Atlas of the receptive anal sex experience among people with prostates.

BACKGROUND: Receptive anal intercourse (RAI) is commonly practiced among individuals of all sexual orientations. However, negative stigmatization by society and health care professionals leads to the underreporting or this practice. AIM: We sought to assess and describe the subjective role of the prostate as a pleasure center in participants with diverse RAI experiences. The secondary aim was to describe nonprostatic areas within the anorectal region that produce erotic sensation and/or pain. METHODS: The exploratory sequential multimethod study design included focus groups and semistructured interviews with 30 individuals with prostates who had engaged in RAI. We used graphic elicitation of natal male anatomy to enhance visualization and assess participant perspectives. OUTCOMES: The main outcome of interest was the identification of anatomic locations of erogenous sensation and pain during RAI. RESULTS: Among the participants (median age 38, range 24-77 years), most participants (90%) identified as cisgender male. Three major themes emerged within the motivations for RAI, including (1) deriving intrinsic pleasure, (2) providing both pleasure for a partner and a way to improve intimacy/connection, and (3) an inability to be the insertive partner due to physical or mental challenges. The data suggest that the anorectal region produces a variety of erogenous sensations which participants find pleasurable. Overall, 2 major areas of erogenous sensation occur along the anterior rectal wall and within the anus. Within the context of RAI, 2 distinct categories of pain emerged, including pain with insertion and pain at other times. CLINICAL IMPLICATIONS: Understanding where erogenous sensation originates for each individual may predict sexual functioning after various surgical interventions. Timing and location of pain may aid in further characterizing anodyspareunia. STRENGTHS AND LIMITATIONS: Our study utilized a sequential design (from focus groups to interviews) with diverse RAI experiences, especially regarding age, geographic location, and prostate pathology. We included individuals of diverse gender identities, but too few to evaluate these groups independently from cisgender men. CONCLUSION: People with prostates experience pleasure in multiple areas during RAI. Contrary to some lay literature, the prostate region is not the subjective pleasure center for all individuals. Timing and location of pain during RAI may inform areas for intervention. Providing a language for pleasure and pain during RAI may improve communication between not only sexual partners but also clinicians and patients.

Relationship between pelvic sensations and lifetime exposure to receptive anal intercourse among people with prostates.

BACKGROUND: Despite the negative stigma on receptive anal intercourse (RAI), this behavior has a positive influence on individuals' sexual and relationship health. No large studies have previously looked at specific sensations experienced during RAI and how these sensations may change with experience. AIM: In this study we aimed to quantify commonly reported pelvic sensations during RAI and determine whether their presentation changes with increasing experience of RAI. METHODS: An internet survey was conducted on sensations felt during RAI among people with prostates from July 2022-January 2023. The survey content was developed based on a mixed-methods qualitative study and inquired about demographic and sexual histories as well as sensations (pleasure, pain, urinary, and bowel) experienced during RAI. We used descriptive statistics to describe demographic and sexual histories. All data were stratified by lifetime exposure to RAI. OUTCOMES: The primary outcomes assessed included the quantification of both the primary sensations experienced during RAI and the associated bother. RESULTS: In total, 975 participants completed the survey. The median age was 32 (range 18-78) years. The average age of first participation in RAI was 21 ± 6.6 years. Most respondents were having sex at least once a week (65%). Nine percent of respondents reported fewer than 10 experiences with RAI, 26% reported 11-50 RAI experiences, 32% reported 51-200 experiences, 16% reported 201-500 experiences, and 18% reported >500 experiences. As the number of experiences with RAI increased (from <10 to >500 exposures), the reported frequency of pleasurable sensation increased from 41% to 92% (P < .0001), whereas severe insertional pain and symptoms of bowel urgency decreased from 39% to 13% and from 21% to 6%, respectively (P < .0001). Urinary urgency sensation did not differ by lifetime RAI experience. CLINICAL IMPLICATIONS: Lifetime RAI exposure can be readily assessed and correlates not only with pelvic sensation but also many other aspects of sexual health. These results imply that the etiology of dissatisfaction with pleasure or anodyspareunia during RAI may differ by lifetime RAI exposure. STRENGTHS AND LIMITATIONS: This is the first study to our knowledge to assess pelvic sensations experienced during RAI among a large sample of individuals. This is a cross-sectional study, and we cannot conclude how pelvic sensations change over time among individuals. Internet-based participants may not be representative of clinical populations. CONCLUSION: Lifetime exposure to RAI is positively associated with pleasure and is negatively associated with pain and bowel urgency. Pelvic sensations experienced during RAI appear to be dependent on lifetime RAI exposure history regardless of age.

Receptive Anal Intercourse: Impact on Colorectal and Urologic Diagnoses.

Purpose: We evaluated the relationship between lifetime receptive anal intercourse (RAI) and the risk of common colorectal and urologic diagnoses. Methods: We conducted an internet-based survey on sensations during RAI between July 2022 and March 2023. We used multivariable logistic regression to assess the independent impact of lifetime RAI exposure on the diagnosis of common urologic and colorectal conditions. Participants completed a main survey and were invited to complete randomly assigned patient-reported outcome measures (PROMs), which measured pelvic symptoms, mental health symptoms, and sexual satisfaction. Results: In total, 1100 participants completed the main survey and 416 completed the PROMs. Participants of the main survey ranged from 18 to 78 years old and the median age of the sample was 32 years. There was no significant association between lifetime RAI exposure and any medical diagnosis, except for anal fissures, which increased linearly with additional RAI exposure. Both sexual satisfaction and mental health symptoms improved with RAI exposure. Conclusions: RAI was not associated with most of the colorectal and urologic diagnoses tested and was associated with fewer mental symptoms and increased sexual satisfaction. Development of anal fissures may be directly related to trauma of the anal canal from penetration.

Anorectal Sexual Function Index: Development and Validation of a Health-related Quality of Life Measure.

OBJECTIVE: To assess the reliability and validity of measuring receptive anal intercourse (RAI) sensation and associated satisfaction and bother. METHODS: Between July 2022 and January 2023, we conducted a survey on sensations during RAI among people with prostates (ie, cisgender men and transgender women). The survey content was developed based on our previous qualitative study. We assessed internal reliability and consistency through time. Sensations experienced during RAI were correlated with health-related quality-of-life measures to ensure construct validity. RESULTS: The final index contained four scales: pleasure (four items), pain (seven items), urinary (four items), and bowel (four items). Overall, 1084 individuals filled out the questionnaire. The internal consistency for all subscales was at or above 0.79. Scores tended to be stable across time with all test-retest coefficients at or above 0.72. Pleasure scores were inversely correlated with pain scores (r = -0.46). Pleasure was positively correlated with erections (r = 0.36) and orgasms (r = 0.44) during RAI, and sexual satisfaction (r = 0.39). Notable positive correlations for pain scores were with bowel scores (r = 0.49), internalized homophobia (r = 0.35), and prostatitis symptoms (r = 0.37). Urinary scores were moderately associated with IPSS scores (r = 0.22). Bowel scores were positively correlated with GI symptoms (r = 0.24), mental health symptoms (r = 0.28), and chronic prostatitis symptoms (r = 0.29). CONCLUSION: The results of the current study provide evidence that the Anorectal Sexual Function Index is both reliable and valid. The Anorectal Sexual Function Index may be a particularly useful health-related quality-of-life measure to assess outcomes regarding a host of urologic issues that may affect RAI.

Mapping accessible chromatin regions using Sono-Seq.

Disruptions in local chromatin structure often indicate features of biological interest such as regulatory regions. We find that sonication of cross-linked chromatin, when combined with a size-selection step and massively parallel short-read sequencing, can be used as a method (Sono-Seq) to map locations of high chromatin accessibility in promoter regions. Sono-Seq sites frequently correspond to actively transcribed promoter regions, as evidenced by their co-association with RNA Polymerase II ChIP regions, transcription start sites, histone H3 lysine 4 trimethylation (H3K4me3) marks, and CpG islands; signals over other sites, such as those bound by the CTCF insulator, are also observed. The pattern of breakage by Sono-Seq overlaps with, but is distinct from, that observed for FAIRE and DNase I hypersensitive sites. Our results demonstrate that Sono-Seq can be a useful and simple method by which to map many local alterations in chromatin structure. Furthermore, our results provide insights into the mapping of binding sites by using ChIP-Seq experiments and the value of reference samples that should be used in such experiments.

Effect of buffer general acid-base catalysis on the stereoselectivity of ester and thioester H/D exchange in D2O.

As part of a comprehensive investigation on the stereochemistry of base-catalyzed 1,2-elimination and H/D exchange reactions of carbonyl compounds, we have found that the stereoselectivity of H/D exchange of 3-hydroxybutyryl N-acetylcysteamine (3) in D(2)O is strongly influenced by the presence of buffers. This buffer effect is also operative with a simple acyclic ester, ethyl 3-methoxybutanoate (7). Buffers whose general-acid components are cyclic tertiary ammonium ions are particularly effective in changing the stereoselectivity. (2)H NMR analysis showed that without buffer, H/D exchange of 3 produces 81-82% of the 2R*, 3R* diastereomer of 2-deuterio 3 (the anti product). In the presence of 0.33 M 3-quinuclidinone buffer, only 44% of the 2R*, 3R* diastereomer was formed. With ester 7, the stereoselectivity went from 93-94% in DO(-)/D(2)O to 60% in the presence of buffer. Phosphate buffer, as well as others, also showed substantial effects. The results are put into the context of what is known about the mechanism of H/D exchange of esters and thioesters, and the relevance of the buffer effect on the mechanism of the enoyl-CoA hydratase reaction is discussed. It is likely that hydrogen bonding in the enolate-buffer acid encounter complex is an important stereochemical determinant in producing a greater amount of the 2R*, 3S* diastereomer (the syn product). Studies that involve the protonation of enolate anions in D(2)O need to include the buffer general acid in any understanding of the stereoselectivity.

Extensive chromatin fragmentation improves enrichment of protein binding sites in chromatin immunoprecipitation experiments.

Extensive sonication of formaldehyde-crosslinked chromatin can generate DNA fragments averaging 200 bp in length (range 75-300 bp). Fragmentation is largely random with respect to genomic region and nucleosome position. ChIP experiments employing such extensively fragmented samples show 2- to 4-fold increased enrichment of protein binding sites over control genomic regions, when compared to samples sonicated to a more conventional size range (300-500 bp). The basis of improved fold enrichments is that immunoprecipitation of protein-bound regions is unaffected by fragment size, whereas immunoprecipitation of control genomic regions decreases progressively along with reduced fragment size due to fewer nonspecific binding sites. The use of extensively sonicated samples improves mapping of protein binding sites, and it extends the dynamic range for quantitative measurements of histone density. We show that many yeast promoter regions are virtually devoid of histones.

Dynamic glycosylation of the transcription factor CREB: a potential role in gene regulation.

We report that CREB (cyclic AMP-responsive element-binding protein), a transcription factor essential for long-term memory, is O-GlcNAc glycosylated in the mammalian brain. Glycosylation occurs at two sites within the Q2 domain and disrupts the interaction between CREB and TAFII130, thereby repressing the transcriptional activity of CREB in vitro. These findings have important implications for the role of O-GlcNAc glycosylation in gene regulation, and they provide a link between O-GlcNAc and information storage processes in the brain.

A chemoenzymatic approach toward the rapid and sensitive detection of O-GlcNAc posttranslational modifications.

We report a new chemoenzymatic strategy for the rapid and sensitive detection of O-GlcNAc posttranslational modifications. The approach exploits the ability of an engineered mutant of beta-1,4-galactosyltransferase to selectively transfer an unnatural ketone functionality onto O-GlcNAc glycosylated proteins. Once transferred, the ketone moiety serves as a versatile handle for the attachment of biotin, thereby enabling chemiluminescent detection of the modified protein. Importantly, this approach permits the rapid visualization of proteins that are at the limits of detection using traditional methods. Moreover, it bypasses the need for radioactive precursors and captures the glycosylated species without perturbing metabolic pathways. We anticipate that this general chemoenzymatic strategy will have broad application to the study of posttranslational modifications.