Early spiral arteriole remodeling in the uterine-placental interface: A rat model.

The mammalian placenta's interface with the parent is a richly vascularized tissue whose development relies upon communication between many different cell types within the uterine microenvironment. The uterine blood vessels of the interface are reshaped during pregnancy into wide-bore, flaccid vessels that convey parental blood to the exchange region of the placenta. Invasive trophoblast as well as parental uterine macrophages and Natural Killer cells are involved in the stepwise remodeling of these vessels and their respective contributions to this crucial process are still being delineated. However, the earliest steps in arteriole remodeling are understudied as they are difficult to study in humans, and other species lack the deep trophoblast invasion that is so prominent a feature of placentation in humans. Here, we further characterize the rat, with deep hemochorial placentation akin to humans, as a model system in which to tease apart the earliest, relatively understudied events in spiral arteriole remodeling. We show that the rat uterine-placental interface increases in size and vascularity rapidly, before trophoblast invasion. The remodeling stages in the arterioles of the rat uterine-placental interface follow a sequence of anatomical changes similar to those in humans, and there are changes to the arterioles' muscular tunica media prior to the marked influx of immune cells. The rat is a tractable model in which to better understand the cell/cell interactions occurring in vivo in an intact tissue microenvironment over time.

Intersection of adverse childhood experiences, suicide and overdose prevention.

Adverse childhood experiences (ACEs), suicide and overdose are linked across the life course and across generations and share common individual-, interpersonal-, community- and societal-level risk factors. The purpose of this review is to summarise the shared aetiology of these public health issues, synthesise evidence regarding potential community- and societal-level prevention strategies and discuss future research and practice directions.Growing evidence shows the potential for community- and societal-level programmes and policies, including higher minimum wage; expanded Medicaid eligibility; increased earned income tax credits, child tax credits and temporary assistance for needy families benefits; Paid Family Leave; greater availability of affordable housing and rental assistance; and increased participation in the Supplemental Nutrition Assistance Program (SNAP), to contribute to ACEs, suicide and overdose prevention. Considerations for future prevention efforts include (1) expanding the evidence base through rigorous research and evaluation; (2) assessing the implications of prevention strategies for equity; (3) incorporating a relational health perspective; (4) enhancing community capacity to implement, scale and sustain evidenced-informed prevention strategies; and (5) acknowledging that community- and societal-level prevention strategies are longer-term strategies.

Adults' exposure to adverse childhood experiences in the United States nationwide and in each state: modeled estimates from 2019-2020.

BACKGROUND: Although preventable, adverse childhood experiences (ACEs) can result in lifelong health harms. Current surveillance data on adults' exposure to ACEs are either unavailable or incomplete for many U.S. states. METHODS: Current estimates of the proportion of U.S. adults with past ACEs exposures were obtained by analysing individual-level data from 2019 to 2020 Behavioural Risk Factor Surveillance System-annual nationally representative survey of noninstitutionalized adults aged 18+years. Standardised questions measuring ACEs exposures (presence of household member with mental illness, substance abuse, or incarceration; parental separation; witnessing intimate partner violence; experiencing physical, emotional, or sexual abuse during childhood) were categorised into 0, 1, 2-3, or 4+ACEs and reported by sociodemographic group in each state. Missing ACEs responses (state did not offer ACEs questions or offered to only some respondents; respondent skipped questions) were modelled through multilevel mixed-effects logistic (MMEL) and jackknifed MMEL regressions. RESULTS: In 2019-2020, an estimated 62.8% of U.S. adults had past exposure to 1+ACEs (range: 54.9% in Connecticut; 72.5% in Maine), including 22.4% of adults who were exposed to 4+ACEs (range: 11.9% in Connecticut; 32.8% in Nevada). At the national and state levels, exposure to 4+ACEs was highest among adults aged 18-34 years, those who did not graduate from high school, or adults who did not have a healthcare provider. Racial/ethnic distribution of adults exposed to 4+ACEs varied by age and state. CONCLUSIONS: ACEs are common but not equally distributed. ACEs exposures estimated by state and sociodemographic group can help decisionmakers focus public health interventions on populations disproportionately impacted in their area.

Emergency Department Visits Involving Mental Health Conditions, Suicide-Related Behaviors, and Drug Overdoses Among Adolescents - United States, January 2019-February 2023.

The U.S. adolescent mental and behavioral health crisis is ongoing,* with high pre-COVID-19 pandemic baseline rates† (1) and further increases in poor mental health (2), suicide-related behaviors (3), and drug overdose deaths (4) reported during 2020-2021. CDC examined changes in U.S. emergency department (ED) visits for mental health conditions (MHCs) overall and for nine specific MHCs,§ suicide-related behaviors (including suspected suicide attempts), and drug-involved overdoses (including opioids) among children and adolescents aged 12-17 years (adolescents) during January 2019-February 2023, overall and by sex. Compared with fall 2021, by fall 2022, decreases in weekly ED visits were reported among all adolescents, and females specifically, for MHCs overall, suicide-related behaviors, and drug overdoses; weekly ED visits among males were stable. During this same period, increases in weekly ED visits for opioid-involved overdoses were detected. Mean weekly ED visits in fall 2022 for suicide-related behaviors and MHCs overall were at or lower than the 2019 prepandemic baseline, respectively, and drug overdose visits were higher. Differences by sex were observed; levels among females were at or higher than prepandemic baselines for these conditions. These findings suggest some improvements as of fall 2022 in the trajectory of adolescent mental and behavioral health, as measured by ED visits; however, poor mental and behavioral health remains a substantial public health problem, particularly among adolescent females. Early identification and trauma-informed interventions, coupled with expanded evidence-based, comprehensive prevention efforts, are needed to support adolescents' mental and behavioral health.

Seasonal Trends in Emergency Department Visits for Mental and Behavioral Health Conditions Among Children and Adolescents Aged 5-17 Years - United States, January 2018-June 2023.

Mental and behavioral health conditions among school-aged children, including substance use disorders and overall emotional well-being, are a public health concern in the United States. Timely data on seasonal patterns in child and adolescent conditions can guide optimal timing of prevention and intervention strategies. CDC examined emergency department (ED) visit data from the National Syndromic Surveillance Program for 25 distinct conditions during January 2018-June 2023 among U.S. children and adolescents aged 5-17 years, stratified by age group. Each year, during 2018-2023, among persons aged 10-14 and 15-17 years, the number and proportion of weekly ED visits for eight conditions increased in the fall school semester and remained elevated throughout the spring semester; ED visits were up to twice as high during school semesters compared with the summer period. Among children aged 5-9 years, the number and proportion of visits increased for five mental and behavioral health conditions. Seasonal increases in ED visits for some conditions among school-aged children warrant enhanced awareness about mental distress symptoms and the challenges and stressors in the school environment. Systemic changes that prioritize protective factors (e.g., physical activity; nutrition; sleep; social, community, or faith-based support; and inclusive school and community environments) and incorporate preparedness for increases in conditions during back-to-school planning might improve child and adolescent mental health.

Web-Based Social Networks of Individuals With Adverse Childhood Experiences: Quantitative Study.

BACKGROUND: Adverse childhood experiences (ACEs), which include abuse and neglect and various household challenges such as exposure to intimate partner violence and substance use in the home, can have negative impacts on the lifelong health of affected individuals. Among various strategies for mitigating the adverse effects of ACEs is to enhance connectedness and social support for those who have experienced them. However, how the social networks of those who experienced ACEs differ from the social networks of those who did not is poorly understood. OBJECTIVE: In this study, we used Reddit and Twitter data to investigate and compare social networks between individuals with and without ACE exposure. METHODS: We first used a neural network classifier to identify the presence or absence of public ACE disclosures in social media posts. We then analyzed egocentric social networks comparing individuals with self-reported ACEs with those with no reported history. RESULTS: We found that, although individuals reporting ACEs had fewer total followers in web-based social networks, they had higher reciprocity in following behavior (ie, mutual following with other users), a higher tendency to follow and be followed by other individuals with ACEs, and a higher tendency to follow back individuals with ACEs rather than individuals without ACEs. CONCLUSIONS: These results imply that individuals with ACEs may try to actively connect with others who have similar previous traumatic experiences as a positive connection and coping strategy. Supportive interpersonal connections on the web for individuals with ACEs appear to be a prevalent behavior and may be a way to enhance social connectedness and resilience in those who have experienced ACEs.

Evaluation of Monoexponential, Stretched-Exponential and Intravoxel Incoherent Motion MRI Diffusion Models in Early Response Monitoring to Neoadjuvant Chemotherapy in Patients With Breast Cancer-A Preliminary Study.

BACKGROUND: There has been a growing interest in exploring the applications of stretched-exponential (SEM) and intravoxel incoherent motion (IVIM) models of diffusion-weighted imaging (DWI) in breast imaging, with the focus on differentiation of breast lesions. However, the use of SEM and IVIM models to predict early response to neoadjuvant chemotherapy (NACT) has received less attention. PURPOSE: To investigate the value of monoexponential, SEM, and IVIM models to predict early response to NACT in patients with primary breast cancer. STUDY TYPE: Prospective. POPULATION: Thirty-seven patients with primary breast cancer (aged 46 ± 11 years) due to undergo NACT. FIELD STRENGTH/SEQUENCES: A 1.5-T MR scanner, T1 -weighted three-dimensional spoiled gradient-echo, two-dimensional single-shot spin-echo echo-planar imaging sequence (DWI) at six b-values (0-800 s mm-2 ). ASSESSMENT: Tumor volume, apparent diffusion coefficient, tissue diffusion (Dt ), pseudo-diffusion coefficient (Dp ), perfusion fraction (f), distributed diffusion coefficient, and alpha (α) were extracted, following volumetric sampling of the tumors, at three time-points: pretreatment, post one and three cycles of NACT. STATISTICAL TESTS: Mann-Whitney test, receiver operating characteristic (ROC) curve. Statistical significance level was P < 0.05. RESULTS: Following NACT, 17 patients were determined to be pathological responders and 20 nonresponders. Tumor volume was significantly larger in nonresponders at each MRI time-point and demonstrated reasonable performance in predicting response (area under the ROC curve [AUC] = 0.83-0.87). No significant differences between groups were found in the diffusion coefficients at each time-point (P = 0.09-1). The parameters α (SEM), f, and f × Dp (IVIM) were able to differentiate between response groups after one cycle of NACT (AUC = 0.73, 0.72, and 0.74, respectively). CONCLUSION: Diffusion coefficients derived from the monoexponential, SEM, and IVIM models did not predict pathological response. However, the IVIM-derived parameters f and f × Dp and the SEM-derived parameter α were able to predict response to NACT in breast cancer patients following one cycle of NACT. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2.

State-led opioid overdose prevention efforts: Challenges, solutions and lessons learned from the CDC Prevention for States Program (PfS).

Background: The Centers for Disease Control and Prevention's Prevention for States (PfS) program funded 29 state health departments to prevent opioid overdose by implementing evidence-based prevention strategies. The objectives of this analysis were to describe the scope of activities implemented across the four PfS strategies and identify implementation challenges. Methods: PfS recipients submitted annual progress reports (APRs) to state support staff at CDC from 2015 to 2017. APR data were used to calculate the number of required and optional activities implemented under each PfS strategy. APR data were qualitatively analyzed using a systematic content analysis approach to identify key implementation challenges. Results: From 2015 to 2017, PfS recipients implemented 177 activities across four strategies from 2015 to 2017. Cross-cutting implementation challenges were (1) multi-sector collaboration, (2) lack of knowledge and misperceptions about opioid used disorder (OUD) among some partners and local communities and; (3) management and access to opioid data among PfS recipients. Conclusions: PfS recipients implemented an array of prevention interventions to address the opioid overdose crisis and encountered several cross-cutting implementation challenges. Challenges and state driven solutions over the course of implementing PfS led to several lessons learned and actions that CDC enacted to continue to support and expand overdose prevention.

Overdose Deaths Involving Opioids, Cocaine, and Psychostimulants - United States, 2015-2016.

During 1999‒2015, 568,699 persons died from drug overdoses in the United States.* Drug overdose deaths in the United States increased 11.4% from 2014 to 2015 resulting in 52,404 deaths in 2015, including 33,091 (63.1%) that involved an opioid. The largest rate increases from 2014 to 2015 occurred among deaths involving synthetic opioids other than methadone (synthetic opioids) (72.2%) (1). Because of demographic and geographic variations in overdose deaths involving different drugs (2,3),† CDC examined age-adjusted death rates for overdoses involving all opioids, opioid subcategories (i.e., prescription opioids, heroin, and synthetic opioids),§ cocaine, and psychostimulants with abuse potential (psychostimulants) by demographics, urbanization levels, and in 31 states and the District of Columbia (DC). There were 63,632 drug overdose deaths in 2016; 42,249 (66.4%) involved an opioid.¶ From 2015 to 2016, deaths increased across all drug categories examined. The largest overall rate increases occurred among deaths involving cocaine (52.4%) and synthetic opioids (100%), likely driven by illicitly manufactured fentanyl (IMF) (2,3). Increases were observed across demographics, urbanization levels, and states and DC. The opioid overdose epidemic in the United States continues to worsen. A multifaceted approach, with faster and more comprehensive surveillance, is needed to track emerging threats to prevent and respond to the overdose epidemic through naloxone availability, safe prescribing practices, harm-reduction services, linkage into treatment, and more collaboration between public health and public safety agencies.

Implementing and Evaluating Comprehensive Evidence-Based Approaches to Prevent Youth Violence: Partnering to Create Communities Where Youth Are Safe From Violence.

Violence, including its occurrence among youth, results in considerable physical, emotional, social, and economic consequences in the U.S. Youth violence prevention work at the Division of Violence Prevention (DVP) at the Centers for Disease Control and Prevention (CDC) emphasizes preventing youth violence-related behaviors, injuries, and deaths by collaborating with academic and community partners and stakeholders. Since 2000, DVP has funded three rounds of CDC's National Centers of Excellence in Youth Violence Prevention (YVPCs) in 5-year cycles, with the goal of supporting university-community partnerships so that the best science can be utilized in order to prevent youth violence. The current YVPCs focus on: (a) partnering with communities to identify community needs; (b) selecting and implementing the best comprehensive evidence-based programs to meet those needs; and (c) rigorously evaluating whether those efforts have a community-level impact on youth violence rates. The introduction to this special issue on the current YVPCs provides a brief historical overview on the YVPC Program; outlines the YVPCs' accomplishments to date; and describes the current YVPCs, their community partners, and their activities. The introduction concludes with an overview of the special issue.

Differential experiences of discrimination among ethnoracially diverse persons experiencing mental illness and homelessness.

BACKGROUND: This mixed methods study explored the characteristics of and experiences with perceived discrimination in an ethnically diverse urban sample of adults experiencing homelessness and mental illness. METHODS: Data were collected in Toronto, Ontario, as part of a 4-year national randomized field trial of the Housing First treatment model. Rates of perceived discrimination were captured from survey questions regarding perceived discrimination among 231 ethnoracially diverse participants with moderate mental health needs. The qualitative component included thirty six in-depth interviews which explored how individuals who bear these multiple identities of oppression navigate stigma and discrimination, and what affects their capacity to do so. RESULTS: Quantitative analysis revealed very high rates of perceived discrimination related to: homelessness/poverty (61.5%), race/ethnicity/skin colour (50.6%) and mental illness/substance use (43.7%). Immigrants and those who had been homeless three or more years reported higher perceived discrimination on all three domains. Analysis of qualitative interviews revealed three common themes related to navigating these experiences of discrimination among participants: 1) social distancing; 2) old and new labels/identities; and, 3) 'homeland' cultures. CONCLUSIONS: These study findings underscore poverty and homelessness as major sources of perceived discrimination, and expose underlying complexities in the navigation of multiple identities in responding to stigma and discrimination. TRIAL REGISTRATION: Current Controlled Trials ISRCTN42520374 . Registered 18 August 2009.

Intra-horn insemination in the alpaca Vicugna pacos: Copulatory wounding and deep sperm deposition.

Alpacas (Vicugna pacos) are reported to be the rare mammal in which the penis enters the uterus in mating. To date, however, only circumstantial evidence supports this assertion. Using female alpacas culled for meat, we determined that the alpaca penis penetrates to the very tips of the uterine horns, abrading the tract and breaking fine blood vessels. All female alpacas sacrificed one hour or 24 hours after mating showed conspicuous bleeding in the epithelium of some region of their reproductive tract, including the hymen, cervix and the tips of each uterine horn, but typically not in the vagina. Unmated females showed no evidence of conspicuous bleeding. Histological examination of mated females revealed widespread abrasion of the cervical and endometrial epithelium, injuries absent in unmated females. Within one hour of mating, sperm were already present in the oviduct. The male alpaca's cartilaginous penis tip with a hardened urethral process is likely responsible for the copulatory abrasion. The entire female reproductive tract interacts with the penis, functioning like a vagina. Alpacas are induced ovulators, and wounding may hasten delivery of the seminal ovulation-inducing factor beta-NGF into the female's blood stream. There is no evidence of sexual conflict in copulation in alpaca, and thus wounding may also be one of a variety of mechanisms devised by mammals to induce a beneficial, short-term inflammatory response that stimulates blastocyst implantation, the uterine remodeling associated with placental development, and thus the success of early pregnancy.

The relationship between parameters measured using intravoxel incoherent motion and dynamic contrast-enhanced MRI in patients with breast cancer undergoing neoadjuvant chemotherapy: a longitudinal cohort study.

Purpose: The primary aim of this study was to explore whether intravoxel incoherent motion (IVIM) can offer a contrast-agent-free alternative to dynamic contrast-enhanced (DCE)-MRI for measuring breast tumor perfusion. The secondary aim was to investigate the relationship between tissue diffusion measures from DWI and DCE-MRI measures of the tissue interstitial and extracellular volume fractions. Materials and methods: A total of 108 paired DWI and DCE-MRI scans were acquired at 1.5 T from 40 patients with primary breast cancer (median age: 44.5 years) before and during neoadjuvant chemotherapy (NACT). DWI parameters included apparent diffusion coefficient (ADC), tissue diffusion (Dt), pseudo-diffusion coefficient (Dp), perfused fraction (f), and the product f×Dp (microvascular blood flow). DCE-MRI parameters included blood flow (Fb), blood volume fraction (vb), interstitial volume fraction (ve) and extracellular volume fraction (vd). All were extracted from three tumor regions of interest (whole-tumor, ADC cold-spot, and DCE-MRI hot-spot) at three MRI visits: pre-treatment, after one, and three cycles of NACT. Spearman's rank correlation was used for assessing between-subject correlations (r), while repeated measures correlation was employed to assess within-subject correlations (rrm) across visits between DWI and DCE-MRI parameters in each region. Results: No statistically significant between-subject or within-subject correlation was found between the perfusion parameters estimated by IVIM and DCE-MRI (f versus vb and f×Dp versus Fb; P=0.07-0.81). Significant moderate positive between-subject and within-subject correlations were observed between ADC and ve (r=0.461, rrm=0.597) and between Dt and ve (r=0.405, rrm=0.514) as well as moderate positive within-subject correlations between ADC and vd and between Dt and vd (rrm=0.619 and 0.564, respectively) in the whole-tumor region. Conclusion: No correlations were observed between the perfusion parameters estimated by IVIM and DCE-MRI. This may be attributed to imprecise estimates of fxDp and vb, or an underlying difference in what IVIM and DCE-MRI measure. Care should be taken when interpreting the IVIM parameters (f and f×Dp) as surrogates for those measured using DCE-MRI. However, the moderate positive correlations found between ADC and Dt and the DCE-MRI parameters ve and vd confirms the expectation that as the interstitial and extracellular volume fractions increase, water diffusion increases.

Adverse Childhood Experiences Among U.S. Adults: National and State Estimates by Adversity Type, 2019-2020.

INTRODUCTION: Although adverse childhood experiences (ACEs) are associated with lifelong health harms, current surveillance data on exposures to childhood adversity among adults are either unavailable or incomplete for many states. In this study, recent data from a nationally representative survey were used to obtain the current and complete estimates of ACEs at the national and state levels. METHODS: Current, complete, by-state estimates of adverse childhood experiences were obtained by applying small area estimation technique to individual-level data on adults aged ≥18 years from 2019-2020 Behavioral Risk Factor Surveillance System survey. The standardized questions about childhood adversity included in the 2019-2020 survey allowed for obtaining estimates of ACE consistent across states. All missing responses to childhood adversity questions (states did not offer such questions or offered them to only some respondents; respondents skipped questions) were predicted through multilevel mixed-effects logistic small area estimation regressions. The analyses were conducted between October 2022 and May 2023. RESULTS: An estimated 62.8% of U.S. adults had past exposure to ACEs (range: 54.9% in Connecticut; 72.5% in Maine). Emotional abuse (34.5%) was the most common; household member incarceration (10.6%) was the least common. Sexual abuse varied markedly between females (22.2%) and males (5.4%). Exposure to most types of adverse childhood experiences was lowest for adults who were non-Hispanic White, had the highest level of education (college degree) or income (annual income ≥$50,000), or had access to a personal healthcare provider. CONCLUSIONS: Current complete estimates of ACEs demonstrate high countrywide exposures and stark sociodemographic inequalities in the burden, highlighting opportunities to prevent adverse childhood experiences by focusing social, educational, medical, and public health interventions on populations disproportionately impacted.

Economic Burden of Health Conditions Associated With Adverse Childhood Experiences Among US Adults.

Importance: Adverse childhood experiences (ACEs) are preventable, potentially traumatic events in childhood, such as experiencing abuse or neglect, witnessing violence, or living in a household with substance use disorder, mental health problems, or instability from parental separation or incarceration. Adults who had ACEs have more harmful risk behaviors and worse health outcomes; the economic burden associated with these issues is uncertain. Objective: To estimate the economic burden of ACE-associated health conditions among US adults. Design, Setting, and Participants: In this economic evaluation, regression models of cross-sectional survey data from the 2019-2020 Behavioral Risk Factor Surveillance System (BRFSS) and previous studies were used to estimate ACE population-attributable fractions (PAFs) (ie, the fraction of total cases associated with a specific exposure) for selected health outcomes (anxiety, arthritis, asthma, cancer, chronic obstructive pulmonary disease, depression, diabetes, heart disease, kidney disease, stroke, and violence) and risk factors (heavy drinking, illicit drug use, overweight and obesity, and smoking) among the 2019 US adult population. Adverse childhood experience PAFs were used to calculate the proportion of total condition-specific medical spending and lost healthy life-years related to ACEs using Global Burden of Disease Study data. Data analysis was performed from September 10, 2021, to November 29, 2022. Exposure: Adverse childhood experiences (age <18 years). Main Outcomes and Measures: Monetary valuation of ACE-associated morbidity and mortality using standard US value of statistical life methods and presented in terms of annual and lifetime per affected person and total population estimates at the national and state levels. Results: A total of 820 673 adults, representing 255 million individuals, participated in the BRFSS in 2019 and 2020. An estimated 160 million of the total 255 million US adult population (63%) had 1 or more ACE, associated with an annual economic burden of $14.1 trillion ($183 billion in direct medical spending and $13.9 trillion in lost healthy life-years). This was $88 000 per affected adult annually and $2.4 million over their lifetimes. The lifetime economic burden per affected adult was lowest in North Dakota ($1.3 million) and highest in Arkansas ($4.3 million). Twenty-two percent of adults had 4 or more ACEs and comprised 58% of the total economic burden-the estimated per person lifetime economic burden for those adults was $4.0 million. Conclusions and Relevance: In this cross-sectional analysis of the US adult population, the economic burden of ACE-related health conditions was substantial. The findings suggest that measuring the economic burden of ACEs can support decision-making about investing in strategies to improve population health.

Adverse Childhood Experiences Among US Adolescents Over the Course of the COVID-19 Pandemic.

BACKGROUND AND OBJECTIVE: A national, longitudinal survey of US adolescents assessed adverse childhood experiences (ACEs) twice during the COVID-19 pandemic. Adolescents with more Wave 1 ACEs were expected to be more likely to experience additional ACEs at Wave 2. METHODS: Adolescents aged 13 to 18 (n = 727, Fall 2020; n = 569, Spring 2021) recruited via a national, probability-based panel (survey completion rate Wave 1, 62.1%; Wave 2, 78.3%) responded to questions about household challenges, violence or neglect, and community ACE exposure at Wave 1 and Wave 2 (since Wave 1). Unweighted frequencies and 95% confidence intervals of demographic characteristics and individual ACEs were calculated by using weighted data. Odds ratios examined associations between ACEs by Wave 1 and Wave 2. RESULTS: Among respondents of both survey waves (n = 506), 27.2% experienced violence or abuse, 50.9% experienced a household challenge, and 34.9% experienced a community ACE by Wave 1. By Wave 2, 17.6% experienced 1 new ACE, 6.1% experienced 2 new ACEs and 2.7% experienced 4 or more new ACEs. Those with ≥4 ACEs by Wave 1 were 2.71 times as likely as those with none to report a new ACE at Wave 2 (confidence interval: 1.18-6.24). CONCLUSIONS: This nationwide, longitudinal study of US adolescents measured exposure to ACEs early in and during the COVID-19 pandemic. Nearly one-third of adolescents experienced a new ACE between survey waves. Prevention and trauma-informed approaches in clinical, school, and community settings may be helpful.

Associations between Adverse Childhood Experiences and Pandemic-Related Stress and the Impact on Adolescent Mental Health during the COVID-19 Pandemic.

Vulnerabilities of adolescents during times of crisis have been previously identified, but little research has investigated the compounding effects of lifetime adversities and pandemic-related stress on adolescent mental health. This study uses adolescent self-report data to model relationships between stress exposures and indicators of poor mental health from the longitudinal COVID Experiences (CovEx) Surveys. These surveys were administered online in English to U.S. adolescents ages 13-19 using the NORC AmeriSpeak® panel, a probability-based panel designed to be representative of the U.S. household population. Two waves of data were collected (Wave 1: October-November 2020, n = 727; Wave 2: March-May 2021, n = 569). Measures included demographics, adverse childhood experiences (ACEs, 8 items), pandemic-related stress (Pandemic-Related Stress Index [PRSI], 7 items), and depression symptoms (Patient Health Questionnaire for Adolescents [PHQ-A], 9 items). Path analyses were conducted to examine pathways between Wave 1 ACEs, Wave 1 PRSI, and Wave 2 PHQ with covariates of sex and race/ethnicity. Females had higher ACEs, PRSI, and PHQ scores than males. The PRSI score at Wave 1 was positively associated with the PHQ at Wave 2 (b = 0.29, SE = 0.14, p < 0.001). ACEs at Wave 1 were positively associated with PRSI at Wave 1 (b = 0.31, SE = 0.03, p < 0.001) and with PHQ at Wave 2 (b = 0.32, SE = 0.12, p < 0.001). The direct effect of ACEs on PHQ (b = 0.23, SE = 0.12, p < 0.001) remained significant even after accounting for the indirect effect of pandemic-related stress (b = 0.09, SE = 0.05, p < 0.001). Pandemic-related stress had a direct, adverse impact on adolescent depressive symptoms and demonstrates a compounding effect of childhood adversity and pandemic-related stress on depression. Findings can aid the design of interventions that promote mental health and support adolescent coping and recovery. Supplementary Information: The online version contains supplementary material available at 10.1007/s40653-022-00502-0.

Perceived Racial/Ethnic Discrimination, Physical and Mental Health Conditions in Childhood, and the Relative Role of Other Adverse Experiences.

Adverse childhood experiences (ACEs) are associated with poor health. Childhood experiences of racial/ethnic discrimination and other forms of racism may underlie or exacerbate other ACEs. We explored health-related associations with perceived racial/ethnic discrimination relative to other ACEs, using data from 2016-2019 National Survey of Children's Health, an annual cross-sectional, nationally representative survey. Parent responses for 88,183 children ages 6-17 years with complete data for ACEs (including racial/ethnic discrimination) were analyzed for associations between racial/ethnic discrimination, other ACEs, demographics, and physical and mental health conditions with weighted prevalence estimates and Wald chi-square tests. To assess associations between racial/ethnic discrimination and health conditions relative to other ACEs, we used weighted Poisson regressions, adjusted for exposure to other ACEs, age, and sex. We assessed effect modification by race/ethnicity. Prevalence of other ACEs was highest among children with racial/ethnic discrimination, and both racial/ethnic discrimination and other ACEs were associated with having one or more health conditions. Adjusted associations between racial/ethnic discrimination and health conditions differed by race/ethnicity (interaction P-values < 0.001) and were strongest for mental health conditions among Hispanic/Latino (adjusted prevalence ratio (aPR)=1.62, 95% confidence interval (CI): 1.24-2.10) and non-Hispanic/Latino Asian American (aPR=2.25, 95% CI: 1.37-3.71) children. Results suggest racial/ethnic discrimination and other ACEs are associated with child health conditions, with differences in relative associations by race/ethnicity. Public health efforts to prevent childhood adversity, including racial/ethnic discrimination and other forms of racism could be associated with improvements in child health.

Nrf2 Downregulation Contributes to Epithelial-to-Mesenchymal Transition in Helicobacter pylori-Infected Cells.

BACKGROUND: Gastric cancer, the fifth most common cancer worldwide, is mainly linked to Helicobacter pylori infection. H. pylori induces chronic inflammation of the gastric mucosa associated with high oxidative stress. Our study aimed at assessing the implication of Nrf2, a major regulator of cellular redox homeostasis, in H. pylori-induced gastric carcinogenesis. METHODS: Using three different gastric epithelial cell lines, a non-cancerous (HFE-145) and two different subtypes of gastric cancer (AGS and MKN74), we analyzed the modulation of Nrf2 expression over time. After invalidation of Nrf2 by CRISPR-cas9, we assessed its role in H. pylori-induced epithelial-to-mesenchymal transition (EMT). Finally, we evaluated the expression of Nrf2 and ZEB1, a central EMT transcription factor, in human gastric tissues. RESULTS: We first demonstrated that the Nrf2 signaling pathway is differentially regulated depending on the infection stage. Rapidly and transiently activated, Nrf2 was downregulated 24 h post-infection in a VacA-dependent manner. We then demonstrated that Nrf2 invalidation leads to increased EMT, which is even exacerbated after H. pylori infection. Finally, Nrf2 expression tended to decrease in human patients' gastric mucosa infected with H. pylori. CONCLUSIONS: Our work supports the hypothesis that Nrf2 downregulation upon H. pylori infection participates in EMT, one of the most important events in gastric carcinogenesis.

Adverse childhood experiences and stimulant use disorders among adults in the United States.

Recent data indicate a resurgence of stimulant use and harms in the United States; thus, there is a need to identify risk factors to inform development of effective prevention strategies. Prior research suggests adverse childhood experiences (ACEs) are common among individuals using stimulants and may be an important target for prevention. National Epidemiological Survey on Alcohol and Related Conditions was used to estimate prevalence of ACEs among U.S. adults using amphetamine-type stimulants (ATS), cocaine, or both. Multivariable logistic regression examined associations between ACEs and stimulant use and use disorders. Among adults reporting lifetime ATS use, 22.1% had ≥4 ACEs, 24.9% had 2-3 ACEs, 22.4% had 1 ACE, 30.6% reported no ACEs. Among adults with lifetime ATS use disorder, 29.3% reported ≥4 ACEs, 28.7% reported 2-3 ACEs, 21.6% reported 1 ACE, and 20.4% reported no ACEs. Multivariable logistic regression found a significant relationship between number of ACEs and stimulant use and use disorders. In conclusion, we found a strong relationship between increasing ACE exposures and stimulant use and use disorders. Advancing comprehensive strategies to prevent ACEs and treating underlying trauma among those using stimulants holds great promise to reduce stimulant use and its health and social consequences in the United States.