Adolescents With Inflammatory Bowel Disease Have Decreased Rates of Health Maintenance Visits.

INTRODUCTION: Inflammatory bowel disease (IBD) commonly presents during adolescence and may affect health care utilization. This study aimed to assess rates of health maintenance examinations (HMEs) in adolescents with IBD with their primary care physicians (PCPs). METHODS: This is a single center, case-control study of adolescents with IBD who received their IBD care and primary care within the same healthcare system. Adolescents diagnosed with IBD between 13 and 17 years of age were matched 1:1 by age, gender, race/ethnicity, and insurance status to healthy controls. Patient demographics, IBD characteristics, and health outcomes were extracted from the medical record. HME rate was defined as having one HME with a PCP during a 12-month period. RESULTS: This study included 150 IBD-control matched pairs. HME rates were similar at baseline between cases and controls (83% vs 85%, P = 0.53) but approached significance in year 1 post-diagnosis (77% vs 85%, P = 0.056). In year 2 post-diagnosis, IBD patients had less frequent HME (62% vs 74%, P = 0.0486). Disease severity did not affect HME rates. IBD patients from under-represented minority groups had lower rates than matched controls (46.2% vs 91.7%, P = 0.03). Meningococcal and human papilloma vaccination rates were lower in cases versus controls (79% vs 94%, P = 0.0005 and 60% vs 84%, P < 0.0001). CONCLUSION: Adolescents with IBD have less frequent HME and lower rates of certain vaccinations than their peers. Those from underrepresented minority groups are at particular risk. Given the important issues addressed at HMEs, gastroenterologists should recommend that adolescents with IBD have ongoing PCP engagement to optimize health outcomes.

Systematic mapping of occluded genes by cell fusion reveals prevalence and stability of cis-mediated silencing in somatic cells.

Both diffusible factors acting in trans and chromatin components acting in cis are implicated in gene regulation, but the extent to which either process causally determines a cell's transcriptional identity is unclear. We recently used cell fusion to define a class of silent genes termed "cis-silenced" (or "occluded") genes, which remain silent even in the presence of trans-acting transcriptional activators. We further showed that occlusion of lineage-inappropriate genes plays a critical role in maintaining the transcriptional identities of somatic cells. Here, we present, for the first time, a comprehensive map of occluded genes in somatic cells. Specifically, we mapped occluded genes in mouse fibroblasts via fusion to a dozen different rat cell types followed by whole-transcriptome profiling. We found that occluded genes are highly prevalent and stable in somatic cells, representing a sizeable fraction of silent genes. Occluded genes are also highly enriched for important developmental regulators of alternative lineages, consistent with the role of occlusion in safeguarding cell identities. Alongside this map, we also present whole-genome maps of DNA methylation and eight other chromatin marks. These maps uncover a complex relationship between chromatin state and occlusion. Furthermore, we found that DNA methylation functions as the memory of occlusion in a subset of occluded genes, while histone deacetylation contributes to the implementation but not memory of occlusion. Our data suggest that the identities of individual cell types are defined largely by the occlusion status of their genomes. The comprehensive reference maps reported here provide the foundation for future studies aimed at understanding the role of occlusion in development and disease.

Identifying protective and risk factors for injurious falls in patients hospitalized for acute care: a retrospective case-control study.

BACKGROUND: Admitted patients who fall and injure themselves during an acute hospitalization incur increased costs, morbidity, and mortality, but little research has been conducted on identifying inpatients at high risk to injure themselves in a fall. Falls risk assessment tools have been unsuccessful due to their low positive predictive value when applied broadly to entire hospital populations. We aimed to identify variables associated with the risk of or protection against injurious fall in the inpatient setting. We also aimed to test the variables in the ABCs mnemonic (Age > 85, Bones-orthopedic conditions, anti-Coagulation and recent surgery) for correlation with injurious fall. METHODS: We performed a retrospective case-control study at an academic tertiary care center comparing admitted patients with injurious fall to admitted patients without fall. We collected data on the demographics, medical and fall history, outcomes, and discharge disposition of injured fallers and control patients. We performed multivariate analysis of potential risk factors for injurious fall with logistic regression to calculate adjusted odds ratios. RESULTS: We identified 117 injured fallers and 320 controls. There were no differences in age, anti-coagulation use or fragility fractures between cases and controls. In multivariate analysis, recent surgery (OR 0.46, p = 0.003) was protective; joint replacement (OR 5.58, P = 0.002), psychotropic agents (OR 2.23, p = 0.001), the male sex (OR 2.08, p = 0.003) and history of fall (OR 2.08, p = 0.02) were significantly associated with injurious fall. CONCLUSION: In this study, the variables in the ABCs parameters were among the variables not useful for identifying inpatients at risk of injuring themselves in a fall, while other non-ABCs variables demonstrated a significant association with injurious fall. Recent surgery was a protective factor, and practices around the care of surgical patients could be extrapolated to reduce the in-hospital fall rates.

Multiple developmental programs are altered by loss of Zic1 and Zic4 to cause Dandy-Walker malformation cerebellar pathogenesis.

Heterozygous deletions encompassing the ZIC1;ZIC4 locus have been identified in a subset of individuals with the common cerebellar birth defect Dandy-Walker malformation (DWM). Deletion of Zic1 and Zic4 in mice produces both cerebellar size and foliation defects similar to human DWM, confirming a requirement for these genes in cerebellar development and providing a model to delineate the developmental basis of this clinically important congenital malformation. Here, we show that reduced cerebellar size in Zic1 and Zic4 mutants results from decreased postnatal granule cell progenitor proliferation. Through genetic and molecular analyses, we show that Zic1 and Zic4 have Shh-dependent function promoting proliferation of granule cell progenitors. Expression of the Shh-downstream genes Ptch1, Gli1 and Mycn was downregulated in Zic1/4 mutants, although Shh production and Purkinje cell gene expression were normal. Reduction of Shh dose on the Zic1(+/-);Zic4(+/-) background also resulted in cerebellar size reductions and gene expression changes comparable with those observed in Zic1(-/-);Zic4(-/-) mice. Zic1 and Zic4 are additionally required to pattern anterior vermis foliation. Zic mutant folial patterning abnormalities correlated with disrupted cerebellar anlage gene expression and Purkinje cell topography during late embryonic stages; however, this phenotype was Shh independent. In Zic1(+/-);Zic4(+/-);Shh(+/-), we observed normal cerebellar anlage patterning and foliation. Furthermore, cerebellar patterning was normal in both Gli2-cko and Smo-cko mutant mice, where all Shh function was removed from the developing cerebellum. Thus, our data demonstrate that Zic1 and Zic4 have both Shh-dependent and -independent roles during cerebellar development and that multiple developmental disruptions underlie Zic1/4-related DWM.

Mental Health of Caregivers of Children with Medical Complexity During COVID-19.

OBJECTIVE: The purpose of this study is to investigate the relationship between mental health and financial burden among caregivers of children with medical complexity (CMC) during the COVID-19 pandemic. METHODS: We conducted a cross-sectional survey on the mental health and financial burden of caregivers of CMC from April 2020 to April 2021. The study sample included 70 caregivers. We analyzed the association between caregiver mental health and caregiver demographics and child characteristics through bivariate linear regressions. We then used multivariate linear regression to assess the association between caregiver mental health and caregiver financial burden adjusting for significant covariates from our bivariate analysis. RESULTS: Caregivers reported lower mental health scores (56.2) and higher financial burden scores (15.5) than reference population means: (72.6; SD 20.2) and (10.4; SD 2.2), respectively. Financial burden [-3.4; p = 0.0003; CI: -5.1 to -1.6] and child age [-0.1; p = 0.02; CI: 0.2-1.8] were significantly associated with caregiver mental health in our bivariate analysis. In our multivariate analysis, caregivers with an increased financial burden had lower mental health scores [-3.0; p = 0.002; CI: -4.8 to -1.2]. CONCLUSION: Caregivers of children with medically complex conditions experienced more mental health symptoms and greater financial burdens than normative samples during the COVID-19 pandemic. Parents with a greater financial burden also tend to have more mental health issues. Eligibility for financial assistance should include financial burden and income when providing help to families in this population. Local and national stakeholders should consider the provision of financial help in their quest to improve the mental health of caregivers.

Association of Neighborhood Characteristics With Pediatric Asthma.

OBJECTIVE: To examine associations between neighborhood characteristics and asthma prevalence and severity among low-income children in a large nationally representative sample. METHODS: Data source: 2018 National Survey of Children's Health, limited to low-income children, ages 0-17 years. We grouped parent responses about neighborhood characteristics into 5 scores: neighborhood support, safety, resources and quality, and a total score. Logistic regression compared rates and severity of asthma by neighborhood scores, adjusting for age, sex, race, and income. RESULTS: Of 8,653 low-income children, those living in neighborhoods with better total neighborhood scores were significantly less likely to have parent-reported asthma; OR = 0.9, 95% CI: 0.8-1.0; P = .02, with similar findings for children living in neighborhoods with higher support, safety, and quality scores. We found no associations between neighborhood scores and asthma severity in this population. CONCLUSIONS: Favorable neighborhoods are associated with lower parent-reported asthma prevalence in low-income children but not asthma severity. These data may support providers and policy makers interested in child asthma in addressing neighborhood improvement.

Emergency Department Utilization of Adolescents and Young Adults with Autism Spectrum Disorder.

This study examined emergency department (ED) utilization by adolescents and young adults, 12-30 years of age (AYA) with autism spectrum disorder (ASD) using the 2016 Healthcare Cost and Utilization Project/National Emergency Department Sample (HCUP/NEDS). We investigated the principal reason for an ED visit, presence of an ambulatory care sensitive condition (ACSC), and likelihood of hospital admission following ED encounter in ASD and Non-ASD cohorts. The ASD cohort had a higher proportion of ED visits for ACSC diagnoses as compared to the Non-ASD cohort. In addition, the likelihood of admission following an ED visit in the ASD cohort was 3.7 times greater than in the Non-ASD cohort.

The Unexpected Risks of COVID-19 on Asthma Control in Children.

Much is being learned about clinical outcomes for adult COVID-19 patients with underlying chronic conditions; however, there is less coverage on how the COVID-19 pandemic impacts the management of chronic medical conditions, such as asthma, in children and youth. Asthma is a common chronic medical condition in children that is uniquely susceptible to changes brought on by COVID-19. Sudden dramatic changes in the environment, medical practice, and medication use have altered the asthma management landscape with potential impacts on asthma outcomes. In this paper, we review how changes in transportation and travel patterns, school attendance, physical activity, and time spent indoors, along with changes in health care delivery since the start of the pandemic, all play a contributing role in asthma control in children. We review potentially important influences of asthma control in children during the COVID-19 pandemic worthy of further study.

Genome-wide association study of behavioral, physiological and gene expression traits in outbred CFW mice.

Although mice are the most widely used mammalian model organism, genetic studies have suffered from limited mapping resolution due to extensive linkage disequilibrium (LD) that is characteristic of crosses among inbred strains. Carworth Farms White (CFW) mice are a commercially available outbred mouse population that exhibit rapid LD decay in comparison to other available mouse populations. We performed a genome-wide association study (GWAS) of behavioral, physiological and gene expression phenotypes using 1,200 male CFW mice. We used genotyping by sequencing (GBS) to obtain genotypes at 92,734 SNPs. We also measured gene expression using RNA sequencing in three brain regions. Our study identified numerous behavioral, physiological and expression quantitative trait loci (QTLs). We integrated the behavioral QTL and eQTL results to implicate specific genes, including Azi2 in sensitivity to methamphetamine and Zmynd11 in anxiety-like behavior. The combination of CFW mice, GBS and RNA sequencing constitutes a powerful approach to GWAS in mice.

Variation in the form of Pavlovian conditioned approach behavior among outbred male Sprague-Dawley rats from different vendors and colonies: sign-tracking vs. goal-tracking.

Even when trained under exactly the same conditions outbred male Sprague-Dawley (SD) rats vary in the form of the Pavlovian conditioned approach response (CR) they acquire. The form of the CR (i.e. sign-tracking vs. goal-tracking) predicts to what degree individuals attribute incentive salience to cues associated with food or drugs. However, we have noticed variation in the incidence of these two phenotypes in rats obtained from different vendors. In this study, we quantified sign- and goal-tracking behavior in a reasonably large sample of SD rats obtained from two vendors (Harlan or Charles River), as well as from individual colonies operated by both vendors. Our sample of rats acquired from Harlan had, on average, more sign-trackers than goal-trackers, and vice versa for our sample of rats acquired from Charles River. Furthermore, there were significant differences among colonies of the same vendor. Although it is impossible to rule out environmental variables, SD rats at different vendors and barriers may have reduced phenotypic heterogeneity as a result of genetic variables, such as random genetic drift or population bottlenecks. Consistent with this hypothesis, we identified marked population structure among colonies from Harlan. Therefore, despite sharing the same name, investigators should be aware that important genetic and phenotypic differences exist among SD rats from different vendors or even from different colonies of the same vendor. If used judiciously this can be an asset to experimental design, but it can also be a pitfall for those unaware of the issue.