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).

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.

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.

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.

Genome-wide copy number variant data for inflammatory bowel disease in a caucasian population.

Genome-wide copy-number association studies offer new opportunities to identify the mechanisms underlying complex diseases, including chronic inflammatory, psychiatric disorders and others. We have used genotyping microarrays to analyse the copy-number variants (CNVs) from 243 Caucasian individuals with Inflammatory Bowel Disease (IBD). The CNV data was obtained by using multiple quality control measures and merging the results of three different CNV detection algorithms: PennCNV, iPattern, and QuantiSNP. The final dataset contains 4,402 CNVs detected by two or three algorithms independently with high confidence. This paper provides a detailed description of the data generation and quality control steps. For further interpretation of the data presented in this article, please see the research article entitled 'Copy number variation-based gene set analysis reveals cytokine signalling pathways associated with psychiatric comorbidity in patients with inflammatory bowel disease'.

Genome-wide analysis identifies rare copy number variations associated with inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD) is an idiopathic, chronic disorder of unclear etiology with an underlying genetic predisposition. Recent genome-wide association studies have identified more than 200 IBD susceptibility loci, but the causes of IBD remain poorly defined. We hypothesized that rare (<0.1% population frequency) gene copy number variations (CNVs) could play an important mechanism for risk of IBD. We aimed to examine changes in DNA copy number in a population-based cohort of patients with IBD and search for novel genetic risk factors for IBD. METHODS: DNA samples from 243 individuals with IBD from the Manitoba IBD Cohort Study and 2988 healthy controls were analyzed using genome-wide SNP microarray technology. Three CNV calling algorithms were applied to maximize sensitivity and specificity of CNV detection. We identified IBD-associated genes affected by rare CNV from comparing the number of overlapping CNVs in IBD samples with the number of overlapping CNVs in controls for each gene. RESULTS: 4,402 CNVs detected by two or three algorithms intersected 7,061 genes, in at least one analyzed sample. Four genes (e.g. DUSP22 and IP6K3) intersected by rare deletions and fourteen genes (e.g. SLC25A10, PSPN, GTF2F1) intersected by rare duplications demonstrated significant association with IBD (FDR-adjusted p-value < 0.01). Of these, ten genes were functionally related to immune response and intracellular signalling pathways. Some of these genes were also identified in other IBD related genome-wide association studies. These suggested that the identified genes may play a role in the risk of IBD. CONCLUSION: Our results revealed new genomic loci associated with IBD, which suggested the role of rare CNVs in IBD risk.

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.

Congenital lactic acidosis, cerebral cysts and pulmonary hypertension in an infant with FOXRED1 related complex 1 deficiency.

Mitochondrial complex I is encoded by 38 nuclear-encoded and 7 mitochondrial-encoded genes. FOXRED1 is one of the 13 additional nuclear genes known as assembly factors. So far, four patients have been described with complex I deficiency caused by autosomal recessive mutations in FOXRED1. Here, we report the fifth patient with FOXRED1 related complex 1 deficiency presenting with prenatal onset of bilateral periventricular cysts, congenital lactic acidosis, and persistent life-limiting pulmonary hypertension. Whole exome sequencing identified a compound heterozygosity for a known pathogenic variant (c.612_615dupAGTG; p.A206SfsX15) (paternal) and a likely pathogenic variant (c.874G>A; p.Gly292Arg) (maternal). Deficiency of complex I was demonstrated by the absence of complex I on Blue Native Gel Electrophoresis and by a significantly reduced complex I enzyme activity in the patient's fibroblasts. Compared with the previous known FOXRED1 cases, unique clinical features observed in our patient include bilateral periventricular cysts and severe pulmonary hypertension. Whole exome sequencing was instrumental in recognizing the underlying gene defect in this patient.

Congenital lactic acidosis, cerebral cysts and pulmonary hypertension in an infant with FOXRED1 related complex I deficiency.

Mitochondrial complex I is encoded by 38 nuclear-encoded and 7 mitochondrial-encoded genes. FOXRED1 is one of the 13 additional nuclear genes known as assembly factors. So far, four patients have been described with complex I deficiency caused by autosomal recessive mutations in FOXRED1. Here, we report the fifth patient with FOXRED1 related complex 1 deficiency presenting with prenatal onset of bilateral periventricular cysts, congenital lactic acidosis, and persistent life-limiting pulmonary hypertension. Whole exome sequencing identified a compound heterozygosity for a known pathogenic variant (c.612_615dupAGTG; p.A206SfsX15) (paternal) and a likely pathogenic variant (c.874G > A; p.Gly292Arg) (maternal). Deficiency of complex I was demonstrated by the absence of complex I on Blue Native Gel Electrophoresis and by a significantly reduced complex I enzyme activity in the patient's fibroblasts. Compared with the previous known FOXRED1 cases, unique clinical features observed in our patient include bilateral periventricular cysts and severe pulmonary hypertension. Whole exome sequencing was instrumental in recognizing the underlying gene defect in this patient.

Living With Inflammatory Bowel Disease: Protocol for a Longitudinal Study of Factors Associated With Symptom Exacerbations.

BACKGROUND: There has been limited longitudinal research that has comprehensively evaluated possible factors in the exacerbation of inflammatory bowel disease (IBD) symptoms with or without associated inflammation. Evolving Web-based technologies facilitate frequent monitoring of patients' experiences and allow a fine-grained assessment of disease course. OBJECTIVE: We aimed to prospectively identify factors associated with symptom exacerbation and inflammation in IBD including psychological functioning, diet, health behaviors, and medication adherence. METHODS: Between June 2015 and May 2017, we enrolled adults with IBD, recruited from multiple sources, who had been symptomatically active at least once within the prior 2 years. They completed a Web-based survey every 2 weeks for 1 year and submitted a stool sample at baseline, 26 weeks, and 52 weeks. Any participant reporting a symptom exacerbation was matched to a control within the cohort, based on disease type, sex, age, and time of enrollment; both were sent a supplemental survey and stool collection kit. Biweekly surveys included validated measures of the disease course, psychological functioning, health comorbidities, and medication use. Intestinal inflammation was identified through fecal calprotectin (positive level >250 µg/g stool). RESULTS: There were 155 participants enrolled with confirmed IBD, 66.5% (103/155) with Crohn disease and 33.5% (52/155) with ulcerative colitis, of whom 98.7% (153/155) completed the study. Over the 1-year period, 47.7% (74/155) participants experienced a symptom exacerbation. The results of analyses on risk factors for symptom exacerbations are pending. CONCLUSIONS: We recruited and retained a longitudinal IBD cohort that will allow the determination of risk factors for symptom exacerbation with and without inflammation. This will increase understanding of symptom exacerbations among persons with IBD. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/11317.

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.

Evidence of Bidirectional Associations Between Perceived Stress and Symptom Activity: A Prospective Longitudinal Investigation in Inflammatory Bowel Disease.

BACKGROUND: Our aim was to explore the relationships among perceived stress, intestinal inflammation, and inflammatory bowel disease (IBD) symptoms over time. METHODS: Participants were recruited from a population-based registry of persons with IBD and assessed at months 0, 3, and 6. Key dependent measures were the Manitoba IBD Index (symptom activity), Cohen's Perceived Stress Scale, and fecal calprotectin in stool (intestinal inflammation). RESULTS: Complete data were available for 417 participants at months 0; 369 provided follow-up data. Active symptoms were reported by 54% of those with Crohn's disease (CD) and 40% of those with ulcerative colitis (UC) and approximately one-third consistently had fecal calprotectin measures ≥250 µg/g, suggestive of active inflammation. A significant proportion of participants had indications of inflammation but no active symptoms over the 6 months. Correlations of month 0 perceived stress and disease activity measures with values at months 3 and 6 for both CD and UC indicated strong temporal stability. In hierarchical multiple regression analyses, month 0 symptom activity was thus a strong predictor of later symptom activity for CD and UC. Perceived stress predicted change in symptom activity from 0 to 3 months for CD, as did use of prednisone for UC. Comparably, month 0 perceived stress was a strong predictor of later perceived stress for CD and UC, while month 0 symptom activity predicted change in perceived stress from 0 to 3 months for both CD and UC. CONCLUSIONS: The analysis revealed prospective bidirectional relationships between perceived stress and IBD symptoms but no relationship between perceived stress and change in intestinal inflammation as assessed by fecal calprotectin.

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.

Treatment of Creatine Transporter (SLC6A8) Deficiency With Oral S-Adenosyl Methionine as Adjunct to L-arginine, Glycine, and Creatine Supplements.

BACKGROUND: Creatine transporter (SLC6A8) deficiency is an X-linked inborn error of metabolism characterized by cerebral creatine deficiency, behavioral problems, seizures, hypotonia, and intellectual developmental disability. A third of patients are amenable to treatment with high-dose oral creatine, glycine, and L-arginine supplementation. METHODS: Given the limited treatment response, we initiated an open-label observational study to evaluate the effect of adjunct S-adenosyl methionine to further enhance intracerebral creatine synthesis. RESULTS: Significant and reproducible issues with sleep and behavior were noted in both male patients on a dose of 50/mg/kg. One of the two patients stopped S-adenosyl methionine and did not come for any follow-up. A safe and tolerable dose (17 mg/kg/day) was identified in the other patient. On magnetic resonance spectroscopy, this 8-year-old male did not show an increase in intracerebral creatine. However, significant improvement in speech/language skills, muscle mass were observed as well as in personal outcomes as defined by the family in activities related to communication and decision making. DISCUSSION: Further research is needed to assess the potential of S-adenosyl methionine as an adjunctive therapy for creatine transporter deficiency patients and to define the optimal dose. Our study also illustrates the importance of pathophysiology-based treatment, individualized outcome assessment, and patient/family participation in rare diseases research.

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.

Radiological prevalence of superior and posterior semicircular canal dehiscence in children.

OBJECTIVE: Establishing the prevalence of semicircular canal dehiscence in a pediatric population using temporal bone CT imaging. STUDY DESIGN: Retrospective analysis of all temporal bone CT scans during a 5-year period (2007-2012). METHODS: CT scan images were reformatted in the plane of the canals and assessed by two independent reviewers with a third to resolve disagreement. Detailed chart review was performed for those found to have dehiscence. Superior and posterior canals were classified as "dehiscent", "possibly dehiscent", "thin" or "normal" for each case. RESULTS: 649 temporal bones were assessed from 334 children (under 18 years of age). The prevalence rate of superior canal dehiscence (SCD) was 1.7% (3.3% of individuals). Posterior canal dehiscence (PCD) was present in 1.2% (2.1% of individuals). There were no cases of bilateral SCD, and one case of bilateral PCD. Age under 3 years was associated with a higher prevalence of thinning but not dehiscence. Congenital inner ear malformation was not related to a higher probability of dehiscence. The superior petrosal sinus was associated with the SCD in three cases (27.3%). Retrospective chart review highlighted possible vestibular symptoms in 3/11 patients with SCD (27.3%). CONCLUSIONS: This forms the largest pediatric study of canal dehiscence to date. This study's prevalence rate is significantly lower than previous reports. The identified association with overlying venous structures may reflect the etiological process involved. The occurrence in children supports the hypothesis of a congenital predisposition for development of canal dehiscence syndrome.