Ambient oxygen levels regulate intestinal dysbiosis and GVHD severity after allogeneic stem cell transplantation.

The severity of T cell-mediated gastrointestinal (GI) diseases such as graft-versus-host disease (GVHD) and inflammatory bowel diseases correlates with a decrease in the diversity of the host gut microbiome composition characterized by loss of obligate anaerobic commensals. The mechanisms underpinning these changes in the microbial structure remain unknown. Here, we show in multiple specific pathogen-free (SPF), gnotobiotic, and germ-free murine models of GI GVHD that the initiation of the intestinal damage by the pathogenic T cells altered ambient oxygen levels in the GI tract and caused dysbiosis. The change in oxygen levels contributed to the severity of intestinal pathology in a host intestinal HIF-1α- and a microbiome-dependent manner. Regulation of intestinal ambient oxygen levels with oral iron chelation mitigated dysbiosis and reduced the severity of the GI GVHD. Thus, targeting ambient intestinal oxygen levels may represent a novel, non-immunosuppressive strategy to mitigate T cell-driven intestinal diseases.

An adherent tissue-inspired hydrogel delivery vehicle utilised in primary human glioma models.

A physical hydrogel cross-linked via the host-guest interactions of cucurbit[8]uril and utilised as an implantable drug-delivery vehicle for the brain is described herein. Constructed from hyaluronic acid, this hydrogel is biocompatible and has a high water content of 98%. The mechanical properties have been characterised by rheology and compared with the modulus of human brain tissue demonstrating the production of a soft material that can be moulded into the cavity it is implanted into following surgical resection. Furthermore, effective delivery of therapeutic compounds and antibodies to primary human glioblastoma cell lines is showcased by a variety of in vitro and ex vivo viability and immunocytochemistry based assays.

Medical causation and expert testimony: allergists at this intersection of medicine and law.

Clinical practice always necessitates proper diagnosis and correct treatment. For most clinical fields, determining the cause of the illness is irrelevant to the intervention. An oncologist, for example, has no need to explore the "cause" of the patient's lymphoma. Allergists, by contrast, have tools and the need to examine the relevant allergen which is the putative "cause" of the patient's allergic symptomatology. In the context of a legal claim, the "cause" of the symptoms or disorder is central, because it determines financial responsibility. However, in the case of an allergic disorder and identified allergen, a claim requires more. Whose allergen? Where did it come from? These are crucial questions that must be answered. This paper explores the approaches to causal assessment which are important for the clinical allergist as he/she navigates the interface between clinical practice and legal proceedings. Its purpose is to help the allergist understand that interface, and to be prepared to enter an unfamiliar legal arena.