Dr. Russell Davies (1914-1991): Pioneer of theatre recovery and of anaesthetics in Yugoslavia.

Dr. Russell Davies is a largely forgotten pioneer of both post-operative theatre recovery but also a key figure in the establishment of anaesthetics services in Yugoslavia in the late 1940s. Davies spent the majority of his career working as an anaesthetist at Queen Victoria Hospital, East Grinstead, Sussex, England, later being promoted to the head anaesthetist role. Davies set up one of the first recovery wards in the United Kingdom at Queen Victoria Hospital, the ward being named after him in 1989. Here he became a founding member of the Guinea Pig Club, alongside Dr. Archibald McIndoe. The Guinea Pig Club was founded in 1941 to support airmen in the Second World War undergoing plastic surgery at Queen Victoria Hospital. Davies was crucial to the pastoral care of the Club, providing clinical care and guiding members over access to pensions they would have previously been denied. Little is recognised of Davies's achievement of establishing anaesthetics services in Yugoslavia. Davies and his contributions have been largely overlooked. Davies should be considered one of the foremost British anaesthetists of the 20th century.

Mindfulness-Based Stress Reduction (MBSR) for Chronic Pain Management in the Community Pharmacy Setting: A Cross-Sectional Survey of the General Public's Knowledge and Perceptions.

Patient access to mindfulness-based stress reduction (MBSR), a complementary and integrative health approach that is proven to reduce chronic pain, can be increased via community pharmacy-based implementation. However, the general public's awareness and preferences regarding MBSR as a treatment option for chronic pain, including provider roles (pharmacist vs. non-pharmacist), are unclear. Therefore, the purpose of this study was to assess the U.S. general public's knowledge, attitudes, barriers, and programmatic preferences regarding MBSR for chronic pain management, particularly in the community pharmacy setting. A cross-sectional, anonymous online survey was distributed to U.S. adults ≥18 years via the Amazon Mechanical Turk (MTurk) online survey platform. The survey instrument was informed by Anderson's framework for health service utilization. Measures were assessed using multiple-choice and 5-point Likert-type scales (1 = strongly disagree, 5 = strongly agree). Primary outcome measures included: (1) knowledge and awareness of MBSR (12-items); (2) confidence in seeking out MBSR for pain (5-items); (3) barriers to receiving MBSR (11-items); (4) beliefs about MBSR in general (12-items); (5) beliefs about community pharmacy-delivered MBSR (15-items); and (6) preferences for MBSR classes/programs (6-items). Outcomes were analyzed using descriptive statistics, and influential factors associated with mean beliefs regarding community pharmacy-delivered MBSR for chronic pain management were assessed via multiple linear regression. Of the 302 survey respondents, the majority were white (79.1%) and female (50.7%), with a mean age of 44.65 years. Respondents' self-rated MBSR knowledge (mean [SD] scale score: 2.30 [0.68]) and confidence (2.65 [0.87]) were low, although perceived barriers to access were low overall (2.22 [0.53]). Beliefs regarding the use of MBSR for treatment of chronic pain were positive in general (3.67 [0.71]), but more negative regarding community pharmacy-delivered MBSR (2.38 [0.56]). Confidence in seeking out MBSR (ß = 0.297, 95% CI = 0.219 to 0.375; p < 0.001) and current opioid use (ß = 0.419, 95% CI = 0.147 to 0.690; p = 0.003) were positively associated with beliefs regarding pharmacy-delivered MBSR, while annual household income (ß = -0.124, 95% CI = -0.244 to -0.004; p = 0.043) and level of bodily pain (ß = -0.149, 95% CI = -0.291 to -0.008; p = 0.039) exerted statistically significant negative influences. Respondents preferred a hybrid MBSR class format including both online and in-person components (29.7%) as well as both group and individual session options (43.7%). In conclusion, further education is necessary to increase the public's perception of community pharmacies as a resource for complementary and integrative health.

Tissue-based IL-10 signalling in helminth infection limits IFNγ expression and promotes the intestinal Th2 response.

Type 2 immunity is activated in response to both allergens and helminth infection. It can be detrimental or beneficial, and there is a pressing need to better understand its regulation. The immunosuppressive cytokine IL-10 is known as a T helper 2 (Th2) effector molecule, but it is currently unclear whether IL-10 dampens or promotes Th2 differentiation during infection. Here we show that helminth infection in mice elicits IL-10 expression in both the intestinal lamina propria and the draining mesenteric lymph node, with higher expression in the infected tissue. In vitro, exogenous IL-10 enhanced Th2 differentiation in isolated CD4+ T cells, increasing expression of GATA3 and production of IL-5 and IL-13. The ability of IL-10 to amplify the Th2 response coincided with its suppression of IFNγ expression and in vivo we found that, in intestinal helminth infection, IL-10 receptor expression was higher on Th1 cells in the small intestine than on Th2 cells in the same tissue, or on any Th cell in the draining lymph node. In vivo blockade of IL-10 signalling during helminth infection resulted in an expansion of IFNγ+ and Tbet+ Th1 cells in the small intestine and a coincident decrease in IL-13, IL-5 and GATA3 expression by intestinal T cells. These changes in Th2 cytokines correlated with reduced expression of type 2 effector molecules, such as RELMα, and increased parasite egg production. Together our data indicate that IL-10 signalling promotes Th2 differentiation during helminth infection at least in part by regulating competing Th1 cells in the infected tissue.

Oral delivery of a functional algal-expressed TGF-ß mimic halts colitis in a murine DSS model.

Inflammatory bowel disease (IBD) is a set of immunological disorders which can generate chronic pain and fatigue associated with the inflammatory symptoms. The treatment of IBD remains a significant hurdle with current therapies being only partially effective or having significant side effects, suggesting that new therapies that elicit different modes of action and delivery strategies are required. TGM1 is a TGF-ß mimic that was discovered from the intestinal helminth parasite Heligmosomoides polygyrus and is thought to be produced by the parasite to suppress the intestinal inflammation response to help evade host immunity, making it an ideal candidate to be developed as a novel anti-inflammatory bio-therapeutic. Here we utilized the expression system of the edible green algae Chlamydomonas reinhardtii in order to recombinantly produce active TGM1 in a form that could be ingested. C. reinhardtii robustly expressed TGM1, and the resultant recombinant protein is biologically active as measured by regulatory T cell induction. When delivered orally to mice, the algal expressed TGM1 is able to ameliorate weight loss, lymphadenopathy, and disease symptoms in a mouse model of DSS-induced colitis, demonstrating the potential of this biologic as a novel treatment of IBD.

A helminth-derived suppressor of ST2 blocks allergic responses.

The IL-33-ST2 pathway is an important initiator of type 2 immune responses. We previously characterised the HpARI protein secreted by the model intestinal nematode Heligmosomoides polygyrus, which binds and blocks IL-33. Here, we identify H. polygyrus Binds Alarmin Receptor and Inhibits (HpBARI) and HpBARI_Hom2, both of which consist of complement control protein (CCP) domains, similarly to the immunomodulatory HpARI and Hp-TGM proteins. HpBARI binds murine ST2, inhibiting cell surface detection of ST2, preventing IL-33-ST2 interactions, and inhibiting IL-33 responses in vitro and in an in vivo mouse model of asthma. In H. polygyrus infection, ST2 detection is abrogated in the peritoneal cavity and lung, consistent with systemic effects of HpBARI. HpBARI_Hom2 also binds human ST2 with high affinity, and effectively blocks human PBMC responses to IL-33. Thus, we show that H. polygyrus blocks the IL-33 pathway via both HpARI which blocks the cytokine, and also HpBARI which blocks the receptor.

Isolation and functional characterisation of lamina propria leukocytes from helminth-infected, murine small intestine.

The use of helminth infections as tools to understand the type 2 immune response is a well-established technique and important to many areas of immunological research. The phenotype and function of immune cell populations at the site of infection is a key determinant of pathogen clearance. However, infections with helminths such as the murine nematode Heligomosmoides polygryrus cause increased mucus production and thickening of the intestinal wall, which can result in extensive cell death when isolating and analysing cells from the lamina propria (LP). Populations of larger immune cells such as macrophages and dendritic cells are often trapped within mucus or dying tissues. Here we describe an optimised protocol for isolating LP leukocytes from the small intestine of H.polygyrus -infected mice, and we demonstrate phenotypic and functional identification of myeloid and CD4+ T cell subsets using cytokine staining and flow cytometry. Our protocol may provide a useful experimental method for the immunological analysis of the affected tissue site during helminth infections.