Immunoregulatory effects of testosterone supplementation combined with exercise training in men with Inclusion Body Myositis: A double‐blind, placebo‐controlled, cross‐over trial

Objectives Sporadic Inclusion Body Myositis (IBM) is an inflammatory muscle disease affecting individuals over the age of 45, leading to progressive muscle wasting, disability and loss of independence. Histologically, IBM is characterised by immune changes including myofibres expressing major histocompatibility complex molecules and invaded by CD8+ T cells and macrophages, and by degenerative changes including protein aggregates organised in inclusion bodies, rimmed vacuoles and mitochondrial abnormalities. There is currently no cure, and regular exercise is currently the only recognised treatment effective at limiting muscle weakening, atrophy and loss of function. Testosterone exerts anti-inflammatory effects, inhibiting effector T-cell differentiation and pro-inflammatory cytokine production. Methods We conducted a double-blind, placebo-controlled, cross-over trial in men with IBM, to assess whether a personalised progressive exercise training combined with application of testosterone, reduced the inflammatory immune response associated with this disease over and above exercise alone. To assess intervention efficacy, we immunophenotyped blood immune cells by flow cytometry, and measured serum cytokines and chemokines by Luminex immunoassay. Results Testosterone supplementation resulted in modest yet significant count reduction in the classical monocyte subset as well as eosinophils. Testosterone-independent immunoregulatory effects attributed to exercise included altered proportions of some monocyte, T- and B-cell subsets, and reduced IL-12, IL-17, TNF-α, MIP-1β and sICAM-1 in spite of interindividual variability. Conclusion Overall, our findings indicate anti-inflammatory effects of exercise training in IBM patients, whilst concomitant testosterone supplementation provides some additional changes. Further studies combining testosterone and exercise would be worthwhile in larger cohorts and longer testosterone administration periods

Eroding abodes and vanished bridges: historical biogeography of the substrate specialist pebble-mound mice (Pseudomys).

Aim: To determine whether the pronounced ecological importance of pebble mounds to pebble-mound mice (Pseudomys) is manifest in their continental biogeography.\ud \ud Location: Northern Australia.\ud \ud Methods: A GIS-based comparison was made between the habitats contained within the potential climatic distributions of mice, representing a null hypothesis of no habitat selection, and their actual distributions based on all known location records.\ud \ud Results: All species had a clear preference for hilly, rocky landscapes with a surficial cover dominated by bedrock. Simple vegetation communities with relatively open eucalypt overstorey and grassy understorey were preferred. Highly degraded rocks and aggradational surfaces and plains were avoided. The extent of the summer monsoon may be important in determining the southern limits of the group's distribution. Major disjunctions between species were attributable to the presence of clay plains and sand sheets.\ud The behavioural requirement of pebble-mound mice for mounds determines their population distribution pattern and the distribution of the different species within the genus.\ud \ud Main conclusions: The behavioural need for pebble mounds drives the distributional pattern of populations and species of pebble-mound mice. The initial spread of pebble-mound mice probably occurred during the late Pliocene or earliest Pleistocene. There has predominantly been degradation of the potential distribution of the group since that time due to the stability of Australian landscapes and Pleistocene planation and sand sheet development over large areas of northern Australia. This process is ongoing, and past regions of rocky contact between current distributions have disappeared, while the distributional limits of several species are steadily being reduced by erosion of hills and the spread of dune fields