Optimizing the Protection of Cattle against Escherichia coli O157: H7 Colonization through Immunization with Different Combinations of H7 Flagellin, Tir, Intimin-531 or EspA

Enterohemorrhagic Escherichia coli (EHEC) are important human pathogens, causing hemorrhagic colitis and hemolytic uraemic syndrome in humans. E. coli O157:H7 is the most common serotype associated with EHEC infections worldwide, although other non-O157 serotypes cause life-threatening infections. Cattle are a main reservoir of EHEC and intervention strategies aimed at limiting EHEC excretion from cattle are predicted to lower the risk of human infection. We have previously shown that immunization of calves with recombinant versions of the type III secretion system (T3SS)-associated proteins EspA, intimin and Tir from EHEC O157:H7 significantly reduced shedding of EHEC O157 from experimentally-colonized calves, and that protection could be augmented by the addition of H7 flagellin to the vaccine formulation. The main aim of the present study was to optimize our current EHEC O157 subunit vaccine formulations by identifying the key combinations of these antigens required for protection. A secondary aim was to determine if vaccine-induced antibody responses exhibited cross-reactive potential with antigens from other EHEC serotypes. Immunization with EspA, intimin and Tir resulted in a reduction in mean EHEC O157 shedding following challenge, but not the mean proportion of calves colonized. Removal of Tir resulted in more prolonged shedding compared with all other groups, whereas replacement of Tir with H7 flagellin resulted in the highest levels of protection, both in terms of reducing both mean EHEC O157 shedding and the proportion of colonized calves. Immunization of calves with recombinant EHEC O157 EspA, intimin and Tir resulted in the generation of antibodies capable of cross-reacting with antigens from non-O157 EHEC serotypes, suggesting that immunization with these antigens may provide a degree of cross-protection against other EHEC serotypes. Further studies are now required to test the efficacy of these vaccines in the field, and to formally test the cross-protective potential of the vaccines against other non-O157 EHEC

Elastography: modality-specific approaches, clinical applications, and research horizons

Manual palpation has been used for centuries to provide a relative indication of tissue health and disease. Engineers have sought to make these assessments increasingly quantitative and accessible within daily clinical practice. Since many of the developed techniques involve image-based quantification of tissue deformation in response to an applied force (i.e., "elastography"), such approaches fall squarely within the domain of the radiologist. While commercial elastography analysis software is becoming increasingly available for clinical use, the internal workings of these packages often remain a "black box," with limited guidance on how to usefully apply the methods toward a meaningful diagnosis. The purpose of the present review article is to introduce some important approaches to elastography that have been developed for the most widely used clinical imaging modalities (e.g., ultrasound, MRI), to provide a basic sense of the underlying physical principles, and to discuss both current and potential (musculoskeletal) applications. The article also seeks to provide a perspective on emerging approaches that are rapidly developing in the research laboratory (e.g., optical coherence tomography, fibered confocal microscopy), and which may eventually gain a clinical foothold

Pull-out strength of patient-specific template-guided vs. free-hand fluoroscopically controlled thoracolumbar pedicle screws: a biomechanical analysis of a randomized cadaveric study

PURPOSE To assess the pull-out strength of thoracolumbar pedicle screws implanted via either a patient-specific template-guided or conventional free-hand fluoroscopically controlled technique in a randomized cadaveric study, and to evaluate the influence of local vertebral bone density, quantified by Hounsfield units (HU), on pedicle screw pull-out strength. METHODS Thoracolumbar pedicles of three spine cadavers were instrumented using either a free-hand fluoroscopically controlled or a patient-specific template-guided technique. Preoperative bone density was quantified by HU measured on CT. Pedicle perforation was evaluated on postoperative CT scans by an independent and blinded radiologist. After dissected vertebrae were embedded in aluminum fixation devices, pull-out testing was initiated with a preload of 50 N and a constant displacement rate of 0.5 mm/s. Subgroup analyses were performed excluding pedicle screws with a pedicle breach (n = 47). RESULTS Pull-out strength was significantly different with 549 ± 278 and 441 ± 289 N in the template-guided (n = 50) versus fluoroscopically controlled (n = 48) subgroups (p = 0.031), respectively. Subgroup analysis limited to screws with an intrapedicular trajectory revealed a tendency toward a higher pull-out strength in the template-guided (n = 30) versus fluoroscopically controlled screws (n = 21) with 587 ± 309 and 454 ± 269 N (p = 0.118), respectively. There was a trend toward a higher pull-out strength (709 ± 418 versus 420 ± 149 N) in vertebrae with a bone density of (>171 HU) versus (<133 HU), respectively (p = 0.061). CONCLUSIONS There was a significantly higher pull-out strength of thoracolumbar pedicle screws when inserted via a patient-specific template-guided versus conventional free-hand fluoroscopically controlled technique, potentially associated with screw trajectory

Exposição ambiental a interferentes endócrinos com atividade estrogênica e sua associação com distúrbios puberais em crianças Environmental exposure to endocrine disruptors with estrogenic activity and the association with pubertal disorders in children

A substância exógena que causa efeitos adversos na saúde de um organismo ou sua descendência, como resultado de distúrbios na função hormonal, é denominada interferente endócrino. Nos últimos anos, produtos ambientais com atividades hormonais têm sido documentados como causadores de anormalidades puberais ou reprodutivas em animais. Os poucos casos comprovados em humanos foram aqueles relacionados a exposições acidentais. Apesar disso, pediatras e pais recomendam a suspensão de todos os alimentos potencialmente contaminados, em especial carne (aves, gado) e derivados da soja quando a criança apresenta alguma alteração puberal. Estas recomendações, se não embasadas cientificamente, podem ter conseqüências deletérias, não apenas pela eliminação de fontes protéicas da dieta, como também por retardar a investigação de causas tratáveis. Por outro lado, a não investigação dos efeitos adversos destes produtos é da mesma forma danosa. Esta revisão descreve os principais interferentes endócrinos responsáveis por alterações puberais em humanos e conclui que, excetuando exposições acidentais a altas quantidades destes produtos, mais estudos são necessários para responsabilizar a ação crônica e em baixas doses destas substâncias na alteração do tempo de desenvolvimento puberal em nossa espécie.<br>Endocrine disruptors are exogenous substances with adverse health effects in intact organisms or their progeny, secondary to changes in endocrine function. Recent years have witnessed constant reports of environmental factors with hormone-like effects causing pubertal or reproductive abnormalities in animals. The few cases proven to be associated with pubertal disorders in humans have been related to accidental exposure. Nevertheless, pediatricians and parents recommend suspending all possible estrogen-contaminated food, especially meat (poultry, beef) and soy products, when the child presents with a pubertal disorder. These recommendations, if not scientifically sound, may have deleterious consequences by eliminating sources of dietary protein and possibly delaying the investigation of other potential and treatable causes. On the other hand, not investigating potential side effects of these products could have similar harmful effects. The current article describes the main endocrine disruptors associated with pubertal disorders in humans and concludes that except for accidental exposure to high doses, more research is needed on the effects of chronic and low-dose exposures in altering human pubertal development