The stigmatization of prolonged grief disorder and disenfranchised grief: A vignette-based experimental study.

People with prolonged grief disorder (PGD) are at risk of public stigma, but research has yet to examine whether stigma is shaped by different types of relationship losses. In an experimental study, we asked participants (N = 306) to read three scenarios in which targets lost their romantic partner, child, or companion animal. Targets with PGD (vs. integrated grief) elicited more negative emotional reactions and attributions, and their experiences were perceived as less legitimate. Targets who lost their companion animal (vs. other relationship losses) were perceived as the most sensitive and their grief as the least legitimate, but they also elicited the lowest prosocial and fear reactions and were perceived as the warmest. Lastly, targets with PGD who lost their companion animal (vs. other relationship losses) elicited more negative emotional reactions and attributions, and their experiences were perceived as less legitimate. Implications and suggestions for future studies are discussed.

Risk Factors Associated with Unsuccessful High-Resolution Manometry.

High-resolution manometry (HRM) is used to evaluate the esophageal motor function. Unfortunately, there are times when testing cannot be performed accurately. Our study aimed to quantify the occurrence of failed HRM and identify the associated risk factors. HRM tests were retrospectively collected between September 2021 and August 2022. HRM reports that could not be interpreted based on standard HRM protocol as per Chicago guidelines were classified as failed tests. Information reviewed included testing indications, patient demographics, previous medical/symptom history, and follow-up testing for failed HRM. We then compared patients with successful vs. unsuccessful HRM based on our pre-specified factors. 152 HRM tests were performed, of which 28 tests (18%) were unsuccessful. Factors associated with failed manometry included a history of nausea/vomiting, dyspepsia, and achalasia. Patients who were unable to tolerate the probe during testing were more likely to have a history of dyspepsia (OR 20.3, p = < 0.001) and/or nausea/vomiting (OR 13.8, p = < 0.001). A history of achalasia was found to have an odds ratio of 13.2 when examining failure because of curling of the manometry catheter (p = 0.012). All seven patients who had repeat HRM with endoscopic placement were successful in obtaining diagnostic information. There are two groups that have risk factors for unsuccessful HRM testing. A history of nausea/vomiting and dyspepsia symptoms were associated with being unable to tolerate the manometry probe. The second group comprises patients with a history of achalasia in whom probe curling is more common. Future research targeting these risk factors may minimize diagnostic and treatment delays.

A Narrative Review of the Dichotomy Between the Social Views of Non-Monogamy and the Experiences of Consensual Non-Monogamous People.

Monogamy is deeply rooted in most Western societies, shaping how people construe and behave in romantic relationships. These normative views facilitate the emergence of negative perceptions and evaluations when people choose not to adhere to mononormativity. Even though people in consensual non-monogamous (CNM) relationships are targets of stigmatization, research shows a dichotomy between these negative views and the relational experiences of CNM people. Indeed, people in CNM and monogamous relationships have comparable relationship functioning and quality and struggle with similar relationship problems. One of the differences is that CNM relationships afford people to explore their sexuality and fulfill their needs with multiple partners, without agreed-upon extradyadic behavior being perceived as infidelity or having deleterious consequences to relationship maintenance. These positive experiences notwithstanding, CNM people are continuously pressured by mononormativity and stigmatization, increasing the risk of internalized CNM negativity and worse personal and relational outcomes. One possible way to counteract CNM stigmatization and improve the lives of CNM people is by changing discourses surrounding non-monogamy and improving acceptance, not only in professional settings but also in the general population. Another strategy is to understand how the relationship beliefs and scripts of younger generations can help promote more inclusive and diverse societies.

Examining the Role of Mononormative Beliefs, Stigma, and Internalized Consensual Non-Monogamy Negativity for Dehumanization.

Interest in consensually non-monogamous (CNM) relationships has been increasing in the general population in recent years. However, given the cultural dominance of monogamy and the normative expectations often imposed through socialization (i.e., mononormativity), people in CNM relationships may experience negativity, which can become internalized and harm their individual and relationship health. The present study investigated if mononormativity beliefs and CNM relationship stigma were associated with more dehumanization and if internalized CNM negativity was an underlying mechanism for these associations. Results showed that participants who endorsed more mononormative beliefs and CNM relationship stigma also reported more internalized CNM negativity. In turn, participants who experienced more internalized CNM negativity attributed more negative (vs. positive) emotions to themselves and treated their partners as more immature, unrefined, exploitable, and emotionless. These results show that mononormativity and internalized negativity can shape the attitudes, perceptions, and behaviors of CNM individuals toward themselves and their partners.

The Role of Perceived Social Support in the Grief Experiences of More Anxious and Self-Compassionate People.

Past research showed that high trait anxiety and low self-compassion, along with lack of perceived social support, have been associated with experiencing stronger grief symptoms. However, research is yet to understand if and how these factors interact among grieving individuals. Results of a cross-sectional study (N = 539) showed that perceived social support interacted differently with trait anxiety and self-compassion to shape grief experiences. Unexpectedly, perceived social support did not buffer the association between higher trait anxiety and stronger grief symptoms. Instead, participants with higher trait anxiety reported stronger symptoms only when they perceived to have less social support. In contrast, participants with higher self-compassion reported less symptoms when they perceived to have more social support. These findings show that social support can emphasize the detrimental role of anxiety and the protective role of self-compassion when people are coping with a loss. Implications and suggestions for future research are discussed.

Altered Esophageal Smooth Muscle Phenotype in Achalasia.

Background/Aims: Achalasia is a disorder characterized by impairment in lower esophageal sphincter relaxation and esophageal aperistalsis, caused primarily by loss of inhibitory innervation. However, little is known about associated changes in esophageal smooth muscle. We examined the contractile phenotype and innervation of the circular smooth muscle, as well as inflammatory status, and correlated these with patient-specific parameters. Methods: Circular smooth muscle biopsies were obtained in consecutive patients with achalasia undergoing peroral endoscopic myotomy. Axonal innervation and neurotransmitter subtypes were determined with immunocytochemistry, and this was used with quantitative Polymerase Chain Reaction (qPCR) to characterize smooth muscle proliferation and cellular phenotype, as well as collagen expression. These were compared to control tissue obtained at esophagectomy and correlated with patient demographic factors including age, onset of symptoms, and Eckhardt score. Results: Biopsies of smooth muscle were obtained from 25 patients with achalasia. Overall, there was increased mast cell number and collagen deposition but increased smooth muscle cell proliferation vs control. There was a striking drop in axon density over controls, with no differences among subtypes of achalasia. Immunocytochemical analysis showed increased expression of the contractile marker α-smooth muscle actin, principally in Type 1 achalasia, that increased with disease duration, while qPCR identified increased mRNA for smoothelin with decreased myosin heavy chain and collagen 3a1, but not collagen 1a1. Conclusions: The thickened circular smooth muscle layer in achalasia is largely denervated, with an altered contractile phenotype and fibrosis. Biopsies obtained during peroral endoscopic myotomy provide a means to further study the pathophysiology of achalasia.

Response to Marabotto et al.

Biopsies have important value in assessing for nonerosive reflux disease.

Study of the ketohexokinase inhibitor PF-06835919 as a clinical cytochrome P450 3A inducer: Integrated use of oral midazolam and liquid biopsy.

PF-06835919, a ketohexokinase inhibitor, presented as an inducer of cytochrome P450 3A4 (CYP3A4) in vitro (human primary hepatocytes), and static mechanistic modeling exercises predicted significant induction in vivo (oral midazolam area under the plasma concentration-time curve [AUC] ratio [AUCR] = 0.23-0.79). Therefore, a drug-drug interaction study was conducted to evaluate the effect of multiple doses of PF-06835919 (300 mg once daily × 10 days; N = 10 healthy participants) on the pharmacokinetics of a single oral midazolam 7.5 mg dose. The adjusted geometric means for midazolam AUC and its maximal plasma concentration were similar following co-administration with PF-06835919 (vs. midazolam administration alone), with ratios of the adjusted geometric means (90% confidence interval [CI]) of 97.6% (90% CI: 79.9%-119%) and 98.9% (90% CI: 76.4%-128%), respectively, suggesting there was minimal effect of PF-06835919 on midazolam pharmacokinetics. Lack of CYP3A4 induction was confirmed after the preparation of subject plasma-derived small extracellular vesicles (sEVs) and conducting proteomic and activity (midazolam 1'-hydroxylase) analysis. Consistent with the midazolam AUCR observed, the CYP3A4 protein expression fold-induction (geometric mean, 90% CI) was low in liver (0.9, 90% CI: 0.7-1.2) and non-liver (0.9, 90% CI: 0.7-1.2) sEVs (predicted AUCR = 1.0, 90% CI: 0.9-1.2). Likewise, minimal induction of CYP3A4 activity (geometric mean, 90% CI) in both liver (1.1, 90% CI: 0.9-1.3) and non-liver (0.9, 90% CI: 0.5-1.5) sEVs was evident (predicted AUCR = 0.9, 90% CI: 0.6-1.4). The results showcase the integrated use of an oral CYP3A probe (midazolam) and plasma-derived sEVs to assess a drug candidate as inducer.

The role of histology in the diagnosis of non-erosive reflux disease: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Non-erosive reflux disease (NERD) accounts for over half of all gastroesophageal reflux cases and is characterized by reflux symptoms with pathologic acid exposure on pH monitoring but no evidence of erosions on upper endoscopy. Ambulatory pH monitoring is limited by availability and patient tolerance. The utility of performing esophageal mucosal biopsies in diagnosing NERD is unclear. We conducted a systematic review and meta-analysis to determine the sensitivity of esophageal mucosal biopsies in diagnosing NERD. METHODS: Data were obtained from Embase and Ovid MEDLINE from inception to April 2021. Studies were included if esophageal mucosal biopsies were taken and analyzed using conventional histopathologic analysis in symptomatic NERD patients. Relevant data was including histologic abnormalities and location of the biopsy. Sensitivity and specificity were calculated against healthy controls or those with functional heartburn. RESULTS: The search yielded 2871 studies, of which 10 studies met our inclusion criteria and contained raw data. Histological abnormalities included histologic sum scores, papillary elongation, basal cell hyperplasia, and dilated intraepithelial spaces. When assessing for the presence of any abnormality, biopsies taken <3 cm from the lower esophageal sphincter (LES) had a pooled sensitivity of 0.71 (95% CI 0.64-0.77) and specificity of 0.64 (95% 0.54-0.73); however, analysis of individual histologic features such as the presence of eosinophils improved the sensitivity. CONCLUSIONS: Although esophageal mucosal biopsies had poor sensitivity at diagnosing NERD, biopsies taken within 3 cm of the LES had higher sensitivity when pathologists reported upon eosinophils and dilated intraepithelial spaces.

Condom Use Beliefs Differ According to Regulatory Focus: A Mixed-Methods Study in Portugal and Spain.

Reports worldwide have been showing increasing rates of sexually transmitted infections (STIs) and condomless sex in recent years. Research has identified several individual and situational variables that can determine the decision to use condoms or forgo their use. We argue that such a decision can also be shaped by motives related to pleasure and safety (i.e., regulatory focus in sexuality). Using open ended questions, we asked 742 Portuguese and Spanish adults to indicate situations and reasons that could inform the decision making process with casual partners and the functions/attributes related to condoms. Using thematic analyses, we coded the drivers of condomless sex and condom use into themes and subthemes, and computed their frequencies. Using quantitative measures, we also asked participants to indicate their condom use expectancies and perceived barriers. Comparing participants according to regulatory focus revealed some differences. Pleasure promotion participants were more likely to consider that condom use decision making is driven by unexpectedness, pleasure, and intimacy pursuit, attached more pleasure reduction functions to condoms, expected more negative outcomes in condom use, and endorsed more sensation and partner barriers in condom use. In contrast, disease prevention participants were more likely to consider that condom use decision making is driven by adequate sexual education, responsibility, and behavioral control, and attached more health protective functions to condoms. These differences can inform the development of tailored intervention and awareness campaigns aimed at helping people to use condoms more consistently with casual partners and to avoid behaviors that put them at risk of STI transmission.

The epidemiology and impact of disorders of gut-brain interaction in Canada: Results from the Rome Foundation Global Epidemiologic Study.

BACKGROUND: Using data from the Rome Foundation Global Epidemiology Study examining prevalence of disorders of gut-brain interaction (DGBI) in 33 countries, this study explored the prevalence of all 22 disorders in Canada. It examined differences related to geography and sociodemographic factors, health impact and compared these findings to other countries. METHODS: The Rome Foundation survey was conducted through the Internet, targeting 2000 Canadian participants. The survey used the validated ROME IV diagnostic questionnaire to identify the 22 DGBI and an in-depth supplemental questionnaire that included quality assurance techniques. KEY RESULTS: There were 2029 respondents with a mean age of 48 years and 50% females. Diagnostic criteria for at least one of the 22 DGBI were met by 41.3%, similar to other countries. Functional constipation, functional diarrhea, and unspecified functional bowel disorders were most common. Irritable bowel syndrome prevalence was 4.2% using Rome IV and 10.1% using ROME III criteria. DGBI were associated with poorer quality of life and increased psychological symptom scores. Prevalence of DGBI ranged from 48% in Quebec to 36% in British Columbia. Prescription pain medication was reported by 17% with DGBI compared to 9% without DGBI and correlated negatively with mental health and physical well-being. Quebecers and francophones were in limited number but reported higher DGBI prevalence and symptom severity compared to others. CONCLUSIONS & INFERENCES: A large proportion of Canadians suffer from DGBI which seriously impact their well-being. Findings highlight the need for further research and education, including understanding whether significant regional and cultural differences contribute to DGBI.

Relationship and Sexual Quality in the Wake of COVID-19: Effects of Individual Regulatory Focus and Shared Concerns over the Pandemic.

Research has shown mixed findings regarding the effect of the COVID-19 pandemic on relationship and sexual quality and activity. We argue that some of these findings might be understood considering people's predisposition to maintain safety (i.e., prevention focus) or take risks (i.e., promotion focus), and sharing concerns with one's partner about the pandemic. A longitudinal study (N = 153) tested if regulatory focus before the pandemic (November 2019) was associated with relationship quality, sexual quality, and joint sexual activity later on (June 2020) and whether these effects were moderated by shared concerns over the pandemic. Results showed that participants more focused on prevention experienced higher relationship quality later on, but also less sexual quality and less frequent joint sexual activity, when they shared fewer (vs. more) concerns with their partner. In contrast, participants more focused on promotion experienced higher relationship quality later on when they shared more (vs. less) concerns with their partner. These results indicate how individuals' regulatory focus and shared concerns in times of crisis, such as the COVID-19 pandemic, can have downstream consequences on people's relational and sexual dynamics. We offer insights for mental health professionals to improve psychosocial health and well-being when people are faced with critical events.

Evaluation of the Impact of Ritlecitinib on Organic Cation Transporters Using Sumatriptan and Biomarkers as Probes.

Ritlecitinib, an inhibitor of Janus kinase 3 and hepatocellular carcinoma family kinases, is in development as potential treatment for several inflammatory diseases. In vitro studies presented ritlecitinib as an inhibitor of hepatic organic cation transporter (OCT) 1, renal transporters OCT2 and multidrug and toxin extrusion (MATE) proteins 1/2K using multiple substrates, and ritlecitinib's major inactive metabolite M2, as an inhibitor of OCT1. A clinical interaction study with an OCT1 drug probe (sumatriptan) and relevant probe biomarkers for OCT/MATE was conducted to assess the effect of ritlecitinib on these transporters in healthy adult participants. The selectivity of sumatriptan for OCT1 was confirmed through a series of in vitro uptake assays. A simple static model was used to help contextualize the observed changes in sumatriptan area under the plasma concentration-time curve (AUC). Coadministration of a single 400-mg dose of ritlecitinib increased sumatriptan AUC from time 0 to infinity (AUCinf ) by ≈30% relative to a single 25-mg sumatriptan administration alone. When administered 8 hours after a ritlecitinib dose, sumatriptan AUCinf increased by ≈50% relative to sumatriptan given alone. Consistent with OCT1 inhibition, the AUC from time 0 to 24 hours of isobutyryl-L-carnitine decreased by ≈15% after ritlecitinib. Based on the evaluation of the renal clearance of N1 -methylnicotinamide, ritlecitinib does not exert clinically meaningful inhibition on renal OCT2 or MATE1/2K. This study confirmed that ritlecitinib and M2 are inhibitors of OCT1 but not OCT2 or MATE1/2K in healthy adults.

Prevent2Protect Project: Regulatory Focus Differences in Sexual Health Knowledge and Practices.

The way people perceive risks and make decisions about their health is regulated by two motivational systems-prevention of harm or promotion of pleasure. People more focused on prevention strive to avoid negative outcomes and enact more health-protective behaviors. In contrast, people more focused on promotion strive to attain positive outcomes and take more risks with their health. Building upon recent evidence extending this framework to sexual behaviors and health, we conducted a pre-registered online survey ( OSF ) with Portuguese and Spanish adults (N = 742; Mage = 31.42, SD = 9.16) to examine whether self-reported STI knowledge and sexual health practices differ based on predominant regulatory focus. This study was part of the Prevent2Protect project ( OSF ). Results showed that prevention-focused participants had heard about more STIs and retrieved more of their knowledge from scientific sources but had been tested for fewer STIs in the past. In contrast, promotion-focused participants indicated they had specific knowledge about more STIs, retrieved more of their knowledge from medical and peer sources, and had been tested for more STIs in the past. They also reported more frequent STI testing, using free testing facilities or asking their family practice doctor to get tested, more routine sexual health check-ups, and more use of other contraceptive methods, such as birth control pills. These results remained unchanged after controlling for demographic differences. Overall, our findings showed that different motives in sexuality shape sexual health knowledge and sexual health practices.

Reliability and Validity of the Colombian Version of the Revised Sociosexual Orientation Inventory.

Sociosexuality refers to an individual's disposition to have casual sex without establishing affective bonds and has been widely studied worldwide using the Revised Sociosexual Orientation Inventory (SOI-R; Penke & Asendorpf, 2008). Despite its many validations in different cultural contexts, no psychometric analyses of this instrument have been conducted in Spanish-speaking Latin American countries. To address this gap in the literature, we examined the psychometric properties of the SOI-R in Colombia. In a cross-sectional study with a large sample of participants (N = 812; 64% women), we conducted exploratory and confirmatory factor analyses to identify different factor structures and determine which had the best fit for our sample and examined the reliability of the scale. Results showed that a three-factor structure, with sociosexual behaviors, attitudes, and desire as first-order factors, and global sociosexuality as a second-order factor, had the best fit indexes. Each factor presented good reliability indexes. Replicating already established gender differences, we also found that men scored higher on each factor when compared to women. These findings show that the SOI-R is a reliable and valid instrument to assess sociosexuality in countries where sociosexuality research is underrepresented.

Focusing on Safety or Pleasure Determine Condom Use Intentions Differently Depending on Condom Availability and STI Risk.

Objective: Regulatory Focus Theory suggests that goal pursuit is driven by two separate and fundamental motives. Being more focused on prevention motivates people to enact safer behaviors and avoid negative outcomes (e.g., to prevent diseases), whereas being more focused on promotion motivates people to take risks and pursue pleasurable experiences (e.g., condomless sex). Methods: A quasi-experimental study (N = 476) examined if differences in regulatory focus (i.e., prevention vs. promotion) determined condom use intentions with a prospective casual partner, depending on condom availability delay and STI risk cues. Results: Participants focused on prevention (vs. promotion) were less likely to consider having condomless sex across condom availability delays conditions. However, STI risk cues changed condom use intentions. When STI risk was lower, condom use intentions decreased as condom availability delays increased (particularly for participants focused on promotion). When STI risk was higher, condom use intentions were stronger and consistent across condom availability delays (particularly for participants focused on prevention). Conclusions: These findings highlight the importance of distinct sexual motives when examining sexual health practices.