Natural vs. Surgical Postmenopause and Psychological Symptoms Confound the Effect of Menopause on Executive Functioning Domains of Cognitive Experience.

Objective: The menopause transition is associated with difficulties in executive function. However, it is unclear whether these difficulties persist past perimenopause. This study investigated whether potential confounders, including natural vs. surgical postmenopause and menopause-related psychological symptoms, influence whether executive dysfunction persists into postmenopause. Study Design: A cross-sectional sample of women aged 35-65 years (N = 1971) in one of four groups, premenopause, perimenopause, natural postmenopause, and surgical postmenopause, were surveyed. Participants self-reported executive functioning with the Brown Attention Deficit Disorder Scale (BADDS), anxiety symptom severity with the Generalized Anxiety Disorder Questionnaire (GAD-7), and depression symptom severity with the Center for Epidemiologic Studies Depression Scale (CES-D). Main Outcome Measures: We analyzed the association between group and BADDS scores using linear regression models - first, by controlling for age, education, and self-reported attention deficit hyperactivity disorder (ADHD) diagnosis (Model #1) and, second, by further controlling for current difficulty sleeping, anxiety, and depression (Model #2). Results: In both models, BADDS scores were significantly elevated (indicating more difficulties in executive function) among women in the perimenopausal and surgical postmenopausal groups compared with those in the premenopausal group. Likewise, the perimenopausal and surgical postmenopausal groups had the highest proportions of participants who reported difficulty sleeping and clinical levels of anxiety and depression. BADDS scores were significantly higher in natural postmenopausal vs. premenopausal women without controlling for difficulty sleeping, anxiety, and depression (Model #1), but not when adjusting for these variables (Model #2). Conclusions: The type of menopause and psychological symptoms are important confounders of the relationship between the menopause transition and executive dysfunction, and help explain whether executive dysfunction persists or recovers in postmenopause.Reprinted from Maturitas 2023; 170:64-73, with permission from Elsevier. Copyright © 2023.

Harnessing technology to improve sleep in frontline healthcare workers: A pilot study of electronic noise-masking earbuds on subjective and objective sleep measures.

Objective: This pilot study assessed the effects of electronic noise-masking earbuds on subjective sleep perception and objective sleep parameters among healthcare workers (HCWs) reporting sleep difficulties during the COVID-19 pandemic. Methods: Using a pre-post design, 77 HCWs underwent 3 nights of baseline assessment followed by a 7-night intervention period. Participants wore an at-home sleep monitoring headband to assess objective sleep measures and completed subjective self-report assessments. The difference in mean sleep measures from baseline to intervention was estimated in linear mixed models. Results: Compared to baseline assessments, HCWs reported significant improvements in sleep quality as measured by the Insomnia Severity Index (ISI) (Cohen's d = 1.74, p < 0.001) and a significant reduction in perceived sleep onset latency (SOL) during the intervention (M = 17.2 minutes, SD = 7.7) compared to baseline (M = 24.7 minutes, SD = 16.1), (Cohen's d = -0.42, p = 0.001). There were no significant changes in objective SOL (p = 0.703). However, there was a significant interaction between baseline objective SOL (<20 minutes vs >20 minutes) and condition (baseline vs intervention) (p = 0.002), such that individuals with objective SOL >20 minutes experienced a significant decrease in objective SOL during the intervention period compared to baseline (p = 0.015). Conclusions: HCWs experienced a significant improvement in perceived SOL and ISI scores after using the electronic noise-masking earbuds. Our data provide preliminary evidence for a nonpharmacological intervention to improve the sleep quality of HCWs which should be confirmed by future controlled studies.

Project Safe Guard: Challenges and opportunities of a universal rollout of peer-delivered lethal means safety counseling at a US military installation.

INTRODUCTION: The US Department of Defense recommends lethal means safety counseling (LMSC) to promote firearm injury prevention via secure storage of personal firearms. We describe the rollout of a universal, peer-delivered adaptation of Project Safe Guard (PSG)-a brief, single-session LMSC discussion-at a US Space Force installation. METHOD: Program evaluation data were collected via anonymous, voluntary, and online surveys. Of approximately 862 eligible active-duty service members and embedded civilians, 324 completed the preprogram survey and 68 and 37 completed the 1- and 2-month follow-ups, respectively. RESULTS: At preprogram, 69.1% agreed that peer-delivered LMSC is appropriate. After rollout, 100% of the 222 firearm locking devices available to service members were requested from the on-base Violence Prevention Integrator. The effectiveness of PSG was indeterminable due to the low survey response rates. CONCLUSIONS: Despite strong preprogram support for peer-delivered LMSC and behavioral indicators of secure firearm storage (e.g., firearm locking device requests), several challenges limited the uptake and evaluability of the PSG program in this naturalistic environment, including military survey fatigue and competing mission priorities. Additional work is needed to determine the effectiveness of peer-delivered LMSC in a military context. Sustained base support and military-civilian collaborations will be critical.

Relationship of Decisional Conflict About Driving Habits Between Older Adult Drivers and Their Family Members and Close Friends.

This study examines the relationship of decisional conflict about driving habits between older adult drivers (≥70 years old) and their family members and close friends. This secondary analysis utilizes data originating from a multi-site randomized controlled trial assessing the effect of a driving decision aid (DDA) intervention. Decisional conflict about stopping or changing driving habits for drivers was measured with the Decisional Conflict Scale (DCS). Dyadic associations between drivers' and study partners' (SPs') DCS scores were analyzed using an actor-partner interdependence model. Among 228 driver-SP dyads, Dyadic DCS was correlated at baseline (r = .18, p < .01), and pre-intervention DCS was associated with post-intervention DCS (p < .001 for SPs [ß = .73] and drivers [ß = .73]). Drivers' baseline DCS and SPs' post-intervention DCS were slighly correlated (ß = .10; p = .036). Higher decisional conflict about driving among older drivers is frequently shared by their SPs. Shared decisional conflict may persist beyond intervening to support decision-making about driving cessation.

Depressed, stressed, and inflamed: C-reactive protein linked with depression symptoms in midlife women with both childhood and current life stress.

To determine whether the relationship between inflammatory factors and clinically significant depression symptoms is moderated by high exposure to adverse childhood experiences and current life stressors in a longitudinal community cohort of midlife women. Methods: Participants from the Penn Ovarian Ageing Study community cohort (age at baseline: M = 45.3 [SD = 3.8]) were included in analyses if they had a blood sample measuring basal inflammatory markers during at least one visit where depression symptom severity and current stressful life events were also assessed (N = 142, average number of visits per participant = 1.75 [SD = 0.92]). Approximately annually over the course of 16 years, participants self-reported depression symptom severity using the Centre for Epidemiologic Studies Depression (CESD) Scale, provided menstrual diaries to determine menopause stage, and contributed blood samples. Residual blood samples were assayed for interleukin (IL)-6, IL 1-beta (IL-1ß), tumour necrosis factor alpha (TNF-α), and high sensitivity C-reactive protein (hsCRP). Early life stress was quantified using the Adverse Childhood Experiences questionnaire (low [0-1 experience(s)] versus high [≥ 2 experiences]). Current stressful life events were assessed using a structured interview (low [0-1 events] vs. high [≥ 2 events]). Generalised estimating equation models were used to model associations with the outcome of interest-clinically significant depression symptoms (CESD ≥16)-and risk factors: inflammatory marker levels (log transformed), adverse childhood experiences group, and current life stressors group. Covariates included menopause stage, age at study baseline, body mass index, race, and smoking status. We found a significant three-way interaction between log hsCRP levels, adverse childhood experiences group, and current life stressors group on likelihood of experiencing clinically significant depression symptoms (OR: 4.33; 95% CI: 1.22, 15.46; p = 0.024) after adjusting for covariates. Solely for women with high adverse childhood experiences and with high current life stressors, higher hsCRP was associated with higher odds of having clinically significant depression symptoms (OR: 1.46; 95% CI 1.07, 1.98; p = 0.016). This three-way interaction was not significant for IL-6, IL-1ß, or TNF-α. For women in midlife with exposure to high adverse childhood experiences and multiple current life stressors, elevated levels of CRP were uniquely associated with clinically significant depression symptoms. Early life adversity and current life stressors represent identifiable individual risk factors whose negative impact may be curtailed with inventions to target inflammation in midlife women.

Migraine headaches are associated with motor vehicle crashes and driving habits among older drivers: Prospective cohort study.

BACKGROUND: Migraine headache is common in older adults, often causing symptoms that may affect driving safety. This study examined associations of migraine with motor vehicle crashes (MVCs) and driving habits in older drivers and assessed modification of associations by medication use. METHODS: In a multi-site, prospective cohort study of active drivers aged 65-79 (53% female), we assessed prevalent migraine (i.e., ever had migraine, reported at enrollment), incident migraine (diagnosis first reported at a follow-up visit), and medications typically used for migraine prophylaxis and treatment. During 2-year follow-up, we recorded self-reported MVCs and measured driving habits using in-vehicle GPS devices. Associations of prevalent migraine with driving outcomes were estimated in multivariable mixed models. Using a matched design, associations of incident migraine with MVCs in the subsequent year were estimated with conditional logistic regression. Interactions between migraine and medications were tested in all models. RESULTS: Of 2589 drivers, 324 (12.5%) reported prevalent migraine and 34 (1.3%) incident migraine. Interactions between migraine and medications were not statistically significant in any models. Prevalent migraine was not associated with MVCs in the subsequent 2 years (adjusted OR [aOR] = 0.98; 95% CI: 0.72, 1.35), whereas incident migraine significantly increased the odds of having an MVC within 1 year (aOR = 3.27; 1.21, 8.82). Prevalent migraine was associated with small reductions in driving days and trips per month and increases in hard braking events in adjusted models. CONCLUSION: Our results suggest substantially increased likelihood of MVCs in the year after newly diagnosed migraine, indicating a potential need for driving safety interventions in these patients. We found little evidence for MVC risk or substantial changes in driving habits associated with prevalent migraine. Future research should examine timing, frequency, and severity of migraine diagnosis and symptoms, and use of medications specifically prescribed for migraine, in relation to driving outcomes.

High levels of alpha-gal with large variation in the salivary glands of lone star ticks fed on human blood.

Tick bites, associated with the secretion of tick saliva containing the xenoglycan galactose-alpha-1, 3-galactose (alpha-gal or aGal), are recognized as the causal factors of alpha-Gal syndrome (AGS; or red meat allergy) in humans. AGS occurs after the increased production of IgE antibodies against aGal, which is found in most mammalian cells, except for the Old World monkey and humans. The aGal sensitization event has been linked to an initial tick bite, followed by consumption of red meat containing the aGal glycan, which triggers the onset of the allergic response resulting in urticaria, anaphylaxis, or even death. In North America, the lone star tick, Amblyomma americanum, has been identified as the main culprit for AGS. However, only a subset of the human population exposed to lone star tick bites develops AGS. This suggests the presence of unidentified variables associated with the sensitization event. To evaluate the quantitative variations of the aGal in ticks, we evaluated the differences in aGal levels in different strains of A. americanum ticks partially fed on different blood sources using an artificial feeding system and animal hosts. We found significantly higher aGal levels in the female ticks fed on human blood than those fed on the blood of other mammals with large variations among different tick populations and individuals. We propose that host-specific genetic components in the A. americanum ticks are involved in the production of high aGal epitope in the tick saliva, which provides a part of the explanation for the variables associated with the AGS sensitization event of the tick bite.

Mild Cognitive Impairment is Associated with Poorer Everyday Decision Making.

BACKGROUND: Older adults are faced with many unique and highly consequential decisions such as those related to finances, healthcare, and everyday functioning (e.g., driving cessation). Given the significant impact of these decisions on independence, wellbeing, and safety, an understanding of how cognitive impairment may impact decision making in older age is important. OBJECTIVE: To examine the impact of mild cognitive impairment (MCI) on responses to a modified version of the Short Portable Assessment of Capacity for Everyday Decision making (SPACED). METHODS: Participants were community-dwelling, actively driving older adults (N = 301; M age = 77.1 years, SD = 5.1; 69.4% with a college degree or higher; 51.2% female; 95.3% White) enrolled in the Advancing Understanding of Transportation Options (AUTO) study. A generalized linear model adjusted for age, education, sex, randomization group, cognitive assessment method, and study site was used to examine the relationship between MCI status and decision making. RESULTS: MCI status was associated with poorer decision making; participants with MCI missed an average of 2.17 times more points on the SPACED than those without MCI (adjusted mean ratio: 2.17, 95% CI: 1.02, 4.61, p = 0.044). CONCLUSION: This finding supports the idea that older adults with MCI exhibit poorer decision-making abilities than cognitively normal older adults. It also suggests that older adults with MCI may exhibit poorer decision making across a wide range of decision contexts.

Effects of pulsatile intravenous follicle-stimulating hormone treatment on ovarian function in women with obesity.

OBJECTIVE: To establish conditions for effective hypothalamic suppression in women with normal and high body mass index (BMI) and test the hypothesis that intravenous (IV) administration of pulsatile recombinant follicle-stimulating hormone (rFSH) can overcome the clinically evident dysfunctional pituitary-ovarian axis in women with obesity. DESIGN: Prospective interventional study. SETTING: Academic medical center. PATIENT(S): Twenty-seven normal-weight women and 27 women with obesity, who were eumenorrheic and aged 21-39 years. INTERVENTION(S): Two-day frequent blood sampling study, in early follicular phase, before and after cetrorelix suppression of gonadotropins and exogenous pulsatile IV rFSH administration. MAIN OUTCOME MEASURE(S): Serum inhibin B and estradiol (E2) levels (basal and rFSH stimulated). RESULT(S): A modified gonadotropin-releasing hormone antagonism protocol effectively suppressed production of endogenous gonadotropins in women with normal and high BMIs, providing a model to address the functional role of FSH in the hypothalamic-pituitary-ovarian axis. The IV rFSH treatment resulted in equivalent serum levels and pharmacodynamics in normal-weight women and those with obesity. However, women with obesity exhibited reduced basal levels of inhibin B and E2 and a significantly decreased response to FSH stimulation. The BMI was inversely correlated with serum inhibin B and E2. In spite of this observed deficit in ovarian function, pulsatile IV rFSH treatment in women with obesity resulted in E2 and inhibin B levels comparable with those in normal-weight women, in the absence of exogenous FSH stimulation. CONCLUSION(S): Despite normalization of FSH levels and pulsatility by exogenous IV administration, women with obesity demonstrate ovarian dysfunction with respect to E2 and inhibin B secretion. Pulsatile FSH can partially correct the relative hypogonadotropic hypogonadism of obesity, thereby providing a potential treatment strategy to mitigate some of the adverse effects of high BMI on fertility, assisted reproduction, and pregnancy outcomes. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov #NCT02478775.

Patterns of Change in Parental Health Literacy in Relation to Children's Oral Health.

BACKGROUND: Although health literacy (HL) skills may change over time, most research treats HL as a constant, using baseline HL to predict other health-related constructs. Few studies have explored change in HL over time. OBJECTIVE: We examined person-level differences in HL trajectories. We identified subgroups (latent classes) based on longitudinal assessments of HL and examined the association of class membership with demographic and oral health variables. METHODS: We used four measurement waves of parental HL data, reflecting the risk of limited HL, collected as part of an intervention to reduce dental decay in American Indian children (N = 579 parent-child dyads at baseline). Repeated measures latent class analysis (RMLCA) models were estimated to identify subgroups of HL trajectories over time. We examined class membership in association with baseline demographics and with 36-month assessments of parental oral health knowledge, beliefs, and behaviors as well as pediatric oral health. KEY RESULTS: A four-class model best fit the data. The largest class (high HL; 49.7% of the sample) was characterized by high levels of HL at all waves. A second class (improving HL; 17.7%) improved over all waves. The remaining two classes were characterized as moderate HL (20%) and low HL (12.6%) and maintained relatively stable HL levels over time. Higher educational attainment was associated with membership in the high HL and improving HL classes. Older age among this young-adult sample and higher income also were associated with high HL class membership. Parents in the high HL and improving HL classes exhibited more favorable performance on measures of oral health knowledge, beliefs, and behavioral adherence than did those in the other classes. Class membership was not associated with pediatric oral health. CONCLUSIONS: RMLCA demonstrated person-level variability in HL trajectories. Longitudinal patterns were associated with baseline demographics and prospectively with parental oral health knowledge, beliefs, and behaviors, but not with pediatric oral health. [HLRP: Health Literacy Research and Practice. 2023;7(2):e89-e98.].

Glycosylation increases active site rigidity leading to improved enzyme stability and turnover.

Glycosylation is the most prevalent protein post-translational modification, with a quarter of glycosylated proteins having enzymatic properties. Yet, the full impact of glycosylation on the protein structure-function relationship, especially in enzymes, is still limited. Here, we show that glycosylation rigidifies the important commercial enzyme horseradish peroxidase (HRP), which in turn increases its turnover and stability. Circular dichroism spectroscopy revealed that glycosylation increased holo-HRP's thermal stability and promoted significant helical structure in the absence of haem (apo-HRP). Glycosylation also resulted in a 10-fold increase in enzymatic turnover towards o-phenylenediamine dihydrochloride when compared to its nonglycosylated form. Utilising a naturally occurring site-specific probe of active site flexibility (Trp117) in combination with red-edge excitation shift fluorescence spectroscopy, we found that glycosylation significantly rigidified the enzyme. In silico simulations confirmed that glycosylation largely decreased protein backbone flexibility, especially in regions close to the active site and the substrate access channel. Thus, our data show that glycosylation does not just have a passive effect on HRP stability but can exert long-range effects that mediate the 'native' enzyme's activity and stability through changes in inherent dynamics.

Adherence to behavioral recommendations of cognitive behavioral therapy for insomnia predicts medication use after a structured medication taper.

STUDY OBJECTIVES: Cognitive behavioral therapy for insomnia (CBTI) has been paired with supervised medication tapering to help hypnotic-dependent individuals discontinue their hypnotics. This study examined the hypothesis that higher participant adherence to behavioral recommendations of CBTI will predict lower odds of using sleep medications 3 months after completion of a combined CBTI/sleep medication tapering protocol. METHODS: Fifty-eight individuals who used sedative hypnotics completed four CBTI sessions followed by sleep medication tapering. Logistic regression was used to examine the association of stability of time in bed and stability of rise time (measured as the within-person standard deviation) at completion of CBTI with two outcomes at 3-month follow-up: use of sedative hypnotics and use of any medication/substance for sleep. RESULTS: Participants with more stability in their rise time after CBTI than at baseline (ie, a decrease in their within-person standard deviation) had 69.5% lower odds of using sedative hypnotics at follow-up (odds ratio = 0.305, 95% confidence interval = 0.095-0.979, P = .046) than individuals who had no change or a decrease in the stability of their rise time. Results were similar for time in bed: participants with more stability in their time in bed after CBTI than at baseline had 83.2% lower odds of using sedative hypnotics (odds ratio = 0.168, 95% confidence interval = 0.049-0.580, P = .005). Increase in stability of rise time and stability of time in bed was also associated with reduced odds of using any medication/substance for sleep at follow-up. CONCLUSIONS: Participants who implement behavioral recommendations of CBTI appear to have more success with discontinuing use of sleep medications. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: The Role of Tapering Pace and Selected Traits on Hypnotic Discontinuation; URL: https://clinicaltrials.gov/ct2/show/NCT02831894; Identifier: NCT02831894. CITATION: Edinger JD, Wamboldt FS, Johnson RL, et al. Adherence to behavioral recommendations of cognitive behavioral therapy for insomnia predicts medication use after a structured medication taper. J Clin Sleep Med. 2023;19(8):1495-1503.

Intersectionality and Adverse Childhood Experiences: Comparing Subgroups of Sex, Race/Ethnicity, and Sexual Orientation.

INTRODUCTION: This study investigated the intersectionality of adverse childhood experiences (ACEs) among subgroups of sex, race/ethnicity, and sexual orientation. METHODS: Using data from the Behavioral Risk Factor Surveillance Survey across 34 states (N=116,712) from 2009 to 2018, authors stratified subgroups of sex (male/female), race/ethnicity (White/Hispanic/Black/multiracial/other), and sexual orientation (heterosexual/bisexual/gay) to investigate the number of ACEs across groups. Analyses were conducted in 2022. RESULTS: Stratification resulted in 30 distinct subgroups (e.g., bisexual Black females, straight multiracial males) with significant post hoc differences per group. Generally, those identifying as sexual minority individuals had the highest number of ACEs (the top 14 of 30 subgroups), whereas seven of the top ten subgroups were female. Surprisingly, no clear patterns emerged by race/ethnicity, although the two largest groups (straight White females and straight White males) were 27th and 28th of 30, respectively. CONCLUSIONS: Although studies have examined ACEs by individual demographic variables, less is known about the extent to which ACEs are present in stratified subgroups. Sexual minority subgroups (particularly female bisexual subgroups) trend toward a higher number of ACEs, whereas heterosexual subgroups (regardless of sex) comprised the lowest 6 groups with respect to ACEs. Implications include further examination of bisexual and female subgroups (including specific ACE domain investigations) to identify the vulnerable population.

Assessment of Firearm Storage Practices in the US, 2022.

Importance: Secure firearm storage may help reduce firearm injury and death. Broad implementation requires more granular assessments of firearm storage practices and greater clarity on circumstances that may prevent or promote the use of locking devices. Objective: To develop a more thorough understanding of firearm storage practices, obstacles to using locking devices, and circumstances in which firearm owners would consider locking unsecured firearms. Design, Setting, and Participants: A cross-sectional, nationally representative survey of adults residing in 5 US states who owned firearms was administered online between July 28 and August 8, 2022. Participants were recruited via probability-based sampling. Main Outcomes and Measures: Firearm storage practices were assessed via a matrix provided to participants in which firearm-locking devices were described both via text and images. Locking mechanisms (key/personal identification number [PIN]/dial vs biometric) were specified for each type of device. Obstacles to the use of locking devices and circumstances in which firearm owners would consider locking unsecured firearms were assessed via self-report items developed by the study team. Results: The final weighted sample included 2152 adult (aged ≥18 years), English-speaking firearm owners residing in the US; the sample was predominantly male (66.7%). Among the 2152 firearm owners, 58.3% (95% CI, 55.9%-60.6%) reported storing at least 1 firearm unlocked and hidden, with 17.9% (95% CI, 16.2%-19.8%) reporting storing at least 1 firearm unlocked and unhidden. Gun safes were the most frequently used device both among participants who use keyed/PIN/dial locking mechanisms (32.4%; 95% CI, 30.2%-34.7%) and those who use biometric locking mechanisms (15.6%; 95% CI, 13.9%-17.5%). Those who do not store firearms locked most frequently noted a belief that locks are unnecessary (49.3%; 95% CI, 45.5%-53.1%) and a fear that locks would prevent quick access in an emergency (44.8%; 95% CI, 41.1%-48.7%) as obstacles to lock usage. Preventing access by children was the most often reported circumstance in which firearm owners would consider locking unsecured firearms (48.5%; 95% CI, 45.6%-51.4%). Conclusions and Relevance: In this survey study of 2152 firearm owners, consistent with prior research, unsecure firearm storage was common. Firearm owners appeared to prefer gun safes relative to cable locks and trigger locks, indicating that locking device distribution programs may not match firearm owners' preferences. Broad implementation of secure firearm storage may require addressing disproportionate fears of home intruders and increasing awareness of the risks associated with household firearm access. Furthermore, implementation efforts may hinge on broader awareness of the risks of ready firearm access beyond unauthorized access by children.

Practices, knowledge, and concerns for out-of-home firearm storage among those with access to firearms: results from a survey in two states.

BACKGROUND: Temporary, voluntary storage of firearms away from the home is a recommended option for individuals with risk of suicide, but it may also be used in other situations (e.g., long trips). Prior work has explored the availability of storage options and the views of storage locations. Little is known about out-of-home storage practices among those who live in homes with firearms (including owners). METHODS: We surveyed English-speaking adults (18 or older) in two states (Colorado and Washington) living in a home with a firearm (June-July 2021). RESULTS: Among the final sample of 1029, most respondents were white (88.1%) and non-Hispanic (85.0%); half were female (50.8%), and the most common age group was ages 35-44 (25.5%). Just over one quarter (27.3%) of respondents indicated they had stored a firearm away from their home/car/garage in the last 5 years. The place most respondents said they were somewhat or very likely to consider was at a family members home (62.7%) or at a self-storage facility (52.5%). CONCLUSION: Out-of-home firearm storage is a relatively common practice and endorsed by many gun-owners, suggesting out-of-home storage is feasible for firearm owners as an approach to suicide prevention.

Maternal adverse childhood experiences impact fetal adrenal volume in a sex-specific manner.

BACKGROUND: The mechanisms by which parental early life stress can be transmitted to the next generation, in some cases in a sex-specific manner, are unclear. Maternal preconception stress may increase susceptibility to suboptimal health outcomes via in utero programming of the fetal hypothalamic-pituitary-adrenal (HPA) axis. METHODS: We recruited healthy pregnant women (N = 147), dichotomized into low (0 or 1) and high (2+) adverse childhood experience (ACE) groups based on the ACE Questionnaire, to test the hypothesis that maternal ACE history influences fetal adrenal development in a sex-specific manner. At a mean (standard deviation) of 21.5 (1.4) and 29.5 (1.4) weeks gestation, participants underwent three-dimensional ultrasounds to measure fetal adrenal volume, adjusting for fetal body weight (waFAV). RESULTS: At ultrasound 1, waFAV was smaller in high versus low ACE males (b = - 0.17; z = - 3.75; p < .001), but females did not differ significantly by maternal ACE group (b = 0.09; z = 1.72; p = .086). Compared to low ACE males, waFAV was smaller for low (b = - 0.20; z = - 4.10; p < .001) and high ACE females (b = - 0.11; z = 2.16; p = .031); however, high ACE males did not differ from low (b = 0.03; z = .57; p = .570) or high ACE females (b = - 0.06; z = - 1.29; p = .196). At ultrasound 2, waFAV did not differ significantly between any maternal ACE/offspring sex subgroups (ps ≥ .055). Perceived stress did not differ between maternal ACE groups at baseline, ultrasound 1, or ultrasound 2 (ps ≥ .148). CONCLUSIONS: We observed a significant impact of high maternal ACE history on waFAV, a proxy for fetal adrenal development, but only in males. Our observation that the waFAV in males of mothers with a high ACE history did not differ from the waFAV of females extends preclinical research demonstrating a dysmasculinizing effect of gestational stress on a range of offspring outcomes. Future studies investigating intergenerational transmission of stress should consider the influence of maternal preconception stress on offspring outcomes.

Natural vs. surgical postmenopause and psychological symptoms confound the effect of menopause on executive functioning domains of cognitive experience.

OBJECTIVE: The menopause transition is associated with difficulties in executive function. However, it is unclear whether these difficulties persist past perimenopause. This study investigated whether potential confounders, including natural vs. surgical postmenopause and menopause-related psychological symptoms, influence whether executive dysfunction persists into postmenopause. STUDY DESIGN: A cross-sectional sample of women aged 35-65 years (N = 1971) in one of four groups, premenopause, perimenopause, natural postmenopause, and surgical postmenopause, were surveyed. Participants self-reported executive functioning with the Brown Attention Deficit Disorder Scale (BADDS), anxiety symptom severity with the Generalized Anxiety Disorder Questionnaire (GAD-7), and depression symptom severity with the Center for Epidemiologic Studies Depression Scale (CESD). MAIN OUTCOME MEASURES: We analyzed the association between group and BADDS scores using linear regression models - first, by controlling for age, education, and self-reported attention deficit hyperactivity disorder (ADHD) diagnosis (Model #1) and, second, by further controlling for current difficulty sleeping, anxiety, and depression (Model #2). RESULTS: In both models, BADDS scores were significantly elevated (indicating more difficulties in executive function) among women in the perimenopausal and surgical postmenopausal groups compared with those in the premenopausal group. Likewise, the perimenopausal and surgical postmenopausal groups had the highest proportions of participants who reported difficulty sleeping and clinical levels of anxiety and depression. BADDS scores were significantly higher in natural postmenopausal vs. premenopausal women without controlling for difficulty sleeping, anxiety, and depression (Model #1), but not when adjusting for these variables (Model #2). CONCLUSIONS: The type of menopause and psychological symptoms are important confounders of the relationship between the menopause transition and executive dysfunction, and help explain whether executive dysfunction persists or recovers in postmenopause.

Adverse childhood experiences and hormonal contraception: Interactive impact on sexual reward function.

The current literature suggests that some women are uniquely vulnerable to negative effects of hormonal contraception (HC) on affective processes. However, little data exists as to which factors contribute to such vulnerability. The present study evaluated the impact of prepubertal adverse childhood experiences (ACEs) on reward processing in women taking HC (N = 541) compared to naturally cycling women (N = 488). Participants completed an online survey assessing current and past HC use and exposure to 10 different adverse childhood experiences (ACEs) before puberty (ACE Questionnaire), with participants categorized into groups of low (0-1) versus high (≥2) prepubertal ACE exposure. Participants then completed a reward task rating their expected and experienced valence for images that were either erotic, pleasant (non-erotic), or neutral. Significant interactions emerged between prepubertal ACE exposure and HC use on expected (p = 0.028) and experienced (p = 0.025) valence ratings of erotic images but not pleasant or neutral images. Importantly, follow-up analyses considering whether women experienced HC-induced decreases in sexual desire informed the significant interaction for expected valence ratings of erotic images. For current HC users, prepubertal ACEs interacted with HC-induced decreased sexual desire (p = 0.008), such that high ACE women reporting decreased sexual desire on HC showed substantially decreased ratings for anticipated erotic images compared to both high prepubertal ACE women without decreased sexual desire (p < 0.001) and low prepubertal ACE women also reporting decreased sexual desire (p = 0.010). The interaction was not significant in naturally cycling women reporting previous HC use, suggesting that current HC use could be impacting anticipatory reward processing of sexual stimuli among certain women (e.g., high prepubertal ACE women reporting HC-induced decreases in sexual desire). The study provides rationale for future randomized, controlled trials to account for prepubertal ACE exposure to promote contraceptive selection informed by behavioral evidence.

A Web-Based Decision Aid for Caregivers of Persons With Dementia With Firearm Access (Safe at Home Study): Protocol for a Randomized Controlled Trial.

BACKGROUND: Firearm safety among individuals with Alzheimer disease and related dementias (ADRD) is an underdiscussed and underresearched concern in the United States, especially given the growing population of community-dwelling adults with ADRD. The "Safety in Dementia" (SiD) web-based decision aid was developed to support caregivers in addressing firearm access; the efficacy of SiD is unknown. OBJECTIVE: Through the SiD decision aid, the Safe at Home (S@H) study aims to support caregivers in making decisions about home safety that align with their goals and values, and behaviors regarding firearm access for persons with ADRD and firearm access. METHODS: The S@H study is a 2-armed randomized controlled trial to test the effect of the SiD decision aid on caregivers of community-dwelling adults with ADRD who have firearm access. S@H aims to recruit 500 ADRD caregivers (age ≥18 years, fluent in English or Spanish, and in the United States) through online or social media advertisements and through relevant organizations. Participants are randomized to view SiD or a control website at their own pace; all participants complete web-based questionnaires at baseline, 2 weeks, 2 months, and 6 months. The primary outcome is immediate preparation for decision-making; secondary outcomes include longitudinal decision outcomes and self-reported modifications to firearm access. The relative reach and effectiveness of each recruitment method (online/social media and through relevant organizations) will be assessed by examining differences in caregiver participation, retention rates, and relative cost. RESULTS: The study enrollment began in May 2022. As of December 2022, a total of 117 participants had enrolled. CONCLUSIONS: The S@H study is the first randomized trial of a firearm safety decision aid for ADRD caregivers. The results from this study will inform how best to support caregivers in decision-making regarding firearm safety. Further, results may guide approaches for recruiting caregivers and for dissemination of resources. TRIAL REGISTRATION: ClinicalTrials.gov NCT05173922; https://clinicaltrials.gov/ct2/show/NCT05173922. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/43702.

Enduring impact of childhood adversity: Affective modulation of acoustic startle response during pregnancy and postpartum.

BACKGROUND: Women with a history of adverse childhood experiences (ACEs) enter pregnancy and the postpartum with a physiologic system programmed by early life stress, potentially reflected in psychophysiologic reactivity. METHODS: We enrolled pregnant, psychiatrically healthy women ≥18 years old. Using the ACE Questionnaire, women were categorized as high (≥2 ACEs; n = 77) or low ACE (<2 ACEs; n = 72). Participants completed an affective modulation of acoustic startle response (ASR) task during pregnancy and postpartum, in which ASR magnitude was measured while participants viewed pleasant, unpleasant, and neutral pictures. Two types of control trials were included (habituation trials presented at baseline and intertrial interval trials presented when no picture was present). RESULTS: Among high ACE women, ASR was significantly higher postpartum compared with pregnancy in the unpleasant (p = 0.002, ß = 0.46, 95% CI [0.18, 0.74], χ2 = 10.12, z = 3.18) and intertrial interval trials (p = 0.002, ß = 0.44, 95% CI [0.16, 0.73], χ2 = 9.25, z = 3.04), accounting for multiple comparisons using a Bonferroni correction at p < 0.005. Among low ACE women, ASR was similar in pregnancy and postpartum. CONCLUSIONS: Physiological reactivity increased in high ACE women from pregnancy to postpartum, but no change was observed in low ACE women.