Power, position and social relations: Is the espoused absence of hierarchy in Open Dialogue naïve?

Open Dialogue practitioners aim to reduce social hierarchies by not privileging any one voice in social network conversations, and thus creating space for a polyphony of voices. This sits in contrast to the traditional privileging of those voices credited with more knowledge or power because of social position or professional expertise. Using qualitative interviews, the aim of this current study was to explore Open Dialogue practitioners' descriptions of challenges in implementing Open Dialogue at a women's health clinic in Australia. Findings revealed how attempts to rhetorically flatten hierarchies among practitioners created challenges and a lack of clarity regarding roles and responsibilities. As the practitioners tried to adjust to new ways of working, they reverted to taking up engrained positions and power aligned with more conventional social and professional roles for leading therapy and decision-making. The findings raise questions about equity-oriented ways of working, such as Open Dialogue, where intentions of creating a flattened hierarchy may allow power structures and their effects to be minimised or ignored, rather than actively acknowledged and addressed. Further research is needed to consider the implications that shifting power relations might have on the roles and responsibilities of practitioners in the move to equity-oriented services.

Revised Model for the Type A Glycan Biosynthetic Pathway in Clostridioides difficile Strain 630Δerm Based on Quantitative Proteomics of cd0241-cd0244 Mutant Strains.

The bacterial flagellum is involved in a variety of processes including motility, adherence, and immunomodulation. In the Clostridioides difficile strain 630Δerm, the main filamentous component, FliC, is post-translationally modified with an O-linked Type A glycan structure. This modification is essential for flagellar function, since motility is seriously impaired in gene mutants with improper biosynthesis of the Type A glycan. The cd0240-cd0244 gene cluster encodes the Type A biosynthetic proteins, but the role of each gene, and the corresponding enzymatic activity, have not been fully elucidated. Using quantitative mass spectrometry-based proteomics analyses, we determined the relative abundance of the observed glycan variations of the Type A structure in cd0241, cd0242, cd0243, and cd0244 mutant strains. Our data not only confirm the importance of CD0241, CD0242, and CD0243 but, in contrast to previous data, also show that CD0244 is essential for the biosynthesis of the Type A modification. Combined with additional bioinformatic analyses, we propose a revised model for Type A glycan biosynthesis.

Identification of novel p-cresol inhibitors that reduce Clostridioides difficile's ability to compete with species of the gut microbiome.

Treatment of Clostridioides difficile infection (CDI) is expensive and complex, with a high proportion of patients suffering infection relapse (20-35%), and some having multiple relapses. A healthy, unperturbed gut microbiome provides colonisation resistance against CDI through competition for nutrients and space. However, antibiotic consumption can disturb the gut microbiota (dysbiosis) resulting in the loss of colonisation resistance allowing C. difficile to colonise and establish infection. A unique feature of C. difficile is the production of high concentrations of the antimicrobial compound para-cresol, which provides the bacterium with a competitive advantage over other bacteria found in the gut. p-cresol is produced by the conversion of para-Hydroxyphenylacetic acid (p-HPA) by the HpdBCA enzyme complex. In this study, we have identified several promising inhibitors of HpdBCA decarboxylase, which reduce p-cresol production and render C. difficile less able to compete with a gut dwelling Escherichia coli strain. We demonstrate that the lead compound, 4-Hydroxyphenylacetonitrile, reduced p-cresol production by 99.0 ± 0.4%, whereas 4-Hydroxyphenylacetamide, a previously identified inhibitor of HpdBCA decarboxylase, only reduced p-cresol production by 54.9 ± 13.5%. To interpret efficacy of these first-generation inhibitors, we undertook molecular docking studies that predict the binding mode for these compounds. Notably, the predicted binding energy correlated well with the experimentally determined level of inhibition, providing a molecular basis for the differences in efficacy between the compounds. This study has identified promising p-cresol production inhibitors whose development could lead to beneficial therapeutics that help to restore colonisation resistance and therefore reduce the likelihood of CDI relapse.

Complementary and Alternative Medicine (CAM): use and views among patients with solid organ and haematological malignancies in Northland, New Zealand.

AIMS: Complementary Alternative Medicine (CAM) use among patients with malignant diagnosis has been rising globally. This study assesses the prevalence of CAM among patients with solid organ or haematological malignancy at a regional outpatient cancer and blood service in Northland, New Zealand. Secondary objectives include determining: i) types of CAM used, ii) sources of information, and iii) patient perspectives on CAM. METHOD: In this single-centre cross-sectional study, patients attending treatment or follow-up appointments at the Jim Carney Cancer Treatment Centre (JCC) between 25 September to 20 October 2017 were invited to complete an anonymous self-administered questionnaire. RESULTS: Of the 306 assessable entries, 29% (n=89) respondents were using CAM, 10% had intentions to use CAM in the future, while 45% were undecided. Word-of-mouth (58%) was the most common source of CAM information, followed by internet sources (36%) and healthcare professionals (27%). Biologically based therapies were the most popular form of CAM used. Common reasons for CAM use include symptom relief (65%), perceived lower toxicity (62%), holistic (52%), natural (51%) and potential for cure (45%). Only 49% of CAM users felt comfortable discussing their CAM use with their oncologist/ haematologist. CONCLUSION: CAM use is common and has relevance across oncology treatment centres nationwide. Local research into CAM use can serve to raise awareness and to assist healthcare professional training in addressing CAM use in a specific patient population.

Organizational Change in Complex Systems: Organizational and Leadership Factors in the Introduction of Open Dialogue to Mental Health Care Services.

Conventional mental health services are frequently criticized for failing to support people and communities in their care. Open Dialogue is a non-conventional humanistic approach to mental health care, which has been implemented in many different settings globally. At two Australian public health care services, implementation of the approach led to positive client outcomes and sustained organizational and clinical change. The aim of the study was to identify and explore the organizational, management, leadership and cultural factors that contributed to sustained implementation in these complex systems. We conducted nine individual semi-structured interviews of health care leaders and managers from the two sites. Transcriptions of the interviews were analyzed thematically. Leaders facilitated a gradual development of clinical and organizational legitimacy for the non-standardized Open Dialogue approach by holding the anxiety and frustration of practitioners and parts of the administration, cultivating cultural change and adaptation and by continually removing organizational obstacles.

Regional single-queue scheduling platform for specialist diagnostics in the lung cancer pathway: accelerating cancer recovery from the COVID-19 pandemic.

Lung cancer is the single biggest cause of cancer death. The diagnostic pathway can be complex, including specialist cancer diagnostics that are not performed at every hospital. One such example is endobronchial ultrasound (EBUS), a day-case bronchoscopic procedure used for nodal staging and tissue diagnosis. In this proof-of-concept pilot in Greater Manchester, we tested a novel digital EBUS booking platform. This platform was accessible across multiple acute care trusts and provided visibility of all available EBUS appointments, allowing referring teams to book directly into the appropriate slot. During a 6-month pilot, 193 EBUS procedures were booked through this new single-queue platform. The median waiting times reduced by 2 days from 9 to 7 days (22% reduction and saving approximately 386 days in total) and reduced variation in waiting times by 1 day from 5 to 4 days (20% reduction). 98% of patients who completed an experience of care survey felt the process was 'very well' or 'well' organised and 77% felt the most important factor in deciding where to have their EBUS was the earliest possible appointment regardless of travel. This proof-of-concept pilot has shown improvements in cancer waiting times with significant future potential in delivering specialist cancer diagnostics.

Regulation of para-cresol production in Clostridioides difficile.

The human pathogen Clostridioides difficile colonises the gastrointestinal tract following antibiotic exposure, which causes perturbations in the beneficial microbiome. An unusual feature of C. difficile among the gut microbiota is its ability to produce high concentrations of the antimicrobial compound para-cresol, which selectively targets Gram-negative bacteria. Production of p-cresol occurs either by: (a) tyrosine fermentation via the intermediate para-hydroxyphenylacetate (p-HPA), or (b) direct turnover of exogenous p-HPA in the human gut. p-HPA is decarboxylated to produce p-cresol, by the action of HpdBCA decarboxylase encoded by the hpdBCA operon. HpdBCA decarboxylase production is induced at the transcriptional level by elevated p-HPA, which causes elevated p-cresol production, that significantly reduces microbiome diversity and richness. This deleterious effect of p-cresol on the beneficial gut microbiome is advantageous for C. difficile pathogenesis and infection relapse. Inhibiting this pathway would provide a highly specific therapeutic.

Production of p-cresol by Decarboxylation of p-HPA by All Five Lineages of Clostridioides difficile Provides a Growth Advantage.

Clostridioides difficile is the leading cause of antibiotic-associated diarrhea and is capable of causing severe symptoms, such as pseudomembranous colitis and toxic megacolon. An unusual feature of C. difficile is the distinctive production of high levels of the antimicrobial compound para-cresol. p-Cresol production provides C. difficile with a competitive colonization advantage over gut commensal species, in particular, Gram-negative species. p-Cresol is produced by the conversion of para-hydroxyphenylacetic acid (p-HPA) via the actions of HpdBCA decarboxylase coded by the hpdBCA operon. Host cells and certain bacterial species produce p-HPA; however, the effects of p-HPA on the viability of C. difficile and other gut microbiota are unknown. Here we show that representative strains from all five C. difficile clades are able to produce p-cresol by two distinct mechanisms: (i) via fermentation of p-tyrosine and (ii) via uptake and turnover of exogenous p-HPA. We observed strain-specific differences in p-cresol production, resulting from differential efficiency of p-tyrosine fermentation; representatives of clade 3 (CD305) and clade 5 (M120) produced the highest levels of p-cresol via tyrosine metabolism, whereas the toxin A-/B+ isolate from clade 4 (M68) produced the lowest level of p-cresol. All five lineages share at least 97.3% homology across the hpdBCA operon, responsible for decarboxylation of p-HPA to p-cresol, suggesting that the limiting step in p-cresol production may result from tyrosine to p-HPA conversion. We identified that elevated intracellular p-HPA, modulated indirectly via CodY, controls p-cresol production via inducing the expression of HpdBCA decarboxylase ubiquitously in C. difficile populations. Efficient turnover of p-HPA is advantageous to C. difficile as p-HPA has a deleterious effect on the growth of C. difficile and other representative Gram-negative gut bacteria, transduced potentially by the disruption of membrane permeability and release of intracellular phosphate. This study provides insights into the importance of HpdBCA decarboxylase in C. difficile pathogenesis, both in terms of p-cresol production and detoxification of p-HPA, highlighting its importance to cell survival and as a highly specific therapeutic target for the inhibition of p-cresol production across C. difficile species.

Clostridioides difficile: innovations in target discovery and potential for therapeutic success.

INTRODUCTION: Clostridioides difficile infection (CDI) remains a worldwide clinical problem. Increased incidence of primary infection, occurrence of hypertoxigenic ribotypes, and more frequent occurrence of drug resistant, recurrent, and non-hospital CDI, emphasizes the urgent unmet need of discovering new therapeutic targets. AREAS COVERED: We searched PubMed and Web of Science databases for articles identifying novel therapeutic targets or treatments for C. difficile from 2001 to 2021. We present an updated review on current preclinical efforts on designing inhibitory compounds against these drug targets and indicate how these could become the focus of future therapeutic approaches. We also evaluate the increasing exploitability of gut microbial-derived metabolites and host-derived therapeutics targeting VEGF-A, immune targets and pathways, ion transporters, and microRNAs as anti-C. difficile therapeutics, which have yet to reach clinical trials. Our review also highlights the therapeutic potential of re-purposing currently available agents . We conclude by considering translational hurdles and possible strategies to mitigate these problems. EXPERT OPINION: Considerable progress has been made in the development of new anti-CDI drug candidates. Nevertheless, a greater comprehension of CDI pathogenesis and host-microbe interactions is beginning to uncover potential novel therapeutic targets, which can be exploited to plug gaps in the CDI drug discovery pipeline.

Multi-family therapy for eating disorders: A systematic scoping review of the quantitative and qualitative findings.

OBJECTIVE: This study reviewed the quantitative and qualitative evidence-base for multi-family therapy (MFT) for eating disorders regarding change in physical and psychological symptoms, broader individual and family factors, and the experience of treatment. METHOD: A systematic scoping review was conducted. Four databases (PsycInfo, Medline, Embase, CENTRAL) and five grey literature databases were searched on 24th June 2021 for relevant peer-reviewed journal articles, book chapters, and dissertations. No beginning time-point was specified. Only papers that presented quantitative or qualitative data were included. No restrictions on age or diagnosis were imposed. Studies were first mapped by study design, participant age, and treatment setting, then narratively synthesized. RESULTS: Outcomes for 714 people who received MFT across 27 studies (one mixed-method, 17 quantitative and nine qualitative) were synthesized. MFT is associated with improvements in eating disorder symptomatology and weight gain for those who are underweight. It is also associated with improvements in other individual and family factors including comorbidities, self-esteem, quality of life, and some aspects of the experience of caregiving, although these findings are more mixed. MFT is generally experienced as both helpful and challenging due to the content addressed and intensive group process. DISCUSSION: MFT is associated with significant improvements in eating disorder symptoms across the lifespan and improvement in broader individual and family factors. The evidence base is small and studies are generally underpowered. Larger, higher-quality studies are needed, as is research investigating the unique contribution of MFT on outcomes, given it is typically an adjunctive treatment.

OBJETIVO: Este estudio revisó la evidencia cuantitativa y cualitativa para la terapia multifamiliar (MFT, por sus siglas en inglés) para los trastornos de la conducta alimentaria con respecto al cambio en los síntomas físicos y psicológicos, los factores individuales y familiares más extensos, y la experiencia del tratamiento. MÉTODO: Se realizó una revisión sistemática del alcance. Se realizaron búsquedas en cuatro bases de datos (PsycInfo, Medline, Embase, CENTRAL) y en cinco bases de datos de literatura gris el 24.06.2021 para obtener artículos relevantes de revistas revisadas por pares, capítulos de libros y disertaciones. No se especificó ningún punto de tiempo inicial. Sólo se incluyeron los artículos que presentaban datos cuantitativos o cualitativos. No se impusieron restricciones de edad o diagnóstico. Los estudios se mapearon primero por el diseño del estudio, la edad de los participantes y el entorno de tratamiento, y luego se sintetizaron narrativamente. RESULTADOS: Se sintetizaron los resultados de 714 pacientes que recibieron MFT en 27 estudios (un método mixto, 17 cuantitativos y nueve cualitativos). MFT se asocia con mejoras en la sintomatología del trastorno de la conducta alimentaria y el aumento de peso para aquellos que tienen bajo peso. También se asocia con mejoras en otros factores individuales y familiares, incluidas las comorbilidades, la autoestima, la calidad de vida y algunos aspectos de la experiencia del cuidador, aunque estos hallazgos son más mixtos. MFT generalmente se experimenta como útil y desafiante debido al contenido abordado y al proceso grupal intensivo. DISCUSIÓN: La MFT se asocia con mejoras significativas en los síntomas del trastorno de la conducta alimentaria a lo largo de la vida y una mejora en factores individuales y familiares más amplios. La base de evidencia es pequeña y los estudios generalmente tienen poco poder. Se necesitan estudios más grandes y de mayor calidad, al igual que la investigación que investiga la contribución única de la MFT en los resultados, dado que generalmente es un tratamiento complementario. PALABRAS CLAVE: terapia multifamiliar (MFT), terapia familiar de Maudsley, tratamiento basado en la familia (FBT), trastornos de la conducta alimentaria, anorexia nerviosa, bulimia nerviosa, niño, adolescente, adulto joven, adulto, cuidador.

Open Dialogue, need-adapted mental health care, and implementation fidelity: A discussion paper.

Open Dialogue is a need-adapted approach to mental health care that was originally developed in Finland. Like other need-adapted approaches, Open Dialogue aims to meet consumer's needs and promote collaborative person-centred dialogue to support recovery. Need-adapted mental health care is distinguished by flexibility and responsiveness. Fidelity, defined from an implementation science perspective as the delivery of distinctive interventions in a high quality and effective fashion is a key consideration in health care. However, flexibility presents challenges for evaluating fidelity, which is much easier to evaluate when manualization and reproducible processes are possible. Hence, it remains unclear whether Open Dialogue and other need-adapted mental health interventions can be meaningfully evaluated for fidelity. The aim of this paper was to critically appraise and advance the evaluation of fidelity in need-adapted mental health care, using Open Dialogue as a case study. The paper opens a discussion about how fidelity should be evaluated in flexible, complex interventions, and identifies key questions that need to be asked by practitioners working in need-adapted mental health care to ensure they deliver these interventions as intended and in an evidence-based fashion.

Extracellular DNA, cell surface proteins and c-di-GMP promote biofilm formation in Clostridioides difficile.

Clostridioides difficile is the leading cause of nosocomial antibiotic-associated diarrhoea worldwide, yet there is little insight into intestinal tract colonisation and relapse. In many bacterial species, the secondary messenger cyclic-di-GMP mediates switching between planktonic phase, sessile growth and biofilm formation. We demonstrate that c-di-GMP promotes early biofilm formation in C. difficile and that four cell surface proteins contribute to biofilm formation, including two c-di-GMP regulated; CD2831 and CD3246, and two c-di-GMP-independent; CD3392 and CD0183. We demonstrate that C. difficile biofilms are composed of extracellular DNA (eDNA), cell surface and intracellular proteins, which form a protective matrix around C. difficile vegetative cells and spores, as shown by a protective effect against the antibiotic vancomycin. We demonstrate a positive correlation between biofilm biomass, sporulation frequency and eDNA abundance in all five C. difficile lineages. Strains 630 (RT012), CD305 (RT023) and M120 (RT078) contain significantly more eDNA in their biofilm matrix than strains R20291 (RT027) and M68 (RT017). DNase has a profound effect on biofilm integrity, resulting in complete disassembly of the biofilm matrix, inhibition of biofilm formation and reduced spore germination. The addition of exogenous DNase could be exploited in treatment of C. difficile infection and relapse, to improve antibiotic efficacy.

Beyond polyphony: Open Dialogue in a Women's Shelter in Australia as a possibility for supporting violence-informed practice.

Open Dialogue is a family/social network-centered psychotherapeutic approach to responding to people in crisis and distress. In 2017, Open Dialogue network meetings were implemented in an Australian inner-city shelter for disadvantaged women. The aim of this study was to explore the experience of participating in these meetings from the perspective of service users and Open Dialogue practitioners. Qualitative interviews were completed with thirteen participants (six service users and seven practitioners) and analyzed thematically. The findings suggested that dialogical processes created safety by attending to multiple voices in nonviolent ways that reduced perceived hierarchies. Notions of expertise were renegotiated, which allowed the women to feel heard in significant ways that were different from their previous experiences with other social and healthcare services. Open Dialogue is an approach that can meaningfully attend to some of the power relations within which women live and within which social and health care services are provided.

"The Food Matches the Mood": Experiences of Eating Disorders in Bipolar Disorder.

Approximately 33% of those with bipolar disorder (BD) have a comorbid eating disorder (ED). However, the trajectory of these conditions has received little research attention. Nine participants who met criteria for BD and an ED participated in qualitative interviews exploring experiences of illness onset, the interaction of these conditions, and service provision. Almost all participants in the sample reported minimal to no screening of ED problems, despite their health professionals' frequent discussion of obesity. Findings suggested that ED features were diverse and evolved over time. Mania and depression were connected to ED features such as overeating and restricting, but this differed between and within participants. Most participants disclosed historic trauma which they considered central to their mental health concerns. This clinical group appears to be underserviced. Clinicians and researchers should routinely screen for ED features when treating and diagnosing BD to inform their physical and mental health interventions.

'Should it fit? Yes. Does it fit? No': Exploring the organisational processes of introducing a recovery-oriented approach to mental health in Australian private health care.

This article explores the implementation of an innovative approach to mental health care in a private health setting. Open Dialogue is a recovery-oriented approach to mental health that emerged in Finland, which emphasises family involvement, interdisciplinary collaboration and a flexible, needs-adapted approach. Early research is promising; however, little research has explored Open Dialogue outside Finland. This study aimed to explore the introduction of this approach at a private, inpatient young-adult mental health unit in Australia. Drawing on data from a long-term ethnographic field study that included 190 hours of observation and qualitative interviews, the findings show that despite staff members being inspired by and supportive of Open Dialogue, the existing ideology and organisational structures of the unit conflicted with the integration of Open Dialogue principles. Dialogical ways of working were challenged by medical dominance and emphasis on economic efficiencies. This study emphasises the importance of a 'good' fit between organisational cultures and innovations. It also highlights the challenges of moving towards recovery-oriented and family-focused models of care in the Australian neoliberal health care context. There is a need for organisational and ideological change in health services that is receptive to, and meaningfully supports, efforts to implement recovery-oriented care.

Clostridioides difficile para-Cresol Production Is Induced by the Precursor para-Hydroxyphenylacetate.

Clostridioides difficile is an etiological agent for antibiotic-associated diarrheal disease. C. difficile produces a phenolic compound, para-cresol, which selectively targets gammaproteobacteria in the gut, facilitating dysbiosis. C. difficile decarboxylates para-hydroxyphenylacetate (p-HPA) to produce p-cresol by the action of the HpdBCA decarboxylase encoded by the hpdBCA operon. Here, we investigate regulation of the hpdBCA operon and directly compare three independent reporter systems; SNAP-tag, glucuronidase gusA, and alkaline phosphatase phoZ reporters to detect basal and inducible expression. We show that expression of hpdBCA is upregulated in response to elevated p-HPA. In silico analysis identified three putative promoters upstream of hpdBCA operon-P1, P2, and Pσ54; only the P1 promoter was responsible for both basal and p-HPA-inducible expression of hpdBCA We demonstrated that turnover of tyrosine, a precursor for p-HPA, is insufficient to induce expression of the hpdBCA operon above basal levels because it is inefficiently converted to p-HPA in minimal media. We show that induction of the hpdBCA operon in response to p-HPA occurs in a dose-dependent manner. We also identified an inverted palindromic repeat (AAAAAG-N13-CTTTTT) upstream of the hpdBCA start codon (ATG) that is essential for inducing transcription of the hpdBCA operon in response to p-HPA, which drives the production of p-cresol. This provides insights into the regulatory control of p-cresol production, which affords a competitive advantage for C. difficile over other intestinal bacteria, promoting dysbiosis.IMPORTANCEClostridioides difficile infection results from antibiotic-associated dysbiosis. para-Cresol, a phenolic compound produced by C. difficile, selectively targets gammaproteobacteria in the gut, facilitating dysbiosis. Here, we demonstrate that expression of the hpdBCA operon, encoding the HpdBCA decarboxylase which converts p-HPA to p-cresol, is upregulated in response to elevated exogenous p-HPA, with induction occurring between >0.1 and ≤0.25 mg/ml. We determined a single promoter and an inverted palindromic repeat responsible for basal and p-HPA-inducible hpdBCA expression. We identified turnover of tyrosine, a p-HPA precursor, does not induce hpdBCA expression above basal level, indicating that exogenous p-HPA was required for p-cresol production. Identifying regulatory controls of p-cresol production will provide novel therapeutic targets to prevent p-cresol production, reducing C. difficile's competitive advantage.

'Every single minute and hour is scrutinised': neoliberalism and Australian private mental health care.

There is little understanding of how recovery-oriented approaches fit within contemporary mental healthcare systems, which emphasise biomedical approaches to care, increased efficiency and cost-cutting. This article examines the established models of service delivery in a private, youth, mental health service and the impacts of the current system on staff. It explores whether the service is prepared or capable of adopting recovery-oriented approaches to care. Qualitative interviews were undertaken with staff and thematically analysed to understand the everyday practices on the unit. Data suggest that economic efficiencies and biomedical dominance largely shaped how health care was organised and delivered, which was perceived by staff as inflexible to change. Additionally, findings suggest that market-oriented principles associated with neoliberalism restricted the capacity of individuals to transform services in line with alternative models of care and lowered staff morale. These finding suggest that, while neoliberal ideologies and biomedical approaches remain dominant in organisations, there will be challenges to adopting alternative recovery-oriented models of care and promoting healthcare systems that understand mental health issues in broader socio-political contexts and can flexibly respond to the needs of service users.

Steps of care for adolescents with anorexia nervosa-A Delphi study.

OBJECTIVE: Anorexia nervosa (AN) commonly develops during adolescence. Existing literature offers some treatment guidelines, but clear clinical criteria for initial recommendations and steps of care are needed. The aim of the present study was to develop expert consensus for a stepped-care algorithm for treatment of adolescents with AN. METHOD: The Delphi approach was used to identify clinical parameters that guide initial treatment recommendations and recommendations for transitions between levels of care. The Delphi approach provides a useful expert consensus when empirical data are limited. Individuals with at least 10 years of experience in the field of adolescent AN and membership in one of three professional organizations were recruited. Twenty-five panelists participated in three rounds of iterative online questionnaires. RESULTS: Consensus was achieved on several features of a treatment algorithm. Hospitalization is recommended when medical instability, suicidality, or acute food refusal are present at any point in treatment. Family-based treatment (FBT) is recommended as the first-line treatment, with a few exceptions. Consensus was not reached on when to transition from a higher level of care to a lower level of care. DISCUSSION: Expert opinion was used to develop a consensus-based algorithm for care of adolescents with AN. Future research is needed to test whether these recommendations can be used to optimize outcomes for adolescents with AN.

Adolescent development in family-based treatment for anorexia nervosa: Patients' and parents' narratives.

Maudsley Family-Based Treatment (FBT) is currently the best supported treatment for adolescents with anorexia nervosa (AN); however, little is known about whether it achieves its stated aim in the final phases of promoting the patient's return to an expected developmental trajectory. This study aimed to explore the perspectives of young people and their parents regarding the developmental impact of AN, and the role of FBT in addressing developmental challenges. Young people ( N = 12) who ceased FBT a minimum 1 year prior, and their parents ( N = 12), completed face-to-face semi-structured interviews, and data were analysed using a narrative inquiry method. All the participants described AN as highly disruptive to adolescent development, with phase one of FBT accentuating this experience. In phases two and three, FBT helped facilitate adolescent development in three key ways: Supporting return to adolescent pursuits, facilitating autonomy and providing freedom to develop post-FBT. This study offers preliminary insights into the variety of developmental challenges and needs experienced by families, as well as approaches clinicians can take to supporting development in phases two and three of FBT.

Para-cresol production by Clostridium difficile affects microbial diversity and membrane integrity of Gram-negative bacteria.

Clostridium difficile is a Gram-positive spore-forming anaerobe and a major cause of antibiotic-associated diarrhoea. Disruption of the commensal microbiota, such as through treatment with broad-spectrum antibiotics, is a critical precursor for colonisation by C. difficile and subsequent disease. Furthermore, failure of the gut microbiota to recover colonisation resistance can result in recurrence of infection. An unusual characteristic of C. difficile among gut bacteria is its ability to produce the bacteriostatic compound para-cresol (p-cresol) through fermentation of tyrosine. Here, we demonstrate that the ability of C. difficile to produce p-cresol in vitro provides a competitive advantage over gut bacteria including Escherichia coli, Klebsiella oxytoca and Bacteroides thetaiotaomicron. Metabolic profiling of competitive co-cultures revealed that acetate, alanine, butyrate, isobutyrate, p-cresol and p-hydroxyphenylacetate were the main metabolites responsible for differentiating the parent strain C. difficile (630Δerm) from a defined mutant deficient in p-cresol production. Moreover, we show that the p-cresol mutant displays a fitness defect in a mouse relapse model of C. difficile infection (CDI). Analysis of the microbiome from this mouse model of CDI demonstrates that colonisation by the p-cresol mutant results in a distinctly altered intestinal microbiota, and metabolic profile, with a greater representation of Gammaproteobacteria, including the Pseudomonales and Enterobacteriales. We demonstrate that Gammaproteobacteria are susceptible to exogenous p-cresol in vitro and that there is a clear divide between bacterial Phyla and their susceptibility to p-cresol. In general, Gram-negative species were relatively sensitive to p-cresol, whereas Gram-positive species were more tolerant. This study demonstrates that production of p-cresol by C. difficile has an effect on the viability of intestinal bacteria as well as the major metabolites produced in vitro. These observations are upheld in a mouse model of CDI, in which p-cresol production affects the biodiversity of gut microbiota and faecal metabolite profiles, suggesting that p-cresol production contributes to C. difficile survival and pathogenesis.