Positive messages may reduce patient pain: A meta-analysis

Introduction Current treatments for pain have limited benefits and worrying side effects. Some studies suggest that pain is reduced when clinicians deliver positive messages. However, the effects of positive messages are heterogeneous and have not been subject to meta-analysis. We aimed to estimate the efficacy of positive messages for pain reduction. Methods We included randomized trials of the effects of positive messages in a subset of the studies included in a recent systematic review of context factors for treating pain. Several electronic databases were searched. Reference lists of relevant studies were also searched. Two authors independently undertook study selection, data extraction, risk of bias assessment, and analyses. Our primary outcome measures were differences in patient- or observer-reported pain between groups who were given positive messages and those who were not. Results Of the 16 randomized trials (1703 patients) that met the inclusion criteria, 12 trials had sufficient data for meta-analysis. The pooled standardized effect size was −0.31 (95% confidence interval [CI] −0.61 to −0.01, p = 0.04, I2 = 82%). The effect size remained positive but not statistically significant after we excluded studies considered to have a high risk of bias (standard effect size −0.17, 95% CI −0.54 to 0.19, P = 0.36, I2 = 84%). Conclusion Care of patients with chronic or acute pain may be enhanced when clinicians deliver positive messages about possible clinical outcomes. However, we have identified several limitations of the present study that suggest caution when interpreting the results. We recommend further high-quality studies to confirm (or falsify) our result. FUNDING Alexander Mebius research has been funded through the ERC grant "Philosophy of Pharmacology: Safety, Statistical Standards, and Evidence Amalgamation" (GA: 639276

Stromal cells of the mouse spleen

The composition and function of stromal cells in the white pulp of the spleen resemble to a large extent the situation in other secondary lymphoid organs such as lymph nodes. The stromal cells play an important role in the support and guidance of lymphocytes and myeloid cells in the T and B cell zones of the spleen. Major differences of the spleen are found in the way cells enter the white pulp and the composition of stromal cells in the red pulp

Mach's Principle and Model for a Broken Symmetric Theory of Gravity

We investigate spontaneous symmetry breaking in a conformally invariant gravitational model. In particular, we use a conformally invariant scalar tensor theory as the vacuum sector of a gravitational model to examine the idea that gravitational coupling may be the result of a spontaneous symmetry breaking. In this model matter is taken to be coupled with a metric which is different but conformally related to the metric appearing explicitly in the vacuum sector. We show that after the spontaneous symmetry breaking the resulting theory is consistent with Mach's principle in the sense that inertial masses of particles have variable configurations in a cosmological context. Moreover, our analysis allows to construct a mechanism in which the resulting large vacuum energy density relaxes during evolution of the universe.Comment: 9 pages, no figure

Mass-Deformed BLG Theory in Light-Cone Superspace

Maximally supersymmetric mass deformation of the Bagger-Lambert-Gustavsson (BLG) theory corresponds to a {non-central} extension of the d=3 N=8 Poincare superalgebra (allowed in three dimensions). We obtain its light-cone superspace formulation which has a novel feature of the dynamical supersymmetry generators being {cubic} in the kinematical ones. The mass deformation picks a quaternionic direction, which breaks the SO(8) R-symmetry down to SO(4)xSO(4). The Hamiltonian of the theory is shown to be a quadratic form of the dynamical supersymmetry transformations, to all orders in the mass parameter, M, and the structure constants, f^{a b c d}.Comment: 23 page

Interference with the Host Haemostatic System by Schistosomes

Schistosomes, parasitic flatworms that cause the tropical disease schistosomiasis, are still a threat. They are responsible for 200 million infections worldwide and an estimated 280,000 deaths annually in sub-Saharan Africa alone. The adult parasites reside as pairs in the mesenteric or perivesicular veins of their human host, where they can survive for up to 30 years. The parasite is a potential activator of blood coagulation according to Virchow's triad, because it is expected to alter blood flow and endothelial function, leading to hypercoagulability. In contrast, hepatosplenic schistosomiasis patients are in a hypocoagulable and hyperfibrinolytic state, indicating that schistosomes interfere with the haemostatic system of their host. In this review, the interactions of schistosomes with primary haemostasis, secondary haemostasis, fibrinolysis, and the vascular tone will be discussed to provide insight into the reduction in coagulation observed in schistosomiasis patients.Interference with the haemostatic system by pathogens is a common mechanism and has been described for other parasitic worms, bacteria, and fungi as a mechanism to support survival and spread or enhance virulence. Insight into the mechanisms used by schistosomes to interfere with the haemostatic system will provide important insight into the maintenance of the parasitic life cycle within the host. This knowledge may reveal new potential anti-schistosome drug and vaccine targets. In addition, some of the survival mechanisms employed by schistosomes might be used by other pathogens, and therefore, these mechanisms that interfere with host haemostasis might be a broad target for drug development against blood-dwelling pathogens. Also, schistosome antithrombotic or thrombolytic molecules could form potential new drugs in the treatment of haemostatic disorders

Determinants of postnatal spleen tissue regeneration and organogenesis

Abstract The spleen is an organ that filters the blood and is responsible for generating blood-borne immune responses. It is also an organ with a remarkable capacity to regenerate. Techniques for splenic auto-transplantation have emerged to take advantage of this characteristic and rebuild spleen tissue in individuals undergoing splenectomy. While this procedure has been performed for decades, the underlying mechanisms controlling spleen regeneration have remained elusive. Insights into secondary lymphoid organogenesis and the roles of stromal organiser cells and lymphotoxin signalling in lymph node development have helped reveal similar requirements for spleen regeneration. These factors are now considered in the regulation of embryonic and postnatal spleen formation, and in the establishment of mature white pulp and marginal zone compartments which are essential for spleen-mediated immunity. A greater understanding of the cellular and molecular mechanisms which control spleen development will assist in the design of more precise and efficient tissue grafting methods for spleen regeneration on demand. Regeneration of organs which harbour functional white pulp tissue will also offer novel opportunities for effective immunotherapy against cancer as well as infectious diseases

Transplantation of embryonic spleen tissue reveals a role for adult non-lymphoid cells in initiating lymphoid tissue organization

In this report we describe a transplantation system where embryonic spleens are grafted into adult hosts. This model can be used to analyze the cellular and molecular requirements for the development and organization of splenic microenvironments.Whole embryonic day 15 (ED15) spleens, grafted under the kidney capsule of adult mice, were colonized by host-derived lymphocytes and DC and developed normal splenic architecture. Grafts were also able to form germinal centers in response to T-dependent antigen. Using this system we demonstrated that adult host-derived lymphotoxin (LT) a was sufficient for the development of ED15 LTa/ grafts. Grafting of ED15 LTa/ spleens into RAG/ hosts followed by transfer of LT a/ splenocytes revealed no requirement for lymphocyte-derived LT a in the induction of CCL21 or the development of T-zone stroma. These data suggest that interactions between adult lymphoid-tissue inducer-like cells and embryonic stromal cells initiated T-zone development. Furthermore,adult lymphoid tissue inducer-like cells were shown to develop from bone marrow-derived progenitors. The model described here demonstrates a method of transferring whole splenic microenvironments and dissecting the stromal and hematopoietic signals involved in spleen development and organization