Association of prenatal substance exposure and the development of the amygdala, hippocampus, and parahippocampus.

CONTEXT: Prenatal substance exposure (PSE) can lead to various harmful outcomes for the developing fetus and is linked to many emotional, behavioral, and cognitive difficulties later in life. Therefore, examination of the relationship between the development of associated brain structures and PSE is important for the development of more specific or new preventative methods. OBJECTIVES: Our study's primary objective was to examine the relationship between the physical development of the amygdala, hippocampus, and parahippocampus following prenatal alcohol, tobacco, and prescription opioid exposure. METHODS: We conducted a cross-sectional analysis of the Adolescent Brain and Cognitive Development (ABCD) Study, a longitudinal neuroimaging study that measures brain morphometry from childhood throughout adolescence. Data were collected from approximately 12,000 children (ages 9 and 10) and parents across 22 sites within the United States. Prenatal opioid, tobacco, and alcohol use was determined through parent self-report of use during pregnancy. We extracted variables assessing the volumetric size (mm3) of the amygdala, hippocampus, and parahippocampal gyrus as well as brain volume, poverty level, age, sex, and race/ethnicity for controls within our adjusted models. We reported sociodemographic characteristics of the sample overall and by children who had PSE. We calculated and reported the means of each of the specific brain regions by substance exposure. Finally, we constructed multivariable regression models to measure the associations between different PSE and the demographic characteristics, total brain volume, and volume of each brain structure. RESULTS: Among the total sample, 24.6% had prenatal alcohol exposure, 13.6% had prenatal tobacco exposure, and 1.2% had prenatal opioid exposure. On average, those with prenatal tobacco exposure were found to have a statistically significant smaller parahippocampus. CONCLUSIONS: We found a significant association between prenatal tobacco exposure and smaller parahippocampal volume, which may have profound impacts on the livelihood of individuals including motor delays, poor cognitive and behavioral outcomes, and long-term health consequences. Given the cumulative neurodevelopmental effects associated with PSE, we recommend that healthcare providers increase screening rates, detection, and referrals for cessation. Additionally, we recommend that medical associations lobby policymakers to address upstream barriers to the effective identification of at-risk pregnant individuals, specifically, eliminating or significantly reducing punitive legal consequences stemming from state laws concerning prenatal substance use.

Association and disparities of food insecurity and exposure to violence: analysis of the National Survey of Children's Health.

CONTEXT: Lack of access to food is a significant concern for child well-being, and it creates many health disparities and adverse social outcomes. Food insecurity and its many associated risk factors increase parental stress, which are strongly correlated with an increased risk of child abuse and maltreatment. Research now identifies being witness to domestic abuse as a form of child maltreatment, and exposure to violence in the community has been shown to result in similar long-term impacts. OBJECTIVES: Given the potential for lifelong adverse effects from experiencing adverse childhood events involving violence and food insecurity, our primary objective was to assess the relationship between the two and disparities among demographic factors. METHODS: We conducted an observational study utilizing data from the National Survey of Children's Health (NSCH) 2016-2021. The NSCH is a United States nationally representative survey completed by primary caregivers of one child per home aged 0-17 years. We determined population estimates (n=216,799; n=83,424,126) and rates of children experiencing food insecurity and parent-reported exposure to violence. We then constructed logistic regression models to assess associations, through odds ratios (ORs), between food security and exposure to violence including demographic factors. RESULTS: Among the sample, 5.42 % of children experienced low food security and 7.4 % were exposed to violence. The odds of exposure to violence are 5.19 times greater for children with low food security compared to food-secure children (95 % confidence interval [CI]: 4.48-6.02). Indigenous and Black children were 7.8 and 6.81 times more likely to experience or witness violence when food insecure compared to food secure White children, respectively (95 % CI: 3.18-19.13, 5.24-8.86 respectively). CONCLUSIONS: Food insecurity was associated with increased odds of children experiencing and/or witnessing violence compared to those who were food secure. The interaction between exposure to violence and food insecurity also disproportionately impacts children with specific demographic factors, notably race/ethnicity including multiracial, Indigenous, and Black children. By developing and adapting strategies to improve food security, it is possible to indirectly reduce the rates of childhood exposure to violence and the long-term impacts that result.

Stress During Pregnancy Associated with Newborn Low Birth Weight: Experiences from the State of Rhode Island.

PURPOSE: Prenatal stress is a known risk for poor birth outcomes. This study specifically looked at reported stress during pregnancy and low birth weight (LBW) in Rhode Island. METHODS: Pregnancy Risk Assessment Monitoring System (PRAMS) data from 2016 to 2018 for the state of Rhode Island was utilized. Stress during most recent pregnancy was dichotomized as: 'none to minimal' and 'moderate to high.' LBW was defined as less than 2,500 g. Multivariable regression analysis was performed, accounting for complex survey design. RESULTS: In this cohort, 24% of pregnant people reported moderate to high stress leading to an adjusted odds of 1.70 (95% CI 1.43-2.03) of having a LBW newborn compared to those with none to minimal stress. Primiparity, previous preterm birth, racism, smoking history, and history of chronic medical problems were also associated with LBW newborns. CONCLUSION: We recommend screening and provision of support services for stress in all settings where pregnant people access care.

Trends in public interest in child abuse in the United States: An infodemiology study of Google Trends from 2004 to 2022.

INTRODUCTION: More than 1 in 7 children in the United States experience abuse annually with rates remaining consistent over the past 2 decades. During this timeframe, several high-profile cases of child abuse and neglect were publicized in national media in addition to multiple investigations uncovering Indigenous children dying from abuse at Indian Boarding Schools. Increased media attention among other public health and medical topics has been linked to increased public interest, thus, our objective was to investigate trends in public interest from 2004 to 2022. METHODS: To assess trends in public interest, we extracted monthly relative search interest in child abuse from Google Trends. We constructed linear regression to determine the long-term trajectory of interest, and also compared the slope of the trend to other topics, such as domestic violence. Further, we compared mean relative search interest (RSI) from Child Abuse Awareness Month (April) to other months via t-test. Lastly, we assess by-state correlations of RSI and number of children abused. RESULTS: Since 2004, search interest in child abuse has significantly declined in the United States-more than other related search terms. Child Abuse Awareness Month showed spikes in RSI which were greater than other months. By-state correlations of RSI and abuse were moderate to weak. CONCLUSION: Despite heavy media attention covering stories of child abuse during the past 2 decades, search interest in child abuse has significantly declined. This trend may be related to aversion to secondary traumatic stress as news broadcasts often include stories of violence-of which child abuse stories may be most provoking. Following journalism guidance from the Centers for Disease Control and Prevention, reporting with focus on resiliency and prevention, rather than the individuals who perpetrated the crime, may provide more community support and increased public interest.

COVID-19 Vaccine Concerns and Acceptability by Language in a Marginalized Population in Rhode Island.

INTRODUCTION: We need to understand the continued concerns and acceptability of COVID-19 vaccines within marginalized communities in the United States. Our study explores the concerns and acceptability of COVID-19 vaccines, by language group, at a Federally Qualified Health Center (FQHC) in Rhode Island. METHODS: We conducted an exploratory, mixed data collection telephone survey in languages spoken in the community (Spanish, Cape Verdean (CV) Creole/Portuguese, and English). Participants were asked about their COVID-19 vaccination status, as well as vaccine concerns and acceptability via 9 closed-ended and 2 open-ended questions. Chi squared and multivariate analysis was used to compare concerns and acceptability across languages. Coding and immersion/crystallization techniques were used to identify qualitative data themes. RESULTS: The overall response rate was 58%. Side effects were cited as the most frequent (66%) concern among all language groups. Concern about the speed of vaccine development, vaccine ingredients, and being in a research trial varied significantly by language. Qualitative findings included concerns about chronic medical conditions and generalized fear of vaccine safety. English speakers were the most likely to report concerns and CV Creole/Portuguese speakers were the least likely to report concerns about the vaccine. Spanish and CV Creole/Portuguese participants who were not yet vaccinated reported higher acceptability to receive the vaccine compared to English speakers, with odds ratios of 2.00 (95% CI: 1.00-4.00) and 1.27 (95% CI: 0.62-2.60), respectively. CONCLUSION: To mitigate the effects of the COVID-19 pandemic and prepare for future pandemics, strategies must be based on understanding the beliefs and perceptions of marginalized communities.

Direct amidation of acid fluorides using germanium amides.

Amide functional groups are an essential linkage that are found in peptides, proteins, and pharmaceuticals and new methods are constantly being sought for their formation. Here, a new method for their preparation is presented where germanium amides Ph3GeNR2 convert acid fluorides directly to amides. These germanium amides serve to abstract the fluorine atom of the acid fluoride and transfer their amide group -NR2 to the carbonyl carbon, and so function as amidation reagents.

A machine learning approach for identifying novel cell type-specific transcriptional regulators of myogenesis.

Transcriptional enhancers integrate the contributions of multiple classes of transcription factors (TFs) to orchestrate the myriad spatio-temporal gene expression programs that occur during development. A molecular understanding of enhancers with similar activities requires the identification of both their unique and their shared sequence features. To address this problem, we combined phylogenetic profiling with a DNA-based enhancer sequence classifier that analyzes the TF binding sites (TFBSs) governing the transcription of a co-expressed gene set. We first assembled a small number of enhancers that are active in Drosophila melanogaster muscle founder cells (FCs) and other mesodermal cell types. Using phylogenetic profiling, we increased the number of enhancers by incorporating orthologous but divergent sequences from other Drosophila species. Functional assays revealed that the diverged enhancer orthologs were active in largely similar patterns as their D. melanogaster counterparts, although there was extensive evolutionary shuffling of known TFBSs. We then built and trained a classifier using this enhancer set and identified additional related enhancers based on the presence or absence of known and putative TFBSs. Predicted FC enhancers were over-represented in proximity to known FC genes; and many of the TFBSs learned by the classifier were found to be critical for enhancer activity, including POU homeodomain, Myb, Ets, Forkhead, and T-box motifs. Empirical testing also revealed that the T-box TF encoded by org-1 is a previously uncharacterized regulator of muscle cell identity. Finally, we found extensive diversity in the composition of TFBSs within known FC enhancers, suggesting that motif combinatorics plays an essential role in the cellular specificity exhibited by such enhancers. In summary, machine learning combined with evolutionary sequence analysis is useful for recognizing novel TFBSs and for facilitating the identification of cognate TFs that coordinate cell type-specific developmental gene expression patterns.