The microbiome mediates epiphyseal bone loss and metabolomic changes after acute joint trauma in mice.

OBJECTIVE: To compare the early responses to joint injury in conventional and germ-free mice. DESIGN: Post-traumatic osteoarthritis (PTOA) was induced using a non-invasive anterior cruciate ligament rupture model in 20-week old germ-free (GF) and conventional C57BL/6 mice. Injury was induced in the left knees of n = 8 GF and n = 10 conventional mice. To examine the effects of injury, n = 5 GF and n = 9 conventional naïve control mice were used. Mice were euthanized 7 days post-injury, followed by synovial fluid recovery for global metabolomic profiling and analysis of epiphyseal trabecular bone by micro-computed tomography (µCT). Global metabolomic profiling assessed metabolic differences in the joint response to injury between GF and conventional mice. Magnitude of trabecular bone volume loss measured using µCT assessed early OA progression in GF and conventional mice. RESULTS: µCT found that GF mice had significantly less trabecular bone loss compared to conventional mice, indicating that the GF status was protective against early OA changes in bone structure. Global metabolomic profiling showed that conventional mice had greater variability in their metabolic response to injury, and a more distinct joint metabolome compared to their corresponding controls. Furthermore, differences in the response to injury in GF compared to conventional mice were linked to mouse metabolic pathways that regulate inflammation associated with the innate immune system. CONCLUSIONS: These results suggest that the gut microbiota promote the development of PTOA during the acute phase following joint trauma possibly through the regulation of the innate immune system.

Estimation of the accessibility of items and the confidence of candidates: a Rasch-based approach.

In Scottish High School mathematics examinations partial credit is normally awarded for answers which are not totally correct but nevertheless contain some of the correct working. As a way of incorporating partial credit in the marking of ICT versions of these examinations, "steps" have been introduced. The use of "steps" also allows for a Rasch analysis that measures the inaccessibility of items and the confidence of candidates in addition to the traditional difficulty of items and ability of candidates. Two Rasch models can be fitted and jointly assessed for fit. The resulting measures can then be investigated for any relationship between ability and confidence and between difficulty and inaccessibility. A small data set has been used to illustrate these ideas.

Cognitive behaviour therapy with adults with intractable epilepsy and psychiatric co-morbidity: preliminary observations on changes in psychological state and seizure frequency.

Cognitive behaviour therapy (CBT) was undertaken with six adults with chronic, poorly controlled seizures and co-existing psychiatric and/or psychosocial difficulties. During 12 sessions of CBT from an experienced CBT Nurse Specialist, treatment focused concurrently on epilepsy-related problems, associated psychopathology and on the development of psychological strategies to reduce seizure occurrence. At the end of treatment participants rated their initial epilepsy-related problem as having less impact on their daily lives and at one-month follow-up reported less deleterious impact on everyday life in terms of their psychological difficulties. In addition participants demonstrated significant improvements in terms of their self-rated work and social adjustment, and in their decreased use of escape-avoidance coping strategies. These positive findings occurred despite the absence of a significant decrease in seizure frequency. Issues raised by the complexity and severity, both of these patients' psychological/psychosocial difficulties and their epilepsy, are discussed in relation to the optimal length of treatment that may be required when adopting a CBT model in this patient group.

Effect of stepping rate on energy costs during StairMaster exercise.

The responses to a self-selected stepping pattern (random) on a StairMaster 4000PT were compared with those obtained in response to the rates established by the manufacturer (cadence) in men (N = 14) and women (N = 14). During the random test the subjects stepped at their own natural, self-selected rate and distance. In cadence trial the subjects were required to step in time with a metronome at a predetermined rates of 60, 77, 95, and 112 steps.min-1. Each trial consisted of four, 5-min continuous workloads during which HRs were recorded and expired air was analyzed using an automated open-circuit gas system each minute. All size dependent variables (i.e., VE and lO2.min-1) as well as relative VO2 (mlO2.kg-1.min-1) were significantly (P < 0.01) higher for the men across all stages and between methods. Although the random test produced slightly higher oxygen consumption values than the cadence trial, these differences were not significant (P > 0.05). The actual METs were significantly (P < 0.01) higher at all stages except at the lowest stepping rate for both methods compared with those estimated by the manufacturer. Equations were established to estimate actual MET costs: Men's METs = 2.675 + 0.935 (rate); women's METs = 2.934 + 0.817 (rate). Cross-validations of 0.975 and 0.957 were obtained on an additional group of men (N = 8) and women (N = 11), respectively.