A Model of Salmonella Colitis with Features of Diarrhea in SLC11A1 Wild-Type Mice

Background: Mice do not get diarrhea when orally infected with S. enterica, but pre-treatment with oral aminoglycosides makes them susceptible to Salmonella colitis. However, genetically susceptible ItyS mice (Nramp1 G169D allele) die from systemic infection before they develop diarrhea, so a new model is needed to study the pathogenesis of diarrhea. We pretreated ItyR mice (Nramp1 G169) with oral kanamycin prior to infecting them with virulent S. Typhimurium strain 14028s in order to study Salmonella-induced diarrhea. We used both a visual scoring system and the measurement of fecal water content to measure diarrhea. BALB/c.D2 Nramp1 congenic started losing weight 5 days post-infection and they began to die from colitis 10–14 days after infection. A SPI-1 (invA) mutant caused cecal, but not colonic inflammation and did not cause diarrhea. A phoP- mutant did not cause manifestations of diarrhea in either normal or NADPHdeficient (gp91 phox) mice. However, strain 14028s caused severe colitis and diarrhea in gp91 phox-deficient mice on an ItyR background. pmr A and F mutants, which are less virulent in orally infected BALB/c mice, were fully virulent in this model of colitis. Conclusions: S. enterica must be able to invade the colonic epithelium and to persist in the colon in order to cause colitis with manifestations of diarrhea. The NADPH oxidase is not required for diarrhea in Salmonella colitis. Furthermore,

Repair of mitral valve prolapse through ePTFE Neochordae: A finite element approach from CMR

Patient-specific finite element (FE) modeling is largely used to quantify mitral valve (MV) biomechanics associated to pathological and post-surgical conditions. We used this approach, integrated with non-invasive cardiac magnetic resonance (CMR) imaging data, to numerically perform the repair of the isolated mitral valve leaflet prolapse through expanded-polytetrafluoroethylene (ePTFE) sutures and quantitatively compare the effects of different techniques of neochordal implantation (NCI). CMR-derived FE models well reproduced MVP-related alterations and were able to assess the efficacy of each repairing technique and its biomechanical effects onMVapparatus; the quantification of biomechanical differences between NCI techniques, especially in terms of both chordal tensions and leaflet stresses redistribution, may impact on the short- and long-term the clinical outcome, potentially opening the way to patient-specific optimization of NCIs and, if extensively and successfully tested, improve surgical planning

Heart valve function: a biomechanical perspective

Heart valves (HVs) are cardiac structures whose physiological function is to ensure directed blood flow through the heart over the cardiac cycle. While primarily passive structures that are driven by forces exerted by the surrounding blood and heart, this description does not adequately describe their elegant and complex biomechanical function. Moreover, they must replicate their cyclic function over an entire lifetime, with an estimated total functional demand of least 3×109 cycles. As in many physiological systems, one can approach HV biomechanics from a multi-length-scale approach, since mechanical stimuli occur and have biological impact at the organ, tissue and cellular scales. The present review focuses on the functional biomechanics of HVs. Specifically, we refer to the unique aspects of valvular function, and how the mechanical and mechanobiological behaviours of the constituent biological materials (e.g. extracellular matrix proteins and cells) achieve this remarkable feat. While we focus on the work from the authors' respective laboratories, the works of most investigators known to the authors have been included whenever appropriate. We conclude with a summary and underscore important future trends