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The article presents the results of studies of the chemical composition, crystal structure, lattice parameters, microstructure, the valence state of the europium ion (at 300 K), electrical resistivity, and differential thermopower (6–400 K) of samples in the Eu(Cu1 − xAgx)2Si2 (0 ≤ x ≤ 1) substitutional solid solutions. A transition of the europium ion from the valence-stable state of Eu2+ in EuAg2Si2 to the state of intermediate (homogeneous) valence (IV) of the europium ion in EuCu2Si2 with an effective valence ϑeff = 2.41 (300 K) has been initiated by a successive replacement of silver atoms by copper atoms. With appropriate sample compositions, the transition passes through a Kondo-type state. The research subject is the patterns of transformations (when the composition of the sample changes), the electronic state, and, accordingly, the electronic transport properties. The simultaneous coexistence of europium ions in different electronic states is assumed. The substitutional solid solution Eu(Cu1 − xAgx)2Si2 (0 ≤ x ≤ 1) exhibits properties related to the competition between the state of the Kondo system, intermediate valence (IV), and magnetic ordering. [ABSTRACT FROM AUTHOR]

Intelligent materials occupy a special place among the huge number of known materials and those, which are being created all the time. Despite the impressive number of publications, no attempt has yet been made to classify compounds with a valence-unstable rare-earth element (R.E.) as smart materials. In this review paper, we show that the valence of the R.E. in some compounds can be changed by external and internal factors, such as temperature, pressure, changes in the occupation of d- and f-levels, and changes in the coordination polyhedra of atoms. Changing the valence of the R.E. may significantly alter the electrical and magnetic properties of compounds. [ABSTRACT FROM AUTHOR]

To assess the prevalence of pelvic pain worsened by orgasm in patients with endometriosis and its associated clinical features, focusing on those related to pelvic floor myalgia, central sensitization, and surgical findings. Prospectively collected data were analysed. Data were collected at three timepoints: pre-appointment patient questionnaire, initial appointment, and surgery. Surgery was done by gynecologists specializing in endometriosis. Tertiary referral centre for pelvic pain and endometriosis. Participants included were aged 18 to 50, pre-menopausal, diagnosed with endometriosis via specified criteria, and underwent surgery at our centre. A total of 358 participants referred to our centre between January 2018 and December 2019 completed the study. The median follow-up (duration between pre-appointment questionnaire and surgery) was 6 months, range 0-28 months. Participants who reported that orgasm worsened their pelvic or lower abdominal pain were compared to those who did not. Among 358 participants, 14% (n=49) reported pelvic pain worsened by orgasm. Pain with orgasm was significantly associated with pelvic floor myalgia (p = 0.01), higher scores on the Central Sensitization Inventory (p < 0.001), Patient Health Quality-9 (p < 0.001), and Generalized Anxiety Disorder-7 (p = 0.002). For surgical findings, there was no difference between the two groups for revised American Society for Reproductive Medicine scores (p=0.07). There was a trend towards ovarian endometriosis more commonly seen in participants without orgasm-associated pain (p=0.049). However, the prevalence of superficial peritoneal endometriosis, deep infiltrating endometriosis, and cul-de-sac obliteration were similar between the two groups. Pelvic pain worsened by orgasm in people with endometriosis may be associated with concurrent pelvic floor myalgia and central sensitization. Interventions targeting these factors may alleviate the symptom. There were no associations with more anatomically severe endometriosis found at surgery. Further research is needed to identify effective treatments. [ABSTRACT FROM AUTHOR]

We have obtained X-ray emission spectra of Ga and Ge in Ca3Ga2Ge4O14, X-ray emission OKα-spectra in Ca3Ga2Ge4O14, Ca3Ga2Ge4O14 + Ce3%, and Ca3Ga2Ge4O14 + Eu4% and Xray photoelectron spectra in Ca3Ga2Ge4O14 . Our X-ray spectral studies of the Ca3Ga2Ge4O14 gallogermanate have shown that the top of the valence band near the Fermi level is formed mainly by p states of gallium and germanium as well as p states of oxygen, whose intensity is sufficiently low. The middle of the valence band is formed by gallium 3d states with oxygen 2s states lying below them. These states are hybridized with 4p states of gallium and germanium because of which there are Kβ′′-satellites in the Kβ2-subbands of gallium and germanium. The bottom of the valence band is formed by 3d states of germanium, whose contribution to chemical bonding is insignificant. The X-ray emission bands of Ga and Ge in Ca3Ga2Ge4O14 and the photoelectron spectrum of the valence electrons of Ca3Ga2Ge4O14 are in good agreement. The OKα-band changes its fine structure only slightly upon doping Ca3Ga2Ge4O14 with Ce or Eu. The investigations of intrinsic luminescence under X-rays excitation of Ca3Ga2Ge4O14 gallogermanate are presented. [ABSTRACT FROM AUTHOR]

We have obtained X-ray emission spectra of Ga and Ge in Ca3Ga2Ge4O14, X-ray emission OKα-spectra in Ca3Ga2Ge4O14, Ca3Ga2Ge4O14 + Ce3%, and Ca3Ga2Ge4O14 + Eu4% and Xray photoelectron spectra in Ca3Ga2Ge4O14 . Our X-ray spectral studies of the Ca3Ga2Ge4O14 gallogermanate have shown that the top of the valence band near the Fermi level is formed mainly by p states of gallium and germanium as well as p states of oxygen, whose intensity is sufficiently low. The middle of the valence band is formed by gallium 3d states with oxygen 2s states lying below them. These states are hybridized with 4p states of gallium and germanium because of which there are Kβ′′-satellites in the Kβ2-subbands of gallium and germanium. The bottom of the valence band is formed by 3d states of germanium, whose contribution to chemical bonding is insignificant. The X-ray emission bands of Ga and Ge in Ca3Ga2Ge4O14 and the photoelectron spectrum of the valence electrons of Ca3Ga2Ge4O14 are in good agreement. The OKα-band changes its fine structure only slightly upon doping Ca3Ga2Ge4O14 with Ce or Eu. The investigations of intrinsic luminescence under X-rays excitation of Ca3Ga2Ge4O14 gallogermanate are presented. [ABSTRACT FROM AUTHOR]

Background: Pelvic pain worsened by orgasm is a poorly understood symptom in patients with endometriosis., Aim: To assess the prevalence of pelvic pain worsened by orgasm in patients with endometriosis and explore its association with potential etiologic factors, including pelvic floor myalgia, uterine tenderness and adenomyosis, and central nervous system sensitization., Methods: An analysis was done of a prospective data registry based at a tertiary referral center for endometriosis. Eligible participants were patients aged 18 to 50 years who were referred between January 1, 2018, and December 31, 2019, diagnosed with endometriosis, and subsequently underwent surgery at the center. Clinical features were compared between participants reporting worsening pelvic pain with orgasm and those without worsening pain with orgasm, including patient-reported variables, physical examination findings, and anatomic phenotyping at the time of surgery. Pelvic floor myalgia and uterine tenderness were assessed by palpation on pelvic examination, adenomyosis by ultrasound, and central nervous system sensitization via the Central Sensitization Inventory (range, 0-100)., Outcomes: Outcomes included pelvic or lower abdominal pain in the last 3 months that worsened with orgasm (yes/no)., Results: Among 358 participants with endometriosis, 14% (49/358) reported pain worsened by orgasm while 86% (309/358) did not. Pain with orgasm was significantly associated with pelvic floor myalgia (55% [27/49] vs 35% [109/309]; Cohen's h = 0.40, P = .01) and higher scores on the Central Sensitization Inventory (mean ± SD, 53.3 ± 17.0 vs 42.7 ± 18.2; Cohen's d = 0.60, P < .001) but not with uterine tenderness or adenomyosis. Other clinical features associated with pain with orgasm were poorer sexual health (higher scores: deep dyspareunia, Cohen's h = 0.60; superficial dyspareunia, Cohen's h = 0.34; and Female Sexual Distress Scale-Revised, Cohen's d = 0.68; all P < .05) and poorer mental health (higher scores: Patient Health Questionnaire-9, 12.9 ± 6.7 vs 9.1 ± 6.3, Cohen's d = 0.59, P < .001; Generalized Anxiety Disorder-7, 9.4 ± 5.6 vs 6.8 ± 5.5, Cohen's d = 0.48, P = .002). Anatomic findings at the time of surgery did not significantly differ between the groups., Clinical Implications: Interventions targeting pelvic floor myalgia and central nervous system sensitization may help alleviate pain worsened by orgasm in patients with endometriosis., Strengths and Limitations: A strength is that pain worsened by orgasm was differentiated from dyspareunia. However, pain with orgasm was assessed by only a binary question (yes/no). Also, the study is limited to a single center, and there were limited data on sexual function., Conclusion: Pelvic pain exacerbated by orgasm in people with endometriosis may be related to concurrent pelvic floor myalgia and central sensitization., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society of Sexual Medicine.)

Background: Deep dyspareunia affects 50% of people with endometriosis. The Ohnut is a set of interlocking rings that fit over the penis/insertive object. One or more rings can be used to limit insertion depth and reduce deep dyspareunia., Aim: We conducted a pilot, parallel, open-label randomized controlled trial (RCT) to investigate the feasibility of the study design and the acceptability and preliminary efficacy of the Ohnut., Method: Participants were recruited from a tertiary center for endometriosis. Eligibility criteria were surgically confirmed endometriosis, age 19-49 years, monogamous sexual relationship with a partner willing to participate in the study, and no comorbid superficial dyspareunia, anxiety, or depression. Couples were randomized into an intervention group or a waitlist control group using a 1:1 allocation ratio. All couples had sex as normal during weeks 1 to 4 (baseline period), and couples in the intervention group used the Ohnut with sex during weeks 5 to 10 (intervention period) while controls had sex as normal. Patient participants used daily diaries to record sexual activity and deep dyspareunia score (0-10) for the 10-week study. Intervention group participants completed an acceptability questionnaire at the end of the study., Outcomes: The primary outcomes were feasibility of the study and acceptability of the Ohnut. We also assessed differences in deep dyspareunia scores in the participants who used the Ohnut compared to the control participants who did not., Results: We recruited approximately 5 couples per month of active recruitment. Of 864 potentially eligible participants, we successfully contacted 44.7% (n = 386), of whom 8.0% (n = 31) consented, 64.8% (n = 250) were ineligible, and 27.2% (n = 105) declined. Thirty-one couples were randomly assigned to the intervention or control group, and 17 couples completed the study. Intervention group couples used the Ohnut for an average of 72.4% (32.7%) of sexual encounters during the intervention period. The mean acceptability index score for the Ohnut was 0.83 (0.078) among patients and 0.83 (0.049) among partners (index between 0 and 1). After controlling for baseline deep dyspareunia, there was a significant difference in the intervention period mean deep dyspareunia scores between the control and intervention group (4.69 (2.44) vs 2.46 (1.82), P = .012)., Clinical Implications: We identified preliminary evidence for the acceptability and efficacy of the Ohnut among both patients and partners, suggesting that the Ohnut may be a useful stand-alone or adjuvant management tool for endometriosis-associated deep dyspareunia., Strengths and Limitations: Strengths of this study were the "real-world" use of the Ohnut and data collection from both patients and partners. Limitations of the study design included the strict eligibility criteria that affected feasibility and generalizability., Conclusion: This pilot RCT indicated that the Ohnut may be an acceptable and effective intervention to reduce endometriosis-associated deep dyspareunia. We identified opportunities to improve design for a larger RCT., Clinical Trial Registration: This clinical trial was registered with clinicaltrials.gov (#NCT04370444)., Competing Interests: R.F. is co-owner of Teumo Health Technologies Inc, a digital health company in sexual medicine., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society for Sexual Medicine.)

Given the limitations of medical treatment for endometriosis, self-management is a critical component of symptom management, and providing patients with information and education is a necessary complement to medical interventions. Though 50 to 70% of people with endometriosis experience dyspareunia (painful sex), there is limited knowledge of self-management specific to painful sex. A comprehensive understanding of the self-management strategies used is foundational to developing supportive care interventions that help ease pain and related psychosocial sequelae. The objective was to describe people's experiences of navigating endometriosis-associated painful sex and developing self-management strategies. We analyzed interview data from 20 women using constant comparative and thematic analysis techniques, guided by qualitative interpretive description methodology. Participants (age range 18-44 years) all identified as women and were predominately Caucasian (90%) and heterosexual (80%). Throughout their lives, the women appeared to gradually develop self-management strategies while navigating painful sexual experiences. This complex journey encompassed four phases: 1) viewing painful sex as normal, 2) experiencing evolving thoughts and emotions, 3) coming to understand painful sex and seeking help, and 4) learning strategies to navigate painful sex, these include preparing mentally and physically for sex and communicating with intimate partner(s). Women in this study developed self-management strategies over time through engagement with others who understood their challenges. Future research is warranted regarding initiatives to counter the normalization of painful sex, develop and disseminate patient-facing information, provide education specific to dyspareunia, improve access to multidisciplinary care, facilitate social connections and support, and enhance communication with intimate partners. PERSPECTIVE: In this paper, we report on the experiences of women with endometriosis-associated painful sex and their self-management strategies. Clinicians may be interested in a qualitative exploration of endometriosis-associated painful sex as they seek to further understand their patient's experiences and what strategies can be implemented to alleviate dyspareunia. DATA AVAILABILITY: The data sets generated during and/or analyzed during the current study are not publicly available as participants did not consent to making their data publicly available but are available from the corresponding author on reasonable request., (Copyright © 2024 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

To correlate pain-related phenotyping for central nervous system sensitization in endometriosis-associated pain with mental health outcomes during the COVID-19 pandemic, the prospective Endometriosis and Pelvic Pain Interdisciplinary Cohort (ClinicalTrials.gov #NCT02911090) was linked to the COVID-19 Rapid Evidence Study of a Provincial Population-Based Cohort for Gender and Sex (RESPPONSE) dataset. The primary outcomes were depression (PHQ-9) and anxiety (GAD-7) scores during the pandemic. The explanatory variables of interest were the Central Sensitization Inventory (CSI) score (0-100) and endometriosis-associated chronic pain comorbidities/psychological variables before the pandemic. The explanatory and response variables were assessed for correlation, followed by multivariable regression analyses adjusting for PHQ-9 and GAD-7 scores pre-pandemic as well as age, body mass index, and parity. A higher CSI score and a greater number of chronic pain comorbidities before the pandemic were both positively correlated with PHQ-9 and GAD-7 scores during the pandemic. These associations remained significant in adjusted analyses. Increasing the CSI score by 10 was associated with an increase in pandemic PHQ-9 by .74 points (P < .0001) and GAD-7 by .73 points (P < .0001) on average. Each additional chronic pain comorbidity/psychological variable was associated with an increase in pandemic PHQ-9 by an average of .63 points (P = .0004) and GAD-7 by .53 points (P = .0002). Endometriosis patients with a history of central sensitization before the pandemic had worse mental health outcomes during the COVID-19 pandemic. As a risk factor for mental health symptoms in the face of major stressors, clinical proxies for central sensitization can be used to identify endometriosis patients who may need additional support. PERSPECTIVE: This article adds to the growing literature of the clinical importance of central sensitization in endometriosis patients, who had more symptoms of depression and anxiety during the COVID-19 pandemic. Clinical features of central sensitization may help clinicians identify endometriosis patients needing additional support when facing major stressors., (Copyright © 2024 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Endometriosis is a gynecological disorder associated with local inflammation and neuroproliferation. Increased nerve bundle density has been attributed to increased expression of nerve growth factor (NGF) and interleukin-1β (IL-1β). Immunohistochemical analysis was carried out on 12 patients presenting with all three anatomic subtypes of endometriosis (deep, superficial peritoneal, endometrioma) at surgery, with at least two surgically excised subtypes available for analysis. Immunolocalization for nerve bundle density around endometriosis using protein gene product 9.5 (PGP9.5), as well as NGF and IL-1β histoscores in endometriosis epithelium/stroma, was performed to evaluate differences in scores between lesions and anatomic subtypes per patient. Intra-individual heterogeneity in scores across lesions was assessed using the coefficient of variation (CV). The degree of score variability between subtypes was evaluated using the percentage difference between mean scores from one subtype to another subtype for each marker. PGP9.5 nerve bundle density was heterogenous across multiple subtypes of endometriosis, ranging from 50.0% to 173.2%, where most patients (8/12) showed CV ≥ 100%. The percentage difference in scores showed that PGP9.5 nerve bundle density and NGF and IL-1β expression were heterogenous between anatomic subtypes within the same patient. Based on these observations of intra-individual heterogeneity, we conclude that markers of neuroproliferation in endometriosis should be stratified by anatomic subtype in future studies of clinical correlation.

Background: As an emerging approach, arts-based research holds potential to advance understanding of the complex and multidimensional experiences of chronic pain and means of communicating this experiential evidence. This scoping review aimed to map and explore the extent of arts-based research in chronic non-cancer pain, understand the rationale behind using arts-based research methods, and identify directions for future research., Methods: Databases PsycINFO, MEDLINE, EMBASE, and CINAHL were searched for eligible English-language articles from inception to November 2022. Out of 1321 article titles and abstracts screened for eligibility, 18 articles underwent full-text screening, with 14 ultimately meeting all inclusion criteria. We conducted a narrative synthesis of data extracted from the 14 reviewed articles., Results: The review articles focused on a wide range of chronic non-cancer pain conditions, with 12/14 employing qualitative methods (86%), one repeated measures experimental design, and another a multiphase, multimethod design. Seven articles described the use of drawing, painting, or mixed-media artwork; four used photography; two used body mapping; and one used e-book creation. The rationale for arts-based research included exploring and better understanding patients' experiences with chronic non-cancer pain, constructing an intervention, and investigating or validating a clinical tool. Nine articles reported that their arts-based research methods produced unintended therapeutic benefits for participants. Recommendations for future research included using arts-based research to better understand and communicate with patients and providers, exploring convergence with art therapy, and designing creative and flexible multiphased studies involving collaboration across disciplines., Conclusions: Despite the wide variation in sample and art modalities across reviewed articles, arts-based methods were considered suitable and highly effective for investigating chronic non-cancer pain., Competing Interests: No potential conflicts of interest are reported by the author(s)., (© 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.)

Background: Sexual pain is a common but neglected disorder that affects approximately 3% to 18% of women and an unmeasured number of gender-diverse people worldwide. Despite its wide prevalence, many people feel reluctant to visit conventional health care services or disclose their symptoms due to the fear of stigmatization. To alleviate this stigma, various web-based interventions have been developed to complement and, in some cases, replace conventional sexual health interventions. However, the way these web-based interventions are developed could inadvertently reproduce, perpetuate, or exacerbate stigma among end user patients., Objective: The purpose of this study was to understand patients' perspectives on how sexual pain-related web platforms can be designed to alleviate stigma or prevent the unintended effects of stigma among patients who use web-based interventions., Methods: Individual semistructured interviews were conducted among 16 participants with lived experiences of painful sex in a large urban city in Western Canada. Participants were recruited via social media platforms, newsletters, and a provincial health volunteer website. Using a sample sexual pain website to provide context, participants were interviewed about their experiences of stigma and how they think web platforms could be designed to address stigma. The interviews were conducted via Zoom (Zoom Technologies Inc) and analyzed using thematic analysis., Results: The findings revealed 4 overarching themes that represented participants' perspectives on designing web platforms that may alleviate or prevent the unintended effects of stigma. These findings suggested the design of inclusive web platforms, having a nonprovocative and calming user interface, having features that facilitate connections among users and between users and providers, and displaying personal testimonials and experiences of sexual pain., Conclusions: This study highlighted patient-centered design approaches that could serve as a reference guide in developing web platforms that alleviate or prevent the unintended effects of stigma, particularly among nonheterosexual and gender-diverse people. While this study was conducted in the context of sexual pain, the results might also apply to web platforms on other potentially stigmatizing health-related disorders or conditions., (©Abdul-Fatawu Abdulai, Hasti Naghdali, Heather Noga, Paul J Yong. Originally published in JMIR Formative Research (https://formative.jmir.org), 15.03.2024.)

Objectives: To prospectively evaluate pain-related quality-of-life (Endometriosis Health Profile-30 [EHP-30] pain subscale) after surgery at an interdisciplinary centre of expertise for endometriosis and pelvic pain., Methods: A prospective cohort study was completed of persons undergoing surgical management for pelvic pain between December 2013 and July 2016 at an interdisciplinary tertiary referral centre for pelvic pain and endometriosis. We compared the change in EHP-30 scores for the following scenarios: (1) type of surgery (conservative surgery vs. hysterectomy), (2) stage of endometriosis (stage I/II vs. III/IV), and (3) age (age <40 vs. age ≥40 years). We used mixed-effects models to evaluate changes in pain during follow-up after surgery., Results: Overall, 595 individuals met our inclusion criteria; the follow-up rate was 65.9% (392/595). In total, 436 (73.3%) underwent conservative surgery, while 159 (26.7%) underwent hysterectomy. Improvements in pain-related quality-of-life were seen for both conservative surgery and hysterectomy but greater improvements were seen with hysterectomy (P < 0.001). For conservative surgery, similar improvements in quality-of-life were observed regardless of endometriosis stage (I/II vs. III/IV) (P = 0.84) or age (<40 or ≥40 years old) (P = 0.87). We also observed similar improvements in quality-of-life regardless of stage (P = 0.24) or age (P = 0.71) after hysterectomy., Conclusions: At an interdisciplinary centre of expertise, there were significant improvements in quality-of-life after endometriosis surgery. These improvements were seen for both conservative surgery and hysterectomy (although greater improvement with the latter), for early and advanced stage disease, and younger and older patients., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

People commonly and increasingly rely on the internet to search for health information, including those related to endometriosis-associated dyspareunia. Yet the content of such websites may be of variable accuracy and quality. This review aims to evaluate the quality, readability, and suitability of web-based resources on endometriosis-associated dyspareunia for patients. We searched 3 databases - Google, Bing, and Yahoo - to identify websites related to endometriosis-associated dyspareunia. Two independent reviewers screened the search results against inclusion and exclusion criteria. Another set of two reviewers evaluated the selected websites using validated measurement instruments. Out of 450 websites, 21 met the inclusion criteria and were evaluated. More than half of the websites had information on content updates, reported on authorship, or disclosed sponsorship information. The mean quality and suitability scores were 47.5 (SD = 13.3) and 65.2 (SD = 13.6) respectively, thus suggesting generally adequate quality and suitability levels. However, the mean readability scores exceeded the recommended level for health-related websites. The poor readability of the websites might limit accessibility for a significant proportion of patients with low educational levels. The findings of this review have implications for designing high-quality, readable and up-to-date web interventions for people who rely on web platforms as an alternative or complementary source of health information on dyspareunia., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Approximately half of people with endometriosis experience deep dyspareunia; however, there is no means of objective self-testing of endometriosis-associated deep dyspareunia., Aim: The aim of this study was to assess the acceptability, test-retest reliability, and validity of a vaginal insert for a self-assessment of endometriosis-associated deep dyspareunia., Methods: Participants were recruited from a tertiary endometriosis center. Inclusion criteria were: 19 to 49 years of age, self-reported deep dyspareunia of ≥4 of 10, and surgically confirmed endometriosis. Participants completed 2 self-assessments using the vaginal insert to self-assess tenderness at the right and left pelvic floor, bladder, cervix-uterus, and posterior cul-de-sac (vaginal fornix). The participants recorded tenderness at each pelvic site and completed a questionnaire regarding the acceptability of the vaginal insert to assess deep dyspareunia. Test-retest reliability was assessed by correlating the tenderness scores between the 2 assessment dates. Over a 4-week period, the participants also recorded deep dyspareunia severity at each penetrative vaginal sex encounter. Validity was assessed by correlating vaginal insert tenderness to deep dyspareunia severity, and also to tenderness reported on a prior gynecologic pelvic examination., Outcomes: The main outcome measures were the acceptability index score, tenderness (0-10) at each pelvic site, and prospective deep dyspareunia scores (0-10) over 4 weeks., Results: There were 19 participants (mean age 34 ± 7 years) who completed the study. The majority identified as female (94.7%), heterosexual (89.5%), and white (89.5%). The median acceptability index score was 0.72 (interquartile range, 0.66-0.81). For test-retest reliability, the intraclass correlation coefficients were 0.79 (P = .001) for the left pelvic floor, 0.82 (P < .001) for the right pelvic floor, 0.54 (P = .07) for the bladder, 0.89 (P < .001) for the cervix-uterus, and 0.77 (P = .003) for the cul-de-sac. The correlation between the highest self-assessed mean tenderness in each participant and self-reported deep dyspareunia over 4 weeks was r = 0.32, but correlations for each pelvic site varied significantly. Tenderness at each site on prior gynecologist pelvic exam was associated with higher self-assessed mean tenderness with the vaginal insert in each participant (effect sizes = 0.42-0.88)., Clinical Implications: The vaginal insert is acceptable and reliable for the objective self-assessment of endometriosis-associated deep dyspareunia, with initial evidence of validity., Strengths and Limitations: A strength was the inclusion of participants who were avoiding sexual activity and a limitation was the small sample size., Conclusion: Future studies with larger sample sizes are required to further establish the validity of the vaginal insert for the self-assessment of endometriosis-associated deep dyspareunia., (© The Author(s) 2023. Published by Oxford University Press on behalf of The International Society of Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: We propose a standardized protocol for measurement of nerve bundle density in endometriosis as a potential biomarker, including in deep endometriosis (DE), ovarian endometriomas (OMA) and superficial peritoneal endometriosis (SUP)., Methods: This was a prospective cohort of surgically excised endometriosis samples from Dec 1st 2013 and Dec 31st 2017 at a tertiary referral center for endometriosis in Vancouver, BC, Canada. Surgical data were available from linked patient registry. Protein gene product 9.5 (PGP9.5) was used to identify nerve bundles on immunohistochemistry. PGP9.5 nerve bundles were counted visually. To calculate nerve bundle density, PGP9.5 nerve bundle count was divided by the tissue surface area (total on the slide). All samples were assessed using NHS Elements software for semi-automated measurement of the tissue surface area. For a subset of samples, high power fields (HPFs) were also counted as manual measurement of the tissue surface area. Intraclass correlation was used to assess intra observer and inter observer reliability. Generalized linear mixed model (GLMM) with random intercepts only was conducted to assess differences in PGP9.5 nerve bundle density by endometriosis type (DE, OMA, SUP)., Results: In total, 236 tissue samples out of 121 participants were available for analysis in the current study. Semi-automated surface area measurement could be performed in 94.5% of the samples and showed good correlation with manually counted HPFs (Spearman's rho = 0.781, p  < 0.001). To assess intra observer reliability, 11 samples were assessed twice by the same observer; to assess inter observer reliability, 11 random samples were blindly assessed by two observers. Intra observer reliability and inter observer reliability for nerve bundle density were excellent: 0.979 and 0.985, respectively. PGP9.5 nerve bundle density varied among samples and no nerve bundles could be found in 24.6% of the samples. GLMM showed a significant difference in PGP9.5 nerve bundle density between the different endometriosis types (X 2  = 87.6, P  < 0.001 after adjusting for hormonal therapy, with higher density in DE and SUP in comparison to OMA)., Conclusion: A standardized protocol is presented to measure PGP9.5 nerve bundle density in endometriosis, which may serve as a biomarker reflecting local neurogenesis in the endometriosis microenvironment., Competing Interests: MK is a consultant for Helix Biopharma, which has no relation to the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Zoet, Tucker, Orr, Alotaibi, Liu, Noga, Köbel and Yong.)

The clinical phenotype of somatic mutations in endometriosis is unknown. The objective was to determine whether somatic KRAS mutations were associated with greater disease burden in endometriosis (i.e. more severe subtypes and higher stage). This prospective longitudinal cohort study included 122 subjects undergoing endometriosis surgery at a tertiary referral center between 2013 and 2017, with 5-9 years of follow-up. Somatic activating KRAS codon 12 mutations were detected in endometriosis lesions using droplet digital PCR. KRAS mutation status for each subject was coded as present (KRAS mutation in at least one endometriosis sample in a subject) or absent. Standardized clinical phenotyping for each subject was carried out via linkage to a prospective registry. Primary outcome was anatomic disease burden, based on distribution of subtypes (deep infiltrating endometriosis, ovarian endometrioma, and superficial peritoneal endometriosis) and surgical staging (Stages I-IV). Secondary outcomes were markers of surgical difficulty, demographics, pain scores, and risk of re-operation. KRAS mutation presence was higher in subjects with deep infiltrating endometriosis or endometrioma lesions only (57.9%; 11/19) and subjects with mixed subtypes (60.6%; 40/66), compared with those with superficial endometriosis only (35.1%; 13/37) (p = 0.04). KRAS mutation was present in 27.6% (8/29) of Stage I cases, in comparison to 65.0% (13/20) of Stage II, 63.0% (17/27) of Stage III, and 58.1% (25/43) of Stage IV cases (p = 0.02). KRAS mutation was also associated with greater surgical difficulty (ureterolysis) (relative risk [RR] = 1.47, 95% CI: 1.02-2.11) and non-Caucasian ethnicity (RR = 0.64, 95% CI: 0.47-0.89). Pain severities did not differ based on KRAS mutation status, at either baseline or follow-up. Re-operation rates were low overall, occurring in 17.2% with KRAS mutation compared with 10.3% without (RR = 1.66, 95% CI: 0.66-4.21). In conclusion, KRAS mutations were associated with greater anatomic severity of endometriosis, resulting in increased surgical difficulty. Somatic cancer-driver mutations may inform a future molecular classification of endometriosis., (© 2023 The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland and John Wiley & Sons Ltd.)

Background: Endometriosis-associated deep dyspareunia is associated with reduced sexual quality of life, lower self-esteem, and impaired sexual function., Objective: The primary objective is to assess the acceptability of a phallus length reducer (brand name: Ohnut [OhnutCo]), which is a buffer worn over the penis or a penetrating object to reduce endometriosis-associated deep dyspareunia, and the feasibility of a definitive randomized controlled trial (RCT). The secondary objective is to obtain estimates of the effectiveness of the buffer. An embedded substudy will explore the acceptability and the preliminary validity and reliability of a vaginal insert for the self-assessment of deep dyspareunia., Methods: Ours is an investigator-initiated, 2-arm RCT. We will recruit 40 patient participants with diagnosed endometriosis between the ages of 19 and 49 years, as well as their sexual partners. The participating couples will be randomized in a 1:1 ratio into the experimental arm or the waitlist control arm. The length of the study period will be 10 weeks, during which time all participants will record deep dyspareunia severity following each episode of sexual intercourse. In weeks 1 to 4, all patient participants will record deep dyspareunia severity at each sexual encounter. In weeks 5 to 10, participants in the experimental arm will use the buffer during vaginal penetration; participants in the waitlist control arm will continue engaging in vaginal penetration as usual. Participants will complete questionnaires for assessing measures of anxiety, depression, and sexual function at baseline, at 4 weeks, and at 10 weeks. In the substudy, patient participants will self-assess dyspareunia by using a vaginal insert on 2 occasions, at least 1 week apart. The primary outcomes-the acceptability and feasibility of the buffer-will be assessed with descriptive statistics, and the secondary outcome-phallus length reducer effectiveness-will be assessed by using an analysis of covariance-based approach. For the vaginal insert, we will assess acceptability, test-retest reliability, and convergent validity via correlation analyses comparing the use of the insert to clinical examination in terms of dyspareunia assessment outcomes., Results: Our pilot will provide initial data on the acceptability and effectiveness of the buffer and the feasibility of the study methodology. The results from our study are expected to be submitted for publication by the spring of 2023. As of September 2021, we have consented 31 couples into the study., Conclusions: Our study will provide preliminary evidence for the self-assessment and management of endometriosis-associated deep dyspareunia. The findings will inform the decision to proceed to a definitive RCT., Trial Registration: ClinicalTrials.gov NCT04370444; https://clinicaltrials.gov/ct2/show/NCT04370444., International Registered Report Identifier (irrid): DERR1-10.2196/39834., (©Sandy X J Zhang, Rebecca G K MacLeod, Gurkiran Parmar, Natasha L Orr, Kate J Wahl, Heather Noga, Arianne Albert, Ryan Flannigan, Lori A Brotto, Paul J Yong. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 27.03.2023.)

Background: Endometriosis is a complex chronic disease characterized by pain, including painful sex, that can contribute to considerable sexual function, self-esteem, and relationship challenges. Digital storytelling is an arts-based, participatory methodology wherein individuals create and share their illness experiences in detailing their lived experiences., Objective: The study objective was to pilot-test a web-based digital storytelling workshop focused on endometriosis to understand storytellers' experiences of workshop participation. We assessed the feasibility of story cocreation and sharing, including the emotional impact of workshop participation, the acceptability of the workshop for the subject matter, and the storytellers' willingness to share their stories with broader audiences as a method for knowledge translation., Methods: This study used a community-based participatory methodology supplemented with patient-oriented research and integrated knowledge translation. Study participants, referred to as storytellers, cocreated 3- to 5-minute individual digital stories about their lived experiences of endometriosis during a web-based workshop (comprising five 2-hour sessions over 6 weeks) facilitated by The Center for Digital Storytelling. Data were collected through participant observations at the workshop, storyteller weekly reflective journals, and an end-of-workshop focus group interview with storytellers. These data were analyzed using a qualitative interpretive description approach., Results: A total of 5 women and 1 nonbinary storyteller aged 19 to 39 years who had experienced endometriosis for 4 to 22 years participated in the study. We characterized storytelling workshop participation and the acceptability of story cocreation by describing participants' experiences of opportunity, commitment, and connection; complex emotions that were healing; and a desire to share. Feasibility was demonstrated through 100% engagement in the workshops. All 6 storytellers reported feeling empowered by publicly sharing their cocreated digital stories through social media and the Sex, Pain & Endometriosis website., Conclusions: Despite the complexities of the story-building process, the workshop and the cocreation and sharing of digital stories were feasible. The storytellers found that this process allowed for emotional healing and personal empowerment by offering a unique way to talk about painful sex, which also facilitated a connection among those in the workshop. The use of digital storytelling as a knowledge translation tool shows promise, and this approach also has potential as a therapeutic intervention., (©A Fuchsia Howard, Heather Noga, Gurkiran Parmar, Lan Kennedy, Sarah Aragones, Roop Bassra, Lauren Gelfer, Edurne Lopez de Arbina, Jessica Sutherland, Catherine Allaire, John L Oliffe, Leanne M Currie, Holly Yager, Paul J Yong. Originally published in JMIR Formative Research (https://formative.jmir.org), 14.03.2023.)

Importance: A subset of people who undergo surgery for endometriosis have persistent pain, suggesting that other factors besides the endometriosis, such as central sensitization, may play a role in this pain. The Central Sensitization Inventory, a validated self-reported questionnaire of central sensitization symptoms, may identify individuals with endometriosis who have more pain after surgery due to pain sensitization., Objective: To examine whether greater baseline Central Sensitization Inventory scores are associated with postsurgical pain outcomes., Design, Setting, and Participants: This prospective, longitudinal cohort study performed at a tertiary center for endometriosis and pelvic pain in British Columbia, Canada, included all patients aged 18 to 50 years with diagnosed or suspected endometriosis and a baseline visit between January 1, 2018, and December 31, 2019, who underwent surgery after the baseline visit. Individuals who were menopausal, had a prior hysterectomy, or were missing data for outcomes or measures were excluded. Data analysis was performed from July 2021 to June 2022., Main Outcomes and Measures: The primary outcome was chronic pelvic pain at follow-up measured on a scale of 0 to 10, with 0 to 3 indicating no pain or mild pain, 4 to 6 indicating moderate pain, and 7 to 10 indicating severe pain. Secondary outcomes were deep dyspareunia, dysmenorrhea, dyschezia, and back pain at follow-up. The main variable of interest was baseline Central Sensitization Inventory score (measured from 0 to 100, consisting of 25 self-reported questions rated from 0 to 4 [never, rarely, sometimes, often, and always, respectively])., Results: A total of 239 patients (mean [SD] age, 34 [7] years; 189 [79.1%] White [11 (5.8%) identified as White mixed with another ethnicity], 1 [0.4%] Black or African American, 29 [12.1%] Asian, 2 [0.8%] Native Hawaiian or Pacific Islander, 16 [6.7%] other, and 2 [0.8%] mixed race or ethnicity) with follow-up data at more than 4 months after surgery were included in this study (71.0% follow-up rate). The mean (SD) baseline Central Sensitization Inventory score was 43.8 (18.2), and the mean (SD) follow-up was 16.1 (6.1) months. Higher baseline Central Sensitization Inventory scores were significantly associated with higher chronic pelvic pain (odds ratio [OR], 1.02; 95% CI, 1.00-1.03; P = .02), deep dyspareunia (OR, 1.03; 95% CI, 1.01-1.04; P = .004), dyschezia (OR, 1.03; 95% CI, 1.01-1.04; P < .001), and back pain (OR, 1.02; 95% CI, 1.00-1.03; P = .02) at follow-up, when controlling for baseline pain scores. The Central Sensitization Inventory scores themselves decreased slightly from baseline to follow-up (mean [SD] score, 43.8 [18.2] vs 41.7 [18.9]; P = .05); however, individuals with high baseline Central Sensitization Inventory scores still had high scores at follow-up., Conclusions and Relevance: In this cohort study of 239 patients with endometriosis, higher Central Sensitization Inventory scores at baseline were associated with worse pain outcomes after endometriosis surgery, when controlling for baseline pain scores. The Central Sensitization Inventory could be used to counsel patients with endometriosis on their expected outcomes after surgery.

Background: Endometriosis is a chronic condition that affects approximately 10% of women worldwide. Despite its wide prevalence, knowledge of endometriosis symptoms, such as pelvic pain, and treatments remains relatively low. This not only leads to a trivialization of symptoms and delayed diagnosis but also fuels myths and misconceptions about pain symptoms. At the same time, the use of web-based platforms for information seeking is particularly common among people with conditions that are perceived as stigmatizing and difficult to discuss. The Sex, Pain, and Endometriosis website is an educational resource designed to provide evidence-based information on endometriosis and sexual pain to help people understand the condition, feel empowered, dispel myths, and destigmatize endometriosis-associated sexual pain., Objective: The study objective is to evaluate the usability of the website and assess for destigmatizing properties of sexual health-related web-based resources., Methods: We conducted a usability analysis by using a think-aloud observation, a postsystem usability questionnaire, and follow-up interviews with 12 women with endometriosis. The think-aloud data were analyzed using the framework by Kushniruk and Patel for analyzing usability video data, the questionnaire data were analyzed using descriptive statistics, and the follow-up interviews were analyzed using simple content analysis. We conducted a usability assessment by deductively analyzing the interview data via a trauma-informed care framework and a content analysis approach., Results: Through usability analysis, we found the website to be simple, uncluttered, satisfying, and easy to use. However, 30 minor usability problems related to navigation; website response; the comprehension of graphics, icons, and tabs; the understanding of content; and mismatch between the website and users' expectations were reported. In our stigma analysis, we found the web content to be nonstigmatizing. The participants suggested ways in which websites could be designed to address stigma, including ensuring privacy, anonymity, inclusiveness, and factual and nonjudgmental content, as well as providing opportunities for web-based engagement., Conclusions: Overall, the participants found the website to be useful, easy to use, and satisfying. The usability problems identified were largely minor and informed the website redesign process. In the context of the limited literature on stigma and website design, this paper offers useful strategies on how sexual health-related websites can be designed to be acceptable and less stigmatizing to individuals with sensitive health issues., (©Abdul-Fatawu Abdulai, A Fuchsia Howard, Paul J Yong, Heather Noga, Gurkiran Parmar, Leanne M Currie. Originally published in JMIR Human Factors (https://humanfactors.jmir.org), 03.03.2022.)

Abstract: A key clinical problem is identifying the patient with endometriosis whose pain is complicated by central nervous system sensitization, where conventional gynecologic treatment (eg, hormonal therapy or surgery) may not completely alleviate the pain. The Central Sensitization Inventory (CSI) is a questionnaire previously validated in the chronic pain population. The objective of this study was an exploratory proof-of-concept to identify a CSI cutoff in the endometriosis population to discriminate between individuals with significant central contributors (identified by central sensitivity syndromes [CSS]) to their pain compared to those without. We analyzed a prospective data registry at a tertiary referral center for endometriosis, and included subjects aged 18 to 50 years with endometriosis who were newly or re-referred to the center in 2018. The study sample consisted of 335 subjects with a mean age of 36.0 ± 7.0 years. An increasing number of CSS was significantly correlated with dysmenorrhea, deep dyspareunia, dyschezia, and chronic pelvic pain scores (P < 0.001), and with the CSI score (0-100) (r = 0.731, P < 0.001). Receiver operating characteristic analysis indicated that a CSI cutoff of 40 had a sensitivity of 78% (95% CI: 72.7%-84.6%) and a specificity of 80% (95% CI: 70.3%-84.5%) for identifying a patient with endometriosis with ≥3 CSS. In the group with CSI ≥ 40, 18% retrospectively self-reported pain nonresponsive to hormonal therapy and 40% self-reported daily pain, compared with 6% and 20% in the CSI < 40 group (P = 0.003 and 0.002, respectively). In conclusion, a CSI ≥ 40 may be a practical tool to help identify patients with endometriosis with pain contributors related to central nervous system sensitization., (Copyright © 2021 International Association for the Study of Pain.)