erapy for the majority of septic patients, understanding the phenotype of pro-inflammatory and pro-apoptotic sepsis is crucial to develop new therapeutic avenues. Indeed, there was a great deal of heterogeneity in both our septic and critically ill patients that may represent either patient-specific or pathogen-specific factors that influence caspase-1 release. Larger future trials may be needed to further describe these relationships. In summary, our results demonstrate that caspase-1 plays a central role in the regulation of apoptosis in an ex vivo model. This novel apoptotic event is dependent upon encapsulation of exogenous caspase-1 into released MVs that allow targeting of the active enzyme to the cytosol of different cells, in this study lymphocytes. Our work provides an opportunity to further describe a specific mechanism in human sepsis by which apoptosis can be induced. The exact mechanism by which these MVs recognize and target lymphocytes remains to 
be elucidated. Chronic wounds represent a significant health problem, especially in diabetic patients. Of the 150 million people with diabetes worldwide, the lifetime incidence of a foot ulcer is,25% and up to 70% of these wounds remain unhealed after 20 weeks of standard treatment. Normal wound healing consists of overlapping phases of inflammation, tissue formation and angiogenesis, and remodeling, but in chronic wounds associated with diabetes all of these phases are compromised. A prolonged accumulation of inflammatory cells, elevated levels of inflammatory cytokines and reduced levels of pro-angiogenic and prohealing growth factors contribute to the impaired angiogenesis and healing. Mechanical energy-based modalities are often used in conjunction with standard treatments for chronic wounds. These treatments use local mechanical stimulation of the wound in an attempt to modify the cellular and biochemical environment to improve angiogenesis and healing. Currently, there is much debate over the efficacy of these treatments and the quality of evidence is often questioned. While there is some evidence that these therapies may improve wound healing, a lack of larger controlled studies of high methodological quality has amounted to insufficient evidence in proving an additional benefit. In the 1235481-90-9 biological activity current study, we investigate a novel therapeutic approach to wound healing whole body low-intensity vibration. LIV has been extensively studied in humans to promote musculoskeletal anabolism, although the precise mechanisms that modulate these cellular responses are unclear. During LIV, subjects stand on a platform that delivers uniform vertical oscillations at various amplitudes and frequencies. Daily exposure to LIV for 1020 minutes has provided promising results as a non-invasive treatment for osteoporosis by increasing production of growth factors, modulating stem cell proliferation and differentiation, and increasing bone mass in individuals with low bone mineral density. Furthermore, a single bout of LIV has been shown to increase systemic and regional blood flow. Thus, although LIV has not yet been investigated as a means to promote skin wound healing it has the potential to induce mechanotransduction PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19632179 both locally in the PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19631704 wound as well as at distant sites that results in a more pro-healing biochemical environment of the wound as well as improved tissue perfusion. The purpose of this study was to assess the effects of whole-body LIV on wound healing in diabetic db/db mice. The centr