Impact of Race, Socioeconomic Status, and Geography on Healthcare Outcomes for Children With Sickle Cell Disease in the United States: A Scoping Review.

A large proportion of patients with sickle cell disease (SCD) identify as Black or African American (AA). Social bias and stigma in healthcare outcomes for children with SCD are impossible to explore without considering the impact of racial/cultural identity, socioeconomic status (SES), and geography. It is important to understand the current influences of social movements, expanded health insurance coverage, and telehealth on these variables when considering healthcare outcomes for patients with SCD. The objective of this study was to determine the roles of racial identity, SES, and geography in healthcare outcomes for the pediatric population of children with SCD in the United States (US). This study is a scoping review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The databases utilized included Cochrane, CINHAL, Medline, and Nursing and Allied Health Collection, all accessed through the EBSCO Information Services. Studies met the following inclusion criteria: published in English, pediatric patients residing in the US, and published between 2017 and 2022. Search terms included "sickle cell" AND "pediatric", which were then combined with "minority" OR "racial" OR "rural" OR "urban" OR "poverty" OR "income" OR "socioeconomic status". The initial search yielded 635 unique articles, with 17 articles meeting full inclusion criteria. Overall, it was clear that there are examples of positive effects of race, low SES, and rural geographic location on positive health outcomes, though a large number of studies oscillated between showing negative associations or no association at all. Barriers to care for patients with SCD are multifaceted, making it difficult to isolate and analyze the impact of individual variables. Many studies demonstrated the significance of family, community, and institutional relationships as positive support for patients with SCD. This review highlights the need for additional research on the healthcare outcome benefits of patient/familial support groups aiming to bring together patients who share racial experience and SCD diagnosis regardless of SES and geography.

Functional Precision Medicine Identifies New Therapeutic Candidates for Medulloblastoma.

Medulloblastoma is among the most common malignant brain tumors in children. Recent studies have identified at least four subgroups of the disease that differ in terms of molecular characteristics and patient outcomes. Despite this heterogeneity, most patients with medulloblastoma receive similar therapies, including surgery, radiation, and intensive chemotherapy. Although these treatments prolong survival, many patients still die from the disease and survivors suffer severe long-term side effects from therapy. We hypothesize that each patient with medulloblastoma is sensitive to different therapies and that tailoring therapy based on the molecular and cellular characteristics of patients' tumors will improve outcomes. To test this, we assembled a panel of orthotopic patient-derived xenografts (PDX) and subjected them to DNA sequencing, gene expression profiling, and high-throughput drug screening. Analysis of DNA sequencing revealed that most medulloblastomas do not have actionable mutations that point to effective therapies. In contrast, gene expression and drug response data provided valuable information about potential therapies for every tumor. For example, drug screening demonstrated that actinomycin D, which is used for treatment of sarcoma but rarely for medulloblastoma, was active against PDXs representing Group 3 medulloblastoma, the most aggressive form of the disease. Functional analysis of tumor cells was successfully used in a clinical setting to identify more treatment options than sequencing alone. These studies suggest that it should be possible to move away from a one-size-fits-all approach and begin to treat each patient with therapies that are effective against their specific tumor. SIGNIFICANCE: These findings show that high-throughput drug screening identifies therapies for medulloblastoma that cannot be predicted by genomic or transcriptomic analysis.

Sexually dimorphic behavioral and neural responses to a predator scent.

Male and female C57BL/6 J mice were tested on the predator odor response task, where they needed to cross through a chamber of scented bedding to reach a sucrose reward. Following the behavioral testing, mouse brains were immunohistochemically labeled for expression of the immediate early gene c-fos. In the presence of the novel odorant methyl valerate (MV), both males and females exhibited increased exploration behaviors and delayed rewards compared to control bedding. However, in the presence of the predator odor phenylethylamine (PEA), males exhibited increased exploration that strongly resembled their behavior in MV (a non-predator odor) while females behaved very similarly to the clean bedding controls, quickly traversing the chamber to achieve the reward. Expression of c-fos exhibited significant sex by odor condition interactions overall across brain regions and in the anterior piriform cortex, cingulate cortex, and dorsomedial hypothalamus specifically. In all three regions we observed the general pattern that PEA exposure evoked elevated c-fos expression in females but suppressed c-fos expression in males. Taken together these data suggest that males and females may adopt different behavioral strategies in the presence of predator threat.