Mutational impact of APOBEC3A and APOBEC3B in a human cell line and comparisons to breast cancer.

A prominent source of mutation in cancer is single-stranded DNA cytosine deamination by cellular APOBEC3 enzymes, which results in signature C-to-T and C-to-G mutations in TCA and TCT motifs. Although multiple enzymes have been implicated, reports conflict and it is unclear which protein(s) are responsible. Here we report the development of a selectable system to quantify genome mutation and demonstrate its utility by comparing the mutagenic activities of three leading candidates-APOBEC3A, APOBEC3B, and APOBEC3H. The human cell line, HAP1, is engineered to express the thymidine kinase (TK) gene of HSV-1, which confers sensitivity to ganciclovir. Expression of APOBEC3A and APOBEC3B, but not catalytic mutant controls or APOBEC3H, triggers increased frequencies of TK mutation and similar TC-biased cytosine mutation profiles in the selectable TK reporter gene. Whole genome sequences from independent clones enabled an analysis of thousands of single base substitution mutations and extraction of local sequence preferences with APOBEC3A preferring YTCW motifs 70% of the time and APOBEC3B 50% of the time (Y = C/T; W = A/T). Signature comparisons with breast tumor whole genome sequences indicate that most malignancies manifest intermediate percentages of APOBEC3 signature mutations in YTCW motifs, mostly between 50 and 70%, suggesting that both enzymes contribute in a combinatorial manner to the overall mutation landscape. Although the vast majority of APOBEC3A- and APOBEC3B-induced single base substitution mutations occur outside of predicted chromosomal DNA hairpin structures, whole genome sequence analyses and supporting biochemical studies also indicate that both enzymes are capable of deaminating the single-stranded loop regions of DNA hairpins at elevated rates. These studies combine to help resolve a long-standing etiologic debate on the source of APOBEC3 signature mutations in cancer and indicate that future diagnostic and therapeutic efforts should focus on both APOBEC3A and APOBEC3B.

Constructive communication patterns as related to relationship satisfaction, seizure severity, and patient activation among people with epilepsy.

PURPOSE: People with epilepsy (PWE) must manage their condition properly for both quality and longevity of life. Effective self-management is critical and can be monitored via levels of patient activation (i.e., a continuum of taking a passive vs active role in personal healthcare) and the presence/severity of seizures. One known influencer of self-management is the quality of one's intimate relationship, a documented area of major concern for PWE. Here we examined a critical facet of PWEs' intimate relationships-(un)constructive communication with their partner. METHODS: Using data from a web-based survey of 89 PWE, and regression-based mediation analyses, we examined associations with patient activation and seizure severity. We added further explanatory utility by examining relationship satisfaction as a mediator of those links. RESULTS: There were positive links between more constructive communication, more patient activation, and less severe seizures. The explanatory path of constructive communication to better relationship satisfaction to lower seizure severity emerged as a significant partial mediation (i.e., direct effect remained significant), while relationship satisfaction fully mediated (i.e., direct effect became non-significant) the link between constructive communication and greater patient activation. CONCLUSION: Our results provide insight into how relationship processes may impact the experience of epilepsy, including seizure severity and patient activation. Future research is needed.

A systems science approach to identifying data gaps in national data sources on adolescent suicidal ideation and suicide attempt in the United States.

BACKGROUND: Suicide is currently the second leading cause of death among adolescents ages 10-14, and third leading cause of death among adolescents ages 15-19 in the United States (U.S). Although we have numerous U.S. based surveillance systems and survey data sources, the coverage offered by these data with regard to the complexity of youth suicide had yet to be examined. The recent release of a comprehensive systems map for adolescent suicide provides an opportunity to contrast the content of surveillance systems and surveys with the mechanisms listed in the map. OBJECTIVE: To inform existing data collection efforts and advance future research on the risk and protective factors relevant to adolescent suicide. METHODS: We examined data from U.S. based surveillance systems and nationally-representative surveys that included (1) observations for an adolescent population and (2) questions or indicators in the data that identified suicidal ideation or suicide attempt. Using thematic analysis, we evaluated the codebooks and data dictionaries for each source to match questions or indicators to suicide-related risk and protective factors identified through a recently published suicide systems map. We used descriptive analysis to summarize where data were available or missing and categorized data gaps by social-ecological level. RESULTS: Approximately 1-of-5 of the suicide-related risk and protective factors identified in the systems map had no supporting data, in any of the considered data sources. All sources cover less than half the factors, except the Adolescent Brain Cognitive Development Study (ABCD), which covers nearly 70% of factors. CONCLUSIONS: Examining gaps in suicide research can help focus future data collection efforts in suicide prevention. Our analysis precisely identified where data is missing and also revealed that missing data affects some aspects of suicide research (e.g., distal factors at the community and societal level) more than others (e.g., proximal factors about individual characteristics). In sum, our analysis highlights limitations in current suicide-related data availability and provides new opportunities to identify and expand current data collection efforts.

Medical Mistrust and Healthcare Seeking Among Women of Color with Chronic Vulvovaginal Pain.

BACKGROUND: Chronic vulvovaginal pain (CVVP), an umbrella term encompassing several gynecological pain conditions (e.g., vulvodynia, vaginismus), has a prevalence rate of 7-8% in the USA and is characterized by considerable diagnostic delay in patient experience research. Furthermore, current research in this area focuses largely on the experiences of white women, while the experiences of women of color are underrepresented. METHOD: In the present cross-sectional study (N = 488), we surveyed women of color (i.e., Asian, Black, and/or Hispanic/Latinx women) with CVVP about their perceptions and experiences with medical mistrust, healthcare seeking, and healthcare avoidance. RESULTS: Using the suspicion subscale of the Group-Based Medical Mistrust Scale, we found significant racial and ethnic differences in medical suspicion scores, with non-Black Hispanic/Latinx women reporting the highest suspicion scores and non-Hispanic/Latinx Black women reporting the lowest scores. Racial differences disappeared, however, after examining medical mistrust and perceived discrimination as predictors for various healthcare outcomes related to the journey to diagnosis and healthcare avoidance behaviors. We found that while suspicion was a reliable predictor of increased diagnostic delay and healthcare avoidance in many contexts, the results for perceived discrimination were more varied, suggesting considerable nuance in the relationship between medical mistrust, perceived discrimination, and healthcare seeking outcomes. CONCLUSION: These findings point to shared experiences of medical mistrust via suspicion that broadly characterize women of color's experiences in seeking CVVP-related care-future research is needed to examine nuances within racial and ethnic groups regarding their healthcare seeking experiences in the CVVP context.

Can Doctors Be Compelled to Prolong the Life of a Dying Patient? The Ongoing Medical, Legal and Social Issues.

The law does not require health professionals to provide medical treatment that is of no benefit to the patient. Despite this, medical staff who are caring for patients at the end of their lives frequently experience pressure from the patients' families to prolong their lives. This article considers the Australian law relating to the right to demand treatment when a loved one is dying, and whether an increasing emphasis on shared decision-making has introduced uncertainty. It discusses factors that affect the application of the law, including widespread ignorance of the law, the difficulty of deciding whether a treatment is futile and the need to ration scarce health care resources. It also introduces the perspectives of three senior medical practitioners on disputes with families of dying patients. The article concludes that community education is needed on legal and medical issues at the end of life, including conversations about advance care directives.

Beyond tokenism in quality management policy and programming: moving from participation to meaningful involvement of people with HIV in New York State.

BACKGROUND: Consumer involvement in health-care policy and quality management (QM) programming is a key element in making health systems people-centered. Involvement of health-care consumers in these areas, however, remains underdeveloped and under-prioritized. When consumer involvement is actively realized, few mechanisms for assessing its impact have been developed. The New York State Department of Health (NYSDOH) embraces consumer involvement of people with HIV in QM as a guiding principle, informed by early HIV/AIDS advocacy and a framework of people-centered quality care. METHOD: HIV consumer involvement is implemented statewide and informs all quality of care programming as a standard for QM in health-care organizations, implemented through four key several initiatives: (i) a statewide HIV Consumer Quality Advisory Committee; (ii) leadership and QM trainings for consumers; (iii) specific tools and activities to engage consumers in QM activities at state, regional and health-care facility levels and (iv) formal organizational assessments of consumer involvement in health-care facility QM programs. RESULTS: We review the literature on this topic and place the methods used by the NYSDOH within a theoretical framework for consumer involvement. CONCLUSION: We present a model that offers a paradigm for practical implementation of routine consumer involvement in QM programs that can be replicated in other health-care settings, both disease-specific and general, reflecting the priority of active participation of consumers in QM activities at all levels of the health system.

Improving PHQ9 Utilization Rates in a Primary Care-Mental Health Integration Setting.

INTRODUCTION: Measurement-based care (MBC) uses standardized measurement to systematically monitor treatment response over time. Although MBC is underutilized in mental health settings, primary care-mental health integration (PC-MHI) settings are expected to provide MBC. This article describes a quality improvement (QI) process to increase Patient Health Questionnaire-9 (PHQ9) utilization within a PC-MHI setting. AIMS: Pre-intervention, rates of baseline and follow-up PHQ9 administration for veterans with a depressive disorder were 76% and 35%, respectively. This article describes a QI process to increase PHQ9 utilization rates within a PC-MHI setting, with the goal to improve provider PHQ9 utilization rates at baseline and within 4-week follow-up to 90%. METHOD: An educational intervention and weekly motivational enhancement sessions were implemented in 2017. Chart review data compared PHQ9 utilization rates from fall 2016 and 2017. RESULTS: Following intervention, provider PHQ9 utilization rates increased to 98% and 88% at baseline and follow-up. CONCLUSIONS: These findings demonstrate that a brief education-based intervention can increase clinician use of MBC within a PC-MHI setting. Meaningful use of MBC to inform treatment was not evaluated in this QI project and is an area for future investigation.

Genetic and biochemical investigations of the role of MamP in redox control of iron biomineralization in Magnetospirillum magneticum.

Magnetotactic bacteria have evolved complex subcellular machinery to construct linear chains of magnetite nanocrystals that allow the host cell to sense direction. Each mixed-valent iron nanoparticle is mineralized from soluble iron within a membrane-encapsulated vesicle termed the magnetosome, which serves as a specialized compartment that regulates the iron, redox, and pH environment of the growing mineral. To dissect the biological components that control this process, we have carried out a genetic and biochemical study of proteins proposed to function in iron mineralization. In this study, we show that the redox sites of c-type cytochromes of the Magnetospirillum magneticum AMB-1 magnetosome island, MamP and MamT, are essential to their physiological function and that ablation of one or both heme motifs leads to loss of function, suggesting that their ability to carry out redox chemistry in vivo is important. We also develop a method to heterologously express fully heme-loaded MamP from AMB-1 for in vitro biochemical studies, which show that its Fe(III)-Fe(II) redox couple is set at an unusual potential (-89 ± 11 mV) compared with other related cytochromes involved in iron reduction or oxidation. Despite its low reduction potential, it remains competent to oxidize Fe(II) to Fe(III) and mineralize iron to produce mixed-valent iron oxides. Finally, in vitro mineralization experiments suggest that Mms mineral-templating peptides from AMB-1 can modulate the iron redox chemistry of MamP.

The South Australian Advance Care Directives Act 2013: How Has the Decision-Making Paradigm Changed?

This article analyses how the Advance Care Directives Act 2013 SA is changing the decision-making paradigm in health care and guardianship in South Australia. It examines the background to the legislation, the main areas that have been transformed by the Act and the amendments to associated legislation. The significant changes include an increased respect for autonomy and a presumption of decision-making capacity, a new paradigm of substitute decision-making, clarification of the decision-making hierarchy, and protections for medical practitioners who decline to give treatment that would have no benefit to a dying patient. Despite some difficulties implementing the new scheme, this article argues that the Act has introduced important changes and clarifications in the law that other States would do well to follow. When it is fully implemented, the Act will ensure that the wishes of patients are respected and that doctors can follow these wishes without fear of prosecution.

A Case of Psoriasis Replaced by Allergic Contact Dermatitis in a 12-Year-Old Boy.

Allergic contact dermatitis is a significant clinical problem in children and one that the use of essential oils and natural remedies probably exacerbates. We report a case of chronic plaque psoriasis replaced by allergic contact dermatitis in a 12-year-old boy. We suspect that the immunologic response to a hapten in lavender oil disrupted the pathogenesis of psoriasis, causing the psoriasis to temporarily "disappear."

Adult-onset immunodeficiency in Thailand and Taiwan.

BACKGROUND: Autoantibodies against interferon-γ are associated with severe disseminated opportunistic infection, but their importance and prevalence are unknown. METHODS: We enrolled 203 persons from sites in Thailand and Taiwan in five groups: 52 patients with disseminated, rapidly or slowly growing, nontuberculous mycobacterial infection (group 1); 45 patients with another opportunistic infection, with or without nontuberculous mycobacterial infection (group 2); 9 patients with disseminated tuberculosis (group 3); 49 patients with pulmonary tuberculosis (group 4); and 48 healthy controls (group 5). Clinical histories were recorded, and blood specimens were obtained. RESULTS: Patients in groups 1 and 2 had CD4+ T-lymphocyte counts that were similar to those in patients in groups 4 and 5, and they were not infected with the human immunodeficiency virus (HIV). Washed cells obtained from patients in groups 1 and 2 had intact cytokine production and a response to cytokine stimulation. In contrast, plasma obtained from these patients inhibited the activity of interferon-γ in normal cells. High-titer anti-interferon-γ autoantibodies were detected in 81% of patients in group 1, 96% of patients in group 2, 11% of patients in group 3, 2% of patients in group 4, and 2% of controls (group 5). Forty other anticytokine autoantibodies were assayed. One patient with cryptococcal meningitis had autoantibodies only against granulocyte-macrophage colony-stimulating factor. No other anticytokine autoantibodies or genetic defects correlated with infections. There was no familial clustering. CONCLUSIONS: Neutralizing anti-interferon-γ autoantibodies were detected in 88% of Asian adults with multiple opportunistic infections and were associated with an adult-onset immunodeficiency akin to that of advanced HIV infection. (Funded by the National Institute of Allergy and Infectious Diseases and the National Institute of Dental and Craniofacial Research; ClinicalTrials.gov number, NCT00814827.).

Pap smear screening, pap smear abnormalities and psychosocial risk factors among women in a residential alcohol and drug rehabilitation facility.

AIM: To compare rates of late- screening, abnormal Pap smears and prevalence of psychosocial factors for cervical cancer between women in the community and women attending a residential drug and alcohol facility. BACKGROUND: Women with drug and alcohol addiction experience higher rates of abnormal Pap smears, late- or under- screening and psychosocial risk factors including domestic violence and sexual assault. DESIGN: A descriptive cross-sectional study of women attending publically funded women's health clinics in the community or in a live-in residential drug and alcohol rehabilitation facility. METHODS: The study was approved in May 2012. Data were collected between October 2012-December 2013 using standardized women's health questionnaires, domestic violence screening tools and Pap smear tests. RESULTS: Women attending the rehabilitation facility had higher rates of abnormal Pap smears (16·7% vs. 1·6%) and self-reported history of abnormal Pap smears (44·4% vs. 20·6%). They also reported higher rates of smoking (72·2% vs. 29·2%), experience of sexual assault (44·1% vs. 16·9%), experience of domestic violence (65·7% vs. 10·9%) and other psychosocial risk factors, than women living in the general community. Unexpectedly, women in the rehabilitation facility reported similar levels of late screening as women in the community (52·8% vs. 55·4%). CONCLUSION: Women with drug and alcohol addiction have significantly higher incidence of risk factors for cervical cancer and abnormal Pap smears. Provision of opportunistic cervical cancer screening during residential treatment appears to reduce incidence of late-screening. Roles of Women's Health Nurses in providing services to vulnerable women should be explored further.

Screening for traumatic brain injury: findings and public health implications.

OBJECTIVE: To provide an overview of a series of projects that used a structured self-report screening tool in diverse settings and samples to screen for lifetime history of traumatic brain injury (TBI). SETTING: Diverse community settings. PARTICIPANTS: Homeless persons (n = 111), individuals with HIV seeking vocational rehabilitation (n = 173), youth in the juvenile justice system (n = 271), public schoolchildren (n = 174), substance users (n = 845), intercollegiate athletes (n = 90), and other community-based samples (n = 396). DESIGN: Cross-sectional. MAIN MEASURE: Brain Injury Screening Questionnaire. RESULTS: Screening using the Brain Injury Screening Questionnaire finds that 27% to 54% of those in high-risk populations report a history of TBI with chronic symptoms. Associations between TBI and social, academic, or other problems are evident in several studies. In non-high-risk community samples, 9% to 12% of individuals report TBI with chronic symptoms. CONCLUSION: Systematic TBI screening can be implemented efficiently and inexpensively in a variety of settings. Lifetime TBI history data gathered using a structured self-report instrument can augment existing estimates of the prevalence of TBI, both as an acute event and as a chronic condition. Identification of individuals with TBI can facilitate primary prevention efforts, such as reducing risk for reinjury in high-risk groups, and provide access to appropriate interventions that can reduce the personal and societal costs of TBI (tertiary prevention).

Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) is a disorder of innate immunity and Th1 activation responsive to IL-1 blockade.

The syndrome of periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) is the most common periodic fever disease in children. However, the pathogenesis is unknown. Using a systems biology approach we analyzed blood samples from PFAPA patients whose genetic testing excluded hereditary periodic fevers (HPFs), and from healthy children and pediatric HPF patients. Gene expression profiling could clearly distinguish PFAPA flares from asymptomatic intervals, HPF flares, and healthy controls. During PFAPA attacks, complement (C1QB, C2, SERPING1), IL-1-related (IL-1B, IL-1RN, CASP1, IL18RAP), and IFN-induced (AIM2, IP-10/CXCL10) genes were significantly overexpressed, but T cell-associated transcripts (CD3, CD8B) were down-regulated. On the protein level, PFAPA flares were accompanied by significantly increased serum levels of chemokines for activated T lymphocytes (IP-10/CXCL10, MIG/CXCL9), G-CSF, and proinflammatory cytokines (IL-18, IL-6). PFAPA flares also manifested a relative lymphopenia. Activated CD4(+)/CD25(+) T-lymphocyte counts correlated negatively with serum concentrations of IP-10/CXCL10, whereas CD4(+)/HLA-DR(+) T lymphocyte counts correlated positively with serum concentrations of the counterregulatory IL-1 receptor antagonist. Based on the evidence for IL-1ß activation in PFAPA flares, we treated five PFAPA patients with a recombinant IL-1 receptor antagonist. All patients showed a prompt clinical and IP-10/CXCL10 response. Our data suggest an environmentally triggered activation of complement and IL-1ß/-18 during PFAPA flares, with induction of Th1-chemokines and subsequent retention of activated T cells in peripheral tissues. IL-1 inhibition may thus be beneficial for treatment of PFAPA attacks, with IP-10/CXCL10 serving as a potential biomarker.

"They didn't think we'd do it!": Community gardening as an act of resistance for people with dementia.

People living with dementia commonly report negative experiences such as disempowerment, stigma, and oppression. Community gardening has demonstrated its potential as a forum for the practice of resistance against the oppressions experienced by other marginalised groups; however, this element of the experience of community gardening has yet to be explored in the context of dementia. A collaboratively-designed community gardening project took place over six weeks, involving six people with dementia. The participants selected all activities undertaken in the garden. Data were collected through semi-structured group interviews with the gardeners and researcher observations. Context-setting semi-structured individual interviews were conducted with four day centre staff members, and three key informants who had experienced working with people with dementia in the garden. The garden acted as a platform for the articulation of both verbal and embodied expressions of resistance against the disempowerment and loss of agency experienced by many people with dementia. The participatory design of the gardening sessions enabled the gardeners to assert their autonomy and independence, and defy the negative stereotypes associated with dementia, which some of the group members appeared to have internalised. Community gardening activities may offer a forum for expressions of resistance against the structures oppressing individuals with dementia. However, in order for this potential to be unlocked, such initiatives must be collaboratively designed, following an approach which recognises the strengths and enduring abilities of people living with dementia. Additionally, the empowering impact of community gardening should not be diluted by positioning the activity as a substitute for adequate statutory health and social care provision, thereby individualising responsibility for the wellbeing of people with dementia.

Concordant B and T Cell Heterogeneity Inferred from the Multiomic Landscape of Peripheral Blood Mononuclear Cells in a Crohn's Disease Cohort.

BACKGROUND AND AIMS: Crohn's disease is characterized by inflammation in the gastrointestinal tract due to a combination of genetic, immune, and environmental factors. Transcriptomic and epigenomic profiling of intestinal tissue of Crohn's disease patients have revealed valuable insights into pathology, however have not been conducted jointly on less invasive peripheral blood mononuclear cells (PBMCs). Furthermore, the heterogeneous responses to treatments among individuals with Crohn's disease imply hidden diversity of pathological mechanisms. METHODS: We employed single nucleus multiomic analysis, integrating both snRNA-seq and snATAC-seq of PBMCs with a variety of open source bioinformatics applications. RESULTS: Our findings reveal a diverse range of transcriptional signatures among individuals, highlighting the heterogeneity in PBMC profiles. Nevertheless, striking concordance between three heterogeneous groups was observed across B cells and T cells. Differential gene regulatory mechanisms partially explain these profiles, notably including a signature involving TGFß signaling in two individuals with Crohn's disease. A mutation mapped to a transcription factor binding site within a differentially accessible peak associated with the expression of this pathway, with implications for a personalized approach to understanding disease pathology. CONCLUSIONS: This study highlights how multiomic analysis can reveal common regulatory mechanisms that underlie heterogeneity of PBMC profiles, one of which may be specific to inflammatory disease.

UV Light Degradation of Polylactic Acid Kickstarts Enzymatic Hydrolysis.

Polylactic acid (PLA) and bioplastics alike have a designed degradability to avoid the environmental buildup that petroplastics have created. Yet, this designed biotic-degradation has typically been characterized in ideal conditions. This study seeks to relate the abiotic to the biotic degradation of PLA to accurately represent the degradation pathways bioplastics will encounter, supposing their improper disposal in the environment. Enzymatic hydrolysis was used to study the biodegradation of PLA with varying stages of photoaging. Utilizing a fluorescent tag to follow enzyme hydrolysis, it was determined that increasing the amount of irradiation yielded greater amounts of total enzymatic hydrolysis by proteinase K after 8 h of enzyme incubation. While photoaging of the polymers causes minimal changes in chemistry and increasing amounts of crystallinity, the trends in biotic degradation appear to primarily be driven by photoinduced reduction in molecular weight. The relationship between photoaging and enzyme hydrolysis appears to be independent of enzyme type, though commercial product degradation may be impacted by the presence of additives. Overall, this work reveals the importance of characterizing biodegradation with relevant samples that ultimately can inform optimization of production and disposal.

Camsites as a Context for Sexual Consent Education: User Experiences.

Understanding sexual consent is essential for the promotion of healthy sexual relationships and the prevention of sexual violence. Emerging sexual technologies can provide opportunities for users to learn about and potentially practice navigating sexual consent with partners, but this field of research is still nascent. In this study, we surveyed 5,828 erotic camsite users to determine whether they learned something new about sexual consent from their use of the site. Participants mostly identified as heterosexual white men, aged 18 to 99. Our results showed that 12% (n = 699) reported learning something new about sexual consent from their camsite use. Those who reported learning something new were prompted to provide a qualitative report of what they had learned; 36% (n = 252) did so. Users reported learning about the importance of respecting boundaries; how consent can change or differ based on the person, context, or time; the implicit and explicit forms of sexual consent, and the need to explicitly communicate about sexual consent; and how consent norms apply to commercial sexual contexts. Our findings show that people are learning about sexual consent from camsites, but the obtained knowledge is complex and sometimes negative. This study sheds light on the potential of emerging sexual technologies as sources for sexual education, and highlights the need for further research exploring the ways in which understandings of digital sexual consent translate to broader contexts.

The lifelong orgasm gap: exploring age's impact on orgasm rates.

Background: Research demonstrates significant gender- and sexual orientation-based differences in orgasm rates from sexual intercourse; however, this "orgasm gap" has not been studied with respect to age. Aim: The study sought to examine age-related disparities in orgasm rates from sexual intercourse by gender and sexual orientation. Methods: A survey sample of 24 752 adults from the United States, ranging in age from 18 to 100 years. Data were collected across 8 cross-sectional surveys between 2015 and 2023. Outcomes: Participants reported their average rate of orgasm during sexual intercourse, from 0% to 100%. Results: Orgasm rate was associated with age but with minimal effect size. In all age groups, men reported higher rates of orgasm than did women. Men's orgasm rates ranged from 70% to 85%, while women's ranged from 46% to 58%. Men reported orgasm rates between 22% and 30% higher than women's rates. Sexual orientation impacted orgasm rates by gender but not uniformly across age groups. Clinical Translation: The persistence of the orgasm gap across ages necessitates a tailored approach in clinical practice and education, focusing on inclusive sexual health discussions, addressing the unique challenges of sexual minorities and aging, and emphasizing mutual satisfaction to promote sexual well-being for all. Strengths and Limitations: This study is the first to examine the orgasm gap with respect to age, and does so in a large, diverse sample. Findings are limited by methodology, including single-item assessments of orgasm and a sample of single adults. Conclusion: This study revealed enduring disparities in orgasm rates from sexual intercourse, likely resulting from many factors, including sociocultural norms and inadequate sex education.