Triclosan administration to humanized UDP-glucuronosyltransferase 1 neonatal mice induces UGT1A1 through a dependence on PPARα and ATF4.

Triclosan (TCS) is an antimicrobial toxicant found in a myriad of consumer products and has been detected in human tissues, including breastmilk. We have evaluated the impact of lactational TCS on UDP-glucuronosyltransferase 1A1 (UGT1A1) expression and bilirubin metabolism in humanized UGT1 (hUGT1) neonatal mice. In hUGT1 mice, expression of the hepatic UGT1A1 gene is developmentally delayed resulting in elevated total serum bilirubin (TSB) levels. We found that newborn hUGT1 mice breastfed or orally treated with TCS presented lower TSB levels along with induction of hepatic UGT1A1. Lactational and oral treatment by gavage with TCS leads to the activation of hepatic nuclear receptors constitutive androstane receptor (CAR), peroxisome proliferator-activated receptor alpha (PPARα), and stress sensor, activating transcription factor 4 (ATF4). When CAR-deficient hUGT1 mice (hUGT1/Car-/-) were treated with TCS, TSB levels were reduced with a robust induction of hepatic UGT1A1, leaving us to conclude that CAR is not tied to UGT1A1 induction. Alternatively, when PPARα-deficient hUGT1 mice (hUGT1/Pparα-/-) were treated with TCS, hepatic UGT1A1 was not induced. Additionally, we had previously demonstrated that TCS is a potent inducer of ATF4, a transcriptional factor linked to the integrated stress response. When ATF4 was deleted in liver of hUGT1 mice (hUGT1/Atf4ΔHep) and these mice treated with TCS, we observed superinduction of hepatic UGT1A1. Oxidative stress genes in livers of hUGT1/Atf4ΔHep treated with TCS were increased, suggesting that ATF4 protects liver from excessive oxidative stress. The increase oxidative stress may be associated with superinduction of UGT1A1. The expression of ATF4 in neonatal hUGT1 hepatic tissue may play a role in the developmental repression of UGT1A1.

Dynamic phase separation of the androgen receptor and its coactivators key to regulate gene expression.

Numerous cancers, including prostate cancer (PCa), are addicted to transcription programs driven by specific genomic regions known as super-enhancers (SEs). The robust transcription of genes at such SEs is enabled by the formation of phase-separated condensates by transcription factors and coactivators with intrinsically disordered regions. The androgen receptor (AR), the main oncogenic driver in PCa, contains large disordered regions and is co-recruited with the transcriptional coactivator mediator complex subunit 1 (MED1) to SEs in androgen-dependent PCa cells, thereby promoting oncogenic transcriptional programs. In this work, we reveal that full-length AR forms foci with liquid-like properties in different PCa models. We demonstrate that foci formation correlates with AR transcriptional activity, as this activity can be modulated by changing cellular foci content chemically or by silencing MED1. AR ability to phase separate was also validated in vitro by using recombinant full-length AR protein. We also demonstrate that AR antagonists, which suppress transcriptional activity by targeting key regions for homotypic or heterotypic interactions of this receptor, hinder foci formation in PCa cells and phase separation in vitro. Our results suggest that enhanced compartmentalization of AR and coactivators may play an important role in the activation of oncogenic transcription programs in androgen-dependent PCa.

Oral arsenic administration to humanizedUDP-glucuronosyltransferase1 neonatal mice induces UGT1A1 through a dependence on Nrf2 and PXR.

Inorganic arsenic (iAs) is an environmental toxicant that can lead to severe health consequences, which can be exacerbated if exposure occurs early in development. Here, we evaluated the impact of oral iAs treatment on UDP-glucuronosyltransferase 1A1 (UGT1A1) expression and bilirubin metabolism in humanized UGT1 (hUGT1) mice. We found that oral administration of iAs to neonatal hUGT1 mice that display severe neonatal hyperbilirubinemia leads to induction of intestinal UGT1A1 and a reduction in total serum bilirubin values. Oral iAs administration accelerates neonatal intestinal maturation, an event that is directly associated with UGT1A1 induction. As a reactive oxygen species producer, oral iAs treatment activated the Keap-Nrf2 pathway in the intestinal tract and liver. When Nrf2-deficient hUGT1 mice (hUGT1/Nrf2-/-) were treated with iAs, it was shown that activated Nrf2 contributed significantly toward intestinal maturation and UGT1A1 induction. However, hepatic UGT1A1 was not induced upon iAs exposure. We previously demonstrated that the nuclear receptor PXR represses liver UGT1A1 in neonatal hUGT1 mice. When PXR was deleted in hUGT1 mice (hUGT1/Pxr-/-), derepression of UGT1A1 was evident in both liver and intestinal tissue in neonates. Furthermore, when neonatal hUGT1/Pxr-/- mice were treated with iAs, UGT1A1 was superinduced in both tissues, confirming PXR release derepressed key regulatory elements on the gene that could be activated by iAs exposure. With iAs capable of generating reactive oxygen species in both liver and intestinal tissue, we conclude that PXR deficiency in neonatal hUGT1/Pxr-/- mice allows greater access of activated transcriptional modifiers such as Nrf2 leading to superinduction of UGT1A1.

Internal capsule microstructure mediates the relationship between childhood maltreatment and PTSD following adulthood trauma exposure.

Childhood trauma is a known risk factor for trauma and stress-related disorders in adulthood. However, limited research has investigated the impact of childhood trauma on brain structure linked to later posttraumatic dysfunction. We investigated the effect of childhood trauma on white matter microstructure after recent trauma and its relationship with future posttraumatic dysfunction among trauma-exposed adult participants (n = 202) recruited from emergency departments as part of the AURORA Study. Participants completed self-report scales assessing prior childhood maltreatment within 2-weeks in addition to assessments of PTSD, depression, anxiety, and dissociation symptoms within 6-months of their traumatic event. Fractional anisotropy (FA) obtained from diffusion tensor imaging (DTI) collected at 2-weeks and 6-months was used to index white matter microstructure. Childhood maltreatment load predicted 6-month PTSD symptoms (b = 1.75, SE = 0.78, 95% CI = [0.20, 3.29]) and inversely varied with FA in the bilateral internal capsule (IC) at 2-weeks (p = 0.0294, FDR corrected) and 6-months (p = 0.0238, FDR corrected). We observed a significant indirect effect of childhood maltreatment load on 6-month PTSD symptoms through 2-week IC microstructure (b = 0.37, Boot SE = 0.18, 95% CI = [0.05, 0.76]) that fully mediated the effect of childhood maltreatment load on PCL-5 scores (b = 1.37, SE = 0.79, 95% CI = [-0.18, 2.93]). IC microstructure did not mediate relationships between childhood maltreatment and depressive, anxiety, or dissociative symptomatology. Our findings suggest a unique role for IC microstructure as a stable neural pathway between childhood trauma and future PTSD symptoms following recent trauma. Notably, our work did not support roles of white matter tracts previously found to vary with PTSD symptoms and childhood trauma exposure, including the cingulum bundle, uncinate fasciculus, and corpus callosum. Given the IC contains sensory fibers linked to perception and motor control, childhood maltreatment might impact the neural circuits that relay and process threat-related inputs and responses to trauma.

Time to diagnosis among young patients with cancer.

BACKGROUND: Sociodemographic and clinical factors associated with diagnostic delays in pediatric, adolescent, and young adult cancers are poorly understood. METHODS: Using the Optum Labs Data Warehouse's de-identified claims data for commercial health plan enrollees, we identified children (0-14 years) and adolescents/young adults (AYAs) (15-39 years) diagnosed with one of 10 common cancers from 2001 to 2017, who were continuously enrolled for 6 months preceding diagnosis. Time to diagnosis was calculated as days between first medical encounter with possible cancer symptoms and cancer diagnosis date. Median times from first symptom to diagnosis were compared using Wilcoxon rank sum test. Multivariable unconditional logistic regression identified sociodemographic factors associated with longer time (>3 months) to cancer diagnosis (from symptom onset). RESULTS: Of 47,296 patients, 87% presented prior to diagnosis with symptoms. Patients with central nervous system (CNS) tumors were most likely to present with symptoms (93%), whereas patients with cervical cancer were least likely (70%). Symptoms varied by malignancy. Of patients with symptoms, thyroid (105 days [range: 50-154]) and cervical (104 days [range: 41-151]) cancer had the longest median time to diagnosis. Females and patients at either end of the age spectrum were more likely to experience diagnosis delays of more than 3 months. CONCLUSION: In a commercially insured population, time to diagnosis varies by cancer type, age, and sex. Further work is needed to understand the patient, provider, and health system-level factors contributing to time from symptom onset to diagnosis, specifically in the very young children and the young adult patient population going forward.

Comparison of S100A8 and PRAME as biomarkers for distinguishing melanoma from melanocytic naevus: a case-control analysis.

BACKGROUND: S100A8 is a melanoma biomarker expressed in the melanoma-associated epidermal keratinocytes, but its diagnostic utility has not been compared with other biomarkers, including PRAME. OBJECTIVES: To compare the utility of S100A8 and PRAME immunohistochemistry (IHC) in the differential diagnosis of melanoma and naevi in a case-control study. METHODS: A previously described cohort of 209 melanomas (case samples) and naevi (control samples) dual-immunostained for S100A8 and PRAME were included. For S100A8, previously reported scores indicating the proportion of tumour-associated epidermis stained (0 = indeterminate; 1 = 0-4%; 2 = 5-25%; 3 = 26-50%; 4 = 51-75%; 5 = > 75%) were utilized. PRAME IHC was reviewed by at least two reviewers and a consensus score assigned, with score indicating the proportion of tumour stained (0 = indeterminate; 1 = 0%; 2 = 1-50%; 3 = > 50%). A positive test was defined as > 50% staining. RESULTS: The area under the receiver operating characteristic curves for S100A8 (0.833) and PRAME (0.874) were not significantly different from each other (P = 0.22). The diagnostic sensitivity and specificity were 42.4% [95% confidence interval (CI) 32.6-52.8%] and 98.2% (95% CI 93.6-99.8%) for S100A8, and 79.8% (95% CI 70.5-87.2%) and 87.3% (95% CI 79.6-92.9%) for PRAME, respectively. A combined test requiring both S100A8 and PRAME IHC positivity had a sensitivity of 39.4% (95% CI 29.7-49.7%) and specificity of 99.1% (95% CI 95.0-100.0%). CONCLUSIONS: S100A8 and PRAME have utility in the diagnostic workup of melanoma, with S100A8 being more specific and PRAME being more sensitive when using this threshold. Our findings suggest that these two immunohistochemical markers may favourably complement one another to improve the detection of melanoma.

Childhood adversity, accelerated GrimAge, and associated health consequences.

Childhood adversity is linked to psychological, behavioral, and physical health problems, including obesity and cardiometabolic disease. Epigenetic alterations are one pathway through which the effects of early life stress and adversity might persist into adulthood. Epigenetic mechanisms have also been proposed to explain why cardiometabolic health can vary greatly between individuals with similar Body Mass Index (BMIs). We evaluated two independent cross-sectional cohorts of adults without known medical illness, one of which explicitly recruited individuals with early life stress (ELS) and control participants (n = 195), and the other a general community sample (n = 477). In these cohorts, we examine associations between childhood adversity, epigenetic aging, and metabolic health. Childhood adversity was associated with increased GrimAge Acceleration (GAA) in both cohorts, both utilizing a dichotomous yes/no classification (both p < 0.01) as well as a continuous measure using the Childhood Trauma Questionnaire (CTQ) (both p < 0.05). Further investigation demonstrated that CTQ subscales for physical and sexual abuse (both p < 0.05) were associated with increased GAA in both cohorts, whereas physical and emotional neglect were not. In both cohorts, higher CTQ was also associated with higher BMI and increased insulin resistance (both p < 0.05). Finally, we demonstrate a moderating effect of BMI on the relationship between GAA and insulin resistance where GAA correlated with insulin resistance specifically at higher BMIs. These results, which were largely replicated between two independent cohorts, suggest that interactions between epigenetics, obesity, and metabolic health may be important mechanisms through which childhood adversity contributes to long-term physical and metabolic health effects.

Choosing Castration: A Thematic Analysis of the Perceived Pros and Cons of Genital Injuries and Ablation by Men Who Voluntarily Sought Castration.

Some men elect castration voluntarily without any clear medical reason. Here we aim to document their perception of genital ablation and injuries to better understand their motivations for castration. Participants completed an online survey with open-ended questions related to their perspectives on castration, genital ablation, and genital injuries. Thematic analyses were performed on the responses to these questions. Responses were obtained from 208 male castrated individuals (51.9 ± 16.0 years old). Among these, 154 were physically castrated, 36 chemically castrated, and 18 nullified (had testicles and penis removed). The majority learned about castration from media (55.8%) or animal castration (23.4%). The circumstances when they first wanted to be castrated varied greatly. Most (46.3%) wished to achieve an idealized self motivated by gender dysphoria, body integrity dysphoria, or wanting to be conspicuously non-sexual. The top themes we identified related to the respondents' perceptions of the pros of genital ablation were physical appearance, psychological benefit (i.e., a "eunuch calm"), and being non-sexual. Conversely, themes related to the cons they saw in having no genitals ranged from no disadvantages to loss of sexual/reproductive capability. Some perceived performing genital injury as a step toward ultimate castration or nullification. The respondents similarly varied in whether they saw any loss in having non-functional testicles. Perceptions in this regard appeared to differ depending on whether the respondents were taking supplemental androgens post-castration. Motivations for castration vary greatly between individuals. Clinicians need to understand men's diverse perceptions on castration in order to provide appropriate care for individuals with strong castration desire.

Veterinary telerehabilitation was as satisfactory as in-person consultations.

Objective: To evaluate client satisfaction with telerehabilitation consultations compared to in-person consultations for veterinary rehabilitation referrals. Animals: We surveyed the owners of 32 client-owned dogs. Procedure: Dog owners were scheduled for telemedicine (telerehabilitation group) or in-person (control group) based on a combination of owner requests and medical recommendations. Medical records were obtained before evaluation. Owners were sent an electronic questionnaire following in-person or telerehabilitation consultations. A total of 32 surveys were received (16 for each group). The response rate was 55% (32/58 surveys sent). Mann-Whitney U tests were used to compare ordinal characteristics between satisfied and unsatisfied clients. Descriptive statistics for the client population, including ranges and medians, were calculated for owner travel distance and patient signalment. Results: Satisfaction regarding scheduling appointments was higher in the telerehabilitation group compared to the group receiving in-person consultations (P < 0.001). For all other aspects of client satisfaction, there were no significant differences between groups. Conclusion: This study demonstrated high client satisfaction with using telemedicine for canine rehabilitation consultations that was comparable to that for in-person consultations. Clinical relevance: Telerehabilitation is a viable option that can be easily implemented by rehabilitation practitioners for assessment, progression, and monitoring of canine patients. Further studies are indicated to evaluate the efficacy of telerehabilitation.

La téléréadaptation vétérinaire a été aussi satisfaisante que les consultations en personne. Objectif: Évaluer la satisfaction des clients à l'égard des consultations de téléréadaptation par rapport aux consultations en personne pour les patients aiguillés en réadaptation vétérinaire. Animaux: Enquêtes auprès des propriétaires de 32 chiens appartenant à des clients. Procédure: Les propriétaires étaient programmés en télémédecine (groupe de téléréadaptation) ou en personne (groupe témoin) en fonction d'une combinaison de demandes de propriétaires ou de recommandations médicales. Les dossiers médicaux ont été obtenus avant l'évaluation. Les propriétaires ont reçu un questionnaire électronique à la suite de consultations en personne ou par téléréadaptation. Au total, 32 sondages ont été reçus (16 pour chaque groupe). Le taux de réponse a été de 55 % (32 sondages sur 58). Les tests Mann-Whitney U ont été utilisés pour comparer les caractéristiques ordinales entre les patients satisfaits et ceux qui ne l'étaient pas. Des statistiques descriptives pour la population de clients, y compris la portée et les médianes, ont été calculées pour la distance de déplacement du propriétaire et la signalisation du patient. Résultats: La satisfaction à l'égard des rendez-vous était plus élevée dans le groupe de la téléréadaptation comparativement aux consultations en personne (P < 0,001). Pour tous les autres aspects de la satisfaction des clients, il n'y avait pas de différences significatives entre les groupes. Conclusion: Cette étude a démontré une satisfaction élevée des clients qui utilisent la télémédecine pour des consultations de réadaptation canine, comparable aux consultations en personne. Pertinence clinique: La téléréadaptation est une option viable qui peut être facilement mise en œuvre par les praticiens de la réadaptation pour l'évaluation, la progression et le suivi des patients canins. D'autres études sont indiquées pour évaluer l'efficacité de la téléréadaptation.(Traduit par les auteurs).

Development of a colorimetric α-ketoglutarate detection assay for prolyl hydroxylase domain (PHD) proteins.

Since the discovery of the prolyl hydroxylases domain (PHD) proteins and their canonical hypoxia-inducible factor (HIF) substrate two decades ago, a number of in vitro hydroxylation (IVH) assays for PHD activity have been developed to measure the PHD-HIF interaction. However, most of these assays either require complex proteomics mass spectrometry methods that rely on the specific PHD-HIF interaction or require the handling of radioactive material, as seen in the most commonly used assay measuring [14C]O2 release from labeled [14C]α-ketoglutarate. Here, we report an alternative rapid, cost-effective assay in which the consumption of α-ketoglutarate is monitored by its derivatization with 2,4-dinitrophenylhydrazine (2,4-DNPH) followed by treatment with concentrated base. We extensively optimized this 2,4-DNPH α-ketoglutarate assay to maximize the signal-to-noise ratio and demonstrated that it is robust enough to obtain kinetic parameters of the well-characterized PHD2 isoform comparable with those in published literature. We further showed that it is also sensitive enough to detect and measure the IC50 values of pan-PHD inhibitors and several PHD2 inhibitors in clinical trials for chronic kidney disease (CKD)-induced anemia. Given the efficiency of this assay coupled with its multiwell format, the 2,4-DNPH α-KG assay may be adaptable to explore non-HIF substrates of PHDs and potentially to high-throughput assays.

Paraphilic Sexual Attraction to Males Without Genitals Is Associated with Traumatic Childhood Experience, Body Image, and Thoughts/Behaviors Related to Genital Ablation.

In rare cases, some male individuals are sexually attracted to men who have their genitals removed. We investigate here if paraphilic attraction to men without genitals was associated with childhood experience, body image, and thoughts/behaviors related to body modification. An online survey, consisting of both validated questionnaires and questions developed by our team, was launched on the Eunuch Archive and MTurk websites. Out of 875 participants, 48.5 and 32.2% reported being attracted to males without testicles or without a penis, respectively; 49.7 and 31.0% felt they would themselves be attractive without testicles and without a penis, respectively. In terms of body modification, many reported having tattoos (19.0%) and piercings (26.1%). About half (48.3%) had played as children with male action figures without genitals, i.e., GI Joe, and Ken dolls. Additionally, some participants reported having: (1) witnessed animal castration (23.7%); (2) having been threatened with castration during their childhood (11.9%); (3) receiving genital injuries inflicted by others (11.0%); (4) pretending to be castrated (60.2%); (5) thinking of self-castration (54.2%); or (6) injuring their own penis (23.4%). Having received genital injuries inflicted by others was associated with attraction to males without testicles (OR = 1.997, p < .05), but not for attraction to males without a penis. Paraphilic attraction to males without genitals (i.e., castrated or penectomized) was associated with feeling attractive without genitals, having pretended to be castrated, considering self-castration, and having injured one's own penis. In conclusion, paraphilic attraction to males without genitals may be associated with traumatic early life events, body image, and desire for one's own genital ablation.

CDKN2A exon 1B deletion predisposing to melanoma and neural system tumour syndrome.

CDKN2A at chromosome positon 9p21 is a tumour suppressor gene encoding the cell cycle regulators p16 and p14ARF. While melanoma is associated with variants affecting both transcripts, families with mutations involving the p14ARF-specific exon 1B may be predisposed to central nervous system tumours. We describe a family with a deletion of exon 1B in CDKN2A, who had multiple cutaneous melanomas, neural tumours and various malignancies.

Modeling the conversion between specific IgE test platforms for nut allergens in children and adolescents.

BACKGROUND: Multiplex tests allow for measurement of allergen-specific IgE responses to multiple extracts and molecular allergens and have several advantages for large cohort studies. Due to significant methodological differences, test systems are difficult to integrate in meta-analyses/systematic reviews since there is a lack of datasets with direct comparison. We aimed to create models for statistical integration of allergen-specific IgE to peanut/tree nut allergens from three IgE test platforms. METHODS: Plasma from Canadian and Austrian children/adolescents with peanut/tree nut sensitization and a cohort of sensitized, high-risk, pre-school asthmatics (total n = 166) were measured with three R&D multiplex IgE test platforms: Allergy Explorer version 1 (ALEX) (Macro Array Dx), MeDALL-chip (Mechanisms of Development of Allergy) (Thermo Fisher), and EUROLINE (EUROIMMUN). Skin prick test (n = 51) and ImmunoCAP (Thermo Fisher) (n = 62) results for extracts were available in a subset. Regression models (Multivariate Adaptive Regression Splines, local polynomial regression) were applied if >30% of samples were positive to the allergen. Intra-test correlations between PR-10 and nsLTP allergens were assessed. RESULTS: Using two regression methods, we demonstrated the ability to model allergen-specific relationships with acceptable measures of fit (r2  = 94%-56%) for peanut and tree nut sIgE testing at the extract and molecular-level, in order from highest to lowest: Ara h 2, Ara h 6, Jug r 1, Ana o 3, Ara h 1, Jug r 2, and Cor a 9. CONCLUSION: Our models support the notion that quantitative conversion is possible between sIgE multiplex platforms for extracts and molecular allergens and may provide options to aggregate data for future meta-analysis.

Basophil activation test shows high accuracy in the diagnosis of peanut and tree nut allergy: The Markers of Nut Allergy Study.

BACKGROUND: Peanut and tree nut allergies are the most important causes of anaphylaxis. Co-reactivity to more than one nut is frequent, and co-sensitization in the absence of clinical data is often obtained. Confirmatory oral food challenges (OFCs) are inconsistently performed. OBJECTIVE: To investigate the utility of the basophil activation test (BAT) in diagnosing peanut and tree nut allergies. METHODS: The Markers Of Nut Allergy Study (MONAS) prospectively enrolled patients aged 0.5-17 years with confirmed peanut and/or tree nut (almond, cashew, hazelnut, pistachio, walnut) allergy or sensitization from Canadian (n = 150) and Austrian (n = 50) tertiary pediatric centers. BAT using %CD63+ basophils (SSClow/CCR3pos) as outcome was performed with whole blood samples stimulated with allergen extracts of each nut (0.001-1000 ng/mL protein). BAT results were assessed against confirmed allergic status in a blinded fashion to develop a generalizable statistical model for comparison to extract and marker allergen-specific IgE. RESULTS: A mixed effect model integrating BAT results for 10 and 100 ng/mL of peanut and individual tree nut extracts was optimal. The area under the ROC curve (AUROC) was 0.98 for peanut, 0.97 for cashew, 0.92 for hazelnut, 0.95 for pistachio, and 0.97 for walnut. The BAT outperformed sIgE testing for peanut or hazelnut and was comparable for walnut (AUROC 0.95, 0.94, 0.92) in a sub-analysis in sensitized patients undergoing OFC. CONCLUSIONS: Basophil activation test can predict allergic clinical status to peanut and tree nuts in multi-nut-sensitized children and may reduce the need for high-risk OFCs in patients.

Opioid Therapy in Cancer Pain.

Cancer is a leading cause of morbidity and mortality, with up to 9.6 million cancer-related deaths worldwide in 2018 [1].

Hormones and visual attention to sexual stimuli in older men: an exploratory investigation.

BACKGROUND: Testosterone is associated with sexual desire and performance in men, but little is known about cognitive mechanisms underlying this relationship. Even less is known about the influence of estradiol, despite its production from testosterone, and high receptor density in brain regions related to male sexual behavior. METHOD: We used eye-tracking to compare men's visual attention to images of fully clothed (i.e. neutral) and minimally clothed (i.e. sexy) models in three groups: androgen-deprived (n = 6) and not androgen-deprived with prostate cancer (n = 11), and healthy controls (n = 7). We also assessed effects of serum testosterone, estradiol, and sex hormone-binding globulin levels. RESULTS: We found no group effect for fixations to sexy compared to neutral images, and no influence of testosterone on either total fixations, or proportion of fixations to sexy images. In contrast, we found that sex hormone binding globulin positively predicted total fixations, and estradiol positively predicted proportion of total fixations on sexy images--regardless of androgen treatment status. CONCLUSION: Our results suggest that visual attention to sexual stimuli in men may be significantly affected by hormones. This has potential implications for clinical populations that experience sexual side effects, such as prostate cancer patients on androgen deprivation therapy.

Sexual Function After Voluntary Castration.

Some genetic males undergo voluntary castration, with and without hormonal supplementation. Here, we investigate the sexual function of 163 such individuals (average age = 52 ± 16-years-old). Specifically, we explored how hormonal, social, and psychological factors play a role in their sexual function. In this study, 47% identified their gender as "eunuch", and 36% identified their gender as "man." Furthermore, 64% were in a relationship (80% with a woman), and 28% had a strong attraction for both sexes (Kinsey 2-4). We found that castrated individuals with androgen supplementation have higher sexual function than those without any hormone supplementation. Individuals with anxiety symptoms reported better sexual parameters (better orgasm satisfaction, easier to achieve an erection and an orgasm) than those without anxiety symptoms. Among those low in anxiety, individuals without hormone supplementation had a weaker sex drive and more difficulty in getting sexually aroused than those on supplemental estrogen or androgen. Hierarchical multiple regressions indicated that control variables (i.e., age, depressive symptoms, time since castration, type of hormone supplementation) accounted for 13-30% of the variances in sexual parameters. Including sexual guilt in the models predicted 4-8% additional variances in all sexual parameters except for ease in getting and maintaining an erection. Adding in participants' sexual trauma scores accounted for an additional 3.7% in the strength of their reported sex drive. In conclusion, various factors-hormone therapy, anxiety, sexual guilt, and childhood trauma-may influence the sexual outcomes for castrated individuals.

Differences in the Psychological, Sexual, and Childhood Experiences Among Men with Extreme Interests in Voluntary Castration.

Some genetic males seek voluntary castration. We designed a survey to compare the psychological, sexual, and childhood experiences for subgroups of men with extreme interest in castration. The survey was posted on the Eunuch Archive, an online platform for individuals interested in the topic. Data from 822 individuals were included in the analyses. Respondents were divided into four groups: Interested (claiming only an interest in castration topics), Fantasy (fantasize about castration sexually, but not desiring castration), Wannabe (considering being castrated in the future), and Castrated (already castrated). More individuals desiring castration (Wannabe and Castrated groups) claimed equal attraction to both sexes than individuals in the Interested group. The Interested group was more religious than the other groups, and the Fantasy group had lower sexual guilt than those with castration desire. All groups had similar psychological well-being and body image acceptance, despite the Castrated group having lower sexual functioning than the others. Childhood trauma was more common in those with castration desire than those without. The Interested group had a lower desire for castration, lower erotic attraction to castration, and pretended to be castrated at a younger age than the others. Childhood trauma and sexual guilt are common, but not limited, predictors for castration desire and erotic attraction to castration, respectively. In conclusion, childhood experiences, as well as psychological and sexual parameters, may vary in different subgroups of males with interests in castration.

A multimodal assessment of tobacco use on a university campus and support for adopting a comprehensive tobacco-free policy.

Many college campuses now prohibit tobacco use. At a private U.S. university, the current study assessed cigarette and e-cigarette use and characterized the climate for adopting a comprehensive tobacco-free policy. Data were gathered January-August 2018 via an: environmental scan; cigarette-urn audit; and representative surveys with campus community members. Despite low prevalence of tobacco (0.5%-8%) and e-cigarette use (0.9%-6%) among all groups, campus cigarette clean-up costs exceeded $114,000 for an estimated >1 million butts left on campus annually. A majority of respondents (63% of N = 2218) favored a campus-wide tobacco-free policy, 16% opposed, and 21% abstained. Most respondents endorsed benefits of supporting health (93%), ensuring tobacco-free air to breathe (92%), reducing litter (88%), preventing tobacco use (84%) and fires (83%), and helping tobacco users quit (65%). Identified challenges included policy enforcement (69%) and stigmatization of smoking (57%); 30% viewed a policy as compromising personal freedoms. In a model explaining 35% of variance in policy support, those more likely to favor comprehensive tobacco-free campus policy were Asian respondents; diagnosed with asthma; exposed to secondhand smoke on campus; who viewed campus cigarette butt litter as problematic; and identified health, prevention, and cessation benefits of a tobacco-free campus. Those less likely in favor were students, those who smoke, and those perceiving impingement upon personal freedoms, stigmatization, and broader (slippery slope) implications. Findings indicate low tobacco use prevalence among the campus community, yet a large volume of butt litter and high tobacco clean-up costs. Predictors of policy support can inform campus outreach efforts.

Functional brain networks involved in lexical decision.

Functional magnetic resonance imaging (fMRI)5 studies on lexical decision (LD)6 attempting to isolate the brain network underlying access to lexical representations can be confounded by attentional and response processes. However, manipulating the "wordlikeness" of the LD stimuli can facilitate functional interpretation of each emerging brain network, providing principles for separation of attentional demand from linguistic processing. This is because activation of difficult-to-access lexical representations (for obscure real words), and avoidance of interfering word properties (for wordlike non-words), are both generally attentionally demanding. Therefore, congruent patterns of activation would be predicted for general-attention-responsive networks, but opposing patterns for language-responsive networks. 59 healthy adults performed a LD task, and multidimensional functional connectivity analysis was used to extract three functional brain networks. A linguistic processing network (LPN) was separated from attention/response networks anatomically (LPN included Broca's and Wernicke's areas), but also temporally by showing reduced activation for the most attentionally demanding condition (i.e., wordlike non-words). This demonstrated that during LD in fMRI a network involved in linguistic processing can be disentangled from attention- and response-specific networks, using a combination of experimental design and multidimensional analysis methods.