seizures. Although CECTS is one of the most well-characterized electroclinical epilepsy syndromes, the natural history of neuropsychiatric outcomes is poorly understood. We report the psychiatric, behavioral, and cognitive profiles over the course of disease from a large, prospectively-enrolled, longitudinal cohort of children with CECTS. We further characterize the detailed seizure course and test the relationship between several proposed risk factors and neuropsychiatric and seizure outcomes in these children., Methods: Patients diagnosed with CECTS were enrolled as part of a community-based study and followed from diagnosis through disease resolution (16.0 ± 3.1 years, N = 60). Twenty sibling controls were also recruited. We report the natural history of premorbid neuropsychiatric concerns, postmorbid neuropsychiatric diagnoses, long-term neuropsychological performance, seizure course, antiseizure medication (ASM) treatment response, and the relationship between duration seizure-free and remission. Age at onset and premorbid neuropsychiatric concerns were tested as predictors of seizure count, epilepsy duration, postmorbid neuropsychiatric diagnoses, and long-term neuropsychological performance. Antiseizure medication treatment duration, seizure count, and epilepsy duration were tested as predictors of postmorbid neuropsychiatric diagnoses and long-term neuropsychological performance., Results: Children with CECTS had a high incidence of ADD/ADHD symptoms (18.3%) or learning difficulties (21.7%) before diagnosis. New or persistent ADHD (20%), mood disorders (23.6%), learning difficulties (14.5%), and behavioral disorders (7.3%) were common after CECTS diagnosis. At 9-year follow-up, performance on formal neuropsychological testing was comparable to population statistics and sibling controls. More than two-thirds of treated children experienced at least one seizure during treatment. Most children (61.7%) had entered terminal resolution after 12 months seizure-free. Among all children, for each month seizure-free, there was a 6-7% increase in the probability of achieving terminal remission (p < 1e-10). The presence of a premorbid neurodevelopmental concern predicted a longer epilepsy duration (p = 0.02), higher seizure count (p = 0.02), and a postmorbid psychiatric or neurodevelopmental diagnosis (p = 0.002). None of the tested features predicted long-term neuropsychological performance., Significance: Children are at high risk of neuropsychiatric symptoms along the course of the disease in CECTS, however, long-term cognitive performance is favorable. The majority of children had a seizure while being treated with ASMs, suggesting that CECTS is not as pharmacoresponsive as assumed or that treatment approaches are not optimized. Among treated and untreated children, future seizure-risk can be estimated from duration seizure-free. The presence of a premorbid neuropsychiatric concern predicted a more severe disease course in CECTS., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The binding affinity between antibiotic ionophores and alkali ions within supported lipid bilayers was evaluated using affinity chromatography. We used zonal elution and frontal analysis methods in nanovolume liquid chromatography to characterize the binding selectivity of the carrier and channel ionophores valinomycin and gramicidin A within different phosphatidylcholine bilayers. Distinct binding sensitivity to the lipid phase, both in affinity and selectivity, is observed for valinomycin, whereas gramicidin is less sensitive to changes in a membrane environment, behavior that is consistent with ion binding occurring within the interior of an established channel. There is good agreement between the chromatographic retention and the reported binding selectivity measured by other techniques. Surface potential near the binding site affects ion retention and the apparent association binding constants, but not the binding selectivity or enthalpy measurements. A model accounting for the surface potential contributions of retained ions during frontal analyses yields values close to intrinsic binding constants for gramicidin A ( K A for K + between 70 and 120 M -1 ) using reasonable estimates of the initial potential that is postulated to arise from the underlying silica.

Introduction: Benign epilepsy with centrotemporal spikes (BECTS) is a common form of childhood epilepsy with the majority of those afflicted remitting during their early teenage years. Seizures arise from the lower half of the sensorimotor cortex of the brain (e.g. seizure onset zone) and the abnormal epileptiform discharges observed increase during NREM sleep. To date no clinical factors reliably predict disease course, making determination of ongoing seizure risk a significant challenge. Prior work in BECTS have shown abnormalities in beta band (14.9-30 Hz) oscillations during movement and rest. Oscillations in this frequency band are modulated by state of consciousness and thought to reflect intrinsic inhibitory mechanisms., Methods: We used high density EEG and source localization techniques to examine beta band activity in the seizure onset zone (sensorimotor cortex) in a prospective cohort of children with BECTS and healthy controls during sleep. We hypothesized that beta power in the sensorimotor cortex would be different between patients and healthy controls, and that beta abnormalities would improve with resolution of disease in this self-limited epilepsy syndrome. We further explored the specificity of our findings and correlation with clinical features. Statistical testing was performed using logistic and standard linear regression models., Results: We found that beta band power in the seizure onset zone is different between healthy controls and BECTS patients. We also found that a longer duration of time spent seizure-free (corresponding to disease remission) correlates with lower beta power in the seizure onset zone. Exploratory spatial analysis suggests this effect is not restricted to the sensorimotor cortex. Exploratory frequency analysis suggests that this phenomenon is also observed in alpha and gamma range activity. We found no relationship between beta power and the presence or rate of epileptiform discharges in the sensorimotor cortex or a test of sensorimotor performance., Conclusion: These results provide evidence that cortical beta power in the seizure onset zone may provide a dynamic physiological biomarker of disease in BECTS., (© 2019 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.)

Benign epilepsy with centrotemporal spikes is a common childhood epilepsy syndrome that predominantly affects boys, characterized by self-limited focal seizures arising from the perirolandic cortex and fine motor abnormalities. Concurrent with the age-specific presentation of this syndrome, the brain undergoes a developmentally choreographed sequence of white matter microstructural changes, including maturation of association u-fibres abutting the cortex. These short fibres mediate local cortico-cortical communication and provide an age-sensitive structural substrate that could support a focal disease process. To test this hypothesis, we evaluated the microstructural properties of superficial white matter in regions corresponding to u-fibres underlying the perirolandic seizure onset zone in children with this epilepsy syndrome compared with healthy controls. To verify the spatial specificity of these features, we characterized global superficial and deep white matter properties. We further evaluated the characteristics of the perirolandic white matter in relation to performance on a fine motor task, gender and abnormalities observed on EEG. Children with benign epilepsy with centrotemporal spikes ( n  = 20) and healthy controls ( n  = 14) underwent multimodal testing with high-resolution MRI including diffusion tensor imaging sequences, sleep EEG recordings and fine motor assessment. We compared white matter microstructural characteristics (axial, radial and mean diffusivity, and fractional anisotropy) between groups in each region. We found distinct abnormalities corresponding to the perirolandic u-fibre region, with increased axial, radial and mean diffusivity and fractional anisotropy values in children with epilepsy ( P  = 0.039, P  = 0.035, P  = 0.042 and P  = 0.017, respectively). Increased fractional anisotropy in this region, consistent with decreased integrity of crossing sensorimotor u-fibres, correlated with inferior fine motor performance ( P  = 0.029). There were gender-specific differences in white matter microstructure in the perirolandic region; males and females with epilepsy and healthy males had higher diffusion and fractional anisotropy values than healthy females ( P  ≤ 0.035 for all measures), suggesting that typical patterns of white matter development disproportionately predispose boys to this developmental epilepsy syndrome. Perirolandic white matter microstructure showed no relationship to epilepsy duration, duration seizure free, or epileptiform burden. There were no group differences in diffusivity or fractional anisotropy in superficial white matter outside of the perirolandic region. Children with epilepsy had increased radial diffusivity ( P  = 0.022) and decreased fractional anisotropy ( P  = 0.027) in deep white matter, consistent with a global delay in white matter maturation. These data provide evidence that atypical maturation of white matter microstructure is a basic feature in benign epilepsy with centrotemporal spikes and may contribute to the epilepsy, male predisposition and clinical comorbidities observed in this disorder., (© The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: Gallbladder cancer (GBC) and cholangiocarcinoma (CCA) are rare entities with relatively poor prognoses. We compared treatment outcomes of definitive resection with or without neoadjuvant therapy in GBC and CCA patients., Methods: All non-metastatic GBC and CCA patients at a single institution who underwent definitive resection from 1992-2016 were analyzed. We compared overall survival (OS), locoregional failure (LRF) and distant failure (DF) in patients who received neoadjuvant therapy (chemotherapy and/or radiation) versus those who did not receive neoadjuvant treatment. OS was analyzed using the Kaplan-Meier method and log rank tests. Cox proportional hazard models were used to analyze time to recurrence., Results: Out of 128 patients, 90 had GBC and 38 had CCA, 25 patients (27%) among GBC and 8 patients (21%) with CCA were T3, T4 or node positive. Overall, 52 (40%) GBC and 25 (20%) CCA patients received neoadjuvant treatment, chemotherapy alone 60 patients (47%) or radiation with or without chemotherapy 17 patients (13%). Chemotherapy was single agent in 44 patients (34%) and multi-agent in 25 (20%). The median OS for GBC patients was 3.1 years with 2.6 years for no neoadjuvant group and 3.1 years for neoadjuvant group (P=0.6786). Median OS was 2.6 years for CCA patients, 3.6 years for no neoadjuvant therapy versus 2.0 years for neoadjuvant group (P=0.1613). There was a trend towards increased DF in patients with CCA and GBC receiving neoadjuvant therapy: HR 2.74, 95% CI, 0.73-10.3, P=0.14 and 0.92, 95% CI, 0.44-1.93, P=0.82 respectively. The hazard ratio for time to LRF in CCA patients receiving neoadjuvant treatment was 3.17, 95% CI, 0.62-16.31, P=0.16 whereas HR was 0.15, 95% CI, 0.10-1.76, P=0.23 for GBC patients. Among GBC patients, the pattern of first failure was locoregional in 8 (10%) having 3 LRF in neoadjuvant group (2 with chemotherapy, 1 with CRT, 0 with RT alone) as compared to 5 in adjuvant group. Among 28 (35%) patients with DF first, 15 patients received neoadjuvant therapy versus 13 patients in non-neoadjuvant group. In CCA patients, LRF occurred first in 6 patients receiving neoadjuvant treatment (3 with chemotherapy, 1 with CRT, 2 with RT alone) as compared to 2 patients who were treated with non-neoadjuvant CRT. DF was the first site of failure in 9 patients treated with neoadjuvant CRT (8 with chemotherapy, 0 with CRT and 1 with RT alone) as compared to 4 patients without neoadjuvant treatment., Conclusions: In this retrospective data set, a trend towards better survival was seen in adjuvantly treated CCA patients, but not in GBC patients. Recurrence patterns also appear different among the two, which might be attributed to treatment modality used, patient selection or unmeasured factors., Keywords: Gallbladder cancer (GBC); cholangiocarcinoma (CCA); neoadjuvant; resection; chemoradiation; chemotherapy., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Objective: Benign epilepsy with centrotemporal spikes (BECTS) is a common, self-limited epilepsy syndrome affecting school-age children. Classic interictal epileptiform discharges (IEDs) confirm diagnosis, and BECTS is presumed to be pharmacoresponsive. As seizure risk decreases in time with this disease, we hypothesize that the impact of IEDs and anticonvulsive drug (ACD) treatment on the risk of subsequent seizure will differ based on disease duration., Methods: We calculate subsequent seizure risk following diagnosis in a large retrospective cohort of children with BECTS (n = 130), evaluating the impact of IEDs and ACD treatment in the first, second, third, and fourth years of disease. We use a Kaplan-Meier survival analysis and logistic regression models. Patients were censored if they were lost to follow-up or if they changed group status., Results: Two-thirds of children had a subsequent seizure within 2 years of diagnosis. The majority of children had a subsequent seizure within 3 years despite treatment. The presence of IEDs on electroencephalography (EEG) did not impact subsequent seizure risk early in the disease. By the fourth year of disease, all children without IEDs remained seizure free, whereas one-third of children with IEDs at this stage had a subsequent seizure. Conversely, ACD treatment corresponded with lower risk of seizure early in the disease but did not impact seizure risk in later years., Significance: In this cohort, the majority of children with BECTS had a subsequent seizure despite treatment. In addition, ACD treatment and IEDs predicted seizure risk at specific points of disease duration. Future prospective studies are needed to validate these exploratory findings.

Objective: Procedures of limited clinical value require pre-authorisation in the National Health Service, of which rhinoplasty and septorhinoplasty are two such operations. This study surveyed clinical commissioning groups within England to document the variable eligibility criteria for rhinoplasty and septorhinoplasty., Methods: In February 2016, a letter was sent to 209 clinical commissioning groups requesting their rhinoplasty and septorhinoplasty commissioning criteria., Results: A total of 200 clinical commissioning groups responded. Although 89.5 per cent allow septorhinoplasty in the presence of nasal obstruction, further criteria, such as documented health problems resulting from nasal blockage, severe functional impairment or a specific percentage of blockage, must be shown for septorhinoplasty to be authorised by most of the clinical commissioning groups., Conclusion: There is great variation within individual clinical commissioning groups in England regarding the criteria for septorhinoplasty and rhinoplasty. Some criteria seem not to be clinically relevant and difficult to demonstrate. It is recommended that the guidelines are reviewed and harmonised nationally in future revisions.

Group I and II ion binding to phospholipid membranes was evaluated by affinity chromatography utilizing a new stationary phase system based on lipid bilayers supported within large-pore particles composed of Stöber silica spheres. Using an inductively coupled plasma mass spectrometer for detection, robust determination of binding selectivity within group II ions is achieved with capillary columns containing nanomole quantities of lipid and using picomoles of metal analyte. Columns with a unique lipid formulation can be prepared within three hours using a solvent-casting assembly method. The observable thermotropic phase behavior of dipalmitoylphosphatidylcholine has a significant effect on alkaline metal binding and demonstrates the dynamic nature of the supported bilayers. Of the group I ions, only lithium exhibits retention with neutral phosphatidylcholine bilayer stationary phases. A comparison of Stöber-based supports with two commercially available large-pore silicas reveals the effect that particle structure has on analyte accessibility to the bilayer surface as evaluated by retention per supported lipid mass., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objective: Research to determine the best approach for providing early intervention for mood and anxiety disorders is imperative. The authors describe a process evaluation of an early-intervention program for transition-age youths with mood or anxiety disorders., Methods: Causal and logic models for pathways to care for the program, as well as descriptive data from 548 participating youths, are presented. Follow-up measures of functional improvement are reported., Results: Diagnostic characterization, symptom severity, and functional impairment of participants indicated that the model selected an appropriate catchment population without creating excessive overinclusion. Self-referred youths reported greater anxiety and substance use. Acceptance by the program was predictive of greater follow-through with treatment. Several variables, including frequent lifetime marijuana use, predicted loss to follow-up. At follow-up, youths were significantly functionally improved., Conclusions: This process evaluation indicated that the model provided appropriate early intervention for youths with mood or anxiety disorders without causing excessive overinclusion.

A method is presented for the assembly of lipid bilayers on silica colloids via reconstitution of dried lipid films solvent-cast from chloroform within packed beds of colloids ranging from 100 nm to 10 μm in diameter. Rapid solvent evaporation from the packed bed void volume results in uniform distribution of dried lipid throughout the colloidal bed. Fluorescence measurements indicate that significant, if not quantitative, retention of DOPC or DPPC films cast between sub-bilayer and multilayer quantities occurs when the colloids are redispersed in aqueous solution. Phospholipid bilayers assembled in this manner are shown to effectively passivate the surface of 250 nm colloids to nonspecific adsorption of bovine serum albumin. The method is shown to be capable of preparing supported bilayers on colloid surfaces that do not generally support vesicle fusion such as poly(ethylene glycol) (PEG) modified silica colloids. Bilayers of lipids that have not been reported to self-assemble by vesicle fusion, including gel-phase lipids and single-chain diacetylene amphiphiles, can also be formed by this method. The utility of the solid-core support is demonstrated by the facile assembly of supported lipid bilayers within fused silica capillaries to generate materials that are potentially suitable for the analysis of membrane interactions in a microchannel format.

Background: Medical students report high levels of stress related to their medical training as well as to other personal and financial factors. The aim of this study is to investigate whether there are differences in course-related stressors reported by medical students on undergraduate problem-based learning (PBL) and non-PBL programmes in the UK., Method: A cross-sectional study of second-year medical students in two UK medical schools (one PBL and one non-PBL programme) was conducted. A 16-question self-report questionnaire, derived from the Perceived Medical Student Stress Scale and the Higher Education Stress Inventory, was used to measure course-related stressors. Following univariate analysis of each stressor between groups, multivariate logistic regression was used to determine which stressors were the best predictors of each course type, while controlling for socio-demographic differences between the groups., Results: A total of 280 students responded. Compared to the non-PBL students (N = 197), the PBL students (N = 83) were significantly more likely to agree that: they did not know what the faculty expected of them (Odds Ratio (OR) = 0.38, p = 0.03); there were too many small group sessions facilitated only by students resulting in an unclear curriculum (OR = 0.04, p < 0.0001); and that there was a lack of opportunity to explore academic subjects of interest (OR = 0.40, p = 0.02). They were significantly more likely to disagree that: there was a lack of encouragement from teachers (OR = 3.11, p = 0.02); and that the medical course fostered a sense of anonymity and feelings of isolation amongst students (OR = 3.42, p = 0.008)., Conclusion: There are significant differences in the perceived course-related stressors affecting medical students on PBL and non-PBL programmes. Course designers and student support services should therefore tailor their work to minimise, or help students cope with, the specific stressors on each course type to ensure optimum learning and wellbeing among our future doctors.

Quinacridone-cored dendrimers with photocrosslinkable cinnamate moieties on the periphery can be patterned down to 5 micron features while retaining luminescence.

Planar supported lipid bilayers that are stable under ambient atmospheric and ultra-high-vacuum conditions were prepared by cross-linking polymerization of bis-sorbylphosphatidylcholine (bis-SorbPC). X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS) were employed to investigate bilayers that were cross-linked using either redox-initiated radical polymerization or ultraviolet photopolymerization. The redox method yields a more structurally intact bilayer; however, the UV method is more compatible with incorporation of transmembrane proteins. UV polymerization was therefore used to prepare cross-linked bilayers with incorporated bovine rhodopsin, a light-activated, G-protein-coupled receptor (GPCR). A previous study (Subramaniam, V.; Alves, I. D.; Salgado, G. F. J.; Lau, P. W.; Wysocki, R. J.; Salamon, Z.; Tollin, G.; Hruby, V. J.; Brown, M. F.; Saavedra, S. S. J. Am. Chem. Soc. 2005, 127, 5320-5321) showed that rhodopsin retains photoactivity after incorporation into UV-polymerized bis-SorbPC, but did not address how the protein is associated with the bilayer. In this study, we show that rhodopsin is retained in supported bilayers of poly(bis-SorbPC) under ultra-high-vacuum conditions, on the basis of the increase in the XPS nitrogen concentration and the presence of characteristic amino acid peaks in the ToF-SIMS data. Angle-resolved XPS data show that the protein is inserted into the bilayer, rather than adsorbed on the bilayer surface. This is the first study to demonstrate the use of ultra-high-vacuum techniques for structural studies of supported proteolipid bilayers.

This report describes the assembly of laterally diffusive lipid layers within the pores of colloidal crystals for potential application in membrane-based sensing. The amount of lipid encapsulated within colloidal crystals depends upon the method used to introduce the lipid to the crystalline substrate. Relative to a planar supported lipid bilayer, lipid loading in a 6.6 microm thick crystal was 15-73 times greater, as observed by fluorescence microscopy. Protein adsorption studies indicate that the crystal pores are open and that the silica surface of the crystal is passivated with respect to adsorption of a model protein when coated with POPC. Furthermore, the mesoporous environment of the colloidal crystal is found to protect lipid films from drying and rehydration processes that destroy planar supported lipid bilayers. The potential of colloidal crystal encapsulated lipid films for chemical sensing is demonstrated by a model protein binding assay.

The utilization of photopolymerized phospholipids for the preparation of spatially defined, chemically functionalized, micron-sized domains within enclosed fluidic channels was recently reported (Ross, E. E.; et al. J. Am. Chem. Soc. 2005, 127, 16756-7). Fabrication of the phospholipid patterns is achieved via self-assembly of photoreactive phospholipid membranes that are subsequently cross-linked via UV-irradiation through a photomask. In this work, we have characterized the chemical and physical stability of the self-assembled, chemically functionalized, cross-linked phospholipid patterns and extended this approach to the preparation of cross-linked phospholipid patterns with multiple chemical functionalities. Poly(bis-SorbPC) patterns were found to withstand a number of chemical and physical challenges, including drying/rehydration, solvent or surfactant rinse, and extended storage without compromising the size or morphology of the cross-linked phospholipid patterns. Nonspecific adsorption of proteins was found to be markedly reduced in the presence of UV-photopolymerized poly(bis-SorbPC) compared to bare silica capillaries. The resulting barcode-like patterns were used to prepare protein-functionalized domains via covalent attachment of fluorescent proteins and active enzymes to chemically functionalized lipid headgroups. We also demonstrate multiple component polymer lipid patterns with adjacent chemically functionalized polymer lipid regions. The unique combination of stability, biocompatibility, reduced nonspecific protein adsorption, and the availability of numerous chemically functionalized lipid headgroups suggests the utility of this approach for preparing a widely applicable platform for multicomponent, high-throughput chemical sensing and screening applications.

Silica colloidal crystals require multiple processing steps before they are useful materials in analytical applications, such as chemical separations, microarrays, sensors, and total internal reflection microscopy. These chemical processing steps include calcination, sintering, surface rehydroxylation, and chemical modification, but these steps have not been fully characterized for colloidal crystals. Silica particles of nominally 200 nm in diameter were prepared, and FTIR, SEM, UV-visible spectroscopy, and refractive index measurements were used to study the changes in chemical composition, particle size, and particle density throughout the process. The final material is shown to be a durable, crack-free crystal of solid particles bearing a fully hydroxylated surface of silanols, which can then be chemically modified.

Analysis of protein and peptide mixtures via capillary electrophoresis is hindered by nonspecific adsorption of analytes to the capillary walls, resulting in poor separations and quantitative reproducibility. Phospholipid bilayer (PLB) coatings are very promising for improving protein and peptide separations due to the native resistance to nonspecific protein adsorption offered by PLBs; however, these coatings display limited chemical and temporal stability. Here, we show the preparation and characterization of a highly cross-linked, polymerized phospholipid capillary coating prepared using bis-SorbPC. Poly(bis-SorbPC) PLB coatings are prepared in situ within fully enclosed fused silica capillaries via self-assembly and radical polymerization. Polymerization of the PLB coating stabilizes the membrane against desorption from the surface and migration in an electric field, improves the temporal and chemical stability, and allows for the separation of both cationic and anionic proteins, while preserving the native resistance to nonspecific protein adsorption of natural PLBs.

The use of polymerized lipid bilayers as substrates for microcontact printing (muCP) of protein films was investigated. We have previously shown that vesicle fusion of bis-SorbPC, a dienoate lipid, on glass and silica substrates, followed by redox-initiated radical polymerization, produces a planar supported lipid bilayer (PSLB) that is ultrastable(1a) [Ross, E. E.; Rozanski, L. J.; Spratt, T.; Liu, S.; O'Brien, D. F.; Saavedra, S. S. Langmuir 2003, 19, 1752] and highly resistant to nonspecific adsorption of dissolved proteins [Ross, E. E.; Spratt, T.; Liu, S.; Rozanski, L. J.; O'Brien, D. F.; Saavedra, S. S. Langmuir 2003, 19, 1766].(1b) Here we demonstrate that muCP of bovine serum albumin (BSA) onto a dried poly(bis-SorbPC) PSLB from a poly(dimethylsiloxane) (PDMS) stamp produces a layer of strongly adsorbed protein, comparable in surface coverage to films printed on glass surfaces. Immobilization of proteins on poly(PSLB)s has potential applications in biosensing, and this work shows that direct muCP of proteins is a technically simple approach to create immobilized monolayers, as well as multilayers of different proteins.

We report a new molecular approach for in situ generation of micron scale, chemically and biochemically functionalized patterns inside three-dimensional, completely enclosed fluidic channels. The formation of chemical patterns is based upon a combination of lipid bilayer self-assembly and UV photopolymerization of photoreactive, cross-linkable phospholipids. Using this approach, we have functionalized capillaries of varying inner diameters with a range of chemistries useful for protein and peptide immobilization. Here, we demonstrate the ability to produce small molecule and protein-based chemical patterns.