Spotlighting racism in schools: Teacher mentors and the mediating effect of school safety.

Youth are more likely to succeed when they feel safe at school and have access to caring relationships with adults. Systemic racism interrupts access to these assets. Within schools, racially/ethnically minoritized youth encounter policies rooted in racism, leading to decreased perceptions of school safety. Having a teacher mentor may mitigate some of the harmful effects of systemic racism and discriminatory practices. Yet, teacher mentors may not be accessible to all students. In this study, the authors tested a putative explanatory hypothesis for differences between Black and white children's access to teacher mentors. Data from the National Longitudinal Study of Adolescent Health were used. Linear regression models were used to predict access to teacher mentors, and a mediational analysis was conducted to determine the effect of school safety on the relationship between race and teacher mentor access. Results indicate that students from higher SES backgrounds and those with parents who have greater educational attainment are more likely to have a teacher mentor. Furthermore, Black students are less likely than white students to have a teacher mentor, and school safety mediates that relationship. The implications of this study suggest that challenging institutional racism and structures may improve perceptions of school safety and teacher mentor accessibility.

Vitamin B5 supports MYC oncogenic metabolism and tumor progression in breast cancer.

Tumors are intrinsically heterogeneous and it is well established that this directs their evolution, hinders their classification and frustrates therapy1-3. Consequently, spatially resolved omics-level analyses are gaining traction4-9. Despite considerable therapeutic interest, tumor metabolism has been lagging behind this development and there is a paucity of data regarding its spatial organization. To address this shortcoming, we set out to study the local metabolic effects of the oncogene c-MYC, a pleiotropic transcription factor that accumulates with tumor progression and influences metabolism10,11. Through correlative mass spectrometry imaging, we show that pantothenic acid (vitamin B5) associates with MYC-high areas within both human and murine mammary tumors, where its conversion to coenzyme A fuels Krebs cycle activity. Mechanistically, we show that this is accomplished by MYC-mediated upregulation of its multivitamin transporter SLC5A6. Notably, we show that SLC5A6 over-expression alone can induce increased cell growth and a shift toward biosynthesis, whereas conversely, dietary restriction of pantothenic acid leads to a reversal of many MYC-mediated metabolic changes and results in hampered tumor growth. Our work thus establishes the availability of vitamins and cofactors as a potential bottleneck in tumor progression, which can be exploited therapeutically. Overall, we show that a spatial understanding of local metabolism facilitates the identification of clinically relevant, tractable metabolic targets.

Enduring dysregulation of nucleus accumbens catecholamine and glutamate transmission by developmental exposure to phenylpropanolamine.

For over 50 years, the sympathomimetic phenylpropanolamine (PPA; ±-norephedrine) was a primary active ingredient in over-the-counter nasal decongestants for both children and adults and continues to be prevalent in the vast majority of countries today. Previously, we reported that juvenile PPA exposure alters the developmental trajectory of catecholamine and amino acid neurotransmitter systems in the nucleus accumbens (NAC), impacting the motivational valence of cocaine in later life. The present study employed a combination of in vivo microdialysis and immunoblotting approaches to better understand how juvenile PPA exposure impacts catecholamine and glutamate function within the NAC. For this, C57BL/6J mice were pretreated repeatedly with PPA (0 or 40 mg/kg) during postnatal days 21-33. Starting at 70 days of age, the function and expression of receptors and transporters regulating extracellular dopamine and glutamate were determined. Juvenile PPA pretreatment completely abolished the capacity of selective dopamine and epinephrine reuptake inhibitors to increase NAC levels of both catecholamines, without impacting D2 or α2 receptor regulation of catecholamine release. Juvenile PPA pretreatment facilitated the rise in NAC glutamate elicited by dopamine, norepinephrine and glutamate transporter inhibitors and blunted mGlu2/3 inhibition of glutamate release in this region. These data confirm that juvenile exposure to PPA produces protracted perturbations in the regulation of extracellular catecholamine and glutamate levels within the NAC and further the hypothesis that early exposure to sympathomimetic drugs found in cough, cold and allergy medicines, have long-lasting effects upon neurotransmission within brain regions gating motivation.

Physician Perspectives on Palliative Care for Children With Neuroblastoma: An International Context.

BACKGROUND: Studies have shown that children with cancer globally lack access to palliative care. Little is known regarding physicians' perceptions of palliative care, treatment access, and self-reported competence in providing palliative care. PROCEDURE: Members of the Global Neuroblastoma Network (online tumor board) were surveyed. Eighty-three respondents met inclusion criteria; 53 (64%) completed the survey. RESULTS: Most respondents trained in high-income countries (HIC) but practice in low- and middle-income countries (LMIC), and care for more than five patients with neuroblastoma annually. WHO Essential Medicines in palliative care varied in availability, with incomplete access across LMIC centers. Nonpharmacologic therapies were inconsistently available. Contrary to international definitions, 17% of respondents inappropriately considered palliative care as that initiated only after curative therapy is stopped. Mean physician competence composite score (Likert scale 1-5, 5 = very competent) in providing symptomatic relief and palliative care across phases of care was 2.93 (95% CI 2.71-3.22). Physicians reported significantly greater competence in symptom management during cure-directed therapy than during end-of-life (P = 0.02) or when patients are actively dying (P = 0.007). Practicing in HIC, prior palliative care training, having access to radiotherapy, and not having to turn patients away due to bed shortages were significantly predictive of perceived competence in providing palliative care at end of life. CONCLUSIONS: An international sample identified gaps in treatment and palliative care service availability, in understanding the definition of palliative care, and in self-reported competence in providing palliative care. Increased perceived competence was associated with training, which supports the need for increased palliative care education and advocacy, especially in LMIC.

Identification of patient subgroups with markedly disparate rates of MYCN amplification in neuroblastoma: A report from the International Neuroblastoma Risk Group project.

BACKGROUND: MYCN gene amplification (MNA) is a hallmark of aggressive neuroblastoma. This study was performed to determine univariate and multivariate predictors of tumor MNA. METHODS: Data from the International Neuroblastoma Risk Group were analyzed for a subset of 7102 patients with known MYCN status. Chi-square testing and logistic regression were used to identify univariate and multivariate predictors of MYCN status. Recursive partitioning was used to identify groups of patients with maximal differences in rates of MNA. RESULTS: All clinical features (age ≥ 18 months, high ferritin levels, high lactate dehydrogenase [LDH] levels, International Neuroblastoma Staging System stage 4, and adrenal sites) and pathological/biological features (DNA index ≤ 1, high mitosis-karyorrhexis index [MKI], undifferentiated/poorly differentiated grade, unfavorable histology according to the International Neuroblastoma Pathology Classification, and segmental chromosomal aberrations [SCAs]) were significantly associated with MNA. LDH (odds ratio [OR], 8.4; P < .001) and chromosomal 1p loss of heterozygosity (OR, 19.8; P < .001) were the clinical and biological variables, respectively, most strongly associated with MNA. In logistic regression, all variables except chromosome 17q aberration and pooled SCAs were independently predictive of MNA. Recursive partitioning identified subgroups with disparate rates of MNA, including subgroups with 85.7% MNA (patients with high LDH levels who had poorly differentiated adrenal tumors with chromosome 1p deletion) and 0.6% MNA (localized tumors having hyperdiploidy and low MKIs and lacking chromosome 1p aberrations). CONCLUSIONS: MNA is strongly associated with other clinical and biological variables in neuroblastoma. Recursive partitioning has identified subgroups of neuroblastoma patients with highly disparate rates of MNA. These findings can be used to inform investigations of molecular mechanisms of MNA.

Knowledge of HIV Transmission and Associated Factors among HIV-Positive and HIV-Negative Patients in Rural Kenya.

Knowledge of HIV transmission is a prerequisite to practicing safer behaviors to prevent HIV infections and may be expected to vary by region because of cultural and socioeconomic determinants. A cross-sectional study was conducted in rural Kenya using a standardized questionnaire assessing HIV transmission knowledge, socio-demographic and other characteristics. Participants were recruited from the voluntary counseling and testing clinic and the general hospital population of Moi District Hospital. "High" HIV transmission knowledge scorers (≥ 81%) (Mean score) were compared with "low" scorers (<81%). Bivariate and multivariate logistic regression analyses were performed to examine factors associated with HIV transmission knowledge. Of 214 participants, 70 (33%) were HIV-positive, 104 (49%) were HIV-negative, and 40 (19%) did not know. Factors associated with low knowledge in multivariate analyses were lower education (OR 2.36, CI 1.03-5.46), lower household money on healthcare (OR 2.03, CI 1.28-3.21), higher clinic transportation costs (OR 3.14, CI 1.20-9.82), sex without a condom (OR 2.18, CI 1.12-4.26), positive HIV status vs. negative (OR 2.50, CI 1.22-5.26) and positive HIV status vs. unknown (OR 3.57, CI 1.33-9.09). Mean HIV transmission knowledge score was relatively high; however, a large proportion of patients demonstrated low knowledge. Identifying individuals at risk for low knowledge will support targeted HIV education and prevention programs.

Protracted 'anti-addictive' effects of adolescent phenylpropanolamine exposure in C57BL/6J mice.

Exposure to the once highly prevalent over-the-counter (OTC) sympathomimetic phenylpropanolamine (PPA; +/--norephedrine) during pre-adolescence alters the developmental trajectory of catecholamine and amino acid neurotransmitter systems in the nucleus accumbens (NAC) that culminate in a 'pro-addictive' phenotype in adulthood. Thus, the present study sought to extend these earlier data by examining the long-term consequences of repeated PPA treatment during adolescence upon the behavioral and neurochemical responses to cocaine. For this, C57BL/6J mice were pre-treated with PPA (0-40 mg/kg) during postnatal days 35-44, and the capacity of cocaine (4 x 15 mg/kg) to elicit a conditioned place-preference, as well as behavioral and neurochemical sensitization within the NAC, were then assessed in adulthood. While adolescent PPA exposure did not influence spontaneous locomotor activity or the motor responses to either acute or repeated cocaine (4 x 15 mg/kg), PPA pre-exposure dose-dependently reduced the expression of a conditioned place-preference. As observed previously for juvenile PPA treatment, adolescent PPA administration blunted the dopamine and norepinephrine response to acute cocaine, prevented the development of catecholamine sensitization but did not influence cocaine-induced elevations in serotonin. However, unlike juvenile PPA treatment, adolescent PPA also prevented the development of glutamate sensitization within the NAC. These data provide evidence that adolescent exposure to a formerly prevalent OTC sympathomimetic produces protracted effects upon cocaine-induced changes in NAC glutamate transmission that may reduce vulnerability to cocaine addiction in later life and further the hypothesis that early exposure to sympathomimetic drugs may be an environmental factor contributing to the etiology of addiction.