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Up to 8% of cisgender women meet diagnostic criteria for Female Sexual Interest/Arousal Disorder (SIAD), a diagnosis in the Diagnostic and Statistical Manual of Mental Disorders , yet treatment research for SIAD remains scarce, particularly for transgender women and non-binary individuals. The treatment relevance of the Approach-Avoidance Motivation Model for SIAD was tested in a sample of cis- and transgender women, and non-binary individuals, who either met criteria for SIAD (n = 45) or reported no sexual concerns (n = 76). Participants completed an online writing exercise previously found to increase the salience of approach or avoidance sexual motivation, or a control writing task. At baseline, and 72 hours following the writing task, they completed measures of sexual motivation, sexual desire, and partnered sexual behaviors. Participants with SIAD in the approach condition significantly increased in approach sexual motivation immediately following the manipulation but these improvements were not maintained 72 hours later. Compared to baseline, participants who wrote about an approach-motivated sexual encounter experienced a decrease in sexual desire and partnered sexual behaviors, while participants who wrote about an avoidance-motivated sexual encounter had decreased motivation but increased partnered sexual behaviors 72 hours following the manipulation. Overall, findings did not show support for the relevance of the approach-avoidance motivation manipulation for SIAD. Future studies might explore novel ways of targeting sexual motivation to address sexual difficulties.

Approximately 1 in 3 women experience low sexual desire. Despite this being a common concern, many women never seek professional help for their difficulties and will instead turn to online resources for information. We sought to address this need for digitally-accessible, evidence-based information on low sexual desire by creating a social media Knowledge Translation (KT) campaign called #DebunkingDesire. Our team led a 10 month social media campaign where our primary outcomes for the campaign were impressions, reach, and engagement. We generated over 300,000 social media impressions; appeared on 11 different podcasts that were listened to/downloaded 154,700 times; hosted and participated in eight online events; and attracted website users from 110 different countries. Over the course of the campaign we compiled lessons learned on what worked for disseminating our key messages and the importance of creating community for this population. These findings point to the utility of using social media as part of KT campaigns in sexual health, and to the importance of collaborating with patient partners and considering social media ads and podcasts to meet reach goals.

Virtual Reality (VR)-based treatments for anxiety disorders are efficacious but there is a lack of research examining anxious responses to VR erotica, which could innovate treatments for sexual difficulties. We examined erotica features that elicited anxiety and sexual presence in women. Thirty-eight women viewed erotic videos from different modalities (2D, VR) and points of view (1 st , 3 rd person) and completed anxiety and sexual presence measures before and after each video. Women experienced greater anxiety for VR than 2D films and reported the most anxiety for VR 1 st person films. Sexual presence was affected by modality and point of view.

Sexual Interest/Arousal Disorder (SIAD) is a common sexual dysfunction in women. Both mindfulness-based cognitive therapy (MBCT) plus psychoeducation and sex therapy, education, and support (STEP; which contains the same educational information as in the MBCT arm but also integrates supportive-expressive therapy), are effective. We tested mediators and moderators of improvements. Each treatment arm consisted of eight sessions delivered weekly, and participants completed measures online pre-treatment, immediately post-treatment, and at 6- and 12-month post-treatment. Depression, self-reported interoceptive awareness, self-compassion, self-criticism, and mindfulness were examined as mediators, and expectations for improvement as a moderator. Of 148 cisgender women who consented, 70 were randomized to the MBCT plus psychoeducation group (mean age 39.3 ± 13.2 yrs) and 78 to the STEP group (mean age 37.9 ± 12.2 yrs). Decreases in depression mediated decreases in sexual distress in the MBCT plus psychoeducation group only. Improvements in interoceptive awareness mediated changes in both sexual desire and arousal, and sexual distress, and to a greater degree after MBCT plus psychoeducation. Changes in self-compassion mediated changes in sexual desire and arousal only for the MBCT plus psychoeducation group and mediated changes in sexual distress in both groups. Reductions in self-criticism mediated improvements in sexual distress to a greater extent after MBCT plus psychoeducation. Changes in mindfulness predicted changes in desire and arousal, and distress only in the MBCT plus psychoeducation group. Expectations for improvement did not moderate any outcomes. The findings have implications for understanding common and potentially distinct pathways by which MBCT plus psychoeducation and supportive sex education improve symptoms of SIAD.

Objectives: We examined changes in frequency of sexual behaviors, dyadic sexual desire, relationship satisfaction, and COVID-19 stress in Canadians across the pandemic, considering partner status., Methods: Participants completed online questionnaires., Results: Participants with live-in partners and single participants decreased in dyadic sexual behaviors. In August-September 2020, participants with live-in partners engaged in more dyadic sexual behaviors than single participants. In November 2021, all partnered participants engaged in more dyadic sexual behaviors than single participants. Decreases in COVID-19 stress were observed., Conclusions: Findings suggest that despite decreases in COVID-19 stress, there may be long-lasting pandemic impacts on sexual behaviors., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2023 Taylor & Francis Group, LLC.)

Background: Immune responses to N-glycan structures from allergens and parasites are often associated with pronounced, high affinity IgE reactivities. Cross-reactive carbohydrate determinants (CCDs) are constituted by modified N-glycan core structures and represent the most frequently recognized epitopes in allergic immune responses. Although recently accepted as potentially allergenic epitopes, the biological and clinical relevance as well as structural and functional characteristics of CCD-specific antibodies remain elusive., Methods: In order to gain structural insights into the recognition of CCDs, two specific antibody fragments were isolated from a leporid immune repertoire library and converted into human/leporid IgE and IgG formats. The antibody formats were assessed by ELISA and surface plasmon resonance, structural and functional analyses were performed by X-ray crystallography, mediator release, and ELIFAB assays., Results: The recombinant IgE exhibited highly specific interactions with different types of CCDs on numerous CCD-carrying glycoproteins. Crystal structures of two CCD-specific antibodies, one of which in complex with a CCD-derived disaccharide emphasize that mechanisms of core glycan epitope recognition are as specific as those governing protein epitope recognition. The rIgE triggered immediate cellular responses via FcεRI cross-linking and mediated facilitated antigen presentation by binding of IgE/antigen complexes to CD23, a process that also could be blocked by IgG of allergic patients., Conclusions: Our study provides evidence for the relevance of N-glycan recognition in T H 2 responses and corroborates that IgE and IgG antibodies to ubiquitous carbohydrate epitopes can be equivalent to those directed against proteinaceous epitopes with implications for diagnostic and immunotherapeutic concepts., (© 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Virtual reality (VR) media using a three-dimensional (3D) camera facilitates an immersive experience compared to traditional two-dimensional (2D) formats. In this novel study, we used high quality, women-centered erotica and examined whether stimulus modality (VR vs. 2D) and point of view (POV: first-person vs. third-person) impacted women's feelings of sexual presence (activation of sexual response induced by the perception of being present), sexual arousal, and sexual desire (dyadic and solitary). We also investigated the effects of stimulus modality on feelings of general presence (a sense of "being there"). Results from 38 women indicated that with medium to large effects, general presence, sexual presence, and sexual arousal were significantly higher for VR videos relative to 2D videos. Sexual presence was higher for first-person POV depending on the order of film exposure. A general trend toward increasing dyadic sexual desire over the course of the study was observed. No significant differences were observed for solitary sexual desire. These findings support the adaptability of VR media to sex research and show that it can induce feelings of sexual presence and presence more generally. That sexual arousal was positively impacted by VR erotica may have implications for addressing the limitations that accompany other stimulus modalities used to elicit sexual responses in women., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: We evaluated various facets of sexual health in Canadians across phases of the COVID-19 pandemic., Methods: Online questionnaires every four weeks from April-August 2020., Results: Higher COVID-19 stress predicted higher baseline dyadic sexual desire, lower relationship satisfaction, higher desire for solitary sexual behavior, and higher likelihood of experiencing sexual coercion among people with a live-in romantic partner. Dyadic sexual desire and pandemic-related stress both decreased with time, whereas solitary sexual behavior decreased and dyadic sexual behavior increased among participants without a live-in romantic partner., Conclusions: Our findings reveal differential impacts of COVID-19 related stress on sexual outcomes., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2021 Taylor & Francis Group, LLC.)

Objective: Sexual interest/arousal disorder (SIAD) is the most prevalent sexual dysfunction in women. Our goal was to compare (a) group mindfulness-based cognitive therapy (MBCT) plus sex education with (b) group supportive sex education and therapy (STEP) for women with SIAD. Method: Eight-session treatments were delivered weekly and participants completed the measures of sexual desire and arousal, sexual distress, relationship satisfaction, rumination, and global impressions of change, at baseline, immediately posttreatment, and at 6- and 12-month posttreatment. Of 148 women who consented, 70 were randomized to MBCT (mean age 39.3 ± 13.2 years) and 78 were randomized to STEP (mean age 37.9 ± 12.2 years). Results: Sexual desire and arousal significantly improved at each time point relative to baseline, with large effect sizes ( d = -1.29 to -1.60), and similarly for MBCT and STEP. Sexual distress also improved at each time point with large effect sizes ( d = 0.83-1.17), and more so for MBCT relative to STEP. Relationship satisfaction significantly improved ( d = -0.17 to -0.20), and rumination about sex improved significantly in both arms, with medium effect sizes ( d = 0.42-0.69), with both outcomes responding more to MBCT. About half the participants across both treatments reported moderate or great improvements in global indicators of desire and overall sexuality. Conclusions: Results support the efficacy of both group MBCT and group supportive sex education for improving symptoms of SIAD with 12-month retention of improvements. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Background: IgE is the central antibody isotype in TH2-biased immunity and allergic diseases. The structure of intact IgE and the impact of IgE-targeting molecules on IgE however remain elusive. In order to obtain insights into IgE biology and the clinical impact, we aimed for structure determination of IgE and the complex of IgE with the anti-IgE antibody ligelizumab., Methods: Structures of two distinct intact IgE with specificity for cross-reactive carbohydrate determinants and Der p 2 as well as complexes of ligelizumab-Fab with IgE and IgE Fc were assessed by negative stain electron microscopy and solution scattering. Inhibition of IgE binding and displacement of receptor-bound IgE were assessed using cellular assays, basophil activation testing and ELIFAB assays., Results: Our data reveal that the investigated IgE molecules share an overall rigid conformation. In contrast to the IgE Fc fragment, the IgE Fc in intact IgE is significantly less asymmetrically bent. The proximal and the distal Fabs are rigidly tethered to the Fc. Binding of ligelizumab to IgE in a 2:1 stoichiometry induces an extended and twofold symmetrical conformation of IgE, which retains a rigid Fab-Fc architecture. Analyses of effector cell activation revealed that ligelizumab inhibits IgE binding without displacing receptor-bound IgE. Together with an interference of CD23 binding, the data underline a functional activity similar to omalizumab., Conclusions: Our data reveal the first structures of intact IgE suggesting that the IgE Fab is fixed relative to the Fc. Furthermore, we provide a structural rationale for the inhibitory mechanism of ligelizumab., (© 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Anti-IgE therapeutics interfere with the ability of IgE to bind to its receptors on effector cells. Here we report the crystal structure of an anti-IgE single-domain antibody in complex with an IgE Fc fragment, revealing how the antibody inhibits interactions between IgE and the two receptors FcεRI and CD23. The epitope overlaps only slightly with the FcεRI-binding site but significantly with the CD23-binding site. Solution scattering studies of the IgE Fc reveal that antibody binding induces a half-bent conformation in between the well-known bent and extended IgE Fc conformations. The antibody acts as functional homolog of CD23 and induces a closed conformation of IgE Fc incompatible with FcεRI binding. Notably the antibody displaces IgE from both CD23 and FcεRI, and abrogates allergen-mediated basophil activation and facilitated allergen binding. The inhibitory mechanism might facilitate strategies for the future development of anti-IgE therapeutics for treatment of allergic diseases.

Molecular cross-reactivity caused by allergen homology or cross-reactive carbohydrate determinants (CCDs) is a major challenge for diagnosis and immunotherapy of insect venom allergy. Venom phospholipases A1 (PLA1s) are classical, mostly non-glycosylated wasp and ant allergens that provide diagnostic benefit for differentiation of genuine sensitizations from cross-reactivity. As CCD-free molecules, venom PLA1s are not causative for CCD-based cross-reactivity. Little is known however about the protein-based cross-reactivity of PLA1 within vespid species. Here, we address PLA1-based cross-reactivity among ten clinically relevant Hymenoptera venoms from Neotropical and temperate regions including Polybia paulista (paulistinha) venom and Vespula vulgaris (yellow jacket) venom. In order to evaluate cross-reactivity, sera of mice sensitized with recombinant PLA1 (rPoly p 1) from P. paulista wasp venom were used. Pronounced IgE and IgG based cross-reactivity was detected for wasp venoms regardless the geographical region of origin. The cross-reactivity correlated well with the identity of the primary sequence and 3-D models of PLA1 proteins. In contrast, these mice sera showed no reaction with honeybee (HBV) and fire ant venom. Furthermore, sera from patients monosensitized to HBV and fire ants did not recognize the rPoly p 1 in immunoblotting. Our findings reveal the presence of conserved epitopes in the PLA1s from several clinically relevant wasps as major cause of PLA1-based in vitro cross-reactivity. These findings emphasize the limitations but also the potential of PLA1-based HVA diagnostics., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The redirection of T cell activity using bispecific antibodies is one of the most promising cancer immunotherapy approaches currently in development, but it is limited by cytokine storm-related toxicities, as well as the pharmacokinetics and tumor-penetrating capabilities of current bispecific antibody formats. Here, we have engineered the ATTACK ( Asymmetric Tandem Trimerbody for T cell Activation and Cancer Killing ), a novel T cell-recruiting bispecific antibody which combines three EGFR-binding single-domain antibodies (V HH ; clone EgA1) with a single CD3-binding single-chain variable fragment (scFv; clone OKT3) in an intermediate molecular weight package. The two specificities are oriented in opposite directions in order to simultaneously engage cancer cells and T cell effectors, and thereby promote immunological synapse formation. EgA1 ATTACK was expressed as a homogenous, non-aggregating, soluble protein by mammalian cells and demonstrated an enhanced binding to EGFR, but not CD3, when compared to the previously characterized tandem bispecific antibody which has one EgA1 V HH and one OKT3 scFv per molecule. EgA1 ATTACK induced synapse formation and early signaling pathways downstream of TCR engagement at lower concentrations than the tandem V HH -scFv bispecific antibody. Furthermore, it demonstrated extremely potent, dose-dependent cytotoxicity when retargeting human T cells towards EGFR-expressing cells, with an efficacy over 15-fold higher than that of the tandem V HH -scFv bispecific antibody. These results suggest that the ATTACK is an ideal format for the development of the next-generation of T cell-redirecting bispecific antibodies.

TH2-biased immunity to parasites and allergens is often associated with increased levels of antigen-specific and high affinity IgE. The role in reacting against minute amounts of target structures and to provoke severe anaphylactic reactions renders IgE a mechanistically outstanding isotype. IgE represents the least abundant serum antibody isotype and exhibits a variety of peculiarities including structure, extensive glycosylation and effector functions. Despite large progress in antibody technologies, however, the recombinant access to isotypes beyond IgG such as IgE still is scarce. The capacity of expression systems has to meet the complex structural conformations and the extensive posttranslational modifications that are indispensable for biological activity. In order to provide alternatives to mammalian expression systems with often low yield and a more complex glycosylation pattern we established the recombinant production of the highly complex IgE isotype in insect cells. Recombinant IgE (rIgE) was efficiently assembled and secreted into the supernatant in yields of >30 mg/L. Purification from serum free medium using different downstream processing methods provided large amounts of rIgE. This exhibited a highly specific interaction with its antigen, therapeutic anti-IgE and its high affinity receptor, the FcεRI. Lectins and glyco-proteomic analyses proved the presence of prototypic insect type N-glycans on the epsilon heavy chain. Mediator release assays demonstrated a biological activity of the rIgE comparable to IgE derived from mammalian cells. In summary the expression in insect cells provides rIgE with variant glycosylation pattern, but retained characteristics and biological activity. Therefore our data contribute to the understanding of functional and structural aspects and potential use of the IgE isotype., (Copyright © 2016 Elsevier Ltd. All rights reserved.)