Contraception and Abortion Attitudes Among Military Medical Students: An Exploratory Study.

OBJECTIVES: To investigate military medical students' attitudes toward contraception and abortion after clerkships. STUDY DESIGN: We adapted a survey of civilian medical student attitudes for military medical students. We asked how clerkships changed perspectives and comfort discussing these topics. RESULTS: Eighty-five (85%) of the one hundred respondents felt more comfortable discussing contraception and abortion after clerkships. More students changed their perspective on contraception than abortion (29% vs. 17%, p=0.043). Students noted limited exposure to abortion care. CONCLUSIONS: Clerkships increased comfort discussing contraception and abortion, but were unlikely to change attitudes towards these topics. More exposure to abortion care is needed.

Emergency contraception for individuals weighing 80 kg or greater: A randomized trial of 30 mg ulipristal acetate and 1.5 mg or 3.0 mg levonorgestrel.

OBJECTIVES: To compare the efficacy of emergency contraception (EC) regimens used within 72 hours of unprotected intercourse in individuals weighing ≥80 kg. STUDY DESIGN: We enrolled reproductive-aged healthy women in a multicenter, single-blind, randomized study of levonorgestrel 1.5 mg (LNG1X) and 3.0 mg (LNG2X) and ulipristal acetate 30 mg (UPA) (enrollment goal 1200). Key eligibility requirements included regular cycles, weight >/= 80kg, unprotected intercourse within 72 hours, no recent use of hormonal contraception, a negative urine pregnancy test (UPT), and willingness to abstain from intercourse until next menses. To assess our primary outcome of incidence of pregnancy, participants completed home UPTs; if no menses by 2-weeks post-treatment, or a positive UPT, they returned for an in-person visit with quantitative serum human chorionic gonadotropin and ultrasound. RESULTS: We enrolled and randomized 532; 44 were not dosed or not evaluable for primary end point, leaving an analyzable sample of 488 (173 LNG1X, 158 LNG2X, 157 UPA) with similar demographics between groups (mean age 29.6 years [5.74], body mass index 37.09 kg/m2 [6.95]). Five pregnancies occurred (LNG1X n = 1, LNG2X n = 1, UPA n = 3); none occurred during the highest at-risk window (day of ovulation and the 3 days prior). We closed the study before achieving our enrollment goal because the low pregnancy rate in all groups established futility based on an interim blinded analysis. CONCLUSIONS: Although slow enrollment limited our study power, we found no differences in pregnancy rates between EC regimens among women weighing 80 kg or more. Our results are not able to refute or support differences between the treatment arms. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clincialtrials.gov Clinical trials#: NCT03537768. IMPLICATIONS: Women weighing 80 kg or more experienced no differences in pregnancy rates between oral EC regimens but due to several significant study limitations including sample size and the lack of a study population at high risk of pregnancy, our results are not able to determine if differences in treatment effectiveness exist.

Use of serum evaluation of contraceptive and ovarian hormones to assess reduced risk of pregnancy among women presenting for emergency contraception in a multicenter clinical trial.

OBJECTIVES: To evaluate ovulation risk among women enrolling in an emergency contraception (EC) study by measuring contraceptive steroids and ovarian hormones. STUDY DESIGN: We used standard chemiluminescent assays to evaluate endogenous hormones (estradiol, progesterone, follicle stimulating hormone, luteinizing hormone) and liquid chromatography-tandem triple quadrupole mass spectrometry to simultaneously analyze concentrations of ethinylestradiol, dienogest, norelgestromin (NGMN), norethindrone (NET), gestodene, levonorgestrel (LNG), etonogestrel (ENG), segesterone acetate, medroxyprogesterone acetate (MPA), and drospirenone in serum samples obtained at the time of enrollment in a recent study comparing oral ulipristal acetate and LNG EC in women with weight ≥80 kg reporting no recent use of hormonal contraception. RESULTS: We enrolled 532 and obtained a valid baseline blood sample from 520 women. Of these, 117 (22.5%) had detectable concentrations of progestin (MPA [n = 58, 11.2%], LNG [50, 9.6%], ENG [11, 2.1%], NET [5, 0.96%], NGMN [3, 0.06%], or drospirenone [1, 0.02%]). LNG was co-detected in all three participants with samples containing NGMN. Multiple progestins were detected in eight other women: ENG/MPA (1), ENG/LNG (2), and MPA/LNG (5). Samples from 55 (10.6%) had concentrations of one or more progestin considered above the minimum level for contraceptive (MPA ≥ 0.1 ng/mL, n = 19; NGMN/LNG ≥ 0.2 ng/mL, n = 31; ENG ≥ 0.09 ng/mL, n = 8; NET ≥ 0.35 ng/mL, n = 4). We detected concentrations of serum progesterone ≥ 3 ng/mL, indicative of luteal phase (postovulation) status, in an additional 194 (37.3%) samples. CONCLUSIONS: More than one-third of enrolled in our clinical trial of oral EC had evidence of prior ovulation at the time of enrollment. Additionally, about 23% had evidence of recent use of hormonal contraception. These results would have decreased the expected risk of pregnancy in the study. IMPLICATIONS: Many participants in a recent clinical trial of oral emergency contraception did not appear to be at risk for pregnancy or would not have benefited from intervention due to cycle timing. Investigators should consider the effects of these findings on expected pregnancy rates when determining sample size in future EC clinical trials, particularly when using noninferiority designs or historical controls.

Menstrual cup use and intrauterine device expulsion in a copper intrauterine device randomized trial.

OBJECTIVE: To evaluate menstrual cup use and intrauterine device (IUD) expulsion. STUDY DESIGN: We performed a secondary analysis of a 3-year contraceptive efficacy trial comparing two copper 380 mm2 IUDs. Investigators randomized participants approximately 1:4 to the TCu380A or NTCu380-Mini IUD. Approximately 12 months after enrollment began, we advised participants against menstrual cup use due to observed IUD expulsions in cup users. We evaluated IUD expulsion (including spontaneous partial and complete expulsion and accidental self-removal) at 12 and 36 months. We used multivariable logistic regression to evaluate IUD expulsion by age, baseline menstrual volume, body mass index, IUD type, menstrual cup use, parity, and uterine length. RESULTS: This analysis included 1046 participants (203 TCu380A and 843 NTCu380-Mini), with 879 (84.0%) nulliparas. Through 12 and 36 months, expulsion occurred in 74 (7.1%, 95% CI 5.5-8.6%) and 133 (12.7%, 95% CI 10.7-14.7%) participants, respectively. Overall, 250 (23.9%) reported menstrual cup use. More menstrual cup users than non-users experienced expulsion through 12 months (32/203 [15.8%] vs. 42/843 [5.0%]) and 36 months (58/250 [23.2%] vs. 75/796 [9.4%]). Through 36 months, NTCu380-Mini menstrual cup users had higher expulsion odds, while TCu380A cup users did not. Menstrual cup users more frequently experienced accidental self-removal than non-users in participants using the TCu380A (3/53 [5.7%] vs. 0/150 [0.0%]) and the NTCu380-Mini (20/197 [10.2%] vs. 7/646 [1.1%]). In multivariable regression, we found increased odds of expulsion through 36 months in participants using menstrual cups with the NTCu380-Mini (aOR 3.13, 95% CI 1.16-8.46) and <25 years (aOR 1.59, 95% CI 1.07-2.34). CONCLUSIONS: We found higher odds of IUD expulsion with menstrual cup and concurrent NTCu380-Mini IUD use over 36 months of use, but not with concurrent TCu380A IUD use. Menstrual cup users experienced higher likelihood of accidental self-removal regardless of IUD type. IMPLICATIONS: Menstrual cup and NTCu380-Mini use may increase IUD expulsion risk and may increase accidental self-removal risk with TCu380A and NTCu380-Mini use. Clinicians should advise patients of these risks and consider warning patients using an IUD shaped like the NTCu380-Mini (Nova-T frames) of expulsion risk with menstrual cup use.

Sister chromatid cohesion is mediated by individual cohesin complexes.

Eukaryotic genomes are organized by loop extrusion and sister chromatid cohesion, both mediated by the multimeric cohesin protein complex. Understanding how cohesin holds sister DNAs together, and how loss of cohesion causes age-related infertility in females, requires knowledge as to cohesin's stoichiometry in vivo. Using quantitative super-resolution imaging, we identified two discrete populations of chromatin-bound cohesin in postreplicative human cells. Whereas most complexes appear dimeric, cohesin that localized to sites of sister chromatid cohesion and associated with sororin was exclusively monomeric. The monomeric stoichiometry of sororin:cohesin complexes demonstrates that sister chromatid cohesion is conferred by individual cohesin rings, a key prediction of the proposal that cohesion arises from the co-entrapment of sister DNAs.

Female-Specific Health Care of Military Female-Designated Service Members and Veterans: A Systematic Overview of Reviews.

INTRODUCTION: Since the War in Afghanistan began in 2001, service members have faced significant health effects related to service during war, with female-designated service members facing unique challenges. Numerous high-quality review articles have been published on the health and care of female-designated service members and veterans. Given the increasing volume of literature, we completed an overview of reviews on the health and health care of female-designated military populations. Our objective was to conduct an overview of reviews on the obstetrics and gynecologic health and health care of female-designated military populations since 2000 to understand female-specific health consequences of military service during war and make clinical recommendations. MATERIALS AND METHODS: On May 10, 2022, a medical librarian performed a comprehensive search across five databases (Ovid Medline, Embase, CINAHL, PsycINFO, Ovid All EBM Reviews, and Web of Science) for all relevant reviews published from 2000 to May 10, 2022. Results were limited to English language. After the removal of duplicates, 2,438 records were reviewed, and 69 studies were included in the final review. The search strategy and methods were registered with PROSPERO and are reported according to the Preferred Reporting Items for Overviews of Reviews (PRIOR) guidelines. Two independent reviewers conducted title and abstract screening and subsequent full text review using Covidence Systematic Review Software. Reviews addressing female-specific and obstetrics and gynecologic health of female-designated service members or veterans, utilizing a clear and systematic methodology, were eligible for inclusion. Quality assessment was conducted by teams of two reviewers. RESULTS: A total of 69 studies were included in the final review. Themes included mental health and impact of sexual assault on service members or veterans, veteran health care, issues of menstruation, pregnancy, and urogenital concerns. Areas with few reviews included occupational risks of military service and impact on obstetric outcomes, eating disorders, and menopause. There were insufficient or no reviews on the impact of military service on fertility, access to abortion care, reproductive health outcomes of lesbian, bisexual and transgender service members, surgical treatment of gynecologic conditions, and screening and treatment for breast, gynecologic, and non-pelvic organ cancers. CONCLUSIONS: Female-designated military populations serving during periods of war face unique health challenges that should be considered in screening practices and the delivery of trauma informed care. Further research and reviews are needed for female-specific oncology, fertility, abortion access, and sexual and non-binary and expansive gender identities to better capture female-designated service member and veteran health during wartime and beyond.

Reducing risk for chronic disease: evaluation of a collective community approach to sustainable evidence-based health programming.

BACKGROUND: Community initiatives can shape health behaviors, such as physical activity and dietary habits, across a population and help reduce the risk of developing chronic disease. To achieve this goal and impact health outcomes, Pasadena Vibrant Community aimed to engage communities in an ongoing dialogue about the importance of healthy behaviors, implement and advance community-based strategies to promote health, and improve diet and physical activity behaviors. The initiative was centered around a collaboration between a backbone organization, steering committee, and 7 collaborating organizations funded to implement multicomponent, evidence-based programs.. The common agenda was detailed in a community action plan, which included 19 interventions targeting healthy eating and active living among adults and youth in Pasadena, Texas. METHODS: A mixed methods evaluation of the initiative was conducted over 4 years. Data sources included document reviews of quarterly progress reports (n = 86) and supplemental data reports (n = 16) provided by collaborating organizations, annual Steering Committee surveys (n = 4), and interviews conducted with staff from a subset of Collaborating Organizations (n = 4). RESULTS: The initiative reached over 50,000 community members per year through 19 evidence-based interventions and impacted health outcomes, including knowledge and adoption of healthy eating practices and increased physical activity. Thirty-one systems-level changes were implemented during the initiative, including 16 environmental changes. Steering Committee meetings and shared goals enabled connections, communication, and cooperation, which allowed Collaborating Organizations to address challenges and combine resources to deliver their programs. CONCLUSIONS: Community initiatives can effectively permeate the community by reaching individuals, improving physical activity and dietary habits, and ensuring sustainability. Based on the experience reported here, the success of a community initiative can be facilitated if collaborating organizations come together to implement evidence-based interventions and tailor them to the community, and if they are empowered by significant leadership and supportive collaboration and aligned by a common agenda.

Novel progestogenic androgens for male contraception: design, synthesis, and activity of C7 α-substituted testosterone†.

Male contraceptive development has included use of testosterone (T) with or without a progestin or the use of a single molecule such as progestogenic androgens (PA) for suppression of testicular T production. Expanding upon the vast amount of data accumulated from nortestosterone (NT), NT analogs, and their prodrugs, a new series of PA, the C7 methyl, and ethyl α-substituted T analogs 7α-Methyltestosterone (7α-MT) and 7α-Ethyltestosterone (7α-ET), respectively, were hypothesized and designed to have superior androgenic and progestogenic activities when compared with parent T. Results from androgen receptor and progesterone receptor competitive binding and transcriptional activation assays showed favorable activities for these T analogs. Additionally, 7α-MT and 7α-ET were shown to be active substrates for aromatase in vitro, mitigating a potential negative impact on bone mineral density with long-term use. In conjunction with this observation, the diminished metabolism of these T analogs by 5α-reductase may reduce potential concerns for prostatic growth. In the Hershberger in vivo rat bioassay, 7α-MT and 7α-ET showed superior androgenic and anabolic activities as compared with T. These C7 α-substituted T analogs also showed clear progestogenic activity in the McPhail bioassay which evaluated endometrial glandular arborization in a rabbit model. The discovery of aromatizable molecules with reduced metabolism by 5α-reductase that have androgenic, anabolic, and progestogenic properties indicates that the core and/or prodrugs of 7α-MT and 7α-ET are promising molecules for further development as male contraceptive PAs.

Impact of Obstetrics and Gynecology Clerkship Order on NBME Exam Scores After a Curriculum Change.

OBJECTIVE: Our Institution instituted curriculum reform in 2013. We sought to examine the impact of rotation order on the end of clerkship National Board of Medical Examiners (NBME) Obstetrics and Gynecology (Ob/Gyn) Subject Exam scores after curriculum restructuring. DESIGN: This is a retrospective analysis of Ob/Gyn NBME scores over 2 years after curriculum reform. At our university, a 15-week block is divided into 5-week intervals of General Surgery, Ob/Gyn, and surgical subspecialties, in any order. During the 16 weeks, students take the NBME Subject Examinations for Ob/Gyn and Surgery. We defined rotation groups by proximity to the shelf exam. Group 1 completed Ob/Gyn first, furthest away from the exam, Group 2 completed Ob/Gyn second, and Group 3 completed Ob/Gyn last, closest to the test. We compared average shelf exam scores between Groups. SETTING: Uniformed Services University of Health Sciences during the clerkship year. PARTICIPANTS: Medical students at the Uniformed Services University. RESULTS: We obtained data from 331 students (118 students in Group 1, 106 in Group 2, and 107 in Group 3). Scores ranged from 55 to 99 (mean 72.5, SD 7.3). Mean (SD) NBME score was 71.9 (6.9) in Group 1, 73.2 (7.2) in Group 2, and 72.6 (7.7) in Group 3 (p = 0.415). CONCLUSION: Rotation order does not affect NBME Ob/Gyn Subject exam scores in a fifteen-week integrated clerkship block.

Participant experiences with a multipurpose vaginal ring for HIV and pregnancy prevention during a phase 1 clinical trial: learning from users to improve acceptability.

Introduction: With high concurrent global rates of HIV incidence and unintended pregnancy, there is a need to provide options beyond condoms to enable users to simultaneously prevent HIV acquisition and pregnancy. Multiple vaginal rings are in development as "MPTs" (multipurpose prevention technologies) as they are shown to provide several co-occurring benefits such as discretion, convenience, reversibility and user control. Methods: In this Phase 1 trial of a 3-month MPT ring in the U.S., 25 participants (low-risk for HIV and pregnancy) were randomized to use the study ring for 90 days continuously or in 28-day cycles with 2-day removal periods in between. All participants completed in-depth interviews at the end of their study participation. Results: Overall, the ring was well tolerated. Participants resoundingly endorsed the concept of an extended-use, dual-purpose vaginal ring, but reported too many functional challenges and side effects to endorse this particular ring. Participants assigned to the continuous regimen reported more positive experiences with ring use than those in the cyclic group. A minority of participants who experienced minimal side effects and did not experience challenges with vaginal retention of the ring found it appealing. However, the majority of participants experienced challenges (ring slippage, expulsions, side effects, vaginal bleeding changes) with product use that outweighed the potential benefits and led them to report that - in the future - they would not be interested in using this specific version of the ring in its current form. A subset expressed interest in using the current MPT ring under certain conditions (e.g., if fewer expulsions, less bleeding, higher risk for HIV/pregnancy). Discussion: User feedback regarding participant experiences and challenges with the study ring was continuously shared with the product developer, underscoring the value of early-stage end-user feedback in product development.

Genotoxic aldehyde stress prematurely ages hematopoietic stem cells in a p53-driven manner.

Aged hematopoietic stem cells (HSCs) display diminished self-renewal and a myeloid differentiation bias. However, the drivers and mechanisms that underpin this fundamental switch are not understood. HSCs produce genotoxic formaldehyde that requires protection by the detoxification enzymes ALDH2 and ADH5 and the Fanconi anemia (FA) DNA repair pathway. We find that the HSCs in young Aldh2-/-Fancd2-/- mice harbor a transcriptomic signature equivalent to aged wild-type HSCs, along with increased epigenetic age, telomere attrition, and myeloid-biased differentiation quantified by single HSC transplantation. In addition, the p53 response is vigorously activated in Aldh2-/-Fancd2-/- HSCs, while p53 deletion rescued this aged HSC phenotype. To further define the origins of the myeloid differentiation bias, we use a GFP genetic reporter to find a striking enrichment of Vwf+ myeloid and megakaryocyte-lineage-biased HSCs. These results indicate that metabolism-derived formaldehyde-DNA damage stimulates the p53 response in HSCs to drive accelerated aging.

Hysterectomy inequities between black and white patients in the US military health system: A retrospective cohort study.

OBJECTIVE: To evaluate multicomponent aspects of hysterectomy-related care in the US Military Health System including the probability of open hysterectomy (versus vaginal or laparoscopic hysterectomy), probability of having a length of stay > 1 day, and discharge milligram morphine equivalent dose (MED). Analyses sought to identify the presence and strength of healthcare inequities between Black and white patients. METHODS: In this retrospective cohort study, records of patients (N = 11,067) ages 18-65 years enrolled in TRICARE who underwent a hysterectomy between January 2017 to January 2021 in US military treatment facilities (direct care) or civilian facilities (purchased care) were included. Graphic representations illustrated provider and facility variation. Generalized additive mixed models (GAMMs) evaluated inequities across outcomes. Sensitivity analyses included only direct care receipt and added a random effect for the facility. RESULTS: There was significant variation in provider use of open versus vaginal or laparoscopic hysterectomies, as well as provider and facility discharge MED. The GAMMs indicated Black patients were more likely to receive an open hysterectomy [log(OR) -0.54, (95 %CI -0.65, -0.43), p < 0.001] and have a length of stay > 1 day [log(OR) 0.18, (95 %CI 0.07, 0.30), p = 0.002], but had similar discharge MED [-2 mg (95% CI -7 mg, 3 mg), p = 0.51], relative to white patients. Patients receiving care in purchased care, relative to direct care, were more likely to receive a vaginal or laparoscopic hysterectomy [log(OR) 0.28, (95 %CI 0.17, 0.38), p = 0.002] and received approximately 21 mg lower discharge MED (95 %CI 16-26 mg less, p < 0.001), but were more likely to have a hospital stay > 1 day [log(OR) 0.95, (95 %CI 0.83, 0.1.10), p < 0.001]. Additional gynecological conditions (e.g., uterine fibroids) and prescription receipt were associated with some, but not all outcomes. CONCLUSION: Improving timely care receipt, especially for uterine fibroids, increasing access to vaginal and laparoscopic hysterectomies, and reducing unwarranted variation in discharge MED could improve care quality and equity in the US Military Health System.

Sleep, Activity, and Nutrition Among an Army Sample: Strengths, Deficits, and Demographic Differences.

Sleep, activity, and nutrition (SAN) are key components in overall health, and an individual's knowledge about and self-confidence to engage in healthy SAN behaviors can have an impact on their actions. This evaluation examined SAN knowledge, self-confidence, and behaviors among U.S. Army Soldiers prior to participating in a health promotion program. Baseline surveys from participating Soldiers provide evidence in this evaluation. U.S. Army Soldiers (N = 11,485) participating in a health promotion program completed surveys. Participants completed an online survey assessing SAN knowledge, self-confidence, and behaviors (among other constructs). We examined the common patterns of SAN behaviors, the associations between them, and the differences based on gender and rank. Knowledge, self-confidence, and behaviors were correlated within each of the three SAN domains. Men reported more aerobic exercise (d = .48) and more resistance training (d = .34) per week than women. Officers reported greater self-confidence in their ability to consume a post-exercise snack (i.e., refuel; d = .38), greater refueling behaviors (d = .43), greater activity knowledge (d = .33), and greater self-confidence in their ability to achieve activity goals (d ranging from .33 to .39), compared to enlisted Soldiers. Finally, greater confidence in one's ability to achieve healthy sleep correlated with getting more sleep, both during workweek (r = .56, p < .001) and weekend (r = .25, p < .001). These baseline data support the need for health promotion of SAN behaviors among these Soldiers.

Attitudes of Clinicians and Patient Safety Culture Before and After the ARRIVE Trial.

OBJECTIVE: To assess the attitudes of intrapartum clinicians about elective induction of labor before and after A Randomized Trial of Induction Versus Expectant Management (ARRIVE) and to assess the effect of different attitudes on patient safety culture. DESIGN: Repeated cross-sectional design. SETTING: Online surveys. PARTICIPANTS: Clinicians (883 nurses and 201 physicians in the before-ARRIVE group and 1,741 nurses and 574 physicians in the after-ARRIVE group) who provided intrapartum care at 35 hospitals in California in 2017 and 57 hospitals in Michigan in 2020 and participated in statewide quality improvement efforts to reduce use of cesarean. METHODS: We used annual nulliparous, term, singleton, vertex cesarean rates to stratify hospitals into performance quartiles. We used cumulative proportional odds logistic regression to examine induction attitudes before and after ARRIVE by role and hospital performance quartile as well as induction attitudes and patient safety culture among clinicians. We used content analysis to examine qualitative data. RESULTS: After ARRIVE, physicians' attitudes shifted in favor of induction at hospitals within the top three performance categories (top quartile: M = 3.48 vs. 2.81, p < .0001), whereas nurses' attitudes did not change (p = .388). After ARRIVE, attitudes among clinicians were more aligned at hospitals with stronger patient safety cultures. Qualitative themes included The Timing of Induction is Important, Who Should Have Inductions, Need for Clear Protocols and More Staff, and Ideas to Improve the Induction of Labor Process. CONCLUSION: Physician attitudes about induction were significantly different before versus after ARRIVE, whereas nurse attitudes were not. Differences in attitudes may erode the quality of team-based care; intentional interdisciplinary engagement is essential when implementing ARRIVE findings.

The Boredom Prone Personality: A Multitrait-Multimethod Approach.

The present investigation reports the convergent and discriminant validity coefficients for two versions of Farmer and Sundberg's (Journal of Personality Assessment, 50(1), 4-17, 1986) boredom proneness scale. Boredom proneness, a trait that refers to an enduring tendency to disengage from the environment, has been neglected by the field of psychology despite its theoretical relevance to performance and psychological well-being. This report sought: (a) to validate a shortened 8-item version of the original Boredom Proneness Scale published by Struk et al. (Assessment, 24(3), 346-359, 2017) and (b) to extensively examine the boredom proneness construct that the long and short versions of this scale assess. We employed a multitrait-multimethod approach that assessed a large number of theorized effects simultaneously. We replicated dozens of theorized and/or previously observed boredom proneness correlates (convergent validity) as well as many theorized null effects (discriminant validity). The overall pattern of significant and null effect sizes provided compelling evidence that the original boredom proneness scale as well as the 8 items that constitute the shorter version are valid measures of one's susceptibility to boredom. We propose that boredom proneness might be an underappreciated yet important theoretical moderator of Person X Situation effects.

Development of an Electronic Screening and Brief Intervention to Address Perinatal Substance Use in Home Visiting: Qualitative User-Centered Approach.

BACKGROUND: Perinatal substance use (SU) is prevalent during pregnancy and the postpartum period and may increase the risks to maternal and child health. Many pregnant and postpartum women do not seek treatment for SU because of fear of child removal. Home visiting (HV), a voluntary supportive program for high-risk families during the perinatal period, is a promising avenue for addressing unmet SU needs. Confidential delivery of screening and brief intervention (BI) for SU via computers has demonstrated high user satisfaction among pregnant and postpartum women as well as efficacy in reducing perinatal SU. This study describes the development of the electronic screening and BI for HV (e-SBI-HV), a digital screening and BI program that is adapted from an existing electronic screening and BI (e-SBI) for perinatal SU and tailored to the HV context. OBJECTIVE: This study aimed to describe the user-centered intervention development process that informed the adaptation of the original e-SBI into the e-SBI-HV, present specific themes extracted from the user-centered design process that directly informed the e-SBI-HV prototype and describe the e-SBI-HV prototype. METHODS: Adaptation of the original e-SBI into the e-SBI-HV followed a user-centered design process that included 2 phases of interviews with home visitors and clients. The first phase focused on adaptation and the second phase focused on refinement. Themes were extracted from the interviews using inductive coding methods and systematically used to inform e-SBI-HV adaptations. Participants included 17 home visitors and 7 clients across 3 Healthy Families America programs in New Jersey. RESULTS: The e-SBI-HV is based on an existing e-SBI for perinatal SU that includes screening participants for SU followed by a brief motivational intervention. On the basis of the themes extracted from the user-centered design process, the original e-SBI was adapted to address population-specific motivating factors, address co-occurring problems, address concerns about confidentiality, acknowledge fear of child protective services, capitalize on the home visitor-client relationship, and provide information about SU treatment while acknowledging that many clients prefer not to access the formal treatment system. The full e-SBI-HV prototype included 2 digital intervention sessions and home visitor facilitation protocols. CONCLUSIONS: This study describes a user-centered approach for adapting an existing e-SBI for SU for use in the HV context. Despite the described challenges, home visitors and clients generally reacted favorably to the e-SBI-HV, noting that it has the potential to fill a significant gap in HV services. If proven effective, the e-SBI-HV could provide a way for clients to receive help with SU within HV, while maintaining their privacy and avoiding the overburdening of home visitors. The next step in this study would be to test the feasibility and preliminary efficacy of the e-SBI-HV.

Continuation rates of two different-sized copper intrauterine devices among nulliparous women: Interim 12-month results of a single-blind, randomised, multicentre trial.

Background: The most widely used copper intrauterine device (IUD) in the world (the TCu380A), and the only product available in many countries, causes side effects and early removals for many users. These problems are exacerbated in nulliparous women, who have smaller uterine cavities compared to parous women. We compared first-year continuation rates and reasons/probabilities for early removal of the TCu380A versus a smaller Belgian copper IUD among nulliparous users. Methods: This 12-month interim report is derived from a pre-planned interim analysis of a sub population and focused on key secondary comparative endpoints. In this participant-blinded trial at 16 centres in the USA, we randomised participants aged 17-40 in a 4:1 ratio to the NT380-Mini or the TCu380A. In the first year, participants had follow-up visits at 6-weeks and 3, 6, and 12-months, and a phone contact at 9 months; we documented continued use, expulsions, and reasons for removal. Among participants with successful IUD placement, we compared probabilities of IUD continuation and specific reasons for discontinuation using log-rank tests. This trial is registered with ClinicalTrials.gov number NCT03124160 and is closed to recruitment. Findings: Between June 1, 2017, and February 25, 2019, we assigned 927 nulliparous women to either the NT380-Mini (n = 744) or the TCu380A (n = 183); the analysis population was 732 (NT380-Mini) and 176 (TCu380A). Participants using the NT380-Mini, compared to the TCu380A, had higher 12-month continuation rates (78·7% [95% CI: 72·9-84·5%] vs. 70·2% [95% CI: 59·7-80·7], p = 0·014), lower rates of removal for bleeding and/or pain (8·1% vs. 16·2%, p = 0·003) and lower IUD expulsion rates (4·8% vs. 8·9%, p = 0·023), respectively. Interpretation: The NT380-Mini offers important benefits for a nulliparous population compared to the TCu380A in the first twelve months, when pivotal experiences typically occur. Higher continuation rates with the NT380-Mini may avert disruptions in contraceptive use and help users avoid unintended pregnancy. Funding: Bill & Melinda Gates Foundation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and Mona Lisa, N.V. (Belgium).

The chromatin remodeller ATRX facilitates diverse nuclear processes, in a stochastic manner, in both heterochromatin and euchromatin.

The chromatin remodeller ATRX interacts with the histone chaperone DAXX to deposit the histone variant H3.3 at sites of nucleosome turnover. ATRX is known to bind repetitive, heterochromatic regions of the genome including telomeres, ribosomal DNA and pericentric repeats, many of which are putative G-quadruplex forming sequences (PQS). At these sites ATRX plays an ancillary role in a wide range of nuclear processes facilitating replication, chromatin modification and transcription. Here, using an improved protocol for chromatin immunoprecipitation, we show that ATRX also binds active regulatory elements in euchromatin. Mutations in ATRX lead to perturbation of gene expression associated with a reduction in chromatin accessibility, histone modification, transcription factor binding and deposition of H3.3 at the sequences to which it normally binds. In erythroid cells where downregulation of α-globin expression is a hallmark of ATR-X syndrome, perturbation of chromatin accessibility and gene expression occurs in only a subset of cells. The stochastic nature of this process suggests that ATRX acts as a general facilitator of cell specific transcriptional and epigenetic programmes, both in heterochromatin and euchromatin.

Male contraception is coming: Who do men want to prescribe their birth control?

OBJECTIVE: To assess men's preferences for healthcare provider from whom they would obtain hormonal male contraceptive (HMC) methods. STUDY DESIGN: We asked participants from 3 clinical trials of investigational HMC methods-an oral pill (11ß-Methyl-19-nortestosterone-17ß-dodecylcarbonate, 11ß-MNTDC), intramuscular or subcutaneous injection (Dimethandrolone undecanoate), and transdermal gel (Nestorone and testosterone)-to rank their top 3 preferred HMC providers from a list including: men's health doctor (urologist/andrologist), hormonal doctor (endocrinologist), reproductive health doctor (OB/GYN), family planning clinician (community health worker, midwife, nurse practitioner), regular doctor (family medicine/internal medicine), and community pharmacist. We examined preferences based on their rankings and conducted bivariate analyses. Collapsing the various specialists (men's health doctor, hormonal doctor, reproductive health doctor, and family planning clinician) into a single provider type, we examined participant demographics against provider preference (regular doctor, pharmacist, or specialist). RESULTS: Participants across the 3 trials (n = 124) ranked their regular doctor (44%) and community pharmacist (18%) as their most preferred HMC provider; these preferences did not differ significantly by trial and drug formulation. Specialists in family planning (13%), men's health (12%), reproductive health (10%), and hormones (4%) were least frequently ranked as their preferred provider. Older and higher educated participants more often preferred specialists over regular doctors and pharmacists (p = 0.02 and p = 0.01). CONCLUSIONS: Despite receiving contraceptive steroid hormones and care from endocrinologists and family planning specialists in a clinical trial, participants would prefer to obtain contraception from their regular doctor. IMPLICATIONS: As most men expect to obtain hormonal male contraceptives from their regular doctor when commercially available, primary care physicians should become familiar with HMCs and be prepared to provide counseling and options accordingly.

RASER-FISH: non-denaturing fluorescence in situ hybridization for preservation of three-dimensional interphase chromatin structure.

DNA fluorescence in situ hybridization (FISH) has been a central technique in advancing our understanding of how chromatin is organized within the nucleus. With the increasing resolution offered by super-resolution microscopy, the optimal maintenance of chromatin structure within the nucleus is essential for accuracy in measurements and interpretation of data. However, standard 3D-FISH requires potentially destructive heat denaturation in the presence of chaotropic agents such as formamide to allow access to the DNA strands for labeled FISH probes. To avoid the need to heat-denature, we developed Resolution After Single-strand Exonuclease Resection (RASER)-FISH, which uses exonuclease digestion to generate single-stranded target DNA for efficient probe binding over a 2 d process. Furthermore, RASER-FISH is easily combined with immunostaining of nuclear proteins or the detection of RNAs. Here, we provide detailed procedures for RASER-FISH in mammalian cultured cells to detect single loci, chromatin tracks and topologically associating domains with conventional and super-resolution 3D structured illumination microscopy. Moreover, we provide a validation and characterization of our method, demonstrating excellent preservation of chromatin structure and nuclear integrity, together with improved hybridization efficiency, compared with classic 3D-FISH protocols.