Testing the efficacy of a narrative short film in educating the public about providing emotional support to individuals with fertility problems.

BACKGROUND: To educate the public on how best to support people with fertility problems, a narrative short film "Ten Things Not to Say to Someone Struggling with Infertility" was created, depicting the impact that helpful versus unhelpful dialogue has on someone with fertility problems. METHODS: Before and after watching the video, 419 participants from the public were presented with a hypothetical vignette describing a woman experiencing fertility problems and asked about the likelihood that they would endorse a series of helpful and unhelpful statements when communicating with the protagonist. Pre and post endorsement of helpful versus unhelpful statements were compared, as were self-perceived knowledge about the mental health aspects of fertility problems, confidence in providing emotional support to someone with fertility problems, and empathy for the protagonist. RESULTS: Participants endorsed fewer unhelpful statements after the video relative to before (M(SD) = 2.2(2.3) vs. 1.3(2.3), p < .001) and fewer participants endorsed at least one unhelpful statement (72% to 47%, p < .001). Self-perceived knowledge of fertility problems, confidence in providing support, and empathy increased at post-test (ps < .001; Cohen's d = .56-.83) indicating medium-large effects. CONCLUSIONS: A narrative short film appears to be an effective dissemination strategy for sensitizing the public to the emotional struggles of individuals experiencing fertility problems.

An Integrative Review Exploring Womens' Experiences of Retraumatization Within Perinatal Services.

INTRODUCTION: Evidence indicates that retraumatization has a detrimental effect for those women who are accessing perinatal services. One in five women worldwide has a history of childhood adversity. Between 18% and 34% of women experience trauma, which is a well-known risk factor for the onset of chronic mental health disorders. There is a lack of evidence on women's experiences on retraumatization in perinatal care settings and how to prevent retraumatization from occurring. The purpose of this study was to conduct an integrative review on women experiences of retraumatization to determine preventive measures within perinatal services. METHODS: This integrative review followed Whittemore and Knafl's 5-stage framework as it allows for the inclusion and integration of diverse research methodologies into an overall synthesis of the evidence. A systematic search of 5 databases was conducted (Web of Science, MEDLINE, CINAHL, ASSIA, and PsychINFO) with no date, language, or geographical limits set due to the paucity of research published in this subject area. This review was conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: Fifteen studies met the inclusion criteria and were included in the thematic synthesis. The review identified that participants across the studies had a history of child sexual abuse, sexual abuse, and rape. Three main themes plus subthemes were identified: (1) activating (subthemes: positions in labor, intimate procedures, communications with health care professionals, loss of control); (2) outcomes (subtheme: emotional responses); and (3) interventions reducing or preventing retraumatization (subthemes: role of the health care professional, screening for abuse and history of trauma). DISCUSSION: Our findings demonstrate that women are experiencing retraumatization in perinatal services, and there is evidence of formalized approaches being applied in clinical settings to prevent retraumatization from occurring. This study is the first to examine the factors that contribute to retraumatization in perinatal services and make recommendations to reduce the harmful practices in place in perinatal care settings.

A novel method for quantifying affective sensitivity to endogenous ovarian hormones.

Increased sensitivity to ovarian hormone changes is implicated in the etiology of reproductive mood disorders across the female lifespan, including menstrually-related mood disorders, perinatal mood disorders, and perimenopausal depression. Developing a method to accurately quantify sensitivity to endogenous hormone fluctuations may therefore facilitate the prediction and prevention of these mental health conditions. Here, we propose one such method applying a synchrony analysis to compute time-lagged cross-correlations between repeated assessments of endogenous hormone levels and self-reported affect. We apply this method to a dataset containing frequent repeated assessments of affective symptoms and the urinary metabolites of estradiol (E2) and progesterone (P4) in 94 perimenopausal females. These preliminary findings suggest that, with further refinement and validation, the proposed method holds promise as a diagnostic tool to be used in clinical practice and to advance research investigating the etiology of reproductive mood disorders.

Acceptance and commitment therapy adapted for women with infertility: a pilot study of the Infertility ACTion program.

BACKGROUND: Approximately one in six couples are currently infertile, defined as unable to achieve pregnancy despite 12 or more months of active attempts to conceive. Experiencing infertility has been disproportionately associated with an array of psychological difficulties, particularly in women. However, currently available psychological interventions have had minimal benefits for distress, anxiety, or depression related to infertility. METHODS: A one-arm pilot study was conducted to test the acceptability of a newly created acceptance and commitment therapy-based self-guided program-Infertility ACTion. Twenty women, located in Canada, completed the program and completed measures assessing expectancy of improvement, treatment credibility, participant satisfaction, treatment completion and retention, psychological flexibility, fertility quality of life, depression, and anxiety. Participants were also asked to provide feedback on how the researchers could improve the intervention. Paired sample t-tests were conducted to compare pre- and post-intervention outcomes. RESULTS: Sixteen out of 20 participants completed the entire intervention. Reported treatment expectancy, credibility and satisfaction were favorable. Eighty-one percent of participants reported that they would recommend the program to a friend and 88% thought the program was worth their time. Medium increases in psychological flexibility and fertility quality of life were observed. Improvements in anxious and depressive symptoms were in the small to medium range but were not significant. Participants had several recommendations for program improvement. CONCLUSIONS: This acceptance and commitment therapy-based self-guided program proved to be an acceptable treatment for infertility-related distress. Participant feedback will be used to adjust the current intervention in preparation for a more rigorous randomized-controlled trial testing this program.

Understanding Adolescents' Experiences With Menstrual Pain to Inform the User-Centered Design of a Mindfulness-Based App: Mixed Methods Investigation Study.

BACKGROUND: Digital interventions are increasingly popular for the provision of nonpharmacological pain interventions, but few exist for adolescents with menstrual pain. User-centered design involves incorporating users across phases of digital health intervention design, development, and implementation and leads to improved user engagement and outcomes. A needs assessment is the first step of this approach. OBJECTIVE: The goal of this study was to conduct a needs assessment to understand menstrual pain management needs and preferences and mindfulness experiences, preferences, and knowledge of adolescents with menstrual pain to inform the future development of an app for managing menstrual pain. METHODS: We used an explanatory sequential mixed method design that included a survey followed by focus groups. Adolescents aged 13-17 years completed a survey (n=111) and participated in focus groups (n=16). Data were analyzed using descriptive statistics and thematic content analysis and synthesized to provide specific recommendations based on adolescent responses. RESULTS: Adolescents (n=111) who completed the survey reported a moderate understanding of mindfulness and menstrual pain. Over three-quarters (n=87, 78%) of participants practiced some form of mindfulness and 87% (n=97) of survey participants used nonpharmacological pain management strategies. Teens had a moderate perception that mindfulness could help their menstrual pain (mean 4.51/10, SD 2.45, with higher scores suggesting more interest). Themes were generated related to mindfulness experiences, menstrual pain knowledge and experiences, and app functionality. These themes underscored adolescents' need for continued support and flexible access to mindfulness activities; their awareness of multiple influences to pain, with potential for further education in this area; and the need for menstrual pain-specific content, along with content relevant to typical day-to-day experiences of adolescents. CONCLUSIONS: Adolescents with menstrual pain have an interest in using a mindfulness app for pain but have unique needs that need to be addressed to ensure app engagement and relevance for this population. Concrete recommendations for future app development are provided.

Promoting good mental health over the menopause transition.

The potential risk for mental health conditions over the menopause transition shapes women's expectations and informs putative physiological mechanisms regulating women's mental health. We review evidence from prospective studies reporting on associations between mental health conditions and the menopause transition. Major depressive disorder and the more prevalent subthreshold depressive symptoms are the most common conditions studied. We reviewed 12 prospective studies reporting depressive symptoms, major depressive disorder, or both over the menopause transition and found no compelling evidence for a universal increased risk for either condition. However, specific subgroups of participants, primarily defined by menopause-related risk factors (ie, vasomotor symptoms that are severe or disturb sleep, a long duration of the transition, or reproductive hormone dynamics) and psychosocial risk factors (eg, stressful life events), were vulnerable to depressive symptoms. The increased risk of major depressive disorder over the menopause transition appears predominantly in individuals with previous major depressive disorder. Greater focus on recognising risk factors in primary care is warranted. On the basis of scarce data, we found no compelling evidence that risk of anxiety, bipolar disorder, or psychosis is universally elevated over the menopause transition. Potential misattribution of psychological distress and psychiatric disorders to menopause could harm women by delaying accurate diagnosis and the initiation of effective psychotropic treatments, and by creating negative expectations for people approaching menopause. A paradigm shift is needed. We conclude with recommendations for the detection and treatment of depressive symptoms or major depressive disorder and strategies to promote good mental health over the menopause transition, while responsibly preparing and supporting those at risk.

Testing an Evidence-Based Self-Help Program for Infertility-Related Distress: Protocol for a Randomized Controlled Trial.

BACKGROUND: Infertility-the inability to achieve pregnancy despite ≥12 months of focused attempts to conceive-is experienced by 1 in 6 couples. Women typically carry a disproportionate share of the psychological burden associated with infertility, experiencing poor quality of life, and 30%-40% experiencing depressive mood or anxiety. Unfortunately, currently available psychological interventions targeting infertility-related distress are associated with modest effects. OBJECTIVE: Our team, in collaboration with patient advisors, has designed a self-help intervention for infertility-related distress involving 7 weekly 10-minute videos addressing the cognitive, behavioral, and interpersonal challenges associated with infertility, delivered through a mobile app. A feasibility study suggests that it is well accepted and highly effective in reducing symptoms of anxiety and depressed mood among distressed individuals dealing with infertility. This study represents the next step in this line of research: a fully powered randomized controlled trial comparing the intervention to a waitlist control group. METHODS: We will recruit 170 individuals struggling to become pregnant in Canada or the United States to be randomized to our 7-week self-help program or a treatment-as-usual condition. The primary outcome will be fertility quality of life, while secondary outcomes will include depressive symptoms, anxious symptoms, and relationship quality, assessed before and after the program as well as biweekly for 16 weeks following completion of the program. Self-reported health care use and the presence of diagnosed mood and anxiety disorders, assessed through a structured psychiatric interview, will also be assessed immediately following the intervention and at the 16-week follow-up assessment. Treatment adherence and retention will also be recorded throughout the intervention. Multilevel modeling will compare the intervention arm to the treatment-as-usual condition in terms of all continuous outcomes across the 9 measurement points. Logistic regression will be used to assess the occurrence of mood and anxiety disorders in the 2 treatment arms at the posttreatment assessment as well as at the 16-week follow-up. Sensitivity analyses will examine potential treatment moderators: membership in the LGBTQIA+ (lesbian, gay, bisexual, transgender, queer, intersex, and asexual) communities, baseline fertility quality of life, cultural background, disability status, and pursuit of conception through medical intervention. RESULTS: We expect our intervention to be more effective than treatment-as-usual in improving all mental health parameters assessed and decreasing health care use related to both mental and reproductive health. Effects are expected to be larger with decreasing baseline quality of life and equally effective regardless of membership in the LGBTQIA+ communities, cultural background, or disability status. CONCLUSIONS: If our intervention is successful, this would suggest that it should be scaled up and made publicly available. The availability of this program would fill an important gap in light of the high rates of psychopathology among those experiencing infertility and considering the current lack of effective psychotherapy approaches for infertility. TRIAL REGISTRATION: Clinicaltrials.gov NCT06006936; https://classic.clinicaltrials.gov/ct2/show/NCT06006936. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/52662.

Gynecologic cancer care in the first year of the COVID-19 pandemic.

OBJECTIVE: To analyze the impact of the early COVID-19 pandemic on the diagnosis and initiation of treatment for patients with gynecologic cancer. METHODS: Patients diagnosed with gynecologic cancer in the National Cancer Database during 2017-2020 were included. For the first aim, incidence rate ratios were calculated to compare gynecologic cancer diagnosis in the first year of the COVID-19 pandemic to the three years prior, and factors associated with a reduction in diagnosis were identified. For the second aim, patients who experienced an 8-week delay in cancer treatment were compared to those who did not. Multivariate logistic regression was used to identify factors associated with treatment delay. Propensity score analysis was utilized to compare the rate of cancer treatment delay in patients who were diagnosed with COVID-19 to those who were not. RESULTS: The incidence rate ratio of being diagnosed with gynecologic cancer in 2020 versus 2017-2019 was 0.90 (95%CI 0.90-0.91). Factors associated with increased risk of missed or delayed diagnosis in 2020 included cervical cancer, earlier cancer stage, younger age, lower levels of medical comorbidity, and lack of health insurance. In 2020, factors associated with treatment delay included COVID-19 diagnosis (aOR 1.50, 95%CI 1.35-1.67), in addition to race and ethnicity, insurance type, comorbidity, cancer stage, and primary site. The risk of treatment delay remained significantly elevated in patients diagnosed with COVID-19 after propensity-score matching. CONCLUSIONS: Gynecologic cancer diagnosis and timely provision of care were negatively impacted during the first year of the COVID-19 pandemic, with certain subgroups at elevated risk.

Preclinical safety and biodistribution of CRISPR targeting SIV in non-human primates.

In this study, we demonstrate the safety and utility of CRISPR-Cas9 gene editing technology for in vivo editing of proviral DNA in ART-treated, virally controlled simian immunodeficiency virus (SIV) infected rhesus macaques, an established model for HIV infection. EBT-001 is an AAV9-based vector delivering SaCas9 and dual guide RNAs designed to target multiple regions of the SIV genome: the viral LTRs, and the Gag gene. The results presented here demonstrate that a single IV inoculation of EBT-001 at each of 3 dose levels (1.4 × 1012, 1.4 × 1013 and 1.4 × 1014 genome copies/kg) resulted in broad and functional biodistribution of AAV9-EBT-001 to known tissue reservoirs of SIV. No off-target effects or abnormal pathology were observed, and animals returned to their normal body weight after receiving EBT-001. Importantly, the macaques that received the 2 highest doses of EBT-001 showed improved absolute lymphocyte counts as compared to antiretroviral-treated controls. Taken together, these results demonstrate safety, biodistribution, and in vivo proviral DNA editing following IV administration of EBT-001, supporting the further development of CRISPR-based gene editing as a potential therapeutic approach for HIV in humans.

Within-person changes in reproductive hormones and cognition in the menopause transition.

OBJECTIVES: Most women complain of cognitive deficits in the menopause transition, though the cause is unclear. The current study investigated the role that within-person changes in reproductive hormones, particularly estradiol, may play in triggering such perimenopausal cognitive difficulties. STUDY DESIGN: Participants were 43 women aged 45-55 years and currently in the menopause transition. Once a week for 12 weeks, participants provided a urine sample for the measurement of estrone glucuronide (E1G), a urinary metabolite of estradiol. Every three weeks across the 12-week period, participants also underwent cognitive testing, including assessments of immediate and delayed memory, attention, and executive function, and completed questionnaires assessing subjective cognitive performance. Potential confounding variables including sleep quality, vasomotor symptoms, and depressive symptoms were also assessed. RESULTS: Within-person E1G was positively associated with objective measures of attention, particularly the ability to passively register auditory information on the first pass, as well as subjective measures of memory, specifically relating to a lower frequency of forgetting things in everyday life. Perimenopausal women with lower estimated levels of intellectual functioning furthermore exhibited a stronger relationship between E1G changes and objective cognitive performance. While depressive mood, poor sleep, and vasomotor symptoms were all negatively associated with at least one aspect of cognitive function, the E1G-cognition relationship was not explained by these factors. CONCLUSIONS: This study provides evidence that validates perimenopausal women's cognitive complaints but also suggests that cognitive deficits are generally mild and transient.

The effect of physical activity on fertility: a mini-review.

Although lifestyle factors such as diet, cigarette smoking, and alcohol consumption are increasingly recognized as important contributors to the risk of subfertility, the role of exercise in fertility remains less clear. As such, it is challenging for healthcare providers to deliver clear, evidence-based recommendations to patients regarding the optimal frequency and intensity with which they should exercise to maximize their chances of conception. Therefore, this review provides a critical overview of the available research for various patient populations.

Menstrual cycle influences on cue-induced smoking cravings and heart rate variability.

Women experience greater difficulties in quitting smoking than men, though the hormonal factors contributing to this sex difference remain to be clarified. The current study aimed to examine menstrual cycle effects on smoking cue-induced cravings as well as examine dynamic reproductive hormone change as a potential mediator underlying any cycle effects observed. Twenty-one women who smoke underwent two laboratory sessions - one in the mid-follicular phase and the other in the late luteal phase - involving an in-vivo smoking cue task, administered before and after exposure to a psychosocial laboratory stressor. Heart rate variability (HRV) and subjective smoking cravings were assessed in response to the cue task. The degree of change in the urinary metabolites of estradiol and progesterone from 2 days before to the day of each laboratory session was measured. Results revealed that both before and following exposure to psychosocial stress, highly nicotine-dependent women exhibited smaller cue-induced increases in HRV relative to the follicular phase. In contrast, less nicotine-dependent women exhibit an increase in HRV in both menstrual cycle phases. Results furthermore suggest that menstrual cycle effects seen in highly nicotine-dependent women are driven by the decline in estradiol and progesterone occurring in the late luteal phase. Though limited by a small sample size, this study suggests that withdrawal from reproductive hormones in the late luteal phase may alter highly nicotine-dependent women's physiological response to smoking cues, which may reflect greater difficulty resisting temptation. These findings may provide some insight regarding women's greater difficulty in maintaining abstinence after quitting smoking.

Strategic self-limiting production of infectious HIV particles by CRISPR in permissive cells.

Post-translational glycosylation of the HIV-1 envelope protein involving precursor glycan trimming by mannosyl oligosaccharide glucosidase (MOGS) is critically important for morphogenesis of virions and viral entry. Strategic editing of the MOGS gene in T lymphocytes and myeloid origin cells harboring latent proviral DNA results in the production of non-infectious particles upon treatment of cells with latency reversal agents. Controlled activation of CRISPR-MOGS by rebound HIV-1 mitigates production of infectious particles that exhibit poor ability of the virus to penetrate uninfected cells. Moreover, exclusive activation of CRISPR in cells infected with HIV-1 alleviates concern for broad off-target impact of MOGS gene ablation in uninfected cells. Combination CRISPR treatment of peripheral blood lymphocytes prepared from blood of people with HIV-1 (PWH) tailored for editing the MOGS gene (CRISPR-MOGS) and proviral HIV-1 DNA (CRISPR-HIV) revealed a cooperative impact of CRISPR treatment in inhibiting the production of infectious HIV-1 particles. Our design for genetic inactivation of MOGS by CRISPR exhibits no detectable off-target effects on host cells or any deleterious impact on cell survival and proliferation. Our findings offer the development of a new combined gene editing-based cure strategy for the diminution of HIV-1 spread after cessation of antiretroviral therapy (ART) and its elimination.

Engaging Multistakeholder Perspectives to Identify Patient-Centered Research Priorities Regarding Vaccine Uptake Among Adults With Autoimmune Conditions.

OBJECTIVE: The study objective was to prioritize topics for future patient-centered research to increase uptake of common vaccines, such as for pneumococcal pneumonia, influenza, herpes zoster, human papillomavirus, and severe acute respiratory syndrome coronavirus 2, among adults living with autoimmune conditions. METHODS: A steering committee (SC) was formed that included clinicians, patients, patient advocates, and researchers associated with rheumatic diseases (psoriatic arthritis, rheumatoid arthritis, vasculitis), inflammatory bowel disease, and multiple sclerosis. Through a scoping review and discussions, SC members identified research topics regarding vaccine uptake and/or hesitancy for prioritization. A larger multistakeholder alliance that included patients and patient advocates, clinicians, researchers, policy makers, regulators, and vaccine manufacturers conducted a modified Delphi exercise online with three rating rounds and one ranking round. Frequency analysis and comparisons across stakeholder groups were conducted. A weighted ranking score was generated for each item in the ranking round for final prioritization. RESULTS: Through the Delphi process, 33 research topics were identified, of which 13 topics were rated as critical by more than 70% of all stakeholders (n = 31). The two highest ranked critical topics per the full stakeholder group were "How well a vaccine works for adults with autoimmune conditions" and "How beliefs about vaccine safety affect vaccine uptake." CONCLUSION: A multistakeholder group identified key topics as critically important priorities for future research to decrease vaccine hesitancy and improve uptake of vaccines for adults with autoimmune conditions.

Androgen receptor expression in low grade serous ovarian cancer; clinical considerations in the diagnosis, treatment and surveillance of disease in a transgender male.

•Low grade serous (LGS) ovarian cancer is an uncommon cancer.•Androgen receptor expression testing is not routinely performed in patients with LGS ovarian cancer.•Systemic androgen levels may be elevated in patients with PCOS or those taking exogenous testosterone.•Consideration should be made to include androgen receptor testing for these patients.

O2 partitioning of sulfur oxidizing bacteria drives acidity and thiosulfate distributions in mining waters.

The acidification of water in mining areas is a global environmental issue primarily catalyzed by sulfur-oxidizing bacteria (SOB). Little is known about microbial sulfur cycling in circumneutral pH mine tailing impoundment waters. Here we investigate biological sulfur oxidation over four years in a mine tailings impoundment water cap, integrating aqueous sulfur geochemistry, genome-resolved metagenomics and metatranscriptomics. The microbial community is consistently dominated by neutrophilic, chemolithoautotrophic SOB (relative abundances of ~76% in 2015, ~55% in 2016/2017 and ~60% in 2018). Results reveal two SOB strategies alternately dominate across the four years, influencing acid generation and sulfur speciation. Under oxic conditions, novel Halothiobacillus drive lower pH conditions (as low as 4.3) and lower [S2O32-] via the complete Sox pathway coupled to O2. Under anoxic conditions, Thiobacillus spp. dominate in activity, via the incomplete Sox and rDSR pathways coupled to NO3-, resulting in higher [S2O32-] and no net significant acidity generation. This study provides genomic evidence explaining acidity generation and thiosulfate accumulation patterns in a circumneutral mine tailing impoundment and has significant environmental applications in preventing the discharge of sulfur compounds that can impact downstream environments. These insights illuminate opportunities for in situ biotreatment of reduced sulfur compounds and prediction of acidification events using gene-based monitoring and in situ RNA detection.

A research and development (R&D) roadmap for broadly protective coronavirus vaccines: A pandemic preparedness strategy.

Broadly protective coronavirus vaccines are an important tool for protecting against future SARS-CoV-2 variants and could play a critical role in mitigating the impact of future outbreaks or pandemics caused by novel coronaviruses. The Coronavirus Vaccines Research and Development (R&D) Roadmap (CVR) is aimed at promoting the development of such vaccines. The CVR, funded by the Bill & Melinda Gates Foundation and The Rockefeller Foundation, was generated through a collaborative and iterative process, which was led by the Center for Infectious Disease Research and Policy (CIDRAP) at the University of Minnesota and involved 50 international subject matter experts and recognized leaders in the field. This report summarizes the major issues and areas of research outlined in the CVR and identifies high-priority milestones. The CVR covers a 6-year timeframe and is organized into five topic areas: virology, immunology, vaccinology, animal and human infection models, and policy and finance. Included in each topic area are key barriers, gaps, strategic goals, milestones, and additional R&D priorities. The roadmap includes 20 goals and 86 R&D milestones, 26 of which are ranked as high priority. By identifying key issues, and milestones for addressing them, the CVR provides a framework to guide funding and research campaigns that promote the development of broadly protective coronavirus vaccines.