Skin in the game: Race, ingroup identification, and attitudes toward paying college athletes.

OBJECTIVES: The present studies examined two dimensions of racial ingroup identification, using them as predictors of Black and White Americans' attitudes toward paying college athletes. Following Leach et al. (2008), the present work distinguished between ingroup self-investment and ingroup self-definition. The central prediction was that respondent race and self-investment would interact in predicting compensation support. METHOD: In three studies (N = 352, N = 476, & N = 562), U.S. residents who were 18 or older and either Black or White completed an online survey in which they completed a self-report measure of racial identification, as well as reporting their opinion of paying college athletes. RESULTS: The results supported the prediction, demonstrating that Black respondents' support was higher than that for Whites, but this was especially the case at high levels of self-investment. The third study suggests that these effects were driven by respondents who believed that Black athletes made up a larger percentage of the pool of likely beneficiaries of compensation. Ingroup self-definition played no role as a moderator. CONCLUSIONS: Broadly speaking, it may be that, for policies whose likely beneficiaries are disproportionately Black, stronger racial self-investment serves to widen racial divides in support. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Ranking microbiome variance in inflammatory bowel disease: a large longitudinal intercontinental study.

OBJECTIVE: The microbiome contributes to the pathogenesis of inflammatory bowel disease (IBD) but the relative contribution of different lifestyle and environmental factors to the compositional variability of the gut microbiota is unclear. DESIGN: Here, we rank the size effect of disease activity, medications, diet and geographic location of the faecal microbiota composition (16S rRNA gene sequencing) in patients with Crohn's disease (CD; n=303), ulcerative colitis (UC; n = 228) and controls (n=161), followed longitudinally (at three time points with 16 weeks intervals). RESULTS: Reduced microbiota diversity but increased variability was confirmed in CD and UC compared with controls. Significant compositional differences between diseases, particularly CD, and controls were evident. Longitudinal analyses revealed reduced temporal microbiota stability in IBD, particularly in patients with changes in disease activity. Machine learning separated disease from controls, and active from inactive disease, when consecutive time points were modelled. Geographic location accounted for most of the microbiota variance, second to the presence or absence of CD, followed by history of surgical resection, alcohol consumption and UC diagnosis, medications and diet with most (90.3%) of the compositional variance stochastic or unexplained. CONCLUSION: The popular concept of precision medicine and rational design of any therapeutic manipulation of the microbiota will have to contend not only with the heterogeneity of the host response, but also with widely differing lifestyles and with much variance still unaccounted for.

Copy number variation-based gene set analysis reveals cytokine signalling pathways associated with psychiatric comorbidity in patients with inflammatory bowel disease.

BACKGROUND: Recent studies discovered many genetic variants associated with both psychiatric and inflammatory disorders, but the role of genetic factors in the development of psychiatric comorbidity (PC) in inflammatory bowel disease (IBD) is underexplored. Particularly, it has been shown that some of the genetic variants have been linked to the concentrations of circulating cytokines and symptoms of the inflammatory cytokine-associated depression. We analysed genomic features of individuals with IBD by comparing IBD patients with PC with those who have IBD but without PC. We hypothesized that cytokine related signalling pathways may be significantly associated with the psychiatric comorbidity in patients with IBD. METHODS: Individuals enrolled in the Manitoba IBD Cohort Study were separated to two groups accordingly to the presence of PC. A sample set comprising 97 IBD individuals with PC (IBD + PC) and 146 IBD individuals without PC (IBD) was first used to identify copy number variations (CNVs) from genome-wide genetic data using three different detection algorithms. IBD + PC and IBD groups were compared by the number of CNVs overlapping each gene; deletions and duplications were analysed separately. Gene set overrepresentation analysis was then conducted using CNV-overlapped genes and the candidate gene sets of neurological and immunological relevance. RESULTS: Medium-sized CNV (size between 100 and 500 kilobase pairs)-burden is significantly higher in IBD + PC than IBD groups. Gene-based CNV association analysis did not show significant differences between the two IBD groups. Gene set overrepresentation analysis demonstrated the significant enrichment of gene sets related to cytokine signalling pathways by the genes overlapped by deletions in the IBD individuals with PC. CONCLUSION: Our results confirm the role of cytokine signalling pathways in the development of PC in IBD. Additionally, our results warrant further study with a larger sample size focusing on cytokine SNPs to further understand the relationship between inflammatory and psychiatric disorders.

Case reports: novel TUBG1 mutations with milder neurodevelopmental presentations.

BACKGROUND: Tubulinopathies result from mutations in tubulin genes, including TUBG1, responsible for cell microtubules, are characterized by brain development abnormalities, microcephaly, early-onset epilepsy, and motor impairment. Only eleven patients with TUBG1 mutations have been previously described in literature to our knowledge. Here we present two new patients with novel de novo TUBG1 mutations and review other cases in the literature. CASE PRESENTATIONS: Both patients have microcephaly and intellectual disability. Patient B further fits a more typical presentation, with well-controlled epilepsy and mild hypertonia, whereas Patient A's presentation is much milder without these other features. CONCLUSION: This report expands the spectrum of TUBG1 mutation manifestations, suggesting the possibility of less severe phenotypes for patients and families, and influencing genetic counselling strategies.

Central adrenal insufficiency following traumatic brain injury: a missed diagnosis in the critically injured.

BACKGROUND: High-dose steroid administration is no longer recommended in the treatment of acute traumatic brain injury (TBI) as it failed to prove beneficial in improving patients' outcome. However, a masked benefit of steroid administration in TBI management was that it provided corticosteroid replacement therapy in patients with TBI-related central adrenal insufficiency. CASE PRESENTATION: We report the case of a 12-year-old boy who suffered a severe TBI from a motor vehicle accident that resulted in complete deficiency of anterior pituitary function. Central adrenal insufficiency was not ruled out by a near normal response to a low-dose ACTH test performed on D11. CONCLUSION: Consideration should be given to the empirical treatment of TBI pediatric patients with stress doses of corticosteroids if injury to the hypothalamus or pituitary gland is possible until a formal assessment of the hypothalamic-pituitary-adrenal axis can be made.

Microbiome profiling of drinking water in relation to incidence of inflammatory bowel disease.

The etiology of inflammatory bowel disease (IBD) is unknown; current research is focused on determining environmental factors. One consideration is drinking water: water systems harbour considerable microbial diversity, with bacterial concentrations estimated at 10(6)-10(8) cells/L. Perhaps differences in microbial ecology of water sources may impact differential incidence rates of IBD. Regions of Manitoba were geographically mapped according to incidence rates of IBD and identified as high (HIA) or low (LIA) incidence areas. Bulk water, filter material, and pipe wall samples were collected from public buildings in different jurisdictions and their population structure analyzed using 16S rDNA sequencing. At the phylum level, Proteobacteria were observed significantly less frequently (P = 0.02) in HIA versus LIA. The abundance of Proteobacteria was also found to vary according to water treatment distribution networks. Gammaproteobacteria was the most abundant class of bacteria and was observed more frequently (P = 0.006) in LIA. At the genus level, microbes found to associate with HIA include Bradyrhizobium (P = 0.02) and Pseudomonas (P = 0.02). Particular microbes were found to associate with LIA or HIA, based on sample location and (or) type. This work lays out a basis for further studies exploring water as a potential environmental source for IBD triggers.

The Relationship Among Perceived Stress, Symptoms, and Inflammation in Persons With Inflammatory Bowel Disease.

OBJECTIVES: Previous studies have demonstrated that stress is associated with increased disease activity in individuals with inflammatory bowel disease (IBD). The association between perceived stress and gastrointestinal inflammation is not well described. METHODS: Participants were recruited from a population-based registry of individuals with known IBD. Symptomatic disease activity was assessed using validated clinical indices: the Manitoba IBD Index (MIBDI) and Harvey Bradshaw Index (HBI) for Crohn's disease (CD), and Powell Tuck Index (PTI) for ulcerative colitis (UC). Perceived stress was measured using Cohen's Perceived Stress Scale (CPSS). Intestinal inflammation was determined through measurement of fecal calprotectin (FCAL), with a level exceeding 250 µg/g indicating significant inflammation. Logistic regressions were used to evaluate the association between intestinal inflammation, perceived stress, and disease activity. RESULTS: Of the 478 participants with completed surveys and stool samples, perceived stress was associated with symptomatic activity (MIBDI) for both CD and UC (1.07 per 1-point increase on the CPSS, 95% confidence interval (CI) 1.03-1.10 and 1.03-1.11, respectively). There was no significant association between perceived stress and intestinal inflammation for either CD or UC. Active symptoms (MIBDI ≤3) were associated with intestinal inflammation in UC (odds ratio (OR) 3.94, 95% CI 1.65-9.43), but not in CD (OR 0.98, 95% CI 0.51-1.88). CONCLUSIONS: Symptomatic disease activity was unrelated to intestinal inflammation in CD and only weakly associated in UC. Although there was a strong relationship between perceived stress and gastrointestinal symptoms, perceived stress was unrelated to concurrent intestinal inflammation. Longitudinal investigation is required to determine the directionality of the relationship between perceived stress, inflammation, and symptoms in IBD.

Treatment of X-linked creatine transporter (SLC6A8) deficiency: systematic review of the literature and three new cases.

BACKGROUND: Creatine transporter deficiency (CTD) is an X-linked inborn error of creatine metabolism characterized by reduced intra-cerebral creatine, developmental delay/intellectual disability, (ID), behavioral disturbance, seizures, and hypotonia in individuals harboring mutations in the SLC6A8 gene. Treatment for CTD includes supplementation with creatine, either alone or in combination with creatine precursors (arginine or glycine). Unlike other disorders of creatine metabolism, the efficacy of its treatment remains controversial. METHODS: We present our systematic literature review (2001-2013) comprising 7 publications (case series/reports), collectively describing 25 patients who met the inclusion criteria, and 3 additional cases treated at our institution. Definitions were established and extracted data analyzed for cognitive ability, psychiatric and behavioral disturbances, epilepsy, and cerebral proton magnetic resonance spectroscopy measurements at pre- and post-treatment. RESULTS: Treatment regimens varied among the 28 cases: 2 patients received creatine-monohydrate supplementation; 7 patients received L-arginine; 2 patients received creatine-monohydrate and L-arginine; and 17 patients received a combination of creatine-monohydrate, L-arginine and glycine. Median treatment duration was 34.6 months (range 3 months-5 years). Level of evidence was IV. A total of 10 patients (36%) demonstrated response to treatment, manifested by either an increase in cerebral creatine, or improved clinical parameters. Seven of the 28 patients had quantified pre- and post-treatment creatine, and it was significantly increased post-treatment. All of the patients with increased cerebral creatine also experienced clinical improvement. In addition, the majority of patients with clinical improvement had detectable cerebral creatine prior to treatment. 90% of the patients who improved were initiated on treatment before nine years of age. CONCLUSIONS: Acknowledging the limitations of this systematic review, we conclude that a proportion of CTD patients show amenability to treatment-particularly milder cases with residual brain creatine, and therefore probable residual protein function. We propose systematic screening for CTD in patients with ID, to allow early initiation of treatment, which currently comprises oral creatine, arginine and/or glycine supplementation. Standardized monitoring for safety and evaluation of treatment effects are required in all patients. This study provides effectiveness on currently available treatment, which can be used to discern effectiveness of future interventions (e.g. cyclocreatine).

Brain MRI abnormalities and spectrum of neurological and clinical findings in three patients with proximal 16p11.2 microduplication.

The phenotype of recurrent ∼600 kb microdeletion and microduplication on proximal 16p11.2 is characterized by a spectrum of neurodevelopmental impairments including developmental delay and intellectual disability, epilepsy, autism and psychiatric disorders which are all subject to incomplete penetrance and variable expressivity. A variety of brain MRI abnormalities were reported in patients with 16p11.2 rearrangements, but no systematic correlation has been studied among patients with similar brain anomalies, their neurodevelopmental and clinical phenotypes. We present three patients with the proximal 16p11.2 microduplication exhibiting significant developmental delay, anxiety disorder and other variable clinical features. Our patients have abnormal brain MRI findings of cerebral T2 hyperintense foci (3/3) and ventriculomegaly (2/3). The neuroradiological or neurological findings in two cases prompted an extensive diagnostic work-up. One patient has exhibited neurological regression and progressive vision impairment and was diagnosed with juvenile neuronal ceroid-lipofuscinosis. We compare the clinical course and phenotype of these patients in regard to the clinical significance of the cerebral lesions and the need for MRI surveillance. We conclude that in all three patients the lesions were not progressive, did not show any sign of malignant transformation and could not be correlated to specific clinical features. We discuss potential etiologic mechanisms that may include overexpression of genes within the duplicated region involved in control of cell proliferation and complex molecular mechanisms such as the MAPK/ERK pathway. Systematic studies in larger cohorts are needed to confirm our observation and to establish the prevalence and clinical significance of these neuroanatomical abnormalities in patients with 16p11.2 duplications.

Crystallization and phase changes in paracetamol from the amorphous solid to the liquid phase.

For the case of paracetamol, we show how terahertz time-domain spectroscopy can be used to characterize the solid and liquid phase dynamics. Heating of supercooled amorphous paracetamol from 295 K in a covered sample under vacuum leads to its crystallization at 330 K. First, form III is formed followed by the transformation of form III to form II at 375 K, to form I at 405 K, and finally melting is observed around 455 K. We discuss the difference between the featureless spectra of the supercooled liquid and its liquid melt. Lastly, we studied the onset of crystallization from the supercooled liquid in detail and quantified its kinetics based on the Avrami-Erofeev model. We determined an effective rate constant of k = 0.056 min(-1) with a corresponding onset of crystallization at T = 329.5 K for a heating rate of 0.4 K min(-1).

Does optic nerve sheath diameter on MRI decrease with clinically improved pediatric hydrocephalus?

INTRODUCTION: Serial change in ventricular size is recognized as an imperfect indicator of ongoing hydrocephalus in children. Potentially, other radiographic features may be useful in determining the success of hydrocephalus interventions. In this study, optic nerve sheath diameter (ONSD), optic nerve tortuosity, and optic disk bulging were assessed as indicators of hydrocephalus control in children who underwent endoscopic third ventriculostomy (ETV) or posterior fossa tumor resection. METHODS: Sixteen children underwent ETV or tumor resection for treatment of hydrocephalus. T2-weighted axial magnetic resonance images of the orbit were obtained, and the ONSD was measured posterior to the optic globe, pre- and post-intervention. Evidence of optic disk bulging and optic nerve tortuosity was also assessed. Ventricular size was estimated using the frontal and occipital horn ratio (FOR). RESULTS: There was a significant reduction in the ONSD post-ETV (n = 9) and after tumor resection (n = 7). Average preoperative ONSD was 6.21 versus 5.71 mm postoperatively (p = 0.0017).There was also an 88% (p = 0.011) and 60% (p = 0.23) reduction in optic disk bulging and tortuosity, respectively. The FOR normalized in the tumor resection group but not the ETV group. After intervention, all patients showed improvement in signs and symptoms of hydrocephalus. CONCLUSION: In our study population, ONSD decreased in response to measures to reduce hydrocephalus. Optic disk bulging also appears to resolve. Serial reduction in ONSD, and optic disk bulging may be indicators of improved hydrocephalus following pediatric neurosurgical interventions.

Neurological morbidity of surgical resection of pediatric cerebellar astrocytomas.

BACKGROUND: Review of children with low-grade cerebellar astrocytoma (LGCA) prior to 1992 showed a 98% rate of gross total resection (GTR) but a concerning incidence of permanent neurological dysfunction. The purpose of this study was to determine the rate of GTR of LGCA since 1992 and frequency of neurologic injury. METHODS: Retrospective review of children with LGCA was performed. CT/MR scans were rereviewed to assess extent of resection. Primary outcomes included incidence of GTR and incidence of permanent new neurological deficits. Other outcomes included late effects severity score (LESS), Bloom score for functional status, and educational assessment. RESULTS: Of 50 LGCA, GTR was achieved in 38 (76%) compared to 43 of 44 (98%) prior to 1992 (p < 0.004). Permanent new neurologic deficits from surgery occurred in 16% compared to 18% in the prior era (p = 0.61). For 35 patients operated on by the 2 surgeons in the prior study, 74% had GTR, with permanent neurological deficits in 8.6%. At latest follow-up, all patients were alive, 16% with residual tumor. LESS was two or less (mild or no deficit) in 94%. Bloom score was one or two (no or mild disability) in 90%. Eighty-six percent attended normal school. CONCLUSIONS: Less aggressive resection of LGCA in children may reduce postoperative neurologic deficits in the hands of the same surgeons as in the prior study but not overall at our institution. The good long-term outcomes suggest that it may be appropriate to do incomplete resection rather than risk additional neurological deficit.

Prevalence of genetic variants associated with inflammatory bowel disease in a healthy First Nations cohort.

BACKGROUND: Inflammatory bowel disease is the result of both genes and environment. Canadian First Nations people, despite living in a region with a high prevalence of inflammatory bowel disease, are relatively protected from this disease. We aimed to compare the carriage of genetic variants associated with inflammatory bowel disease in healthy First Nations and white people. METHODS: DNA was extracted from the venous blood of healthy First Nations (n = 340) and white (n = 285) participants from Manitoba. Genotyping was performed for 69 single nucleotide polymorphisms (SNPs) with known or suspected associations with inflammatory bowel disease. We compared the genotypes between groups by logistic regression, adjusting for multiple testing. We calculated a risk score for the NOD2 gene by adding the number of risk alleles at three important NOD2 SNPs (G908R, R702W and 3020insC). RESULTS: We found genetic variation between white and First Nations participants at 45 of 69 SNPs. Notably, carriage of the ATG16L1 T300A mutation was lower in First Nations participants (p = 4.1 × 10(-30)). Cumulative carriage of important NOD2 variants was significantly lower among First Nations participants (3.9% v. 15.2%; p < 0.0001 for risk score) than among white participants. Risk variants in IL23R (p = 0.014) and IL12B (p = 1.2 × 10(-16)), among others, were more prevalent among First Nations participants than among white participants. INTERPRETATION: The low prevalence of variants associated with bacterial processing and handling in First Nations people may explain their relative protection from inflammatory bowel disease. Increased carriage of a number of risk variants, for example in the interleukin-23/Th17 pathway, is especially intriguing given their importance in other inflammatory diseases of high incidence in First Nations populations.

Intracranial tumors in infants: long-term functional outcome, survival, and its predictors.

OBJECTIVE: Intracranial tumors are rare in the first year of life. This study evaluates survival rates and functional outcomes of survivors at least 5 years after diagnosis and the predictors of this outcome. METHODS: A retrospective chart review of all infants with a primary intracranial tumor was carried out. Radiology and pathology were re-reviewed. Outcome was assessed at 5 years or more after diagnosis using Bloom's categories (Bloom 1-2 = good outcome, the rest = poor outcome) and late effects severity scoring. Age, tumor location, size, extent of tumor resection, type of adjuvant therapy given, and WHO grade of tumor histology were evaluated as predictors of outcome. RESULTS: Among 35 infants, 20 (57%) survived, with 12 (34%) having a good outcome. Deficits among the survivors included neurological dysfunction in 14 (70%), visual impairment in 9 (45%), endocrine dysfunction in 5 (25%), and auditory disability in 3 (15%). Ten of the 20 survivors were either attending regular school or were engaged in a skilled job. At presentation, older age and an infratentorial location of the tumor are predictors of poor outcome. After histopathological diagnosis, the WHO grading of tumor is the only independent predictor of survival (p = 0.002) and functional outcome (p < 0.001). CONCLUSION: About a third of the infants diagnosed with brain tumors (34%) had a good functional outcome and approximately a quarter of them (28%) were able to attend regular school or take up a skilled job. After tissue diagnosis, histological grade of tumor is the only independent predictor associated with outcome.

Expanding the clinical phenotype of the mitochondrial m.13513G>A mutation with the first report of a fatal neonatal presentation.

Diagnosis of mitochondrial disease is often a challenge because of the extreme heterogeneity of the clinical phenotype and the variety of underlying gene defects. Insight into the range of clinical phenotypes associated with a particular mitochondrial DNA mutation will facilitate better recognition of patients at risk by focused gene testing. We present a family affected by the mitochondrial m.13513G>A (p.D393N, ND5) mutation, illustrating a previously unreported degree of clinical heterogeneity, varying from mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS) in a 10-year-old female, to a fatal neonatal course with metabolic acidosis and hypotonia in a younger sister, to absence of medical problems in the mother. The mutation loads ranging from 66% in the deceased neonate to 30% in the female with MELAS and 7% in the asymptomatic mother, correlated with severity of the clinical phenotype. The importance of proactive collection and storage of appropriate samples during the diagnostic work-up of an acutely ill or deceased neonate, allowing subsequent mitochondrial investigations, is hereby illustrated.

Assessing inflammatory bowel disease-associated antibodies in Caucasian and First Nations cohorts.

BACKGROUND: First Nation populations in Canada have a very low incidence of inflammatory bowel disease (IBD). Based on typical infections in this population, it is plausible that the First Nations react differently to microbial antigens with a different antibody response pattern, which may shed some light as to why they experience a low rate of IBD. OBJECTIVE: To compare the positivity rates of antibodies known to be associated with IBD in Canadian First Nations compared with a Canadian Caucasian population. METHODS: Subjects with Crohn's disease, ulcerative colitis (UC), rheumatoid arthritis (RA) (as an immune disease control) and healthy controls without a personal or family history of chronic immune diseases, were enrolled in a cohort study aimed to determine differences between First Nations and Caucasians with IBD or RA. Serum from a random sample of these subjects (n=50 for each of First Nations with RA, First Nations controls, Caucasians with RA, Caucasians with Crohn's disease, Caucasians with UC and Caucasians controls, and as many First Nations with either Crohn's disease or UC as could be enrolled) was analyzed in the laboratory for the following antibodies: perinuclear antineutrophil cytoplasmic antibody (pANCA), and four Crohn's disease-associated antibodies including anti-Saccharomyces cerevisiae, the outer membrane porin C of Escherichia coli, I2 - a fragment of bacterial DNA associated with Pseudomonas fluorescens, and the bacterial flagellin CBir-1. The rates of positive antibody responses and mean titres among positive results were compared. RESULTS: For pANCA, First Nations had a positivity rate of 55% in those with UC, 32% in healthy controls and 48% in those with RA. The pANCA positivity rate was 32% among Caucasians with RA. The rates of the Crohn's disease-associated antibodies for the First Nations and Caucasians were comparable. Among First Nations, up to one in four healthy controls were positive for any one of the Crohn's disease-associated antibodies. First Nations had significantly higher pANCA titres in both the UC and RA groups than Caucasians. DISCUSSION: Although First Nation populations experience a low rate of IBD, they are relatively responsive to this particular antibody panel. CONCLUSIONS: The positivity rates of these antibodies in First Nations, despite the low incidence of IBD in this population, suggest that these antibodies are unlikely to be of pathogenetic significance.

Spontaneous regression of septum pellucidum/forniceal pilocytic astrocytomas--possible role of Cannabis inhalation.

INTRODUCTION: Spontaneous regression of pilocytic astrocytoma after incomplete resection is well recognized, especially for cerebellar and optic pathway tumors, and tumors associated with Neurofibromatosis type-1 (NF1). The purpose of this report is to document spontaneous regression of pilocytic astrocytomas of the septum pellucidum and to discuss the possible role of cannabis in promoting regression. CASE REPORT: We report two children with septum pellucidum/forniceal pilocytic astrocytoma (PA) tumors in the absence of NF-1, who underwent craniotomy and subtotal excision, leaving behind a small residual in each case. During Magnetic Resonance Imaging (MRI) surveillance in the first three years, one case was dormant and the other showed slight increase in size, followed by clear regression of both residual tumors over the following 3-year period. Neither patient received any conventional adjuvant treatment. The tumors regressed over the same period of time that cannabis was consumed via inhalation, raising the possibility that the cannabis played a role in the tumor regression. CONCLUSION: We advise caution against instituting adjuvant therapy or further aggressive surgery for small residual PAs, especially in eloquent locations, even if there appears to be slight progression, since regression may occur later. Further research may be appropriate to elucidate the increasingly recognized effect of cannabis/cannabinoids on gliomas.

Association Between Change in Inflammatory Aspects of Diet and Change in IBD-related Inflammation and Symptoms Over 1 Year: The Manitoba Living With IBD Study.

BACKGROUND: We aimed to investigate (1) the stability of inflammatory aspects of diet over 1 year among persons with inflammatory bowel disease (IBD) and (2) the impact of change in diet on changes in inflammation and IBD symptoms over 1 year. METHODS: Participants were recruited to the Manitoba Living with IBD Study and completed the Harvard Food Frequency Questionnaire (FFQ). The Dietary Inflammatory Index (DII) and the Empirical Dietary Inflammatory Index (EDII) were used to calculate the inflammatory potential of the diet. Inflammation was measured by fecal calprotectin (≥250 µg/g). Symptoms were measured by the IBD Symptom Inventory (IBDSI). All measures were obtained at baseline and 1 year. Dietary Inflammatory Index and Empirical Dietary Inflammatory Index scores >0 and <0 reflect pro- and anti-inflammatory diet, respectively. Variance components analyses were used to describe diet stability. Associations between changes in diet and changes in active inflammation and symptoms were assessed using ordinal logistic regression and multilevel linear regression modeling. RESULTS: One hundred thirty-five participants (66% CD) were included. Approximately one third of the variance in EDII (36%) and DII (33%) scores was explained by changes in diet over time. Each unit increase in the change in EDII (baseline to follow-up) was associated with a greater odds of FCAL, indicating active inflammation (>250 µg/g; odds ratio, 3.1; 95% confidence interval [CI], 1.02-9.93; P = 0.04) and with a rise in IBDSI of 6.7 (95% CI, 1.0-12.4; P = 0.022; theoretical IBDSI range, 0-81). There was no association between changes in DII and changes in FCAL or IBDSI. CONCLUSION: The EDII, but not the DII, may have utility to identify the inflammatory potential of diet. This inflammatory potential can contribute to inflammation and/or disease symptoms in persons with IBD.

Trametinib therapy for children with neurofibromatosis type 1 and life-threatening plexiform neurofibroma or treatment-refractory low-grade glioma.

PURPOSE: To describe a series of children with extensive PNF or treatment refractory PLGG treated on a compassionate basis with trametinib. METHODS: We report on six patients with NF-1 treated with trametinib on a compassionate basis at British Columbia Children's Hospital since 2017. Data were collected retrospectively from the patient record. RAPNO and volumetric criteria were used to evaluate the response of intracranial and extracranial lesions, respectively. RESULTS: Subjects were 21 months to 14 years old at the time of initiation of trametinib therapy and 3/6 subjects are male. Duration of therapy was 4-28 months at the time of this report. All patients had partial response or were stable on analysis. Two patients with life-threatening PNF had a partial radiographic response in tandem with significant clinical improvement and developmental catch up. One subject discontinued therapy after 6 months due to paronychia and inadequate response. The most common adverse effect (AE) was grade 1-2 paronychia or dermatitis in 5/6 patients. There were no grade 3 or 4 AEs. At the time of this report, five patients remain on therapy. CONCLUSION: Trametinib is an effective therapy for advanced PNF and refractory PLGG in patients with NF-1 and is well tolerated in children. Further data and clinical trials are required to assess tolerance, efficacy and durability of response, and length of treatment required in such patients.