Screening and treatment of anxiety symptoms within an interdisciplinary comprehensive epilepsy center.

Youth with epilepsy (YWE) are at elevated risk for anxiety, yet anxiety is often undetected and understudied in this population. Most research on anxiety in YWE is based on parent proxy-report and broad-band measures with limited sensitivity. The aim of the current study was to: 1) examine rates of anxiety symptoms in YWE using a diagnosis-specific, self-report measure of anxiety symptoms, 2) assess differences in anxiety symptoms by sociodemographic and medical variables, and 3) evaluate changes in anxiety symptoms following a brief behavioral health intervention delivered within an interdisciplinary epilepsy clinic visit. As part of routine clinical care, 317 YWE [Mage=13.4+2.5 years (range 7-19 years); 54% female; 84% White: Non-Hispanic] completed the Multidimensional Anxiety Scale for Children, self-report (MASC-10), with a subset completing the MASC-10 at a second timepoint (n=139). A retrospective chart review was completed and sociodemographic, medical variables and behavioral health interventions were collected. Thirty percent of YWE endorsed elevated anxiety symptoms, with higher rates in those who were younger. YWE who received a behavioral health intervention for anxiety (n=21) demonstrated greater decreases in anxiety symptoms from Time 1 to Time 2 compared to those who did not receive a behavioral intervention (n=108). The integration of psychologists into pediatric epilepsy clinics may have allowed for early identification of anxiety symptoms, as well behavioral interventions to address these symptoms, which has the potential to decrease the need for more intensive services.

Vaccine Attitudes Mediate Relationships Between Caregiver Political Ideology and Likelihood of Child Vaccination for COVID-19.

INTRODUCTION: The COVID-19 vaccine has become available to children ages 5-12, yet vaccine uptake is suboptimal. Political ideology is a correlate of COVID-related beliefs and vaccine likelihood among US adults. However, since political ideology is not easily modifiable, attention to modifiable mechanisms that may explain links between political ideology and vaccine hesitancy is important in addressing this public health crisis. Caregiver attitudes around vaccine safety and efficacy have been related to vaccine uptake in other populations and warrant additional study in the context of COVID-19. The current study examined whether caregiver's attitudes regarding the safety and efficacy of the COVID-19 vaccine mediated the relationship between caregiver political ideology and likelihood of having their child vaccinated. METHODS: 144 US caregivers of children (6-12 years) completed an online survey in summer 2021 to assess political ideology, vaccine-related beliefs, and likelihood of having their child vaccinated against COVID-19. RESULTS: Caregivers with more liberal political views reported higher likelihood of eventual child vaccination compared to caregivers who reported a more conservative views (t(81) = 6.08, BCa CI [2.97, 5.67]). Moreover, parallel mediation models indicated caregiver?s perceptions of risks (BCa CI [-.98, -.10]) and efficacy (BCa CI [-3.16, -2.15]) of the vaccine each mediated the aforementioned relationship, with perceived efficacy explaining significantly more variance than risks. CONCLUSIONS: Findings extend knowledge by identifying social cognitive factors that impact caregiver vaccine hesitancy. Interventions to address caregiver's hesitancy to have their child vaccinated through modifying caregiver's inaccurate beliefs regarding vaccines or enhancing perceptions of vaccine efficacy is warranted.

Genome-wide copy number alterations in subtypes of invasive breast cancers in young white and African American women.

Genomic copy number alterations (CNA) are common in breast cancer. Identifying characteristic CNAs associated with specific breast cancer subtypes is a critical step in defining potential mechanisms of disease initiation and progression. We used genome-wide array comparative genomic hybridization to identify distinctive CNAs in breast cancer subtypes from 259 young (diagnosed with breast cancer at <55 years) African American (AA) and Caucasian American (CA) women originally enrolled in a larger population-based study. We compared the average frequency of CNAs across the whole genome for each breast tumor subtype and found that estrogen receptor (ER)-negative tumors had a higher average frequency of genome-wide gain (P < 0.0001) and loss (P = 0.02) compared to ER-positive tumors. Triple-negative (TN) tumors had a higher average frequency of genome-wide gain (P < 0.0001) and loss (P = 0.003) than non-TN tumors. No significant difference in CNA frequency was observed between HER2-positive and -negative tumors. We also identified previously unreported recurrent CNAs (frequency >40%) for TN breast tumors at 10q, 11p, 11q, 16q, 20p, and 20q. In addition, we report CNAs that differ in frequency between TN breast tumors of AA and CA women. This is of particular relevance because TN breast cancer is associated with higher mortality and young AA women have higher rates of TN breast tumors compared to CA women. These data support the possibility that higher overall frequency of genomic alteration events as well as specific focal CNAs in TN breast tumors might contribute in part to the poor breast cancer prognosis for young AA women.

Drosophila growth and development in the absence of dMyc and dMnt.

Myc oncoproteins are essential regulators of the growth and proliferation of mammalian cells. In Drosophila the single ortholog of Myc (dMyc), encoded by the dm gene, influences organismal size and the growth of both mitotic and endoreplicating cells. A null mutation in dm results in attenuated endoreplication and growth arrest early in larval development. Drosophila also contains a single ortholog of the mammalian Mad/Mnt transcriptional repressor proteins (dMnt), which is thought to antagonize dMyc function. Here we show that animals lacking both dMyc and dMnt display increased viability and grow significantly larger and develop further than dMyc single mutants. We observe increased endoreplication and growth of larval tissues in these double mutants and disproportionate growth of the imaginal discs. Gene expression analysis indicates that loss of dMyc leads to decreased expression of genes required for ribosome biogenesis and protein synthesis. The additional loss of dMnt partially rescues expression of a small number of dMyc and dMnt genes that are primarily involved in rRNA synthesis and processing. Our results indicate that dMnt repression is normally overridden by dMyc activation during larval development. Therefore the severity of the dm null phenotype is likely due to unopposed repression by dMnt on a subset of genes critical for cell and organismal growth. Surprisingly, considerable growth and development can occur in the absence of both dMyc and dMnt.

The transcriptional repressor dMnt is a regulator of growth in Drosophila melanogaster.

The Myc-Max-Mad/Mnt network of transcription factors has been implicated in oncogenesis and the regulation of proliferation in vertebrate cells. The identification of Myc and Max homologs in Drosophila melanogaster has demonstrated a critical role for dMyc in cell growth control. In this report, we identify and characterize the third member of this network, dMnt, the sole fly homolog of the mammalian Mnt and Mad family of transcriptional repressors. dMnt possesses two regions characteristic of Mad and Mnt proteins: a basic helix-loop-helix-zipper domain, through which it dimerizes with dMax to form a sequence-specific DNA binding complex, and a Sin-interacting domain, which mediates interaction with the dSin3 corepressor. Using the upstream activation sequence/GAL4 system, we show that expression of dMnt results in an inhibition of cellular growth and proliferation. Furthermore, we have generated a dMnt null allele, which results in flies with larger cells, increased weight, and decreased life span compared to wild-type flies. Our results demonstrate that dMnt is a transcriptional repressor that regulates D. melanogaster body size.

dMyc is required for larval growth and endoreplication in Drosophila.

Members of the Myc family of proto-oncogenes have long been implicated in regulating proliferation, apoptosis and oncogenesis. Recently, transcriptional and biological studies have suggested a direct role for Myc in regulating growth. We have used dm(4), a new null allele of the Drosophila diminutive (dm) gene, which encodes dMyc on the X chromosome, to investigate a role for dMyc in larval endoreplicating tissues, where cellular growth and DNA replication occur in the absence of cell division. Hemizygous dm(4)/Y mutants arrest as second instar larvae, and fat body nuclei of dm(4)/Y mutants fail to attain normal size and normal levels of DNA, resulting from a reduced frequency of S-phase. Thus, dMyc is required for endoreplication and larval growth. In support of this, dMyc, as well as its antagonist dMnt, are expressed in larval tissues in a pattern consistent with their involvement in regulating endoreplication. Overexpression of dMyc in endoreplicating cells results in dramatic increases in nuclear DNA content and cell and nucleolar size, whereas dMnt overexpression has the opposite effect. BrdU incorporation and Cyclin E protein levels continue to oscillate in dMyc-overexpressing cells, indicating that the normal cell cycle control mechanisms are not disrupted. dMyc driven growth and endoreplication are strongly attenuated when the endocycle is blocked with Cyclin E or the cdk inhibitor p21. By contrast, the ability of dMyc to promote growth and endoreplication is only partly reduced when PI3K activity is blocked, suggesting that they influence distinct growth pathways. Our results indicate that larval growth and endoreplication are coupled processes that, although linked to cell cycle control mechanisms, are regulated by dMyc and dMnt.