Effectiveness of laparoscopic removal of isolated superficial peritoneal endometriosis for the management of chronic pelvic pain in women (ESPriT2): protocol for a multi-centre randomised controlled trial.

BACKGROUND: Endometriosis affects 190 million women and those assigned female at birth worldwide. For some, it is associated with debilitating chronic pelvic pain. Diagnosis of endometriosis is often achieved through diagnostic laparoscopy. However, when isolated superficial peritoneal endometriosis (SPE), the most common endometriosis subtype, is identified during laparoscopy, limited evidence exists to support the common decision to surgically remove it via excision or ablation. Improved understanding of the impact of surgical removal of isolated SPE for the management of chronic pelvic pain in women is required. Here, we describe our protocol for a multi-centre trial to determine the effectiveness of surgical removal of isolated SPE for the management of endometriosis-associated pain. METHODS: We plan to undertake a multi-centre participant-blind parallel-group randomised controlled clinical and cost-effectiveness trial with internal pilot. We plan to randomise 400 participants from up to 70 National Health Service Hospitals in the UK. Participants with chronic pelvic pain awaiting diagnostic laparoscopy for suspected endometriosis will be consented by the clinical research team. If isolated SPE is identified at laparoscopy, and deep or ovarian endometriosis is not seen, participants will be randomised intraoperatively (1:1) to surgical removal (by excision or ablation or both, according to surgeons' preference) versus diagnostic laparoscopy alone. Randomisation with block-stratification will be used. Participants will be given a diagnosis but will not be informed of the procedure they received until 12 months post-randomisation, unless required. Post-operative medical treatment will be according to participants' preference. Participants will be asked to complete validated pain and quality of life questionnaires at 3, 6 and 12 months after randomisation. Our primary outcome is the pain domain of the Endometriosis Health Profile-30 (EHP-30), via a between randomised group comparison of adjusted means at 12 months. Assuming a standard deviation of 22 points around the pain score, 90% power, 5% significance and 20% missing data, 400 participants are required to be randomised to detect an 8-point pain score difference. DISCUSSION: This trial aims to provide high quality evidence of the clinical and cost-effectiveness of surgical removal of isolated SPE. TRIAL REGISTRATION: ISRCTN registry ISRCTN27244948. Registered 6 April 2021.

A Dose of Truth: A Qualitative Assessment of Reactions to Messages about Fentanyl for People Who Use Drugs.

Background: Fentanyl-related overdoses are occurring at alarming rates and developing campaigns to increase awareness about fentanyl and harm-reduction strategies is critical. A Dose of Truth is an educational campaign aiming to increase knowledge about the threat of fentanyl and risk of exposure among people who use drugs (PWUD). The current study tests preliminary concepts and messages for the campaign. Methods: Twenty-one one-on-one interviews were conducted with young adults ages 18-35 who use drugs. Participants discussed knowledge of fentanyl and perceived risk of exposure, and provided feedback on four concepts. Thematic analysis of transcripts generated insights about promising approaches and topics. Results: Findings demonstrated that fentanyl awareness is growing among PWUD, but they perceive low risk of exposure because they trust a source. Messaging that challenged that trust, by highlighting that contaminated drug supplies are increasingly widespread, made personal risk salient. Additionally, messaging conveyed through a personal narrative that encouraged carrying naloxone to protect friends was perceived as personally relevant. Conclusions: While opioid- and fentanyl-related campaigns exist, few have used an evidence-based process to guide campaign development. Addressing gaps in knowledge and developing messages that are personally relevant are foundational steps in creating effective campaigns on fentanyl and other substances.

This Free Life Campaign: Increasing Intention to Quit Among LGBTQ+ Young Adult Nondaily Smokers in Minneapolis.

PURPOSE: LGBTQ+ young adults smoke at disproportionately higher rates than their non-LGBTQ+ counterparts, but prevention efforts are limited. Furthermore, prior to This Free Life (TFL), no known campaigns target LGBTQ+ nondaily smokers. In this study Blue Cross and Blue Shield of Minnesota evaluated a local partnership extension of the Food and Drug Administration (FDA) Center for Tobacco Products' TFL campaign. METHODS: The intervention featured a variety of LGBTQ+-tailored events, social/digital media, and out-of-home media placed in locations with a high density of LGBTQ+ young adults. Cross-sectional surveys (n = 1215) were collected from LGBTQ+ young adult (18-26) nondaily smokers at 4 time points between 2016 and 2019. The national TFL campaign was tracked in a separate evaluation conducted by the FDA. RESULTS: 43.0% of nondaily LGBTQ+ smokers reported awareness of the campaign (n = 522), and 63.4% of those also engaged with TFL (n = 330). Engagement was highest for gay, lesbian and transgender participants, and for Asian and Black/African American participants. Each additional instance of campaign engagement increased participants' odds of intending to quit smoking by 20% (AOR = 1.20; 95% CI = 1.05, 1.36). The relationship between campaign engagement and intention to quit was fully mediated by the campaign's impact on attitudes against smoking and perceived normative trends, but not by perceived behavioral control. CONCLUSION: The local extension of TFL increased intentions to quit for LGBTQ+ nondaily smokers. Future research should further explore the relationship between perceived behavioral control and intentions to quit for nondaily smokers.

Unrequited love: The role of prior commitment, motivation to remain friends, and friendship maintenance.

This study tested a moderated mediation model that commitment prior to an unrequited love episode will be related to higher levels of friendship maintenance behaviors after the episode and that this relationship will be mediated by the individual's motivations to remain friends with the rejecter. We predicted that rejection distress would weaken the mediational model among those reporting high distress. Participants wrote about an unrequited love experience as a pursuer and completed measures of pre-unrequited love commitment, rejection distress, motivations to remain friends, and friendship maintenance behaviors. Our results confirmed the moderated mediation model when the motivations to remain friends measure overall score, the interpersonal connection motivation, or the social connections motivation was the mediator. When covariates were added, only the model with the overall motivations score as mediator was supported. These data can help laypersons and mental health professionals understand and potentially repair friendships following an unrequited love episode.

Freedom From Chew: Using Social Branding to Reduce Chewing Tobacco Use Among Country Peer Crowd Teens.

BACKGROUND: Peer crowds are macro-level, reputation-based subcultures with shared preferences, values, and behavior. The Country peer crowd has been the focus of tobacco industry research and marketing but has yet to be the primary focus of public health research. The current study explores the utility of Down and Dirty, a Social Branding tobacco education campaign, in changing Virginia Country teens' chewing tobacco-related attitudes and behavior. The relationship between chew use and Country peer crowd identification was also explored. METHOD: To evaluate the campaign, a cross-sectional survey was administered online for 3 years from 2014 to 2016. Responses were collected via social media advertisements targeting 13- to 18-year-old Country youth from Virginia (total n = 1,264). Participants reported peer crowd identification, chew-related attitudes and behavior, and campaign engagement and appeal. RESULTS: Compared with Wave 1, Waves 2 and 3 Country teens who engaged with Down and Dirty had greater odds of holding strong attitudes against chew. Among campaign-engaged Country teens, odds of chew use were lower at Waves 2 and 3, and lower odds were associated with liking the campaign. Related to chew prevalence, Country teens demonstrated greater odds of past 30-day chew use compared to non-Country teens, and higher Country identification was associated with greater odds of chew use. DISCUSSION: Down and Dirty is a promising intervention associated with positive attitudinal and behavioral outcomes for high-risk Country teens. Additionally, this study helps document tobacco-related behavioral patterns of the Country peer crowd, a priority for ongoing tobacco education, especially around chew.

Pericellular interphotoreceptor matrix dictates outer retina critical surface tension.

Retinal detachments create two pathological surfaces, the surface of the outer neural retinal, and an apical retinal-pigmented epithelium (RPE) surface. The physicochemical properties of these two new surfaces are poorly understood. At a molecular level little is known how detachments form, how to optimize reattachment, or prevent extension of the detachment. A major limitation is lack of information about the biophysical consequences of the retina-RPE separation. The primary challenge is determining the molecular properties of the pathological interface surfaces. Here, using detached bovine retina, we show that this hurdle can be overcome through a combination of biophysical and ultrastructural approaches. The outer surface of freshly detached bovine neural retina, and isolated molecular components of the outer retina were subjected to: 1) Contact angle goniometry to determine the critical surface tension of the outer retinal surface, isolated insoluble interphotoreceptor matrix (IPM) and purified interphotoreceptor retinoid binding protein (IRBP); 2) Multiple attenuated internal reflectance infrared (MAIR-IR) spectroscopy was used to characterize the molecular composition of the retinal surface. MAIR-IR depth penetration was established through ellipsometric measurement of barium-stearate films. Light microscopy, immunohistochemistry and electron microscopy defined the structures probed spectroscopically. Furthermore, the data were correlated to IR spectra of docosahexaenoic acid, hyaluronan, chondroitin-6-sulfate and IRBP, and imaging by IR-microscopy. We found that the retinal critical surface tension is 24 mN/m, similar to isolated insoluble IPM and lower than IRBP. Barium-stearate calibration studies established that the MAIR-IR spectroscopy penetration depth was 0.2 µm. Ultrastructural observations and MAIR-IR studies of isolated outer retina components determined that the pericellular IPM coating the outer retinal surface is primarily responsible for these surface properties. The critical surface tension of detached bovine retina is dictated not by the outer segments, but by a pericellular IPM covering the outer segment tips.

Effect of air drying on bacterial viability: A multiparameter viability assessment.

The effect of desiccation on the viability of microorganisms is a question of great interest for a variety of public health questions and industrial applications. Although viability is traditionally assessed by plate counts, cultivation-independent methods are increasingly applied with the aim to gain more insight into why cells might not form colonies and to optimize production processes. To evaluate their usefulness, we applied in this study a multiparameter viability assay to selected bacteria (Escherichia coli, Pseudomonas aeruginosa, Enterococcus hirae, and Staphylococcus aureus) subjected to air-drying in the absence or presence of supplements. Tests included growth on solid culture medium and the measurement of membrane integrity, membrane potential, esterase and respiratory activities using fluorescent dyes. All measured parameters were responsive to desiccation stress. Results suggested that extending plate count analysis with cultivation-independent methods can greatly enhance resolution especially for moderate stress conditions, which do not get reflected in plate counts due to cellular recovery. Whereas plate counts reflect the final effect on viability, immediate measurement of cellular functions provides a snapshot picture of the fitness status at a specific point in time. Special emphasis was given to MgCl(2) which in concentrations≥50mM dramatically increased the bacterial susceptibility to desiccation in the case of the gram-negative bacteria and to a lesser extent also for the gram-positive bacteria. The study in addition confirmed a good agreement of results obtained with the recently developed real-time viability (RTV) assay and the BacLight LIVE/DEAD method in combination with a fluorescence plate reader.

Use of propidium monoazide for live/dead distinction in microbial ecology.

One of the prerequisites of making ecological conclusions derived from genetic fingerprints is that bacterial community profiles reflect the live portion of the sample of interest. Propidium monoazide is a membrane-impermeant dye that selectively penetrates cells with compromised membranes, which can be considered dead. Once inside the cells, PMA intercalates into the DNA and can be covalently cross-linked to it, which strongly inhibits PCR amplification. By using PCR after PMA treatment, the analysis of bacterial communities can theoretically be limited to cells with intact cell membranes. Four experiments were performed to study the usefulness of PMA treatment of mixed bacterial communities comprising both intact and compromised cells in combination with end-point PCR by generating community profiles from the following samples: (i) defined mixtures of live and isopropanol-killed cells from pure cultures of random environmental isolates, (ii) wastewater treatment plant influent spiked with defined ratios of live and dead cells, (iii) selected environmental communities, and (iv) a water sediment sample exposed to increasing heat stress. Regions of 16S rRNA genes were PCR amplified from extracted genomic DNA, and PCR products were analyzed by using denaturing gradient gel electrophoresis (DGGE). Results from the first two experiments show that PMA treatment can be of value with end-point PCR by suppressing amplification of DNA from killed cells. The last two experiments suggest that PMA treatment can affect banding patterns in DGGE community profiles and their intensities, although the intrinsic limitations of end-point PCR have to be taken into consideration.