Effect of MDMA-assisted therapy on mood and anxiety symptoms in advanced-stage cancer (EMMAC): study protocol for a double-blind, randomised controlled trial.

BACKGROUND: Symptoms of anxiety and depression are common in patients with terminal illness and multiple challenges exist with timely and effective care in this population. Several centres have reported that one dose of the serotonergic psychedelic psilocybin, combined with therapeutic support, improves these symptoms for up to 6 months in this patient group. Drawing upon related therapeutic mechanisms, 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy may have the potential to achieve similar, positive mental health outcomes in this group. Preliminary evidence also supports the tolerability of MDMA-assisted therapy for anxiety and depression in advanced-stage cancer. METHODS: Up to 32 participants with advanced-stage cancer and associated depression and anxiety will be randomised in a 1:1 ratio into one of two blinded parallel treatment arms. The intervention group will receive 120 mg (+ 60 mg optional supplemental dose) MDMA-assisted therapy. The psychoactive control group will receive 20 mg oral (+ 10 mg optional supplemental dose) methylphenidate-assisted therapy. For each medication-assisted therapy session, participants will undergo two 90-min therapeutic support sessions in the week preceding, and one 90-min support session the day after the experimental session. A battery of measures (mood, anxiety, quality of life, mystical experience, spiritual wellbeing, attitudes towards death, personality traits, holistic health and wellbeing, connectedness, demoralisation, expectations, qualitative data and safety measures) will be assessed at baseline and through to the end of the protocol. Participants will be followed up until either 12 months post-randomisation or death, whichever occurs first. DISCUSSION: This study will examine the effect of MDMA-assisted therapy on symptoms of anxiety and depression in advanced-stage cancer. Potential therapeutic implications include establishing the safety and effectiveness of a novel treatment that may relieve mental suffering in patients with life-threatening illness. TRIAL REGISTRATION: Trial registered on Australian New Zealand Clinical Trials Registry. REGISTRATION NUMBER: ACTRN12619001334190p. Date registered: 30/09/2019. URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=378153&showOriginal=true&isReview=true.

PAM trial protocol: a randomised feasibility study of psychedelic microdosing-assisted meaning-centred psychotherapy in advanced stage cancer patients.

BACKGROUND: An advanced cancer diagnosis can be associated with a significant profile of distress. Psychedelic compounds have shown clinically significant effects in the treatment of psychological distress in patients with advanced-stage cancer. Given the challenges of delivering timely and effective intervention in the advanced cancer context, it is possible that an alternative, more pragmatic, approach lies in psychedelic 'microdosing'. Microdosing refers to repeated administration of psychedelics in sub-hallucinogenic doses. The purpose of this study is to evaluate the feasibility of conducting a full-scale randomised controlled trial comparing psychedelic microdose-assisted-meaning-centred psychotherapy (PA-MCP) to standard meaning-centred psychotherapy (MCP) in New Zealand indigenous (Maori) and non-indigenous people with advanced cancer and symptoms of anxiety and/or depression. Although MCP is a well-established psychotherapeutic treatment in advanced cancer populations, the potential efficacy and effectiveness of this therapy when delivered alongside a standardised microdose regimen of a psychedelic compound have not been investigated. METHODS: Participants with advanced-stage cancer and symptoms of anxiety and/or depression (N = 40; 20 Maori, 20 non-Maori) will be randomised under double-blind conditions to receive 7 sessions of MCP alongside 13 doses of either an LSD microdose (4-20 µg) (PA-MCP) or inactive placebo (placebo-MCP). The feasibility, acceptability, and safety of this intervention and physiological and psychological measures will be recorded at baseline, at each session of MCP, and at a 1-month and 6-month follow-up. DISCUSSION: Our findings will evaluate the feasibility, acceptability, and safety of a larger randomised controlled trial and provide an initial indication of the potential benefits of psychedelic microdosing for psychological distress in advanced-stage indigenous and non-indigenous cancer patients. TRIAL REGISTRATION: NZCTR, ACTRN12623000478617. Registered 11 May 2023.  https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=385810&isReview=true .

An open-label pilot trial assessing tolerability and feasibility of LSD microdosing in patients with major depressive disorder (LSDDEP1).

BACKGROUND: Globally, an estimated 260 million people suffer from depression [1], and there is a clear need for the development of new, alternative antidepressant therapies. In light of problems with the tolerability and efficacy of available treatments [2], a global trend is emerging for patients to self-treat depression with microdoses of psychedelic drugs such as lysergic acid diethylamide (LSD) and psilocybin [3]. Beyond anecdotal reports from those who self-medicate in this way, few clinical trials have evaluated this practice. In our recently published phase 1 study in healthy volunteers [4], we determined that LSD microdosing was relatively safe and well tolerated in that cohort. Furthermore, the data demonstrated that conducting such microdosing trials is broadly feasible, with excellent adherence and compliance to the regimen observed. In this open-label pilot trial of patients with major depressive disorder (LSDDEP1), we will test the tolerability and feasibility of an 8-week regimen of LSD microdosing in this patient group prior to a larger subsequent randomised controlled trial (LSDDEP2). METHODS: Twenty patients meeting the DSM-5 criteria for major depressive disorder will receive an 8-week LSD microdosing treatment regimen. The treatment protocol will use a sublingual formulation of LSD (MB-22001) delivered twice per week under a titration schedule using a dose of 5-15 µg. Tolerability will be assessed by quantifying the percentage of participants who withdraw from the trial due to adverse events attributable to the treatment regimen, while feasibility will be assessed by quantifying the percentage of attended clinic visits once enrolled. To determine whether there is any antidepressant response to the LSD microdosing regimen, MADRS scores will be assessed at baseline and 2, 4, 6, and 8 weeks after the commencement of the regimen. DISCUSSION: The results of LSDDEP1 will provide valuable information regarding the tolerability and feasibility of a proposed LSD microdosing regimen in patients with MDD. Such information is critically important to optimise trial design prior to commencing a subsequent and more resource-intensive randomised controlled trial. TRIAL REGISTRATION: ANZCTR, ACTRN12623000486628. Registered on 12 May 2023.

Syphilis and the host: multi-omic analysis of host cellular responses to Treponema pallidum provides novel insight into syphilis pathogenesis.

Introduction: Syphilis is a chronic, multi-stage infection caused by the extracellular bacterium Treponema pallidum ssp. pallidum. Treponema pallidum widely disseminates through the vasculature, crosses endothelial, blood-brain and placental barriers, and establishes systemic infection. Although the capacity of T. pallidum to traverse the endothelium is well-described, the response of endothelial cells to T. pallidum exposure, and the contribution of this response to treponemal traversal, is poorly understood. Methods: To address this knowledge gap, we used quantitative proteomics and cytokine profiling to characterize endothelial responses to T. pallidum. Results: Proteomic analyses detected altered host pathways controlling extracellular matrix organization, necroptosis and cell death, and innate immune signaling. Cytokine analyses of endothelial cells exposed to T. pallidum revealed increased secretion of interleukin (IL)-6, IL-8, and vascular endothelial growth factor (VEGF), and decreased secretion of monocyte chemoattractant protein-1 (MCP-1). Discussion: This study provides insight into the molecular basis of syphilis disease symptoms and the enhanced susceptibility of individuals infected with syphilis to HIV co-infection. These investigations also enhance understanding of the host response to T. pallidum exposure and the pathogenic strategies used by T. pallidum to disseminate and persist within the host. Furthermore, our findings highlight the critical need for inclusion of appropriate controls when conducting T. pallidum-host cell interactions using in vitro- and in vivo-grown T. pallidum.

Anxiety, Disability, and Pain Predict Outcomes of Complex Regional Pain Syndrome: An 8-year Follow-up of a Prospective Cohort.

Factors contributing to the varied outcomes of complex regional pain syndrome (CRPS) are not well known. This study aimed to determine whether baseline psychological factors, pain, and disability influence long-term CRPS outcomes. We conducted an 8-year follow-up from a previous prospective study of CRPS outcomes. Sixty-six people diagnosed with acute CRPS were previously assessed at baseline, 6 months, and 12 months and in the current study, 45 were followed up after 8 years. At each timepoint, we measured signs and symptoms of CRPS, pain, disability, and psychological factors. Mixed-model repeated measures were used to identify baseline predictors of CRPS severity, pain, and disability at 8 years. Predictors of greater CRPS severity at 8 years were female sex, greater baseline disability, and greater baseline pain. Predictors of greater pain at 8 years were greater baseline anxiety and disability. The only predictor of greater disability at 8 years was greater baseline pain. Findings suggest CRPS is best understood from a biopsychosocial perspective, and baseline anxiety, pain, and disability may influence the trajectory of CRPS outcomes as far as 8 years later. These variables could be used to identify those at risk of poor outcomes or form targets for early interventions. PERSPECTIVE: This paper presents the findings of the first study to prospectively investigate predictors of CRPS outcomes over 8 years. Baseline anxiety, pain, and disability predicted greater CRPS severity, pain, and disability over 8 years. These factors could identify those at risk of poor outcomes or form targets for early interventions.

MHCII+CD80+ thymic eosinophils increase in abundance during neonatal development in mice and their accumulation is microbiota dependent.

Eosinophils are present in the thymus of mammals, yet their function at this site during homeostatic development is unknown. We used flow cytometry to determine the abundance and phenotype of eosinophils (here defined as SSchigh SiglecF+ CD11b+ CD45+ cells) in the thymus of mice during the neonatal period, the later postnatal period, and into adulthood. We show that both the total number of thymic eosinophils and their frequency among leukocytes increase over the first 2 wk of life and that their accumulation in the thymus is dependent on the presence of an intact bacterial microbiota. We report that thymic eosinophils express the interleukin-5 receptor (CD125), CD80, and IDO, and that subsets of thymic eosinophils express CD11c and major histocompatibility complex II (MHCII). We found that the frequency of MHCII-expressing thymic eosinophils increases over the first 2 wk of life, and that during this early-life period the highest frequency of MHCII-expressing thymic eosinophils is located in the inner medullary region. These data suggest a temporal and microbiota-dependent regulation of eosinophil abundance and functional capabilities in the thymus.

The perceptions of cancer health-care practitioners in New Zealand and the USA toward psychedelic-assisted therapy with cancer patients: A cross-sectional survey.

OBJECTIVES: A resurgence of research investigating the administration of psychedelic compounds alongside psychotherapy suggests that this treatment is a promising intervention for anxiety, depression, and existential distress in people with cancer. However, psychedelic treatment that induces a mind-altering experience potentially poses barriers to vulnerable cancer patients, and health-care practitioners may have concerns about referring their patients to trials investigating this approach. The aim of the current study was to investigate the perceptions of cancer health-care practitioners based in New Zealand and the USA related to psychedelic-assisted therapy. METHODS: This study utilized a cross-sectional survey of cancer health-care practitioners in New Zealand and the USA via convenience sampling to identify their perceptions about the concept of conducting psychedelic-assisted therapy with cancer patients. RESULTS: Participants perceived that (1) psychedelic-assisted therapy has the potential to provide benefit for cancer patients, (2) research in this area across a variety of domains is important, (3) work should consider spiritual and indigenous perspectives of health, and (4) there was willingness to refer patients to trials in this area, especially patients with advanced disease who were no longer going through curative treatment. Participants in the USA had greater awareness of psychedelics than the New Zealand sample; however, New Zealand participants more strongly believed that spiritual/indigenous factors should be considered in psychedelic-assisted therapy. SIGNIFICANCE OF RESULTS: Cancer health-care practitioners in our sample considered research investigating the potential for psychedelic-assisted therapies to be important and may be more open to studies that start in palliative and end-of-life contexts.

Digital competency of Psychologists in Aotearoa New Zealand: A cross-sectional survey.

Background: The increasing implementation of digital health into psychological practice is transforming mental health services. Limited clinical resources and the high demand for psychological services, alongside the restrictions imposed on services during the global COVID-19 pandemic, have been a catalyst for significant changes in the way psychologists work. Ensuring Psychologists have the skills and competence to use these tools in practice is essential to safe and ethical practice. Aim: This study aimed to explore the digital competence of psychologists working in Aotearoa New Zealand and their use of digital tools in the practice. Methods: A cross-sectional online survey was conducted with Aotearoa New Zealand Registered Psychologists (n = 195) between July and November 2021. Results: Participants reported varying degrees of competence across the digital tasks presented, with participants most commonly reporting moderate to high competence for engaging in remote supervision via digital means (86%) and obtaining client's informed consent for digital work (82%). In contrast, tasks that participants most reported not being moderately or highly competent in included working with interpreters remotely and evaluating the effectiveness and security of smartphone apps. Motivations to use digital technologies included meeting client preferences and needs, necessity for continuity of care, and the benefits of increased accessibility and reach. In contrast, the barriers to using digital technologies included client characteristics or preference, clinical factors, clinician preferences and skills, and workplace or technical issues or concerns. The majority (91.1%) were potentially interested in further training in this area. Conclusions: The current study offers insights into the digital competencies of a workforce that has required rapid incorporation of technologies into professional practice over recent years. This snapshot of the digital skills of psychologists demonstrates a large variation in digital competence. In the current context, developing digital competencies seems a fundamental requirement for psychologists to work in ways that appropriately and safely deliver client-centred care.

An Investigation of Virtual Reality Nature Experiences in Patients With Metastatic Breast Cancer: Secondary Analysis of a Randomized Controlled Trial.

BACKGROUND: Connection with nature has well-established physical and psychological benefits. However, women with metastatic breast cancer (MBC) are often unable to access nature because of physical limitations, psychological barriers, and treatment demands. Virtual reality (VR) nature experiences offer an alternative means of connecting with nature and may be of particular benefit to patients with cancer who are house- or hospital-bound. OBJECTIVE: This study aims to explore whether VR nature experiences are associated with physical and psychological benefits for women with MBC who are disconnected with nature. METHODS: This secondary analysis of a previous randomized controlled crossover trial recruited participants from the emailing lists of breast cancer support organizations. Participants were provided VR headsets for daily use in their homes for over 3 weeks. In the first week, participants used 1 of 2 VR nature experiences (Ripple or Happy Place) daily, followed by a 1-week washout period, before using the other VR experience every day for the final week. Outcomes assessed changes between baseline and postintervention scores in quality of life (EQ-5D-5L), pain (Brief Pain Inventory Short Form), fatigue (Functional Assessment of Chronic Illness Therapy-fatigue), depression (Depression, Anxiety, and Stress Scale-depression), anxiety (Depression, Anxiety, and Stress Scale-anxiety), and spiritual well-being (Functional Assessment of Chronic Illness Therapy- Spiritual Well-being) and investigated whether benefits were greater in participants who were not strongly connected with nature at baseline. RESULTS: A total of 38 women with MBC completed the VR interventions and were included in the analyses. Participants reported significantly less fatigue (P=.001), less depression (P<.001), and greater quality of life (P=.02) following the interventions than at baseline. Women with a weaker connection to nature reported greater fatigue (P=.03), depression (P=.006), and anxiety (P=.001), and poorer spirituality (P=.004) than their strongly connected counterparts. Only those with a weaker baseline connection with nature showed improvements in depression following the intervention (P=.03), with similar trends observed in fatigue (P=.07) and quality of life (P=.10). CONCLUSIONS: This study provides preliminary evidence that feeling connected with nature is associated with better physical and psychological status in patients with MBC and that VR nature interventions might be beneficial for this clinical population. Future studies should focus on activities that encourage connection with nature (rather than simply exposure to nature) and investigate the aspects of VR nature interventions that have the greatest therapeutic potential. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12619001480178; https://tinyurl.com/et6z3vac.

Virtual reality-based training for mental health staff: a novel approach to increase empathy, compassion, and subjective understanding of service user experience.

BACKGROUND: Mental health service users report that staff empathy is key to developing positive therapeutic relationships but promoting empathy in staff training is challenging. Staff may struggle to maintain their compassion, particularly in challenging settings, and have limited clinical confidence when treating conditions of which they lack subjective understanding. Novel interventions are required to address these needs. MAIN BODY OF THE TEXT: Virtual reality-based simulation training has been shown to be an effective training modality for healthcare professionals; it has the potential to deliver crucial empathy-building learning for frontline mental health staff due to its capacity to increase staff understanding of service users' experiences. Virtual reality and simulation technology take interactivity and experiential learning to a level beyond which we have seen in teaching and training before. Subjective understanding is elicited because this is a technology for enhanced experiential learning, which in turn fosters greater empathy and compassion. Increased empathy in the workforce is likely to yield significant benefits for service users. Greater empathy in nursing is linked with reduced restrictive practices and reduced conflict between staff and service users. Restrictive practices, including restraint and seclusion, are widely used in mental health settings within the UK, and are an aspect of mental health nursing that is at odds with the therapeutic role of nursing. Despite these innovative developments, there are challenges ahead. Many nurses feel that complete eradication of restrictive practices is impossible and that barriers include a limitation of resources, communication, management, and lack of education. There is a need to make simulation training economically viable so that it can be upscaled and widely available. Therefore, greater investment and resources are needed to bring this innovative training to the wider workforce to support staff and to realise the benefits for service users. SHORT CONCLUSION: Virtual reality-based training has great potential for mental health staff, which could have important consequences in terms of improved staff empathy and reductions in harmful restrictive practices. Further research and funding for such training is necessary so that it can be more widely available.

Identification and Functional Characterization of Peptides With Antimicrobial Activity From the Syphilis Spirochete, Treponema pallidum.

The etiological agent of syphilis, Treponema pallidum ssp. pallidum, is a highly invasive "stealth" pathogen that can evade the host immune response and persist within the host for decades. This obligate human pathogen is adept at establishing infection and surviving at sites within the host that have a multitude of competing microbes, sometimes including pathogens. One survival strategy employed by bacteria found at polymicrobial sites is elimination of competing microorganisms by production of antimicrobial peptides (AMPs). Antimicrobial peptides are low molecular weight proteins (miniproteins) that function directly via inhibition and killing of microbes and/or indirectly via modulation of the host immune response, which can facilitate immune evasion. In the current study, we used bioinformatics to show that approximately 7% of the T. pallidum proteome is comprised of miniproteins of 150 amino acids or less with unknown functions. To investigate the possibility that AMP production is an unrecognized defense strategy used by T. pallidum during infection, we developed a bioinformatics pipeline to analyze the complement of T. pallidum miniproteins of unknown function for the identification of potential AMPs. This analysis identified 45 T. pallidum AMP candidates; of these, Tp0451a and Tp0749 were subjected to further bioinformatic analyses to identify AMP critical core regions (AMPCCRs). Four potential AMPCCRs from the two predicted AMPs were identified and peptides corresponding to these AMPCCRs were experimentally confirmed to exhibit bacteriostatic and bactericidal activity against a panel of biologically relevant Gram-positive and Gram-negative bacteria. Immunomodulation assays performed under inflammatory conditions demonstrated that one of the AMPCCRs was also capable of differentially regulating expression of two pro-inflammatory chemokines [monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8)]. These findings demonstrate proof-of-concept for our developed AMP identification pipeline and are consistent with the novel concept that T. pallidum expresses AMPs to defend against competing microbes and modulate the host immune response.

The benefits and acceptability of virtual reality interventions for women with metastatic breast cancer in their homes; a pilot randomised trial.

BACKGROUND: Women with metastatic breast cancer (MBC) report debilitating physical and psychological symptoms, including fatigue, anxiety, and pain, that greatly impact their quality of life. Immersive virtual reality (VR) has been proposed as an adjunctive pain therapy for patients with cancer, and evidence suggests it may also decrease symptoms of anxiety and depression. The purpose of this pilot study was to assess whether VR should be pursued as a feasible and acceptable adjunctive therapy to alleviate physical and psychological symptoms in women with MBC. METHODS: We conducted a pilot study testing the acceptability and efficacy of VR interventions with MBC patients to improve quality of life and to produce enduring decreases in fatigue, pain, depression, anxiety, and stress. Participants completed two different week-long VR experiences, reporting the prevalence of symptoms immediately before and after each study week, and 48 h later. Linear mixed models including fixed effects (VR intervention, counterbalancing order, and study week) and random effects (participant) were used to assess the effect of immersive VR on all outcome measures. RESULTS: Thirty-eight women with MBC completed the VR interventions and were included in analyses. Significant improvements post-intervention and/or 48 h later were demonstrated for quality of life, fatigue, pain, depression, anxiety, and stress. Across the entire study period, these differences met the criteria of a clinically important difference for quality of life, fatigue, depression, and stress. Participants reported feelings of relaxation and enjoyment and were highly likely to use the interventions gain. CONCLUSIONS: Our results demonstrate that VR experiences offer enduring benefits to the physical and psychological well-being of women with MBC. VR interventions are a feasible and acceptable intervention that can be conducted in a patient's own home. Such interventions are worthy of future investigation as a novel approach to improving quality of life in a patient population that have often been overlooked. TRIAL REGISTRATION: Prospectively registered on 25th October 2019 with Australian New Zealand Clinical Trials Registry (ref: ACTRN12619001480178 ).

Will I have sex to please you? Evaluating whether mindfulness buffers links between attachment and sexual motivations in daily life.

Insecurely attached individuals are more likely to report more maladaptive sexual motivations that predict worse personal and interpersonal outcomes. Given that mindfulness has been linked with improved relationship and sexual experiences, and that these effects may be moderated by attachment, the current study examined the possible buffering role of trait mindfulness on the links between attachment insecurity and daily sexual motives. Participants from New Zealand (N = 70) took part in a daily diary study that overcame limitations associated with previous cross-sectional research in the area (e.g., recall and aggregation biases). Online measures of trait mindfulness and attachment were completed, before participants reported their sexual motivations on each day they had sex for the next 14 days. Results provided some evidence that trait mindfulness has a therapeutic effect among more anxiously attached persons insofar as it reduced the degree to which attachment concerns manifested in maladaptive daily sexual motivations. In contrast, trait mindfulness did not buffer (and in some cases intensified) the links between attachment avoidance and maladaptive sexual motives. No significant interactions were detected between attachment insecurity and mindfulness in the prediction of adaptive daily sexual motivations. These findings suggest that mindfulness may differentially affect the manifestations of anxious and avoidant attachment. Practical and theoretical implications of the findings are discussed.

Mental health professionals' perceived barriers and enablers to shared decision-making in risk assessment and risk management: a qualitative systematic review.

BACKGROUND: Risk assessment and risk management are fundamental processes in the delivery of safe and effective mental health care, yet studies have shown that service users are often not directly involved or are unaware that an assessment has taken place. Shared decision-making in mental health systems is supported by research and advocated in policy. This systematic review (PROSPERO: CRD42016050457) aimed to explore the perceived barriers and enablers to implementing shared decision-making in risk assessment and risk management from mental health professionals' perspectives. METHODS: PRISMA guidelines were followed in the conduct and reporting of this review. Medline, CINAHL, EMBASE, PsycINFO, AMED and Internurse were systematically searched from inception to December 2019. Data were mapped directly into the Theoretical Domains Framework (TDF), a psychological framework that includes 14 domains relevant to behaviour change. Thematic synthesis was used to identify potential barriers and enablers within each domain. Data were then matched to the three components of the COM-B model: Capability, Opportunity, and Motivation. RESULTS: Twenty studies met the eligibility criteria. The findings of this review indicate that shared decision-making is not a concept commonly used in mental health services when exploring processes of risk assessment and risk management. The key barriers identified were 'power and best interest' (social influences) and 'my professional role and responsibility' (social/professional role and identity). Key enablers were 'therapeutic relationship' (social influences) and 'value collaboration' (reinforcement). The salient barriers, enablers and linked TDF domains matched COM-B components 'opportunity' and 'motivation'. CONCLUSION: The review highlights the need for further empirical research to better understand current practice and mental health professionals' experiences and attitudes towards shared decision-making in risk assessment and risk management.

Small Intestinal Levels of the Branched Short-Chain Fatty Acid Isovalerate Are Elevated during Infection with Heligmosomoides polygyrus and Can Promote Helminth Fecundity.

Heligmosomoides polygyrus is a helminth which naturally infects mice and is widely used as a laboratory model of chronic small intestinal helminth infection. While it is known that infection with H. polygyrus alters the composition of the host's bacterial microbiota, the functional implications of this alteration are unclear. We investigated the impact of H. polygyrus infection on short-chain fatty acid (SCFA) levels in the mouse intestine and sera. We found that helminth infection resulted in significantly upregulated levels of the branched SCFA isovaleric acid, exclusively in the proximal small intestine, which is the site of H. polygyrus colonization. We next set out to test the hypothesis that elevating local levels of isovaleric acid was a strategy used by H. polygyrus to promote its own fitness within the mammalian host. To test this, we supplemented the drinking water of mice with isovalerate during H. polygyrus infection and examined whether this affected helminth fecundity or chronicity. We did not find that isovaleric acid supplementation affected helminth chronicity; however, we found that it did promote helminth fecundity, as measured by helminth egg output in the feces of mice. Through antibiotic treatment of helminth-infected mice, we found that the bacterial microbiota was required in order to support elevated levels of isovaleric acid in the proximal small intestine during helminth infection. Overall, our data reveal that during H. polygyrus infection there is a microbiota-dependent localized increase in the production of isovaleric acid in the proximal small intestine and that this supports helminth fecundity in the murine host.

Cancer Healthcare Workers' Perceptions toward Psychedelic-Assisted Therapy: A Preliminary Investigation.

Recent clinical trials suggest that psychedelic-assisted therapy is a promising intervention for reducing anxiety and depression and ameliorating existential despair in advanced cancer patients. However, little is known about perceptions toward this treatment from the key gatekeepers to this population. The current study aimed to understand the perceptions of cancer healthcare professionals about the potential use of psychedelic-assisted therapy in advanced cancer patients. Twelve cancer healthcare professionals including doctors, nurses, psychologists and social workers took part in a semi-structured interview which explored their awareness and perceptions toward psychedelic-assisted therapy with advanced cancer patients. Data were analysed using thematic analysis. Four inter-connected themes were identified. Two themes relate to the role and responsibility of being a cancer healthcare worker: (1) 'beneficence: a need to alleviate the suffering of cancer patients' and (2) 'non-maleficence: keeping vulnerable cancer patients safe', and two themes relate specifically to the potential for psychedelic-assisted therapy as (3) 'a transformative approach with the potential for real benefit' but that (4) 'new frontiers can be risky endeavours'. The findings from this study suggest intrigue and openness in cancer healthcare professionals to the idea of utilising psychedelic-assisted therapy with advanced cancer patients. Openness to the concept appeared to be driven by a lack of current effective treatment options and a desire to alleviate suffering. However, acceptance was tempered by concerns around safety and the importance of conducting rigorous, well-designed trials. The results from this study provide a useful basis for engaging with healthcare professionals about future research, trial design and potential clinical applications.

MDLSD: study protocol for a randomised, double-masked, placebo-controlled trial of repeated microdoses of LSD in healthy volunteers.

BACKGROUND: Regular ingestion of sub-hallucinogenic doses of psychedelics, referred to as "microdosing", has gained increasing popularity and attention in the press and in online forums, with reported benefits across multiple cognitive and emotional domains. Rigorously controlled studies to date, however, have been limited in scope and have failed to produce results comparable to those reported in the grey literature. METHODS: Eighty healthy male participants will receive 14 doses of placebo or 10 µg lysergic acid diethylamide orally every 3rd day over a 6-week treatment protocol. A battery of personality, creativity, mood, cognition, and EEG plasticity measures, as well as resting-state fMRI imaging, will be administered at baseline and at the end of the protocol. Creativity, mood, and plasticity measures will additionally be assessed in the acute phase of the first dose. Daily functioning will be monitored with questionnaires and a wearable sleep and activity tracker. DISCUSSION: This study will rigorously examine the claims presented in the microdosing grey literature by pairing a comparable dosing protocol with objective measures. Potential therapeutic implications include future clinical trials to investigate microdosed psychedelics as a standalone treatment or as an augmentation of psychotherapy in the treatment of depression, addiction, eating disorders, obsessive-compulsive disorders, and palliative care. TRIAL REGISTRATION: ACTRN12621000436875 . Registered on 19 February 2021.

"I Don't Identify with It": A Qualitative Analysis of People's Experiences of Living with Complex Regional Pain Styndrome.

OBJECTIVE: Complex regional pain syndrome (CRPS) is a painful limb condition known to cause significant disability and distress. However, little previous research has explored CRPS from a patient perspective. The present qualitative study aimed to describe the experiences of people living with CRPS. SUBJECTS: Forty-eight people with CRPS participated in this research. METHODS: Participants completed a face-to-face or telephone interview about their perceptions and experiences of CRPS and completed three drawings to illustrate their experiences. Data were analyzed through reflexive thematic analysis, and images in drawings were grouped and coded by theme. RESULTS: Three overarching themes encapsulated the data, including that 1) people experience CRPS as a source of severe symptoms and emotional difficulties, 2) CRPS undermines personal and social identity, and 3) this results in psychological responses that protect against the emotional and social impact of severe symptoms. Psychological responses include: a) searching for an explanation, b) "nothing is my fault," emphasizing a lack of personal responsibility and personal control, and c) detaching the limb from the self. CONCLUSIONS: CRPS is experienced as highly threatening to physical ability, psychological state, and identity. In response to these threats, people may develop their own explanations for CRPS and may mentally detach themselves from responsibility, control, and the painful limb itself. Future research could explore the impact of these factors on psychological well-being and CRPS symptoms and outcomes.

Impaired host resistance to Salmonella during helminth co-infection is restored by anthelmintic treatment prior to bacterial challenge.

Intestinal helminth infection can impair host resistance to co-infection with enteric bacterial pathogens. However, it is not known whether helminth drug-clearance can restore host resistance to bacterial infection. Using a mouse helminth-Salmonella co-infection system, we show that anthelmintic treatment prior to Salmonella challenge is sufficient to restore host resistance to Salmonella. The presence of the small intestine-dwelling helminth Heligmosomoides polygyrus at the point of Salmonella infection supports the initial establishment of Salmonella in the small intestinal lumen. Interestingly, if helminth drug-clearance is delayed until Salmonella has already established in the small intestinal lumen, anthelmintic treatment does not result in complete clearance of Salmonella. This suggests that while the presence of helminths supports initial Salmonella colonization, helminths are dispensable for Salmonella persistence in the host small intestine. These data contribute to the mechanistic understanding of how an ongoing or prior helminth infection can affect pathogenic bacterial colonization and persistence in the mammalian intestine.