Functional Analysis of RE1 Silencing Transcription Factor as a Putative Tumor Suppressor in Human Endometrial Cancer.

Uterine cancer is the most common gynecologic malignancy in the United States, with endometrioid endometrial adenocarcinoma (EC) being the most common histologic sub-type. Considering the molecular classifications of EC, efforts have been made to identify additional biomarkers that can assist in diagnosis, prognosis, and individualized therapy. We sought to explore the relationship of Repressor Element 1 (RE1) silencing transcription factor (REST), which downregulates neuronal genes in non-neuronal tissue, along with matrix metalloproteinase-24 (MMP24) and EC. We analyzed the expression of REST and MMP24 in 31 cases of endometrial cancer and 16 controls. We then explored the baseline expression of REST and MMP24 in two EC cell lines (Ishikawa and HEC-1-A) compared to a benign cell line (t-HESC) and subsequently evaluated proliferation, migration, and invasion in the setting of loss of REST gene expression. REST and MMP24 expression were significantly lower in human EC samples compared to control samples. REST was highly expressed in EC cell lines, but decreasing REST gene expression increased proliferation (FC: 1.13X, p < 0.0001), migration (1.72X, p < 0.0001), and invasion (FC: 7.77X, p < 0.05) in Ishikawa cells, which are hallmarks of cancer progression and metastasis. These findings elicit a potential role for REST as a putative tumor suppressor in EC.

Uterine cyclin A2 deficient mice as a model of female early pregnancy loss.

Proper action of the female sex steroids, 17ß-estradiol (E2) and progesterone (P4) on endometrium is essential for fertility. Beyond its role in regulating the cell cycle, cyclin A2 (CCNA2) also mediates E2 and P4 signaling in vitro, but a potential role in modulating steroid action for proper endometrial tissue development and function is unknown. To fill this gap in our knowledge, we examined human endometrial tissue from fertile and infertile women for CCNA2 expression and correlated this with pregnancy outcome. Functional assessment of CCNA2 was validated in vivo using a conditional Ccna2 uterine deficient mouse model while in vitro function was assessed using human cell culture models. We found that CCNA2 expression was significantly reduced in endometrial tissue, specifically the stromal cells, from women undergoing in vitro fertilization who failed to achieve pregnancy. Conditional deletion of Ccna2 from mouse uterine tissue resulted in an inability to achieve pregnancy which appears to be due to alterations in the process of decidualization, which was confirmed using in vitro models. From these studies, we conclude that CCNA2 expression during the proliferative/regenerative stage of the menstrual cycle acts as a safeguard allowing for proper steroid responsiveness, decidualization and pregnancy. When CCNA2 expression levels are insufficient there is impaired endometrial responsiveness, aberrant decidualization and loss of pregnancy.

A Vaping Cessation Text Message Program for Adolescent E-Cigarette Users: A Randomized Clinical Trial.

Importance: E-cigarettes are the most commonly used tobacco product among adolescents. Despite known harms of nicotine exposure among teens, there are no empirically tested vaping cessation interventions. Objective: To compare the effectiveness of a text message program for nicotine vaping cessation among adolescents with assessment-only control. Design, Setting, and Participants: A parallel, 2-group, double-blind, individually randomized clinical trial with follow-ups at 1 and 7 months after randomization was conducted from October 1, 2021, to October 18, 2023. Participants were recruited via social media ads; the intervention was delivered via text message; and assessments were completed online or by telephone. Eligible individuals were US residents aged 13 to 17 years who reported past 30-day e-cigarette use, were interested in quitting within 30 days, and owned a mobile phone with an active text message plan. To optimize study retention, all participants received monthly assessments via text message about e-cigarette use. Interventions: Assessment-only controls (n = 744) received only study retention text messages. Intervention participants (n = 759) also received an automated, interactive text message program for vaping cessation that delivers cognitive and behavioral coping skills training and social support. Main Outcomes and Measures: The primary outcome was self-reported 30-day point-prevalence abstinence from vaping at 7 months analyzed as intention-to-treat, with missingness coded as vaping. Results: Among n = 1503 adolescents randomized, average age was 16.4 (SD, 0.8) years. The sample was 50.6% female, 42.1% male, and 7.4% nonbinary/other; 10.2% Black/African American, 62.6% White, 18.5% multiracial, and 8.7% another race; 16.2% Hispanic; 42.5% sexual minority; and 76.2% vaped within 30 minutes of waking. The 7-month follow-up rate was 70.8%. Point-prevalence abstinence rates were 37.8% (95% CI, 34.4%-41.3%) among intervention participants and 28.0% (95% CI, 24.9%-31.3%) among control participants (relative risk, 1.35 [95% CI, 1.17-1.57]; P < .001). No baseline variables moderated the treatment-outcome relationship. There was no evidence that adolescents who quit vaping transitioned to combustible tobacco products. Conclusions and Relevance: A tailored, interactive text message intervention increased self-reported vaping cessation rates among adolescents recruited via social media channels. Trial Registration: ClinicalTrials.gov Identifier: NCT04919590.

Prefoldin-5 Expression Is Elevated in Eutopic and Ectopic Endometriotic Epithelium and Modulates Endometriotic Epithelial Cell Proliferation and Migration In Vitro.

Endometriosis is a common disease among women of reproductive age in which endometrial tissue grows in ectopic localizations, primarily within the pelvic cavity. These ectopic "lesions" grow as well as migrate and invade underlying tissues. Despite the prevalence of the disease, an understanding of factors that contribute to these cellular attributes remains poorly understood. Prefoldin-5 (PFDN5) has been associated with both aberrant cell proliferation and migration, but a potential role in endometriosis is unknown. As such, the purpose of this study was to examine PFDN5 expression in endometriotic tissue. PFDN5 mRNA and protein were examined in ectopic (lesion) and eutopic endometrial tissue from women with endometriosis and in eutopic endometrium from those without endometriosis using qRT-PCR and immunohistochemistry, respectively, while function of PFDN5 in vitro was evaluated using cell count and migration assays. PFDN5 mRNA and protein were expressed in eutopic and ectopic endometrial tissue, predominantly in the glandular epithelium, but not in endometrium from control subjects. Expression of both mRNA and protein was variable among endometriotic eutopic and ectopic endometrial tissue but showed an overall net increase. Knockdown of PFDN5 by siRNA transfection of endometriotic epithelial 12Z cells was associated with reduced cell proliferation/survival and migration. PFDN5 is expressed in eutopic and ectopic glandular epithelium and may play a role in proliferation and migration of these cells contributing to disease pathophysiology.

The Role of Seed Users in Nurturing an Online Health Community for Smoking Cessation Among People With HIV/AIDS.

BACKGROUND: To nurture a new online community for health behavior change, a fruitful strategy is to recruit "seed users" to create content and encourage participation. PURPOSE: This study evaluated the impact of support from seed users in an online community for smoking cessation among people living with HIV/AIDS and explored the linguistic characteristics of their interactions. METHODS: These secondary analyses examined data from a randomized trial of a smoking cessation intervention for HIV+ smokers delivered via an online health community (OHC). The analytic sample comprised n = 188 participants randomized to the intervention arm who participated in the community. Independent variables were OHC interactions categorized by participant interlocutor type (study participant, seed user) and interaction type (active, passive). The primary outcome was biochemically verified 7-day abstinence from cigarettes measured 3 months post-randomization; 30-day abstinence was examined for robustness. RESULTS: Logistic regression models showed that participants' interactions with seed users were a positive predictor of abstinence but interactions with other study participants were not. Specifically, the odds of abstinence increased as the number of posts received from seed users increased. Exploratory linguistic analyses revealed that seed users wrote longer comments which included more frequent use of "we" and "you" pronouns and that study participants users used more first-person singular pronouns ("I"). CONCLUSIONS: Seeding a community at its inception and nurturing its growth through seed users may be a scalable way to foster behavior change among OHC members. These findings have implications for the design and management of an OHC capable of promoting smoking cessation.

Online health communities (OHCs) are a popular means for people with similar health concerns to exchange information and support. The success of OHCs depends on members' active participation and on the formation of meaningful relationships. Jumpstarting a new OHC with active members (seed users) can promote engagement and foster its growth. Using data from a multisite randomized controlled trial of a web-based smoking cessation intervention developed specifically for people living with HIV/AIDS (PLWH), we examined whether support provided by seed users in the OHC was a stronger predictor of abstinence from smoking compared with support from other tobacco users who are also trying to quit. These secondary analyses focused on 188 urban, predominantly Black PLWH who smoked that were randomized to the intervention arm and participated in the online community. The primary outcome was biochemically verified 7-day abstinence from cigarettes measured 3 months following study enrollment. Receiving support from seed users was a positive predictor of abstinence among smokers in the trial whereas interactions with other study participants did not relate to abstinence. These findings suggest that for a new OHC, seed users can be critical for generating engagement and promoting health behavior change.

Changes over time in reasons for quitting vaping among treatment-seeking young people from 2019 to 2022.

Objectives: The landscape of availability, policies, and norms around e-cigarette use and cessation has changed rapidly in the last few years. There is also high interest in quitting vaping among teens and young adults. Understanding the motivation of those who want to quit vaping is important for effective intervention development. This analysis compares user-submitted reasons for quitting (RFQ) vaping from 2022 to a previous analysis from 2019 to determine whether motivations have shifted among young people. Methods: We reviewed 2000 RFQ submissions from users who enrolled in a vaping cessation text message program in 2022. Each response was coded by ≥ 2 researchers and categorized into one of 16 themes. Findings were compared to the 2019 analysis using item-wise comparisons. Results: The most frequent RFQ in 2022 were health (56.1%), social influence (15.8%), and other (11.7%). In comparison to 2019, health remained the top reason, but the rank order of all other reasons shifted. Theme prevalence changed significantly, with cost decreasing and health increasing. Among health-related sub-categories, current and mental health increased compared to 2019 submissions. Discussion: RFQ among young people shifted between 2019 and 2022. We observed greater concern about current and mental health, possibly from experiencing negative health impacts from vaping or from increased awareness of these impacts. The lower prevalence of cost may reflect the widespread availability of cheaper e-cigarettes. RFQ likely change rapidly with the fluctuating e-cigarette landscape and should be considered in cessation interventions, promotional campaigns, and policy.

Targeting c-MYC: a potential non-hormonal therapeutic approach for endometriosis treatment.

Endometriosis is a benign gynecological disease in which eutopic endometrial tissue composed of glands and stroma grow within the pelvic cavity. The disease affects females of reproductive age and is characterized by pelvic pain, infertility and reduced quality of life. The majority of pharmacologic treatment modalities for endometriosis focus on suppression of estradiol production and/or action; an approach associated with adverse side effects. c-MYC is elevated in eutopic endometrium and endometriotic lesion tissue in patients with endometriosis and the disease shares many similar pathological characteristics with that of endometrial carcinoma. While targeting of c-MYC with Omomyc has recently gained substantial interest in the field of cancer research, there has been no recent attempt to evaluate the potential utility in targeting c-MYC for endometriosis treatment. The following perspective article compares the similarities between endometriosis and endometrial cancer and presents preliminary data suggesting that targeting c-MYC with Omomyc reduces endometriotic cell proliferation and viability in vitro. Future application of targeting c-MYC in endometriosis treatment and potential pros and cons are then discussed.

E-cigarette cessation interest and quit attempts among young adults reporting exclusive e-cigarette use or dual use with other tobacco products: How can we reach them?

INTRODUCTION: There is limited evidence to inform e-cigarette quitting interventions. This mixed-methods study examined: 1) e-cigarette and other tobacco product perceptions and cessation-related factors; and 2) potential behavioral intervention strategies among young adults reporting exclusive e-cigarette use or dual use with other tobacco products. METHODS: We analyzed Fall 2020 survey data from 726 participants reporting past 6-month e-cigarette use (mean age=24.15 years, 51.1% female, 38.5% racial/ethnic minority) from 6 US metropolitan areas and Spring 2021 qualitative interview data from a subset (n=40), comparing tobacco-related perceptions and cessation-related factors among those reporting exclusive use versus dual use. RESULTS: Among survey participants (35.5% exclusive e-cigarette use, 64.5% dual use), those reporting dual use indicated greater importance of quitting all tobacco or nicotine products (mean=5.28, SD=3.44 vs mean=4.65, SD=3.75, p=0.033), whereas those reporting exclusive use expressed greater confidence in quitting e-cigarettes (mean=7.59, SD=3.06 vs mean=7.08, SD=3.01, p=0.029) and all tobacco and nicotine products (mean=7.00, SD=3.16 vs mean=6.31, SD=3.13, p=0.008), as well as less favorable perceptions (i.e. more harmful to health and addictive, less socially acceptable) of cigarettes, cigars, and smokeless tobacco (p<0.05). Interview participants (50.0% exclusive e-cigarette use; 50.0% dual use) attributed previous failed e-cigarette quit attempts to their inability to cope with social influences, stress, and withdrawal symptoms. Although most expressed disinterest in quitting due to belief of eventually outgrowing e-cigarettes (among those reporting exclusive use) or unreadiness to abstain from nicotine (among those reporting dual use), many acknowledged the need for quitting interventions. CONCLUSIONS: Young adult e-cigarette cessation interventions should target risk perceptions, cessation barriers, and social influences/support.

Co-use of cigarettes and cannabis among people with HIV: Results from a randomized controlled smoking cessation trial.

Significance: People with HIV (PWH) who smoke cigarettes have lower cessation rates than the general population. This study investigated whether changes in cannabis use frequency impedes cigarette cessation among PWH who are motivated to quit. Methods: Between 2016-2020, PWH who smoked cigarettes were enrolled in a randomized controlled trial for cigarette cessation. Analyses were limited to PWH who reported on their past 30-day (P30D) cannabis use during four study visits (baseline, 1-month, 3-month, and 6-month) (N=374). Descriptive statistics and multivariable logistic regression were used to evaluate changes in cannabis use frequency from baseline to 6 months and associations with cigarette abstinence at 6 months among PWH who reported no use during all four visits (n=176), as well as those who reported use during at least one visit and who increased (n=39), decreased (n=78), or had no change (n=81) in use frequency. Results: Among those who reported cannabis use during at least one visit (n=198), at baseline, 18.2% reported no use. At 6 months, 34.3% reported no use. Controlling for covariates, increased cannabis use frequency from baseline was associated with reduced odds of cigarette abstinence at 6 months versus decreased use frequency (aOR=0.22, 95% CI=0.03, 0.90) or no use at either time-point (aOR=0.25, 95% CI=0.04, 0.93). Conclusions: Increased cannabis use over 6 months was associated with reduced odds of cigarette smoking abstinence among PWH who were motivated to quit. Additional factors that influence cannabis use and cigarette cessation simultaneously are in need of further study.

Aerosol Particle Size Influences the Infectious Dose and Disease Severity in a Golden Syrian Hamster Model of Inhalational COVID-19.

Background: Significant evidence suggests that SARS-CoV-2 can be transmitted via respiratory aerosols, which are known to vary as a function of respiratory activity. Most animal models examine disease presentation following inhalation of small-particle aerosols similar to those generated during quiet breathing or speaking. However, despite evidence that particle size can influence dose-infectivity relationships and disease presentation for other microorganisms, no studies have examined the infectivity of SARS-CoV-2 contained in larger particle aerosols similar to those produced during coughing, singing, or talking. Therefore, the aim of the present study was to assess the influence of aerodynamic diameter on the infectivity and virulence of aerosols containing SARS-CoV-2 in a hamster model of inhalational COVID-19. Methods: Dose-response relationships were assessed for two different aerosol particle size distributions, with mass median aerodynamic diameters (MMADs) of 1.3 and 5.2 µm in groups of Syrian hamsters exposed to aerosols containing SARS-CoV-2. Results: Disease was characterized by viral shedding in oropharyngeal swabs, increased respiratory rate, decreased activity, and decreased weight gain. Aerosol particle size significantly influenced the median doses to induce seroconversion and viral shedding, with both increasing ∼30-fold when the MMAD was increased. In addition, disease presentation was dose-dependent, with seroconversion and viral shedding occurring at lower doses than symptomatic disease characterized by increased respiratory rate and decreased activity. Conclusions: These results suggest that aerosol particle size may be an important factor influencing the risk of COVID-19 transmission and needs to be considered when developing animal models of disease. This result agrees with numerous previous studies with other microorganisms and animal species, suggesting that it would be generally translatable across different species. However, it should be noted that the absolute magnitude of the observed shifts in the median doses obtained with the specific particle sizes utilized herein may not be directly applicable to other species.

Development of an international glossary for clinical guidelines collaboration.

OBJECTIVES: Clinical practice guidelines (CPGs) are often created through collaboration among organizations. The use of inconsistent terminology may cause poor communication and delays. This study aimed to develop a glossary of terms related to collaboration in guideline development. STUDY DESIGN AND SETTING: A literature review of collaborative guidelines was performed to develop an initial list of terms related to guideline collaboration. The list of terms was presented to the members of the Guideline International Network Guidelines Collaboration Working Group, who provided presumptive definitions for each term and proposed additional terms to be included. The revised list was subsequently reviewed by an international, multidisciplinary panel of expert stakeholders. Recommendations received during this pre-Delphi review were implemented to augment an initial draft glossary. The glossary was then critically evaluated and refined through two rounds of Delphi surveys and a virtual consensus meeting with all panel members as Delphi participants. RESULTS: Forty-nine experts participated in the pre-Delphi survey, and 44 participated in the two-round Delphi process. Consensus was reached for 37 terms and definitions. CONCLUSION: Uptake and utilization of this guideline collaboration glossary by key organizations and stakeholder groups may facilitate collaboration among guideline-producing organizations by improving communication, minimizing conflicts, and increasing guideline development efficiency.

Effect of Messaging Content on Engagement With a Short Messaging Service for Perioperative Smoking Cessation.

INTRODUCTION: We determined whether a tobacco cessation intervention targeting brief perioperative abstinence ("quit for a bit") increased engagement of surgical patients with treatment compared with an intervention targeting long-term postoperative abstinence ("quit for good"). AIMS AND METHODS: Surgical patients who smoke were stratified according to intended duration of postoperative abstinence, and then randomized within strata to receive either a "quit for a bit" or a "quit for good" intervention. Both employed initial brief counseling and short message service (SMS) to deliver treatment up to 30 days after surgery. The primary outcome of treatment engagement was defined as the rate at which subjects actively responded to system requests delivered via SMS. RESULTS: The engagement index did not differ between intervention groups (median [25th, 75th] of 23.7% [8.8, 46.0] for "quit for a bit" group (n = 48) and 22.2% [4.8, 46.0] for "quit for good" group (n = 50), p = .74), nor did the proportion of patients continuing SMS use after study completion (33% and 28%, respectively). Exploratory abstinence outcomes on the morning of surgery and 7 and 30 days after surgery did not differ between groups. Program satisfaction was high in both groups and did not differ. There was no significant interaction between intended abstinence duration and any outcome, ie, alignment of intent with intervention did not affect engagement. CONCLUSIONS: Tobacco cessation treatment delivered via SMS was well accepted by surgical patients. Tailoring an SMS intervention to focus on the benefits of short-term abstinence for surgical patients did not increase engagement in treatment or perioperative abstinence rates. IMPLICATIONS: Treatment of surgical patients for tobacco use is efficacious and reduces postoperative complications. However, implementation in clinical practice has proved challenging, and new methods of engaging these patients in cessation treatment are needed. We found that tobacco use treatment delivered via SMS was feasible and well utilized by surgical patients. Tailoring an SMS intervention to focus on the benefits of short-term abstinence for surgical patients did not increase engagement in treatment or perioperative abstinence rates. CLINICAL TRIAL NUMBER: NCT03839043. Registry URL: https://clinicaltrials.gov/ct2/show/NCT03839043.

A pilot randomized controlled trial of automated and counselor-delivered text messages for e-cigarette cessation.

INTRODUCTION: Automated text messaging programs show promise for e-cigarette cessation. Adding live text counseling could make them more engaging. We developed Quit the Vape (QTV), an automated e-cigarette cessation text messaging program, designed to be delivered as stand-alone or with counselor-delivered messages (QTV-C), and evaluated the acceptability and preliminary efficacy of QTV and QTV-C. METHODS: Between May and August 2021, we recruited 58 e-cigarette users, aged 20-43 years, 53.5% male, 63.8% non-Hispanic White, from an ongoing cohort study in the United States. Inclusion criteria were: using nicotine-containing e-cigarettes on ≥4 days per month; smartphone ownership; and not receiving tobacco cessation treatment. Motivation to quit did not impact eligibility. Participants were randomized to QTV (n=20), QTV-C (n=19), or control (link to e-cigarette cessation website, n=19). At end-of-treatment, we assessed program engagement and satisfaction, and self-reported quitting behaviors (e.g. point prevalence abstinence, PPA). RESULTS: At baseline, average past-month e-cigarette use was 26.8 days (SD=6.2). At follow-up at 4 weeks, among QTV and QTV-C participants, ≥85% replied to ≥1 message, ≥35% set a quit date, and ≤15% opted out. More QTV and QTV-C participants (55.6%) versus control (17.7%) reported program satisfaction (p=0.034). QTV-C participants (vs QTV and control) trended more favorably on 7-day e-cigarette PPA [27.8% (95% CI: 11.5-53.3) vs 11.1% (95% CI: 2.6-37.0) and 5.9% (95% CI: 0.7-34.5)] and quit attempts [66.7% (95% CI: 41.6-84.9) vs 50.0% (95% CI: 27.4-72.6) and 52.9% (95% CI: 29.2-75.5)]. CONCLUSIONS: Adding live text counseling to an automated text messaging program is acceptable and shows promise for e-cigarette cessation. A larger trial is warranted to assess its efficacy.

RPLP1 Is Up-Regulated in Human Adenomyosis and Endometrial Adenocarcinoma Epithelial Cells and Is Essential for Cell Survival and Migration In Vitro.

Adenomyosis is defined as the development of endometrial epithelial glands and stroma within the myometrial layer of the uterus. These "ectopic" lesions share many cellular characteristics with endometriotic epithelial cells as well as endometrial adenocarcinoma cells, including enhanced proliferation, migration, invasion and progesterone resistance. We recently reported that the 60S acidic ribosomal protein P1, RPLP1, is up-regulated in endometriotic epithelial cells and lesion tissue where it plays a role in cell survival. To evaluate if a similar pattern of expression and function for RPLP1 exists in adenomyosis and endometrial cancer, we examined RPLP1 expression in adenomyosis and endometrial cancer tissue specimens and assessed its function in vitro using well-characterized cell lines. A total of 12 control endometrial biopsies and 20 eutopic endometrial and matched adenomyosis biopsies as well as 103 endometrial adenocarcinoma biopsies were evaluated for RPLP1 localization by immunohistochemistry. Endometrial adenocarcinoma cell lines, Ishikawa, HEC1A, HEC1B and AN3 were evaluated for RPLP1 protein and transcript expression, while in vitro function was evaluated by knocking down RPLP1 expression and assessing cell survival and migration. RPLP1 protein was up-regulated in eutopic epithelia as well as in adenomyosis lesions compared to eutopic endometria from control subjects. RPLP1 was also significantly up-regulated in endometrial adenocarcinoma tissue. Knockdown of RPLP1 in endometrial adenocarcinoma cell lines was associated with reduced cell survival and migration. RPLP1 expression is up-regulated in eutopic and ectopic adenomyotic epithelia as well as in the epithelia of endometrial cancer specimens. In vitro studies support an essential role for RPLP1 in mediating cell survival and migration, processes which are all involved in pathophysiology associated with both diseases.

Prevalence and associated factors of post-traumatic stress disorder in parents whose infants have single ventricle heart disease.

INTRODUCTION: Post-traumatic stress disorder occurs in parents of infants with CHD, contributing to psychological distress with detrimental effects on family functioning and well-being. We sought to determine the prevalence and factors associated with post-traumatic stress disorder symptoms in parents whose infants underwent staged palliation for single ventricle heart disease. MATERIALS AND METHODS: A large longitudinal multi-centre cohort study evaluated 215 mothers and fathers for symptoms of post-traumatic stress disorder at three timepoints, including post-Norwood, post-Stage II, and a final study timepoint when the child reached approximately 16 months of age, using the self-report questionnaire Impact of Event Scale - Revised. RESULTS: The prevalence of probable post-traumatic stress disorder post-Norwood surgery was 50% of mothers and 39% of fathers, decreasing to 27% of mothers and 24% of fathers by final follow-up. Intrusive symptoms such as flashbacks and nightmares and hyperarousal symptoms such as poor concentration, irritability, and sudden physical symptoms of racing heart and difficulty breathing were particularly elevated in parents. Higher levels of anxiety, reduced coping, and decreased satisfaction with parenting were significantly associated with symptoms of post-traumatic stress disorder in parents. Demographic and clinical variables such as parent education, pre-natal diagnosis, medical complications, and length of hospital stay(s) were not significantly associated with symptoms of post-traumatic stress disorder. DISCUSSION: Parents whose infants underwent staged palliation for single ventricle heart disease often reported symptoms of post-traumatic stress disorder. Symptoms persisted over time and routine screening might help identify parents at-risk and prompt referral to appropriate supports.

Using Protection Motivation Theory to Predict Intentions for Breast Cancer Risk Management: Intervention Mechanisms from a Randomized Controlled Trial.

The purpose of this study is to evaluate the direct and indirect effects of a web-based, Protection Motivation Theory (PMT)-informed breast cancer education and decision support tool on intentions for risk-reducing medication and breast MRI among high-risk women. Women with ≥ 1.67% 5-year breast cancer risk (N = 995) were randomized to (1) control or (2) the PMT-informed intervention. Six weeks post-intervention, 924 (93% retention) self-reported PMT constructs and behavioral intentions. Bootstrapped mediations evaluated the direct effect of the intervention on behavioral intentions and the mediating role of PMT constructs. There was no direct intervention effect on intentions for risk-reducing medication or MRI (p's ≥ 0.12). There were significant indirect effects on risk-reducing medication intentions via perceived risk, self-efficacy, and response efficacy, and on MRI intentions via perceived risk and response efficacy (p's ≤ 0.04). The PMT-informed intervention effected behavioral intentions via perceived breast cancer risk, self-efficacy, and response efficacy. Future research should extend these findings from intentions to behavior. ClinicalTrials.gov Identifier: NCT03029286 (date of registration: January 24, 2017).

The Application of Bystander Intervention Scripts: Implications for Guardianship in Action.

Responding to high rates of interpersonal victimization and perpetration among adolescents, schools have implemented bystander intervention (BI) training to educate students to intervene to prevent or stop violence. These trainings function much like an application of scripts for guardianship in action. The current study builds on the overlapping and complementary bodies of BI and routine activities research by testing whether participation in BI training, namely Green Dot (GD), influences individuals' underlying ability to intervene. Using four years of survey data collected from high school students (N = 2,374-3,443), we use item response theory to model the difficulty of engaging in different BI behaviors. We then estimate multivariate ordinary least squares regression models, one for each year, to estimate the effect of GD training on students' ability to intervene. The item response theory results show that BI behaviors differ in terms of how "difficult" they are for respondents to engage in. Findings show that in each year, GD training increased students' underlying ability to intervene. Our findings suggest BI training and guardianship in action scripts should take into account this varying difficulty of intervention behaviors to best train individuals for successful intervention to prevent victimization.

Loss of the repressor REST affects progesterone receptor function and promotes uterine leiomyoma pathogenesis.

Uterine leiomyomas (UL) are benign tumors that arise in the myometrial layer of the uterus. The standard treatment option for UL is hysterectomy, although hormonal therapies, such as selective progesterone receptor modulators, are often used as temporary treatment options to reduce symptoms or to slow the growth of tumors. However, since the pathogenesis of UL is poorly understood and most hormonal therapies are not based on UL-specific, divergent hormone signaling pathways, hallmarks that predict long-term efficacy and safety of pharmacotherapies remain largely undefined. In a previous study, we reported that aberrant expression of repressor element 1 silencing transcription factor/neuron-restrictive silencing factor (REST/NRSF) target genes activate UL growth due to the near ubiquitous loss of REST. Here, we show that ablation of the Rest gene in mouse uterus leads to UL phenotype and gene-expression patterns analogous to UL, including altered estrogen and progesterone signaling pathways. We demonstrate that many of the genes dysregulated in UL harbor cis-regulatory elements bound by REST and progesterone receptor (PGR) adjacent to each other. Crucially, we identify an interaction between REST and PGR in healthy myometrium and present a putative mechanism for the dysregulation of progesterone-responsive genes in UL ensuing in the loss of REST. Using three Rest conditional knockout mouse lines, we provide a comprehensive picture of the impact loss of REST has in UL pathogenesis and in altering the response of UL to steroid hormones.

Tailored text message and web intervention for smoking cessation in U.S. socioeconomically-disadvantaged young adults: A randomized controlled trial.

The prevalence of cigarette smoking in young adults is higher among those with socioeconomic disadvantage than those without. Low treatment-seeking among young adult smokers is compounded by few efficacious smoking cessation interventions for this group, particularly socioeconomically-disadvantaged young adults (SDYA) who smoke cigarettes. The goal of this study was to test a tailored smoking-cessation intervention for SDYA. 343 SDYA aged 18-30 living in the U.S. (85% female) who smoke cigarettes with access to a smartphone and interest in quitting smoking in the next six months were recruited online in Spring 2020 and randomized to referral to online quit resources (usual care control; n = 171) or a 12-week tailored text message smoking-cessation program with a companion web-based intervention (n = 172). Intent to treat analyses examined associations between study condition, self-reported 30-day point prevalence abstinence (PPA), and confidence to quit smoking at 12 weeks, controlling for potential confounders. Intervention group participants had greater self-reported 30-day PPA at 12-weeks than controls (adjusted relative risk 3.93, 95% CI 2.14-7.24). Among those who continued smoking, the intervention increased confidence to quit (0.81 points, 95% confidence interval 0.08-1.53). Weekly engagement in the intervention predicted greater cessation. A tailored text message intervention for SDYA increased smoking abstinence and confidence to quit at the end-of-treatment. Findings may have been influenced by recruitment at the start of the COVID pandemic but suggest that text messaging is an acceptable and efficacious cessation strategy for SDYA smokers. Future studies should examine the impact on longer-term smoking-cessation and importance of intervention tailoring for SDYA.