Mechanism of 2'-fucosyllactose degradation by human-associated Akkermansia.

Among the first microorganisms to colonize the human gut of breastfed infants are bacteria capable of fermenting human milk oligosaccharides (HMOs). One of the most abundant HMOs, 2'-fucosyllactose (2'-FL), may specifically drive bacterial colonization of the intestine. Recently, differential growth has been observed across multiple species of Akkermansia on various HMOs including 2'-FL. In culture, we found growth of two species, A. muciniphila MucT and A. biwaensis CSUN-19,on HMOs corresponded to a decrease in the levels of 2'-FL and an increase in lactose, indicating that the first step in 2'-FL catabolism is the cleavage of fucose. Using phylogenetic analysis and transcriptional profiling, we found that the number and expression of fucosidase genes from two glycoside hydrolase (GH) families, GH29 and GH95, vary between these two species. During the mid-log phase of growth, the expression of several GH29 genes was increased by 2'-FL in both species, whereas the GH95 genes were induced only in A. muciniphila. We further show that one putative fucosidase and a ß-galactosidase from A. biwaensis are involved in the breakdown of 2'-FL. Our findings indicate that the plasticity of GHs of human-associated Akkermansia sp. enables access to additional growth substrates present in HMOs, including 2'-FL. Our work highlights the potential for Akkermansia to influence the development of the gut microbiota early in life and expands the known metabolic capabilities of this important human symbiont.IMPORTANCEAkkermansia are mucin-degrading specialists widely distributed in the human population. Akkermansia biwaensis has recently been observed to have enhanced growth relative to other human-associated Akkermansia on multiple human milk oligosaccharides (HMOs). However, the mechanisms for enhanced growth are not understood. Here, we characterized the phylogenetic diversity and function of select genes involved in the growth of A. biwaensis on 2'-fucosyllactose (2'-FL), a dominant HMO. Specifically, we demonstrate that two genes in a genomic locus, a putative ß-galactosidase and α-fucosidase, are likely responsible for the enhanced growth on 2'-FL. The functional characterization of A. biwaensis growth on 2'-FL delineates the significance of a single genomic locus that may facilitate enhanced colonization and functional activity of select Akkermansia early in life.

Effect of Selective Lesions of Nucleus Accumbens µ-Opioid Receptor-Expressing Cells on Heroin Self-Administration in Male and Female Rats: A Study with Novel Oprm1-Cre Knock-in Rats.

The brain µ-opioid receptor (MOR) is critical for the analgesic, rewarding, and addictive effects of opioid drugs. However, in rat models of opioid-related behaviors, the circuit mechanisms of MOR-expressing cells are less known because of a lack of genetic tools to selectively manipulate them. We introduce a CRISPR-based Oprm1-Cre knock-in transgenic rat that provides cell type-specific genetic access to MOR-expressing cells. After performing anatomic and behavioral validation experiments, we used the Oprm1-Cre knock-in rats to study the involvement of NAc MOR-expressing cells in heroin self-administration in male and female rats. Using RNAscope, autoradiography, and FISH chain reaction (HCR-FISH), we found no differences in Oprm1 expression in NAc, dorsal striatum, and dorsal hippocampus, or MOR receptor density (except dorsal striatum) or function between Oprm1-Cre knock-in rats and wildtype littermates. HCR-FISH assay showed that iCre is highly coexpressed with Oprm1 (95%-98%). There were no genotype differences in pain responses, morphine analgesia and tolerance, heroin self-administration, and relapse-related behaviors. We used the Cre-dependent vector AAV1-EF1a-Flex-taCasp3-TEVP to lesion NAc MOR-expressing cells. We found that the lesions decreased acquisition of heroin self-administration in male Oprm1-Cre rats and had a stronger inhibitory effect on the effort to self-administer heroin in female Oprm1-Cre rats. The validation of an Oprm1-Cre knock-in rat enables new strategies for understanding the role of MOR-expressing cells in rat models of opioid addiction, pain-related behaviors, and other opioid-mediated functions. Our initial mechanistic study indicates that lesioning NAc MOR-expressing cells had different effects on heroin self-administration in male and female rats.SIGNIFICANCE STATEMENT The brain µ-opioid receptor (MOR) is critical for the analgesic, rewarding, and addictive effects of opioid drugs. However, in rat models of opioid-related behaviors, the circuit mechanisms of MOR-expressing cells are less known because of a lack of genetic tools to selectively manipulate them. We introduce a CRISPR-based Oprm1-Cre knock-in transgenic rat that provides cell type-specific genetic access to brain MOR-expressing cells. After performing anatomical and behavioral validation experiments, we used the Oprm1-Cre knock-in rats to show that lesioning NAc MOR-expressing cells had different effects on heroin self-administration in males and females. The new Oprm1-Cre rats can be used to study the role of brain MOR-expressing cells in animal models of opioid addiction, pain-related behaviors, and other opioid-mediated functions.

Precision editing of the gut microbiota ameliorates colitis.

Inflammatory diseases of the gastrointestinal tract are frequently associated with dysbiosis, characterized by changes in gut microbial communities that include an expansion of facultative anaerobic bacteria of the Enterobacteriaceae family (phylum Proteobacteria). Here we show that a dysbiotic expansion of Enterobacteriaceae during gut inflammation could be prevented by tungstate treatment, which selectively inhibited molybdenum-cofactor-dependent microbial respiratory pathways that are operational only during episodes of inflammation. By contrast, we found that tungstate treatment caused minimal changes in the microbiota composition under homeostatic conditions. Notably, tungstate-mediated microbiota editing reduced the severity of intestinal inflammation in mouse models of colitis. We conclude that precision editing of the microbiota composition by tungstate treatment ameliorates the adverse effects of dysbiosis in the inflamed gut.

Assessing Psychological Remission in Adolescent Anorexia Nervosa: A Comparison of Patient and Parent Report.

OBJECTIVE: The definition and assessment of remission in anorexia nervosa (AN) needs greater consensus. Particularly in adolescents, the use of patient-reported composite indices (such as the Eating Disorder Examination [EDE] Global Score) as the sole measure of psychological remission has the potential to obscure patients' true clinical status, given developmental factors and the propensity towards symptom minimization in AN. METHOD: End of treatment (EOT) data from a randomized controlled trial comparing two formats of manualized family-based treatment for adolescents with AN (N = 106) were analyzed. Participants completed the EDE, and their parents completed a parent-as-informant version of the EDE (Parent Eating Disorder Examination; PEDE). Rates of remission were compared across indices (i.e., EDE Global Score vs. diagnostic item analysis) and informant (i.e., adolescent vs. parent), both independently and in combination with the achievement of a percent median body mass index (% mBMI) greater than or equal to 95%. RESULTS: For both adolescent and parent reports, there were higher rates of remission when defined by Global Score than when defined by EDE or PEDE diagnostic items. There were no significant differences in remission rates based on informant. DISCUSSION: In the assessment of remission in AN, the EDE Global Score may not detect some adolescents who continue to exhibit clinically significant psychological symptoms. This study supports a detailed, multidimensional approach to assessing remission in adolescent AN to optimize sensitivity to patients' diagnostic profile. Future research should explore whether parent-child concordance on measures of ED psychopathology varies over the course of treatment.

Translating government policy into practice: How new UK medical schools enact widening participation.

INTRODUCTION: Increasing the diversity of medical students, or widening participation (WP), is critical for social justice and healthcare delivery, and many governments are setting policies to encourage WP. However, establishing policy is only the first step in an educational change process: we also need to know "how" policy is enacted or how medical schools interpret and put into practice WP policy. Addressing this gap, the aim of this study was to examine policy enactment in six new UK medical schools with an explicit WP mandate. METHODS: This qualitative study, underpinned by social constructivism, used semi-structured interviews to explore the experiences of key actors (6 Deans and 14 Admissions staff) of putting policy into practice when setting up a new medical school. Data coding and analysis were initially inductive, using thematic analysis. We then applied Ball's theory of policy enactment to organise the data into four contextual dimensions of 'situation', 'professional', 'material' and 'external'. RESULTS: On the surface, there were many similarities across the six schools in terms of the four dimensions. However, how these dimensions interacted illuminated tensions and differences. For example, some schools found themselves increasingly subjected to local and extra-local rule systems, including pressure to follow host university norms and hosts struggling to accept that medical schools are heavily regulated. There were also tensions between the new medical schools and the medical education "establishment", including lack of power and being judged by overly narrow outcomes. DISCUSSION: Different contexts seem to influence the enactment of WP to medicine in different places, even in the same country, even in medical schools established at the same time. That policy enactment is a complex, non-linear process of enactment is important to acknowledge: context is critical. Our findings will inform future policies and practices that aim to increase WP in medicine.

Involvement of children and young people in the conduct of health research: A rapid umbrella review.

BACKGROUND: Patient and public involvement and engagement (PPIE) have long been considered important to good research practice. There is growing, yet diverse, evidence in support of PPIE with children and young people (CYP). We must now understand the various approaches to involvement of CYP in research. AIMS: This rapid umbrella review aimed to provide an overview of when, how and to what extent CYP are involved in the conduct of health research, as well as the reported benefits, challenges, and facilitators of involvement. METHODS: We searched OVID Medline, Embase and PubMed. Published reviews were included if they reported meaningful involvement of CYP in the conduct of health research. Extracted data were synthesised using thematic analysis. RESULTS: The 26 reviews included were predominately systematic and scoping reviews, published within the last decade, and originating from North America and the United Kingdom. CYPs were involved in all stages of research across the literature, most commonly during research design and data collection, and rarely during research funding or data sharing and access. Researchers mostly engaged CYP using focus groups, interviews, advisory panels, questionnaires, and to a lesser extent arts-based approaches such as photovoice and drawing. Visual and active creative methods were more commonly used with children ≤12 years. The evidence showed a shared understanding of the benefits, challenges, and facilitators for involvement of CYP, such as time and resource commitment and building partnership. CONCLUSION: Overall, the review identified consistency in the range of methods and approaches used, and stages of research with which CYP are commonly involved. There is a need for more consistent reporting of PPIE in the literature, both in terminology and detail used. Furthermore, the impact of approaches to CYP involvement on research and community outcomes must be better evaluated. PATIENT/PUBLIC CONTRIBUTION: This review forms part of broader research initiatives being led by the authors. Together, these projects aim to support embedding of child voices in research practice and to explore the desirability and suitability of Young Persons Advisory Groups within birth cohort studies. The findings from this review, alongside public and stakeholder consultation, will inform development of resources such as practice recommendations to guide future involvement of CYP in health research undertaken at the author's respective institutions.

A new network analysis model in anorexia nervosa patients based on self-reported eating disorder symptoms, psychological distress, and cognitive flexibility.

OBJECTIVES: Cognitive flexibility and psychological distress, such as depression and anxiety, have been implicated in the aetiology of Anorexia Nervosa (AN). Despite the known associations between eating disorder (ED) symptoms, depression, anxiety, and cognitive flexibility, the specific pathways that connect these constructs are unclear. We therefore used network analysis to examine the relationship between these symptoms in an AN sample. METHODS: One hundred and ninety-three treatment-seeking individuals diagnosed with AN (95.6% female, M = 26.89 [SD = 9.45] years old) completed self-report measures assessing depression, anxiety, cognitive flexibility, and ED symptoms. To determine each symptom's influence in the network, we calculated the expected influence. RESULTS: The two relationships with the greatest edges were those between (1) weight/shape concerns and eating/dietary restraint and (2) weight/shape concerns and psychological distress (a measure that combined depression and anxiety). Cognitive flexibility was not connected to weight/shape concerns but had negative partial associations with eating concerns/dietary restraint and psychological distress. There was also a slight, non-zero connection between eating concerns/dietary restraint and psychological distress. CONCLUSIONS: The findings underscore the importance of weight/shape, eating/dietary concerns, and psychological distress in the AN network and suggest that addressing cognitive flexibility may be a useful target for eating concerns/dietary restraint and psychological distress. Future studies assessing the longitudinal course of psychopathology within the AN network structure may help in identifying whether specific symptoms function as risk factors or maintaining factors for this co-occurrence.

The development of a novel sexual health promotion intervention for young people with mental ill-health: the PROSPEct project.

BACKGROUND: Young people with mental ill-health experience higher rates of high-risk sexual behaviour, have poorer sexual health outcomes, and lower satisfaction with their sexual wellbeing compared to their peers. Ensuring good sexual health in this cohort is a public health concern, but best practice intervention in the area remains under-researched. This study aimed to co-design a novel intervention to address the sexual health needs of young people with mental ill-health to test its effectiveness in a future trial undertaken in youth mental health services in Melbourne, Australia. METHODS: We followed the 2022 Medical Research Council (MRC) guidelines for developing and evaluating complex interventions. This involved synthesising evidence from the 'top down' (published evidence) and 'bottom up' (stakeholder views). We combined systematic review findings with data elicited from qualitative interviews and focus groups with young people, carers, and clinicians and identified critical cultural issues to inform the development of our intervention. RESULTS: Existing evidence in the field of sexual health in youth mental health was limited but suggested the need to address sexual wellbeing as a concept broader than an absence of negative health outcomes. The Information-Motivation-Belief (IMB) model was chosen as the theoretical Framework on which to base the intervention. Interviews/focus groups were conducted with 29 stakeholders (18 clinicians, three carers, and eight young people). Synthesis of the evidence gathered resulted in the co-design of a novel intervention consisting of an initial consultation and four 60-90-minute sessions delivered individually by a young 'sex-positive' clinician with additional training in sexual health. Barriers and supports to intervention success were also identified. CONCLUSIONS: Using the MRC Framework has guided the co-design of a potentially promising intervention that addresses the sexual health needs of young people with mental ill-health. The next step is to test the intervention in a one-arm feasibility trial.

Validating and developing a shortened version of the detail and flexibility (DFlex) questionnaire for eating disorders, anxiety and depression.

OBJECTIVE: To validate the original and a shortened version of the Detail and Flexibility (DFlex) Questionnaire. METHOD: Confirmatory factor analyses, internal consistency, and discriminant validity estimates were conducted within individuals with a diagnosis of an eating disorder (ED) (n = 124), an anxiety disorder and/or depression (n = 219), and a community sample (n = 852) (Part 1). Convergent validity of the DFlex through comparisons with the Autism Spectrum Quotient, Wisconsin Card Sorting Task, and Group Embedded Figures Task was undertaken within a combined ED and community sample (N = 68). Test-retest reliability of the DFlex was also examined across 2 years in a community sample (N = 85) (Part 2). RESULTS: The original factor structure of the DFlex was not supported. Hence, a shortened version, the DFlex-Revised, was developed. Good discriminant validity was obtained for the DFlex and DFlex-Revised, however, support for convergent validity was mixed. Finally, the 2-year test-retest reliability for the two DFlex versions was found to be low, suggesting potential malleability in construct over this timeframe. CONCLUSIONS: Further research is needed to validate the DFlex in clinical and non-clinical populations using different neurocognitive tests. Test-retest, using varied time intervals, should also be assessed.

Development of a Novel Tool To Demystify Drug Distribution at Tissue-Blood Barriers.

Tissue endothelial cells express ABC-transporter enzymes that change the concentration of small molecules within different tissue compartments. These "blood-tissue barriers" have been shown to directly affect the efficacy and toxicity of anticancer, antimicrobial, psychiatric, and anti-epileptic drugs. Currently this phenomenon is best studied for the blood-brain barrier, but remains enigmatic for most other tissues. In addition, canonical pharmacokinetic theory specifically assumes an equal concentration of free drug within all tissue compartments. Inspired by Lipinski's "rule of 5," we here clarify current knowledge on drug-tissue distribution by: 1) curating the in-vivo literature on 73 drugs across 23 tissues and 2) developing two graphical web-based applications to visually describe and interpret data. These curated in-vivo dataset and visualization tools enabled us to achieve new insights into the logic of the barrier-tissue organization and showed remarkable correspondence to whole-body imaging of radiolabeled molecules.

The effect of COVID-19 on women's experiences of pregnancy, birth and postpartum in Indonesia: a rapid online survey.

BACKGROUND: The interrelationship of psychological and social factors in the current COVID-19 pandemic has been highlighted in research mainly focused on the global north. The impact of lockdowns can exacerbate psychological distress and affect access to services. Less is known about the psychosocial impact on women in the context of lower-middle income countries (LMICs); the aim of this study was to capture the impact of COVID-19 on women's experiences of pregnancy, birth and postpartum in Indonesia. METHODS: We conducted a rapid cross-sectional online survey of women across all 34 provinces in Indonesia to capture participants' experiences. Data were collected between 10th July to 9th August 2020 including demographics, effects on general and mental health and impact on service use. Descriptive statistics and thematic analysis were used to analyse responses, including those women who self-identified with a pre-existing mental health problem. RESULTS: Responses were obtained from 1137 women, this included pregnant women (n = 842) and postpartum women (n = 295). The majority of women (97%) had accessed antenatal care during their pregnancy, but 84% of women reporting feeling fearful and anxious about attending visits, resulting in some women not attending or changing provider. A small number (13%) were denied the presence of a birth companion, with 28% of women reporting that their babies had been removed at birth due to protocols or baby's health. Feeling anxious was a common experience among women (62%) during their pregnancy, birth or postnatal period, with a small number (9%) feeling depressed. Lockdown measures led to tensions within personal and family relationships. CONCLUSIONS: Women in Indonesia reported that the pandemic added an increased burden in pregnancy, birth and post-partum period: physically, psychologically, spiritually and financially. Maternity services were disrupted and health insurance cover lacked responsiveness, which either directly or indirectly impacted on women's choices, and equal access to care. Given the longevity of the current pandemic there is a need to develop tailored supportive interventions for women and their families and develop bespoke training for midwives and other relevant health professionals.

The impact of patient skin colour on diagnostic ability and confidence of medical students.

Previous literature has explored unconscious racial biases in clinical education and medicine, finding that people with darker skin tones can be underrepresented in learning resources and managed differently in a clinical setting. This study aimed to examine whether patient skin colour can affect the diagnostic ability and confidence of medical students, and their cognitive reasoning processes. We presented students with 12 different clinical presentations on both white skin (WS) and non-white skin (NWS). A think aloud (TA) study was conducted to explore students' cognitive reasoning processes (n = 8). An online quiz was also conducted where students submitted a diagnosis and confidence level for each clinical presentation (n = 185). In the TA interviews, students used similar levels of information gathering and analytical reasoning for each skin type but appeared to display increased uncertainty and reduced non-analytical reasoning methods for the NWS images compared to the WS images. In the online quiz, students were significantly more likely to accurately diagnose five of the 12 clinical presentations (shingles, cellulitis, Lyme disease, eczema and meningococcal disease) on WS compared to NWS (p < 0.01). With regards to students' confidence, they were significantly more confident diagnosing eight of the 12 clinical presentations (shingles, cellulitis, Lyme disease, eczema, meningococcal disease, urticaria, chickenpox and Kawasaki disease) on WS when compared to NWS (p < 0.01). These findings highlight the need to improve teaching resources to include a greater diversity of skin colours exhibiting clinical signs, to improve students' knowledge and confidence, and ultimately, to avoid patients being misdiagnosed due to the colour of their skin.

Sexual health services in urban, suburban, and rural outpatient mental healthcare settings in New York: findings from a survey of practices and gaps.

We surveyed all licensed outpatient mental health programs in New York to examine sexual health services and training needs of providers. Gaps were found in processes for assessing whether patients were sexually active, engaging in sexual risk behaviours, and in need of HIV testing and pre-exposure prophylaxis. Significant differences between urban, suburban, and rural settings statewide were found in how the following sexual health services were delivered: education; on-site sexually transmitted infection screenings; and condom distribution and barriers to distribution. Staff training in sexual health services delivery is critically needed for optimal sexual health and recovery of patients in community mental healthcare.

When eating disorder attitudes and cognitions persist after weight restoration: An exploratory examination of non-cognitive responders to family-based treatment for adolescent anorexia nervosa.

OBJECTIVE: Family-based treatment (FBT) is a well-established intervention for adolescent anorexia nervosa (AN). Although FBT is efficacious in promoting weight gain and improvements in psychological symptoms, for some adolescents, cognitive/attitudinal recovery lags behind weight gain. This study conducted an exploratory post hoc analysis of outcomes of adolescents who achieved weight gain by the end of FBT but continued to experience elevated psychological symptoms post-treatment. METHODS: Data were drawn from two randomised controlled trials (RCTs) testing two forms of FBT (conjoint/whole family and parent-focussed). Descriptive statistics and generalised estimating equations were used to examine differences in treatment outcomes between non-cognitive responders (NCRs) (those who regained weight but continued to experience psychological symptoms) and full responders (FRs) (those who achieved both weight and cognitive restoration by the end of treatment) (n = 80; 83.7% female, Agemean [SD] = 14.66 [1.73]). RESULTS: By 12 months post-treatment, there were no differences in weight between NCRs and FRs. However, NCRs had a slower trajectory of weight gain than FRs and continued to have elevated levels of psychological symptoms throughout the follow-up period. CONCLUSIONS: A subset of adolescents appear to continue to experience clinically significant levels of eating pathology up to 12 months after FBT even when weight restoration is achieved.

Prevalence of HBV Infection, Vaccine-Induced Immunity, and Susceptibility Among At-Risk Populations: US Households, 2013-2018.

BACKGROUND AND AIMS: In the USA, HBV is one of the leading causes of chronic liver disease and cirrhosis and is a major cause of liver cancer. We aimed to estimate the prevalence of past and present HBV infection, susceptibility to HBV infection, and vaccine-induced immunity to hepatitis B among the US population during 2013-2018. APPROACH AND RESULTS: Prevalence estimates and 95% CIs were analyzed using 2013-2018 data from the National Health and Nutrition Examination Survey. Serologic testing among noninstitutionalized persons aged ≥ 6 years was used for classifying persons as total hepatitis B core antibody (anti-HBc), indicative of current or previous (ever having had) HBV infection; HBsAg, indicative of current HBV infection; and antibody to ABsAg (anti-HBs), indicative of immunity attributable to hepatitis B vaccination. Persons who tested negative for anti-HBc, HBsAg, and anti-HBs were considered susceptible to HBV infection. Non-US-born residents accounted for 69.1% of the population with chronic HBV infection and were 9.1 times more likely to be living with chronic hepatitis B, compared with US-born persons. Among adults aged ≥ 25 years who resided in US households, an estimated 155.8 million persons (or 73.4%) were susceptible to HBV infection, and an estimated 45.4 million had vaccine-induced immunity to hepatitis B. Men who have sex with men (MSM) were 3.6 times more likely to have ever been infected with HBV; however, MSM were just as likely to have vaccine-induced immunity to hepatitis B as non-MSM. CONCLUSION: Despite increasing immune protection among young persons vaccinated after birth, the estimated prevalence of persons living with chronic hepatitis B in the USA has remained unchanged at 0.3% since 1999.

Barriers to the management of sexual dysfunction among people with psychosis: analysis of qualitative data from the REMEDY trial.

BACKGROUND: More than half of people who use antipsychotic medication for psychosis report having sexual dysfunction. The REMEDY trial aimed to find out if switching antipsychotic medication provides an effective way to reduce sexual dysfunction among people with psychosis. We set out to recruit 216 participants over a two-year period, but recruitment was stopped after an extended 12-month pilot phase, during which we recruited only 10 participants. As part of a nested process evaluation, we conducted qualitative interviews with front-line clinicians to examine barriers to recruitment to the trial. METHODS: We developed a semi-structured interview schedule to explore staff views on factors that influenced whether they referred potential participants to the study. We interviewed a purposive sample of 51 staff from four National Health Service (NHS) Trusts in England, ensuring a range of different backgrounds, seniority, and levels of involvement in the trial. Audio recordings of interviews were transcribed for verbatim, and data were analysed using an inductive approach to thematic analysis. RESULTS: Nine interconnected themes were generated. Six themes concerned barriers to recruitment; including; prioritising patients' mental stability, mutual discomfort and embarrassment about discussing a "taboo" subject, and concerns about unintended consequences of asking people with psychosis about their sexual functioning. Three themes, including the quality of treatment relationships and strategies for opening dialogue suggested ways to improve recognition of these "hidden" side effects. CONCLUSION: The identification and management of sexual dysfunction among people with psychosis are not priorities for mental health services in England at this time. Many staff working in front-line services feel unprepared and uncomfortable asking people with psychosis about these problems. While greater use of screening tools may improve the identification of sexual dysfunction among people with psychosis, the evaluation and implementation of interventions to manage them will continue to be challenging unless NHS leaders and senior clinicians demonstrate greater commitment to changing current clinical practice. TRIAL REGISTRATION: Current Controlled Trials ISRCTN12307891.

Bridging of childhood obsessive-compulsive personality disorder traits and adult eating disorder symptoms: A network analysis approach.

OBJECTIVES: Obsessive-compulsive personality disorder (OCDP) traits are commonly associated with eating disorders (EDs), with evidence demonstrating that these traits predispose and exacerbate the ED illness course. However, limited research has examined the symptomatic interplay between ED and OCDP traits. We used network analysis to (1) identify the most central symptoms in a network comprised of OCPD traits retrospectively assessed in childhood and ED symptoms and (2) to identify symptoms which bridged OCPD traits and ED symptoms. METHODS: Participants were 320 females with an ED (anorexia nervosa n = 227, bulimia nervosa n = 93), who completed the semi-structured EATATE interview and the Eating Disorder Inventory-2. Expected influence (EI) was computed to determine each symptom's influence in the network. Bridge symptoms were identified by computing bridge EI. RESULTS: A regularised partial correlation network showed that ascetism, social insecurity, ineffectiveness, and impulsivity had the highest EI in the OCPD and ED network. With respect to bridging symptoms, interpersonal distrust emerged as a possible bridging node between the OCPD and ED trait/symptom clusters. DISCUSSION: These findings highlight the centrality of non-specific ED symptoms in the ED symptom network and suggest that interpersonal distrust may play a functional role through which childhood OCPD traits and ED symptoms are connected.

Gender-based clinical differences in evidence-based treatment for adolescent anorexia nervosa: analysis of aggregated randomized controlled trials.

PURPOSE: Boys represent a small proportion of samples in randomized clinical trials (RCT) investigating evidence-based treatment for adolescents with anorexia nervosa (AN). Consequently, knowledge of potential gender differences in clinical characteristics and treatment response in adolescents is considerably limited. METHODS: Secondary analyses of aggregated data from two RCTs were used to characterize baseline and end-of-treatment clinical features in male and female adolescents with AN (n = 228, 10.53% male). Mixed analyses of variance were used to investigate potential gender differences in treatment response relative to weight outcomes (% median BMI) and eating disorder cognitions (Eating Disorder Examination Global scores; EDE). RESULTS: There were no significant gender differences in prior inpatient care, illness duration, psychiatric comorbidity, or psychotropic medication use at baseline. Nor were there significant gender differences in binge eating, purging, or driven exercise at baseline or end-of-treatment. Girls reported elevated weight and shape concern compared to boys at baseline but overall reduction in EDE Global scores over the course of treatment did not differ according to gender. Boys gained more relative weight during treatment than girls, but this difference was statistically non-significant. CONCLUSION: Overall findings do not suggest significant differences in treatment outcome relative to weight or ED cognitions, by gender. Current evidence suggests that, with the exception of shape and weight concerns, boys present with cognitive and behavioral symptoms as severe as their female counterparts which underscores the need for increased accuracy in assessment of these disorders in boys and young men. LEVEL OF EVIDENCE: Level 1, secondary data analysis of randomized controlled trials.

Family-based treatment for adolescent anorexia nervosa: Outcomes of a stepped-care model.

OBJECTIVE: Stepped-care models of treatment are underexplored in eating disorders. To enhance treatment outcomes, and informed by literature about adaptations to family-based treatment (FBT), we developed an FBT-based stepped-care model for adolescents with anorexia nervosa (AN) that was consistent with family preference (i.e., tailored) and responsive to adolescent needs (i.e., intensity). The aim of this study was to evaluate the effectiveness of this model in terms of remission at end-of-treatment. METHOD: Adolescents (N = 82), aged 12-18 years (M = 15.1, SD = 1.8) and meeting Diagnostic and Statistical Manual of Mental Disorders 5th Edition criteria for AN, were assessed at baseline, Weeks 24 and 48. FBT was tailored to family preference and clinical need, with 16-18 sessions by Week 24. This was followed by three FBT booster sessions or an extension of FBT plus booster sessions (Week 48). The primary outcome was defined as weight > 95% of %median body mass index plus within 1 SD of the Eating Disorder Examination (EDE) global score community norms. RESULTS: Remission rates were 45.1% and 52.4% at Weeks 24 and 48, respectively. Commensurable improvements were evident across secondary outcomes (e.g., EDE subscale scores). As a reference point, remission rates compared positively with results from a recent randomized clinical trial from the same center and at the same time points (Week 24:45.1% vs. 32.1% and Week 48:52.4% vs. 30.2%). Controlling for propensity score, no statistically significant differences were observed. DISCUSSION: This stepped-care model, designed to be responsive to the individual needs of adolescents and their families, achieved encouraging rates of remission. This study provides an important signal that supports future clinical trials of stepped-care models for adolescents with AN.

Do orthorexia and intolerance of uncertainty mediate the relationship between autism spectrum traits and disordered eating symptoms?

PURPOSE: Autism spectrum disorder traits have been implicated in the psychopathology of eating disorders and may also be relevant for the development of orthorexia symptoms. Further, intolerance of uncertainty (IUS) may indirectly contribute to the development of disordered eating, as the displacement of anxiety onto food may help achieve a sense of control and maximise certainty. We examined a new cognitive model of eating pathology which assessed the role of IU and orthorexia symptoms as potential mediators of the relationship between autistic traits and disordered eating in a community sample. METHODS: Three-hundred-and-ninety-six female participants (M = 20.07, SD = 4.52 years old) completed an online self-report questionnaire which assessed the variables of interest. RESULTS: Despite finding significant bivariate correlations, our model results showed that autistic traits did not directly predict disordered eating or orthorexia symptoms. Significant indirect relationships were found between autistic traits and eating disorder symptoms through both IU and orthorexia symptoms. CONCLUSION: The findings provide partial support for our proposed model suggesting that autistic traits may increase the vulnerability for disordered eating, not directly, but through their associations with mechanisms such as IU and the development of problematic eating behaviours typical of orthorexia. Future research should focus on whether targeting IU may assist in preventing the development of disordered eating. LEVEL OF EVIDENCE: Level V, cross-sectional descriptive study.