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 .

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.

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.

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 ).

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.

Stigma in the face of cancer disfigurement: A systematic review and research agenda.

INTRODUCTION: An emerging body of work has reported on the psychological impact of disfigurement on cancer patients; however, the extent of research focusing on stigmatisation in this context is unclear. This review aimed to evaluate how stigma associated with disfigurement impacts on cancer patients. METHODS: A systematic review of literature was conducted using SCOPUS, Web of Science, MEDLINE and PubMed databases. Articles were included if they described a qualitative or quantitative study that investigated the impact of stigma and disfigurement on individuals with cancer and/or their families. Included studies were appraised for methodology and narratively synthesised. RESULTS: Of the 16 studies which met the inclusion criteria, ten were qualitative and six were quantitative. Publication dates ranged from 1994 to 2020. Results highlighted the varying impact of felt and enacted stigma in people with cancer disfigurement. While individuals cope with stigma in different ways and outcomes can sometimes be positive, most articles documented a negative impact to well-being including emotions such as disgust and shame. CONCLUSION: This review identified negative and (sometimes) positive consequences of disfigurement and stigma on cancer patients; however, the main finding is that relevant research is in its infancy. Several areas of future research are warranted.

The "Ick" Factor: An Unrecognized Affective Predictor of Physical Symptoms During Chemotherapy.

BACKGROUND: Patients undergoing chemotherapy experience a range of aversive symptoms. These symptoms vary across individuals and at least some of this variation can be predicted by psychological factors, such as distress. However, while psychological distress predicts some of the symptoms, it is limited in important ways. PURPOSE: To (a) assess the viability of disgust-a discrete emotion that specifically evolved for health-related reasons-as a predictor of chemotherapy-related symptoms (particularly, taste- and smell-related changes) and (b) compare the predictive utility of disgust sensitivity and propensity against the most commonly used affective predictor, that is, psychological distress. METHODS: Patients with cancer (N = 63) about to initiate chemotherapy were recruited in a prospective observational study. Psychosocial predictor variables were assessed at baseline, and outcomes (i.e., physical symptoms, body mass index [BMI], and food-based sensory-processing changes) were assessed at both baseline and 6 week follow-up. RESULTS: Psychological distress did not predict any of the outcomes. Both disgust sensitivity (ß = .53, p = .003) and propensity (ß = -.56, p = .002) predicted greater food-based sensory-processing changes, while disgust sensitivity marginally predicted greater chemotherapy-related physical symptoms (ß = .34, p = .060); neither of these two forms of disgust predicted BMI. CONCLUSIONS: The study provides first evidence showing (a) associations between trait disgust and food sensory-processing changes that arise during chemotherapy and (b) disgust as being a more useful predictor of food- and digestion-related symptoms than psychological distress. In doing so, it opens new doors for better care to be provided to patients undergoing chemotherapy.

"Somebody else's business": The challenge of caring for patients with mental health problems on medical and surgical wards.

WHAT IS KNOWN ON THE SUBJECT?: People with mental health problems have higher rates of physical health concerns and hospital admissions than those without mental health problems. These patients have poorer outcomes from surgery and have worse experiences of care when admitted for medical or surgical procedures. WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE?: This paper looks to understand why care may be poorer for patients with mental health problems by speaking to staff providing care in these settings. We spoke to 30 general hospital staff about mental health on the wards and found that a lack of leadership and ownership for prioritising mental health led to people not seeing it as their job, and that it was somebody else's business to manage that side of care. We also found that the emotional effect of caring for people who had attempted suicide or had self-harm injuries was difficult for staff, impacting on staff well-being and leading them to distance themselves from providing care in those cases. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: There is a need for staff to be supported from the top-down, with management providing clear leadership around issues and pathways for mental health needs so they know the best way to provide care and encourage collaborative working. In addition, bottom-up support is needed to help staff personally manage their own well-being and mental health, including supervision and debriefing from mental health specialists to improve understanding from the patient's perspective and to provide emotional support to manage difficulties. RELEVANCE STATEMENT: This paper places focus on the care of patients with mental health problems in medical and surgical care settings highlighting the interplay between mental and physical health from a perspective that is less often explored. This paper provides insights into the multidisciplinary nature of nursing and the need for integrated care. This provides findings that build a picture of how mental health nursing specialism is needed beyond psychiatric wards and within medical and surgical settings. ABSTRACT: Introduction Evidence shows that patients with mental health problems have poorer physical health outcomes, increased mortality and experience poorer care during surgery and medical admissions. Issues related to lack of training, stigmatizing attitudes, fear or hopelessness may help understand these poor outcomes. Aim To explore the experiences of staff in providing care for people with mental health problems. Method A qualitative service evaluation approach was used. Participants working in an acute care hospital in inner-city London were recruited across professions and job levels using a self-selection sampling method. A total of 30 participants took part in semi-structured interviews (n = 17) and two focus groups (n = 13), and data were thematically analysed. Relevant organizational documents and service use data were utilized to inform the evaluation. Results Key themes were organized across the macro, meso and micro levels to understand the levels of disconnection and silence around mental health in acute care. Themes include systemic factors surrounding the institutional culture, ward cultures and collaborative working, and individuals' sense-making of mental health and personal well-being. Implications for practice These findings signpost the growing need for greater mental health nursing input on medical and surgical wards and within these teams to provide informed knowledge, support and supervision.

Microfluidic Shear Processing Control of Biological Reduction Stimuli-Responsive Polymer Nanoparticles for Drug Delivery.

We demonstrate microfluidic manufacturing of glutathione (GSH)-responsive polymer nanoparticles (PNPs) with controlled in vitro pharmacological properties for selective drug delivery. This work leverages previous fundamental work on microfluidic control of the physicochemical properties of GSH-responsive PNPs containing cleavable disulfide groups in two different locations (core and interface, DualM PNPs). In this paper, we employ a two-phase gas-liquid microfluidic reactor for the flow-directed manufacturing of paclitaxel-loaded or DiI-loaded DualM PNPs (PAX-PNPs or DiI-PNPs, where DiI is a fluorescent drug surrogate dye). We find that both PAX-PNPs and DiI-PNPs exhibit similar flow-tunable sizes, morphologies, and internal structures to those previously described for empty DualM PNPs. Fluorescent imaging of DiI-PNP formulations shows that microfluidic manufacturing greatly improves the homogeneity of drug dispersion within the PNP population compared to standard bulk microprecipitation. Encapsulation of PAX in DualM PNPs significantly increases its selectivity to cancerous cells, with various PAX-PNP formulations showing higher cytotoxicity against cancerous MCF-7 cells than against non-cancerous HaCaT cells, in contrast to free PAX, which showed similar cytotoxicity in the two cell lines. In addition, the characterization of DualM PNP formulations formed at various microfluidic flow rates reveals that critical figures of merit for drug delivery function-including encapsulation efficiencies, GSH-triggered release rates, rates of cell uptake, cytotoxicities, and selectivity to cancerous cells-exhibit microfluidic flow tunability that mirrors trends in PNP size. These results highlight the potential of two-phase microfluidic manufacturing for controlling both structure and drug delivery function of biological stimuli-responsive nanomedicines toward improved therapeutic outcomes.

When mental illness and cancer collide: An investigation of the predictors of outcomes for cancer patients with a history of mental health problems.

OBJECTIVE: People with a serious mental health condition are no more likely to receive a diagnosis of cancer than the general population but fare more poorly in terms of outcomes. The current study investigated whether a background of mental health problems (measured by contact with mental health services and psychotropic medication) predicted treatment outcomes over and above demographic and medical confounds for cancer patients at Counties Manukau Health. METHODS: The sample consisted of 1652 patients diagnosed with cancer in the period 1 January 2016 to 31 December 2016. The sample was split into three groups: non-mental health, moderate mental health, and serious mental health. RESULTS: Patients in the serious and moderate mental health groups were more likely to have physical comorbidities. Those in the serious mental health group were also marginally more likely to have advanced cancer at diagnosis. There were no differences between groups in terms of treatment delays, but patients in the serious mental health group were more likely to be hospitalised and die in the 12 months following diagnosis. Whilst differences in mortality may be explained by greater clinical complexity (being older, having other physical comorbidities) and later stage at presentation, mental health history was independently associated with hospitalisations. CONCLUSIONS: Cancer patients with a history of more serious mental health issues fare more poorly than those with moderate mental health issues or no such history. The clinical complexity of working with these patients, indexed by mental and physical comorbidities, may be a factor contributing to this disparity.

Emotional predictors of bowel screening: the avoidance-promoting role of fear, embarrassment, and disgust.

BACKGROUND: Despite considerable efforts to address practical barriers, colorectal cancer screening numbers are often low. People do not always act rationally, and investigating emotions may offer insight into the avoidance of screening. The current work assessed whether fear, embarrassment, and disgust predicted colorectal cancer screening avoidance. METHODS: A community sample (N = 306) aged 45+ completed a questionnaire assessing colorectal cancer screening history and the extent that perceptions of cancer risk, colorectal cancer knowledge, doctor discussions, and a specifically developed scale, the Emotional Barriers to Bowel Screening (EBBS), were associated with previous screening behaviours and anticipated bowel health decision-making. RESULTS: Step-wise logistic regression models revealed that a decision to delay seeking healthcare in the hypothetical presence of bowel symptoms was less likely in people who had discussed risk with their doctor, whereas greater colorectal cancer knowledge and greater fear of a negative outcome predicted greater likelihood of delay. Having previously provided a faecal sample was predicted by discussions about risk with a doctor, older age, and greater embarrassment, whereas perceptions of lower risk predicted a lower likelihood. Likewise, greater insertion disgust predicted a lower likelihood of having had an invasive bowel screening test in the previous 5 years. CONCLUSIONS: Alongside medical and demographic factors, fear, embarrassment and disgust are worthy of consideration in colorectal cancer screening. Understanding how specific emotions impact screening decisions and behaviour is an important direction for future work and has potential to inform screening development and communications in bowel health.

The "ick" Factor Matters: Disgust Prospectively Predicts Avoidance in Chemotherapy Patients.

BACKGROUND: Chemotherapy can be physically and psychologically demanding. Avoidance and withdrawal are common among patients coping with these demands. PURPOSE: This report compares established emotional predictors of avoidance during chemotherapy (embarrassment; distress) with an emotion (disgust) that has been unstudied in this context. METHODS: This report outlines secondary analyses of an RCT where 68 cancer patients undergoing chemotherapy were randomized to mindfulness or relaxation interventions. Self-reported baseline disgust (DS-R), embarrassment (SES-SF), and distress (Distress Thermometer) were used to prospectively predict multiple classes of avoidance post-intervention and at 3 months follow-up. Measures assessed social avoidance, cognitive and emotional avoidance (IES Avoidance), as well as information seeking and treatment adherence (General Adherence Scale). RESULTS: Repeated-measures ANOVAs evaluated possible longitudinal changes in disgust and forward entry regression models contrasted the ability of the affective variables to predict avoidance. Although disgust did not change over time or vary between groups, greater disgust predicted greater social, cognitive, and emotional avoidance, as well as greater information seeking. Social avoidance was predicted by trait embarrassment and distress predicted non-adherence. CONCLUSIONS: This report represents the first investigation of disgust's ability to prospectively predict avoidance in people undergoing chemotherapy. Compared to embarrassment and distress, disgust was a more consistent predictor across avoidance domains and its predictive ability was evident across a longer period of time. Findings highlight disgust's role as an indicator of likely avoidance in this health context. Early identification of cancer patients at risk of deleterious avoidance may enable timely interventions and has important clinical implications (ACTRN12613000238774).

Direct measurement of oxidative and nitrosative stress dynamics in Salmonella inside macrophages.

Many significant bacterial pathogens have evolved virulence mechanisms to evade degradation and exposure to reactive oxygen (ROS) and reactive nitrogen species (RNS), allowing them to survive and replicate inside their hosts. Due to the highly reactive and short-lived nature of ROS and RNS, combined with limitations of conventional detection agents, the mechanisms underlying these evasion strategies remain poorly understood. In this study, we describe a system that uses redox-sensitive GFP to nondisruptively measure real-time fluctuations in the intrabacterial redox environment. Using this system coupled with high-throughput microscopy, we report the intrabacterial redox dynamics of Salmonella enterica Typhimurium (S. Typhimurium) residing inside macrophages. We found that the bacterial SPI-2 type III secretion system is required for ROS evasion strategies and this evasion relies on an intact Salmonella-containing vacuole (SCV) within which the bacteria reside during infection. Additionally, we found that cytosolic bacteria that escape the SCV experience increased redox stress in human and murine macrophages. These results highlight the existence of specialized evasion strategies used by intracellular pathogens that either reside inside a vacuole or "escape" into the cytosol. Taken together, the use of redox-sensitive GFP inside Salmonella significantly advances our understanding of ROS and RNS evasion strategies during infection. This technology can also be applied to measuring bacterial oxidative and nitrosative stress dynamics under different conditions in a wide variety of bacteria.

The Effect of Examiner Variability on Multiple Canine Stifle Kinematic Gait Collections in a 3-Dimensional Model.

OBJECTIVE: To evaluate examiner variability in a superficial skin marker model of canine stifle kinematics. STUDY DESIGN: Experimental. ANIMALS: Six clinically normal dogs. METHODS: Dogs had 11 retroreflective markers fixed to the skin on the right hindlimb. Dogs were trotted 5 times through the calibrated testing space and this was repeated on 4 different testing days. Examiner A applied all markers to a dog and collected 6 good trials for analysis. The markers were then removed and Examiner B immediately repeated the process on the same dog. This was repeated for each dog on the 4 testing days. The dogs were trotted at a velocity of 1.70-2.10 m/s through the testing space to obtain the dynamic data sets. Comparisons were performed with Fourier analysis and Generalized Indicator Function Analysis (GIFA). Significance was set at P < .05 for all comparisons. RESULTS: Fourier analysis and GIFA found differences within and between examiners. Fourier analysis found no differences in sagittal and transverse planes for the experienced (A) and novice examiner (B), respectively. Fourier analysis detected fewer differences for the experienced examiner (A). CONCLUSION: Variability occurs within and between examiners using the same kinematic model. Transverse and frontal plane kinematics produce variable results between examiners. Prior experience with the model reduces the amount of variability and results in consistent and repeatable sagittal plane kinematic data collection.

MyD88 signaling inhibits protective immunity to the gastrointestinal helminth parasite Heligmosomoides polygyrus.

Helminth parasites remain one of the most common causes of infections worldwide, yet little is still known about the immune signaling pathways that control their expulsion. C57BL/6 mice are chronically susceptible to infection with the gastrointestinal helminth parasite Heligmosomoides polygyrus. In this article, we report that C57BL/6 mice lacking the adapter protein MyD88, which mediates signaling by TLRs and IL-1 family members, showed enhanced immunity to H. polygyrus infection. Alongside increased parasite expulsion, MyD88-deficient mice showed heightened IL-4 and IL-17A production from mesenteric lymph node CD4(+) cells. In addition, MyD88(-/-) mice developed substantial numbers of intestinal granulomas around the site of infection, which were not seen in MyD88-sufficient C57BL/6 mice, nor when signaling through the adapter protein TRIF (TIR domain-containing adapter-inducing IFN-ß adapter protein) was also ablated. Mice deficient solely in TLR2, TLR4, TLR5, or TLR9 did not show enhanced parasite expulsion, suggesting that these TLRs signal redundantly to maintain H. polygyrus susceptibility in wild-type mice. To further investigate signaling pathways that are MyD88 dependent, we infected IL-1R1(-/-) mice with H. polygyrus. This genotype displayed heightened granuloma numbers compared with wild-type mice, but without increased parasite expulsion. Thus, the IL-1R-MyD88 pathway is implicated in inhibiting granuloma formation; however, protective immunity in MyD88-deficient mice appears to be granuloma independent. Like IL-1R1(-/-) and MyD88(-/-) mice, animals lacking signaling through the type 1 IFN receptor (i.e., IFNAR1(-/-)) also developed intestinal granulomas. Hence, IL-1R1, MyD88, and type 1 IFN receptor signaling may provide pathways to impede granuloma formation in vivo, but additional MyD88-mediated signals are associated with inhibition of protective immunity in susceptible C57BL/6 mice.

Trait and state disgust: an experimental investigation of disgust and avoidance in colorectal cancer decision scenarios.

OBJECTIVE: To evaluate whether trait and experimentally manipulated state disgust independently and/or interactively predict immediate and anticipated avoidance in decision scenarios related to colorectal cancer (CRC). METHOD: Eighty participants, aged 18 to 66 years, completed questionnaires assessing trait disgust prior to a laboratory session. Participants were gender block randomized to disgust or control conditions before completing tasks assessing immediate avoidance of a CRC disgust elicitor (stoma bag) and anticipated avoidance in hypothetical CRC scenarios. RESULTS: Manipulation checks confirmed the elicitation of disgust in the experimental condition. Persons in the experimental condition were more likely to exhibit immediate avoidance behaviors in response to a commonly used bowel disease device (stoma bag), and trait disgust predicted time to touch the device. Trait disgust also moderated the influence of state disgust on anticipated avoidance, namely delay in help seeking for bowel symptoms and predicted rating disgusting side effects as more deterring to adherence. CONCLUSIONS: The current report suggests the importance of examining disgust in CRC contexts and provides the first empirical demonstration that state and trait aspects of disgust may interactively operate to deter certain types of decisions. It thus furthers understanding of emotions and avoidance in a health context that has had surprisingly little focus to date.

Decision Making about Risk of Infection by Young Adults with CF.

Young people with cystic fibrosis (CF) are asked to avoid a number of environments associated with increased infection risk, but in practice they need to balance this with competing priorities such as building and sustaining relationships with friends and family. This study explored the process by which young people make these decisions. Mixed methods were used: a vignette study presenting choices around engaging in activities involving a degree of infection risk and a thematic analysis of participant's accounts of their decision making. The eight participants chose to engage in high risk behaviours in 59% of the choices. All participants chose to engage in at least one risky behavior, though this was less likely when the risk was significant. Thematic analysis revealed large areas of misunderstanding and lack of knowledge, leading to some potentially worrying misconceptions about the nature of infections and risk. Young people with CF are not currently making informed decisions around activities that involve increased risk of infection, and there is an urgent need for CF teams to address this in information provision.

Disgust and behavioral avoidance in colorectal cancer screening and treatment: a systematic review and research agenda.

BACKGROUND: The emotion of disgust appears to promote psychological and behavioral avoidance, a dynamic that has significant implications in physical and psychological outcomes in colorectal cancer (CRC). Patients, caregivers, and health professionals alike are all potentially susceptible to responding with disgust and the associated avoidance. OBJECTIVE: This article aimed to review the early-stage literature related to disgust and CRC, consider the clinical implications, and suggest an appropriate research agenda. METHODS: Given limited research in this area, a systematic review of the literature was broadened to include disgust and all cancers. MEDLINE, Web of Science, SCOPUS, and ProQuest Dissertations and Theses databases were searched, with additional works sourced by reviewing citation lists and/or by contacting the lead authors. RESULTS: Nine studies were identified relating to disgust and cancer screening, and 6 related to disgust and cancer treatment. Two broad findings emerged: (1) disgust appears to be promoting aversion to (and avoidance of) CRC screening, and (2) several known elicitors of disgust are widely apparent in CRC contexts. CONCLUSIONS: Disgust likely represents a key emotional substrate for avoidance among CRC patients, caregivers, and health professionals. Further research is required to identify disgust's elicitors and effects in CRC contexts, informing interventions that target early identification of persons at risk of maladaptive outcomes. Exposure therapies and mindfulness training may be well suited to treating disgust-generated avoidance. IMPLICATIONS FOR PRACTICE: Disgust has significant implications in CRC contexts. Oncology nurses are uniquely positioned to guide clinical interventions and ultimately improve outcomes in this area.