Rationale Matrix metalloproteinase (MMP)-28 regulates the inflammatory and extracellular matrix (ECM) responses in cardiac aging, but the roles of MMP-28 after myocardial infarction (MI) have not been explored. Objective To determine the impact of MMP-28 deletion on post-MI remodeling of the left ventricle (LV) Methods and Results Adult C57BL/6J wild type (WT, n=76) and MMP null (MMP-28−/−, n=86) mice of both sexes were subjected to permanent coronary artery ligation to create MI. MMP-28 expression decreased post-MI, and its cell source shifted from myocytes to macrophages. MMP-28 deletion increased day 7 mortality as a result of increased cardiac rupture post-MI. MMP-28−/− mice exhibited larger LV volumes, worse LV dysfunction, a worse LV remodeling index, and increased lung edema. Plasma MMP-9 levels were unchanged in the MMP-28−/− mice but increased in WT mice at day 7 post-MI. The mRNA levels of inflammatory and ECM proteins were attenuated in the infarct regions of MMP-28−/− mice, indicating reduced inflammatory and ECM responses. M2 macrophage activation was impaired when MMP-28 was absent. MMP-28 deletion also led to decreased collagen deposition and fewer myofibroblasts. Collagen cross-linking was impaired, due to decreased expression and activation of lysyl oxidase in the infarcts of MMP-28−/− mice. The LV tensile strength at day 3 post-MI, however, was similar between the two genotypes Conclusions MMP-28 deletion aggravated MI induced LV dysfunction and rupture, due to defective inflammatory response and scar formation by suppressing M2 macrophage activation.

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Rough path theory is a mathematical toolbox providing for the deterministic modelling of interactions between highly oscillatory systems (rough paths). The theory is rich enough to capture and extend classical Itô stochastic calculus but has far wider significance. Fundamental to this approach is the realisation that the evolving state of the system is best described or measured over short time intervals by considering the realised effect of the system on certain controlled systems (the measurement instruments). The approach is crucially more efficient than an approach based on sampling. Even in the limit, the sequence of time series obtained through finer sampling need not provide a sufficient statistic that could predict the effects of a Brownian motion in an interaction ([13])! This divergence in the analysis arising from the choice of feature set is relevant in any context where the data streams are highly oscillatory on normal time scales.We bring the theory of rough paths to the study of non-parametric statistics on streamed data and particularly to the problem of regression where the input variable is a stream of information, and the dependent response is also (potentially) a path or a stream. We explain how a certain graded feature set of a stream, known in the rough path literature as the signature of the path, has a universality that allows one to characterise the functional relationship summarising the conditional distribution of the dependent response. At the same time this feature set allows explicit computational approaches through linear regression.Truncating the signature of a stream leads to an efficient local description for a rough path. The intrinsic non-linearity provides a provable efficiency gain for the signature over linear descriptions of the path

Avascular necrosis (AVN) of the head of the femur is a potentially crippling disease which mainly affects young adults. Although treatment by exposure to hyperbaric oxygen (HBO) is reported as being beneficial, there has been no study of its use in treated compared with untreated patients. We selected 12 patients who suffered from Steinberg stage-I AVN of the head of the femur (four bilateral) whose lesions were 4 mm or more thick and/or 12.5 mm or more long on MRI. Daily HBO therapy was given for 100 days to each patient. All smaller stage-I lesions and more advanced stages of AVN were excluded. These size criteria were chosen in order to compare outcomes with an identical size of lesion in an untreated group described earlier. Overall, 81% of patients who received HBO therapy showed a return to normal on MRI as compared with 17% in the untreated group. We therefore conclude that hyperbaric oxygen is effective in the treatment of stage-I AVN of the head of the femur.