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Noise-induced hearing loss is a leading cause of occupational and recreational injury and disease, and a major determinant of age-related hearing loss. No therapeutic agent has been approved for the prevention or treatment of this disorder. In animal models, glutathione peroxidase 1 (GPx1) activity is reduced after acute noise exposure. Ebselen, a novel GPx1 mimic, has been shown to reduce both temporary and permanent noise-induced hearing loss in preclinical studies. We assessed the safety and efficacy of ebselen for the prevention of noise-induced hearing loss in young adults in a phase 2 clinical trial. In this single-centre, randomised, double-blind, placebo-controlled phase 2 trial, healthy adults aged 18–31 years were randomly assigned (1:1:1:1) at the University of Florida (Gainsville, FL, USA) to receive ebselen 200 mg, 400 mg, or 600 mg, or placebo orally twice daily for 4 days, beginning 2 days before a calibrated sound challenge (4 h of pre-recorded music delivered by insert earphones). Randomisation was done with an allocation sequence generated by an independent third party. The primary outcome was mean temporary threshold shift (TTS) at 4 kHz measured 15 min after the calibrated sound challenge by pure tone audiometry; a reduction of 50% in an ebselen dose group compared with the placebo group was judged to be clinically relevant. All participants who received the calibrated sound challenge and at least one dose of study drug were included in the efficacy analysis. All randomly assigned patients were included in the safety analysis. This trial is registered with ClinicalTrials.gov, number NCT01444846. Between Jan 11, 2013, and March 24, 2014, 83 participants were enrolled and randomly assigned to receive ebselen 200 mg (n=22), 400 mg (n=20), or 600 mg (n=21), or placebo (n=20). Two participants in the 200 mg ebselen group were discontinued from the study before the calibrated sound challenge because they no longer met the inclusion criteria; these participants were excluded from the efficacy analysis. Mean TTS at 4 kHz was 1·32 dB (SE 0·91) in the 400 mg ebselen group compared with 4·07 dB (0·90) in the placebo group, representing a significant reduction of 68% (difference −2·75 dB, 95% CI −4·54 to −0·97; p=0·0025). Compared with placebo, TTS at 4 kHz was non-significantly reduced by 21% in the 200 mg ebselen group (3·23 dB [SE 0·91] vs 4·07 dB [0·90] in the placebo group; difference −0·84 dB, 95% CI −2·63 to 0·94; p=0·3542) and by 7% in the 600 mg ebselen group (3·81 dB [0·90] vs 4·07 dB [0·90] in the placebo group; difference −0·27, 95% CI −2·03 to 1·50; p=0·7659). Ebselen treatment was well tolerated across all doses and no significant differences were seen in any haematological, serum chemistry, or radiological assessments between the ebselen groups and the placebo group. Treatment with ebselen was safe and effective at a dose of 400 mg twice daily in preventing a noise-induced TTS. These data lend support to a role of GPx1 activity in acute noise-induced hearing loss. Sound Pharmaceuticals.

Background The Eating Disorder Examination – Questionnaire Short (EDE-QS) was developed as a 12-item version of the Eating Disorder Examination Questionnaire (EDE-Q) with a 4-point response scale that assesses eating disorder (ED) symptoms over the preceding 7 days. It has demonstrated good psychometric properties at initial testing. The purpose of this brief report is to determine a threshold score that could be used in screening for probable ED cases in community settings. Methods Data collected from Gideon et al. (2016) were re-analyzed. In their study, 559 participants (80.86% female; 9.66% self-reported ED diagnosis) completed the EDE-Q, EDE-QS, SCOFF, and Clinical Impairment Assessment (CIA). Discriminatory power was compared between ED instruments using receiver operating characteristic (ROC) curve analyses. Results A score of 15 emerged as the threshold that ensured the best trade-off between sensitivity (.83) and specificity (.85), and good positive predictive value (.37) for the EDE-QS, with discriminatory power comparable to other ED instruments. Conclusion The EDE-QS appears to be an instrument with good discriminatory power that could be used for ED screening purposes.

Plastic surgery is growing in popularity. Despite this, there has been little exploration to date regarding the psychosocial consequences of seeking plastic surgery. Our study investigated how women seeking plastic surgery are perceived by others. We presented a random sample of 985 adults (men = 54%, M age = 35.84 years, SD age = 10.59) recruited via Amazon’s Mechanical Turk with a series of experimental stimuli consisting of a photographed woman (attractive versus unattractive) and a vignette describing an activity she plans to engage in (plastic surgery versus control activity). Participants rated stimuli on perceived warmth, competence, morality, and humanness. We ran linear mixed-effect models to assess all study hypotheses. There was a negative plastic surgery effect; that is, women seeking plastic surgery were perceived less favorably than those planning to complete control activities across all outcome variables (warmth, competence, morality, and humanness). These relationships were moderated by physical attractiveness; while attractive women planning to undergo plastic surgery were perceived less favorably than attractive women planning to engage in control activities, perceptions of unattractive individuals remained unchanged by plastic surgery status. We theorized that empathy toward unattractive women seeking plastic surgery mitigated the negative plastic surgery effect for these women. In sum, our results suggest that perceptions of attractive women are worsened when these women decide to seek cosmetic surgery. Perceptions of warmth and competence have implications for an individual’s self-esteem and interpersonal relationships, while perceptions of morality and humanness can impact an individual’s ability to fulfil their psychological needs. As such, we concluded that attractive women seeking plastic surgery are potentially subject to experience negative psychosocial outcomes. Future research ought to examine whether perceptions and outcomes differ for women seeking reconstructive plastic surgery (versus cosmetic plastic surgery) and whether they differ across different types of surgeries (i.e. face versus body).

Pigments and phytotoxins are crucial for the survival and spread of plant pathogenic fungi. The genome of the tomato biotrophic fungal pathogen Cladosporium fulvum contains a predicted gene cluster (CfPKS1, CfPRF1, CfRDT1 and CfTSF1) that is syntenic with the characterized elsinochrome toxin gene cluster in the citrus pathogen Elsinoë fawcettii. However, a previous phylogenetic analysis suggested that CfPks1 might instead be involved in pigment production. Here, we report the characterization of the CfPKS1 gene cluster to resolve this ambiguity. Activation of the regulator CfTSF1 specifically induced the expression of CfPKS1 and CfRDT1, but not of CfPRF1. These co-regulated genes that define the CfPKS1 gene cluster are orthologous to genes involved in 1,3-dihydroxynaphthalene (DHN) melanin biosynthesis in other fungi. Heterologous expression of CfPKS1 in Aspergillus oryzae yielded 1,3,6,8-tetrahydroxynaphthalene, a typical precursor of DHN melanin. Δcfpks1 deletion mutants showed similar altered pigmentation to wild type treated with DHN melanin inhibitors. These mutants remained virulent on tomato, showing this gene cluster is not involved in pathogenicity. Altogether, our results showed that the CfPKS1 gene cluster is involved in the production of DHN melanin and suggests that elsinochrome production in E. fawcettii likely involves another gene cluster.

Background To date, over 1.3 billion videos with the hashtag #bodyneutrality have been viewed on TikTok. Despite this, little existing literature has unpacked how body neutrality is conceptualised on TikTok. We examined how TikTok creators construct meaning and generate discourse surrounding #bodyneutrality. Methods Extending on previous works in the body neutrality space, we conducted a hybrid content/thematic analysis of TikTok videos in three different languages (English, Spanish, and Italian). Initially, 300 videos displaying “#bodyneutrality” were identified on TikTok. The first 178 TikTok videos were analysed, following the principles of data saturation and feasibility. Results We developed three themes: (1) The normalisation of diverse bodies, (2) The rejection of appearance as fundamentally important, and (3) Body neutrality is (better than) body positivity. Conclusions In line with conceptualisations of body neutrality in existing literature, some content emphasised the importance of devaluing physical appearance. Building on existing definitions, most creators also framed body neutrality as speaking to the fundamental humanness of owning a body and attempted to normalise various body shapes/sizes. Conversely, some content employed #bodyneutrality to promote or examine body positivity principles or to condemn appearance-based stigmatisation. Our study is one of the first to examine how body neutrality is understood and employed by people in the real world. Plain English summary Content promoting body neutrality, often shared with #bodyneutrality, has recently become more popular on social media, especially on the widely-used platform TikTok. Consequently, the current study aimed to examine how body neutrality is represented and discussed on TikTok. After conducting a hybrid content/thematic analysis of 178 TikTok videos in English, Spanish, and Italian, we identified three main themes to describe body neutrality: (1) The normalisation of diverse bodies, (2) The rejection of appearance as fundamentally important, and (3) Body neutrality is (better than) body positivity. In the analysed videos, body neutrality content depicted the experience of having a body as fundamentally normal, natural, and human. Moreover, many videos deemphasized the importance placed on beauty in favour of individual characteristics (e.g., hobbies). Finally, some videos compared body neutrality with body positivity, highlighting similarities and differences between the two.

Anthraquinones are a large family of secondary metabolites (SMs) that are extensively studied for their diverse biological activities. These activities are determined by functional group decorations and the formation of dimers from anthraquinone monomers. Despite their numerous medicinal qualities, very few anthraquinone biosynthetic pathways have been elucidated so far, including the enzymatic dimerization steps. In this study, we report the elucidation of the biosynthesis of cladofulvin, an asymmetrical homodimer of nataloe-emodin produced by the fungus Cladosporium fulvum. A gene cluster of 10 genes controls cladofulvin biosynthesis, which begins with the production of atrochrysone carboxylic acid by the polyketide synthase ClaG and the beta-lactamase ClaF. This compound is decarboxylated by ClaH to yield emodin, which is then converted to chrysophanol hydroquinone by the reductase ClaC and the dehydratase ClaB. We show that the predicted cytochrome P450 ClaM catalyzes the dimerization of nataloe-emodin to cladofulvin. Remarkably, such dimerization dramatically increases nataloe-emodin cytotoxicity against mammalian cell lines. These findings shed light on the enzymatic mechanisms involved in anthraquinone dimerization. Future characterization of the ClaM enzyme should facilitate engineering the biosynthesis of novel, potent, dimeric anthraquinones and structurally related compound families.

Background The ubiquity of social media has increased exposure to idealised beauty standards, often unrealistic and harmful. Repeated exposure has been linked to body dissatisfaction, harmful behaviours, and potentially the development of eating disorders (ED). Given the volume of content produced daily, effective harm mitigation strategies (automated or user-driven) are essential, requiring an informed understanding of the contexts and nuances surrounding harmful content. Objective The study has two key aims: (1) to understand the perspectives of experts by profession and people with lived experience of ED, on what makes social media content harmful in the context of body image and ED, including why and how this harm occurs; and (2) to explore how technology might help mitigate these effects. Methods We engaged n  = 30 participants, including 12 interviews with experts by profession ( n  = 2 ED support service providers and n  = 10 body image and ED experts), and five focus groups with experts by lived experience ( n  = 18 people with lived experience of ED). Results Using the Framework Method guided by inductive thematic analysis, we developed six prominent themes: (1) Spectrum of harmful and ambiguous content on social media, (2) The “echo chamber” of harmful content amplified by social media algorithms, (3) Balancing safety, freedom and responsibility in social media moderation, (4) Shared responsibility and collaboration for safer social media environments, (5) The role of representation and diversity in social media recovery and support, and (6) Harnessing digital innovation to reduce harm on social media. We developed an eight-category framework of harmful social media content, offering an underlying contextual understanding of harmful content and guidance for harm-reducing technologies. Conclusions Manual safeguards place significant responsibility on users. This work supports informed distinctions between harmful, ambiguous and safe content and provides design insights for classification systems and adaptable automated moderation. Plain English summary Constant exposure to idealised beauty standards online can lead to negative body image, unhealthy behaviours and eating disorders (ED). To reduce these harms, we need effective ways to identify and moderate harmful content. However, first, we must understand why and how this content causes harm. We consulted n  = 30 participants, including interviews with n  = 12 professionals in ED support and research, and five focus groups with n  = 18 individuals with lived experience of ED. Six major themes were developed using the Framework Method guided by inductive thematic analysis: the range of harmful and ambiguous content, social media’s contribution to an ED “echo chamber,” challenges in content moderation, the need for shared responsibility in creating safer spaces, the importance of diverse representation and the potential for technology to help mitigate harm. From this analysis, we developed eight categories of harmful social media content related to body image and ED, clarifying how individuals may be negatively affected and providing structure for future interventions. Participants highlighted the powerful influence of algorithms in promoting harmful content and called for shared responsibility among users, content creators, platforms, and policymakers. The findings offer guidance for designing technologies that mitigate social media harm.

Fulvia fulva and Dothistroma septosporum are closely related apoplastic pathogens with similar lifestyles but different hosts: F. fulva is a pathogen of tomato, whilst D. septosporum is a pathogen of pine trees. In 2012, the first genome sequences of these pathogens were published, with F. fulva and D. septosporum having highly fragmented and near‐complete assemblies, respectively. Since then, significant advances have been made in unravelling their genome architectures. For instance, the genome of F. fulva has now been assembled into 14 chromosomes, 13 of which have synteny with the 14 chromosomes of D. septosporum, suggesting these pathogens are even more closely related than originally thought. Considerable advances have also been made in the identification and functional characterization of virulence factors (e.g., effector proteins and secondary metabolites) from these pathogens, thereby providing new insights into how they promote host colonization or activate plant defence responses. For example, it has now been established that effector proteins from both F. fulva and D. septosporum interact with cell‐surface immune receptors and co‐receptors to activate the plant immune system. Progress has also been made in understanding how F. fulva and D. septosporum have evolved with their host plants, whilst intensive research into pandemics of Dothistroma needle blight in the Northern Hemisphere has shed light on the origins, migration, and genetic diversity of the global D. septosporum population. In this review, we specifically summarize advances made in our understanding of the F. fulva–tomato and D. septosporum–pine pathosystems over the last 10 years. In this review we summarize advances from the last decade in understanding the molecular basis of how the closely related fungal pathogens Fulvia fulva and Dothistroma septosporum interact with their respective tomato and pine hosts.

Background Very few programs aimed at improving body image among adolescent boys have been effective, and there is still no clear evidence as to what will work for universal prevention of eating disorders and body dissatisfaction with this group. We combined two previously efficacious programs and used a design thinking framework to optimise program content alongside potential end-users including adolescent boys, teachers, parents, and experts. Goodform is a four-session universal program that aims to reduce body dissatisfaction and prevent the use of muscle-building supplements among 14-to-16 year old adolescent boys. Methods/design Goodform will be trialled using a cluster randomised controlled trial (RCT) conducted in Australian schools, with Year 9 boys as participants. The intervention is teacher-delivered. Data will be collected at three time points: baseline, post-intervention, and follow-up (2 months). Three primary outcome constructs will be examined, including body dissatisfaction (Male Body Attitudes Scale-Revised) and attitudes towards appearance and performance enhancing substances (APES; Outcome Expectations for Steroid and Supplement Use, Intentions to use APES) and actual use of APES at each time point. Three secondary outcome constructs will be examined, which are social norms for APES (adapted Peer Norms Scale), negative body talk (Male Body Talk Scale), and internalisation of and pressure to attain appearance ideals (Sociocultural Attitudes Towards Appearance Questionnaire-4 Revised). Internalisation of appearance ideals will also be examined as a mediator of change in primary outcomes. Teachers will provide data on adherence to lessons, student engagement/enjoyment, and understanding of the content. Discussion The GoodForm RCT will trial a novel, generalizable, and extensively developed program intended to improve boys’ body image and reduce actual and intended APES use. We anticipate that it will provide a novel contribution to the field of boys’ body dissatisfaction prevention. Trial registration This trial was retrospectively registered with the Australian and New Zealand Clinical Trials Registry on May 14th 2019, registration number ACTRN12619000725167 .

Cosmetic surgery is extremely popular. Despite this, negative attitudes towards cosmetic surgery recipients prevail. Across two pre-registered studies, we examined whether intrasexual competitiveness explains these negative attitudes. Participants in Study 1 were 343 (mean age = 24.74) single heterosexual American women and participants in Study 2 were 445 (mean age = 19.03) single heterosexual Australian women. Participants in both studies were primed for either low or high intrasexual competitiveness. Contrary to our predictions, we found that priming condition did not influence participants’ derogation and social exclusion of cosmetic surgery recipients. We did, however, find evidence for a ‘relative attractiveness’ halo effect: participants engaged in less derogation and social exclusion when they assumed cosmetic surgery recipients were more attractive than themselves. This suggests that 'pretty privilege' extends not only to women who meet conventional beauty standards, but also to those who are perceived as relatively closer to meeting these standards than the individual with whom they are engaging. Overall, we concluded that intrasexual competitiveness does not encourage the stigmatisation of cosmetic surgery recipients and examined alternative explanations for this phenomenon.