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Intestinal helminths have well-characterized modulatory effects on mammalian immune pathways. Ongoing helminth infection has been associated with both the suppression of allergies and an altered susceptibility to microbial infections. Enteric helminths share a niche with the intestinal microbiota, and the presence of helminths alters the microbiota composition and the metabolic signature of the host. Recent studies have demonstrated that the helminth-modified intestinal microbiome has the capacity to modify host immune responses even in the absence of live helminth infection. This article discusses the mechanisms by which helminths modify the intestinal microbiome of mammals, and reviews the evidence for a helminth-modified microbiome directly influencing host immunity during infectious and inflammatory diseases. Understanding the multifaceted mechanisms that underpin helminth immunomodulation will pave the way for novel therapies to combat infectious and inflammatory diseases.

Key Points The recent rise in the incidence of allergic disease suggests that changing environmental factors can influence the risk of allergic sensitization. Environmental exposures that occur during the first few months of life can influence the risk of allergy development in later childhood. The timing of the first exposure to potential allergens, as well as the route of the first exposure, can influence whether tolerance or allergic sensitization occurs. Cutaneous antigen exposure predisposes towards a T helper 2 (T H 2) cell-skewing environment, which leads to allergic sensitization, whereas oral antigen exposure predisposes towards tolerogenic responses that are mediated by retinal dehydrogenase 2 (RALDH2)-expressing CD103 + dendritic cells. Exposure to microbial endotoxins alongside potential allergens can protect against allergic sensitization through the stimulation of innate pattern recognition receptors. Many of the environmental factors that are associated with allergy development modify the composition and diversity of the microbiota. Recent studies have demonstrated that the microbiota composition in the first few months of life can be predictive of allergy development in later childhood, and studies in mice have demonstrated that the absence of key bacterial microbiota species can be a driving factor in allergy development. Infection with pathogens can protect against allergic sensitization by promoting tolerogenic responses or can exacerbate existing disease by promoting the release of T H 2 cell-skewing cytokines. Fungal infections and certain bacterial and viral species are associated with the exacerbation of existing allergies, whereas helminth species and certain bacterial and viral species are associated with protection against allergic sensitization. It is clear that there are notable differences in the quality of immune responses to foreign antigens and stimuli even in the few weeks after birth in mice; how this developmental time window translates into the setting of human neonates is not yet clear. Both microorganism-derived and helminth-derived molecules have great potential for therapeutic and prophylactic use in infants who are at a high risk of developing allergies. Accumulating evidence suggests that environmental experiences during childhood can result in the development of allergies that persist into adulthood. In this Review, the authors present the evidence for specific early life exposures that may tip the balance between tolerance and allergic sensitization. The incidence of allergic disease continues to rise in industrialized countries. The rapid increase in the incidence of allergic disease throughout the past half century suggests that recently altered environmental factors are driving allergy development. Accumulating evidence suggests that environmental experiences that occur during the first months of life can influence the risk of allergic sensitization. In this Review, we present the evidence relating to specific early life exposures that affect future allergy development, and discuss how these exposures may promote either tolerance or allergic sensitization.

aim: Psychedelic-assisted therapies are gaining interest as an innovative treatment for problems with mental health and addictions, and there are several clinical trials in this area currently being conducted in Aotearoa New Zealand. However, many stakeholder groups hold concerns about cultural acceptability and safety. While psychedelic substances have a long history overseas in various Indigenous populations for spiritual and ritualistic purposes, their traditional use with Māori in Aotearoa New Zealand is unclear. Given our Te Tiriti o Waitangi obligations and the significant health inequities for Māori, any new treatments should be developed considering Te Ao Māori (Māori worldview) perspectives. This study aimed to explore Māori healthcare professionals’ current awareness, attitudes and perspectives on psychedelics and psychedelic-assisted therapy. methods: To explore these aims, 13 Māori healthcare professionals were recruited to participate in semi-structured qualitative interviews investigating psychedelic awareness, knowledge and attitudes using Māori health models Te Whare Tapa Whā and Te Wheke as a framework for data collection and analysis. results: Four key themes were identified, including 1) greater awareness leads to greater openness towards psychedelic-assisted therapy (PAT), 2) more research and education about PAT is needed, 3) PAT has the potential to align with Te Ao Māori, and 4) equitable access is critical for Māori. conclusion: Our sample of Māori healthcare professionals generally supported research investigating psychedelic therapies in Aotearoa New Zealand. Improving awareness of this novel treatment is likely to influence its acceptability as a treatment option and will inform the cultural safety of its use with Māori.

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 ).

Environmental enteropathy (EE) is a subclinical chronic inflammatory disease of the small intestine and has a profound impact on the persistence of childhood malnutrition worldwide. However, the aetiology of the disease remains unknown and no animal model exists to date, the creation of which would aid in understanding this complex disease. Here we demonstrate that early-life consumption of a moderately malnourished diet, in combination with iterative oral exposure to commensal Bacteroidales species and Escherichia coli , remodels the murine small intestine to resemble features of EE observed in humans. We further report the profound changes that malnutrition imparts on the small intestinal microbiota, metabolite and intraepithelial lymphocyte composition, along with the susceptibility to enteric infection. Our findings provide evidence indicating that both diet and microbes combine to contribute to the aetiology of EE, and describe a novel murine model that can be used to elucidate the mechanisms behind this understudied disease. Environmental enteropathy is a disorder of the small intestine that contributes to the persistence of childhood malnutrition worldwide. Here, Brown et al . show in mice that early-life malnourishment, in combination with exposure to commensal bacteria, remodels the small intestine to resemble features of the disease.

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. Significance To date, inadequate analytical methods have severely limited our ability to understand virulence strategies used by intracellular bacterial pathogens to evade reactive oxygen species (ROS) during infection. We have developed a system that is based on redox-sensitive GFP for real-time and nondisruptive measurement of redox stress experienced by Salmonella inside phagocytic cells. Using this system, we directly report intrabacterial redox dynamics during Salmonella infection of macrophages. This biosensor, which can easily be applied to other bacteria, enables a detailed study of ROS/reactive nitrogen species (RNS) evasion strategies, even detecting differences between individual bacteria. Additionally, this technique can be used for directly measuring redox responses in different environmental conditions for many bacteria.

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.

Heligmosomoides polygyrus is a natural intestinal parasite of mice, which offers an excellent model of the immunology of gastrointestinal helminth infections of humans and livestock. It is able to establish long-term chronic infections in many strains of mice, exerting potent immunomodulatory effects that dampen both protective immunity and bystander reactions to allergens and autoantigens. Immunity to the parasite develops naturally in some mouse strains and can be induced in others through immunization; while the mechanisms of protective immunity are not yet fully defined, both antibodies and a host cellular component are required, with strongest evidence for a role of alternatively activated macrophages. We discuss the balance between resistance and susceptibility in this model system and highlight new themes in innate and adaptive immunity, immunomodulation, and regulation of responsiveness in helminth infection.

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.

Abstract 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.