Citations

Directional mesenchymal cell invasion in vivo is understood to be a stimulated event and to be regulated by cytokines, chemokines, and types of extracellular matrix (ECM). Instead, by focusing on the cellular response to ECM stiffness, we found that soft ECM (low stiffness) itself is sufficient to prevent stable cell-to-cell adherens junction formation, up-regulate matrix metalloproteinase (MMP) secretion, promote MMP activity, and induce invadosome-like protrusion (ILP) formation. Consistently, similar ILP formation was also detected in a three-dimensional directional invasion assay in soft matrix. Primary human fibroblasts spontaneously form ILPs in a very narrow range of ECM stiffness (0.1–0.4 kPa), and such ILP formation is Src family kinase dependent. In contrast, spontaneous ILP formation in malignant cancer cells and fibrosarcoma cells occurs across a much wider range of ECM stiffness, and these tumor cell ILPs are also more prominent at lower stiffness. These findings suggest that ECM softness is a natural stimulator for cellular invasiveness.

The treatment of hip dysplasia should be customised for patients individually based on radiographic findings, patient age, and the patient’s overall articular cartilage status. In many patients, restoration of hip anatomy as close to normal as possible with a PAO is the treatment of choice. Cite this article: Bone Joint J 2013;95-B, Supple A:21–5.

This paper begins with a patient perspective from the first author. Faced with cascading health problems, this author describes her gradual embrace of alternative treatments. While these improved her health, they also set her apart and prompted antagonism from those in conventional medicine. She found she was not alone in benefiting from a more open view of healing, and not alone in being buffeted by the opposing medical views. Two invited commentaries from medical professionals follow, as well as the first author’s response.

Objectives Asthmatics have increased risks of airway-related infections. Little is known about whether this is true for non-airway-related serious infections such as Escherichia coli bloodstream infection (BSI). We assessed whether asthma is associated with a risk of developing community-acquired E coli BSI. Design The study was designed as a population-based retrospective case–control study. Setting This population-based study was conducted in Olmsted County, Minnesota. Participants The study included 259 all eligible community-acquired E coli BSI cases in Olmsted County, MN between 1998 and 2007 and 259 birthday-matched, gender-matched and residency-matched controls. Primary and secondary outcome measures Only community-acquired E coli BSI cases as the primary outcome was included. Asthma status as an exposure was ascertained by predetermined criteria. An adjusted OR and 95% CI for the association between asthma and risk of community-acquired E coli BSI was calculated using conditional logistic regression. Results Of 259 eligible cases, 179 (69%) were women and mean age was 61±22 years. Of the 259 cases 37 (14%) and 16 (6%) of 259 controls had a prior history of asthma (adjusted OR 2.74; 95% CI 1.11 to 6.76; p=0.029). The population attributable risk of asthma for community-acquired E coli BSI was 9%. Although not statistically significant, there was a borderline association between having a history of food allergy and increased risk of community-acquired E coli BSI (6% vs 2%; adjusted OR 3.51; 95% CI 0.94 to 13.11; p=0.062). Conclusions Based on the findings of the current population-based, case–control investigation, a history of asthma may be associated with risk of community-acquired E coli BSI. The impact of asthma on risk of microbial infections may go beyond airways.