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931.
932.
SifA is a bi-functional Type III Secretion System (T3SS) effector protein that plays an important role in Salmonella virulence. The N-terminal domain of SifA binds SifA-Kinesin-Interacting-Protein (SKIP), and via an interaction with kinesin, forms tubular membrane extensions called Sif filaments (Sifs) that emanate from the Salmonella Containing Vacuole (SCV). The C-terminal domain of SifA harbors a WxxxE motif that functions to mimic active host cell GTPases. Taken together, SifA functions in inducing endosomal tubulation in order to maintain the integrity of the SCV and promote bacterial dissemination. Since SifA performs multiple, unrelated functions, the objective of this study was to determine how each functional domain of SifA becomes processed. Our work demonstrates that a linker region containing a caspase-3 cleavage motif separates the two functional domains of SifA. To test the hypothesis that processing of SifA by caspase-3 at this particular site is required for function and proper localization of the effector protein domains, we developed two tracking methods to analyze the intracellular localization of SifA. We first adapted a fluorescent tag called phiLOV that allowed for type-III secretion system (T3SS) mediated delivery of SifA and observation of its intracellular colocalization with caspase-3. Additionally, we created a dual-tagging strategy that permitted tracking of each of the SifA functional domains following caspase-3 cleavage to different subcellular locations. The results of this study reveal that caspase-3 cleavage of SifA is required for the proper localization of functional domains and bacterial dissemination. Considering the importance of these events in Salmonella pathogenesis, we conclude that caspase-3 cleavage of effector proteins is a more broadly applicable effector processing mechanism utilized by Salmonella to invade and persist during infection. 相似文献
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935.
Gadepalli SK Selewski DT Drongowski RA Mychaliska GB 《Journal of pediatric surgery》2011,46(4):630-635
Purpose
Patients with congenital diaphragmatic hernia (CDH) requiring extracorporeal life support (ECLS) are at increased risk for acute kidney injury (AKI). We hypothesized that AKI would be associated with increased mortality. We further hypothesized that vasopressor requirement, nephrotoxic medications, and infections would be associated with AKI.Methods
We performed a retrospective chart review in all patients with CDH requiring ECLS from 1999 to 2009 (n = 68). Patient variables that could potentiate renal failure were collected. We used a rise in creatinine from baseline by the RIFLE (risk, 1.5×; injury, 2×; failure, 3×; loss; and end-stage renal disease) criteria to define AKI. Statistical analysis was performed via SPSS (SPSS, Chicago, IL) using Student t test and χ2 analysis, with P < .05 being considered significant.Results
Survival to hospital discharge was 37 (54.4%) of 68. Acute kidney injury was identified in 48 (71%) of 68 patients, with 15 (22% of all patients) qualifying as injury and 33 (49% of all patients) qualifying as failure by the RIFLE criteria. Patients who qualified as failure by the RIFLE criteria had a significant decrease in survival (27.3% with failure vs 80% without failure; P = .001). Patients who qualified as failure also had increased length of ECLS (314 ± 145 vs 197 ± 115 hours; P = .001) and decreased ventilator-free days in the first 60 days (1.39 ± 5.3 vs 20.17 ± 17.4 days; P = .001). There was no significant difference in survival when patients qualified as risk or injury.Conclusions
This is the first report using a systematic definition of AKI in patients with CDH on ECLS. There is a high incidence of AKI in these patients, and when it progresses to failure, it is associated with higher mortality, increased ECLS duration, and increased ventilator days. This highlights the importance of recognizing AKI in patients with CDH requiring ECLS and the potential benefit of preventing progression of AKI or early intervention. 相似文献936.
Gadepalli SK Hirschl RB Tsai WC Caird MS Vanderhave KL Strouse PJ Drongowski RA Farley FA 《Journal of pediatric surgery》2011,46(1):77-80
Purpose
Vertical expandable prosthetic titanium rib (VEPTR) insertion and expansion has been advocated to increase thoracic volume and pulmonary function in patients with thoracic insufficiency syndrome. We reviewed our experience with VEPTR implantation to determine if lung function and growth is augmented, to determine the children's functional status, and if the scoliosis is controlled.Methods
From 2006 to 2010, 29 insertions and 57 expansions were performed in 26 patients at our institution. Demographic data were reviewed in conjunction with complications, scoliosis angles, pulmonary function tests (PFTs), and computed tomography-guided 3D reconstructions to determine lung volumes; and quality of life scores were determined using a modified Scoliosis Research Society (SRS) questionnaire preoperatively and postoperatively. The groups were also stratified by age (because of lung growth potential), disease (congenital or infantile scoliosis, Jeune syndrome, neuromuscular, other structural thoracic disorders), and sex. Analyses using SPSS (SPSS, Chicago, Ill) were performed with P < .05 considered significant.Results
Each patient underwent 3.03 ± 1.8 surgeries, spending 0.97 ± 1.8 days in the intensive care unit and 4.41 ± 6 days in the hospital for each procedure. Mean age was 90.7 ± 41 months. Of the 36 complications, most were because of infection (12), half requiring operative repair (hardware removal). The average PFT percent predicted values for forced expiratory volume in 1 second, forced vital capacity, and RV were 54.6 ± 22, 58.1 ± 24, and 145.3 ± 112, respectively, preoperatively and 51.8 ± 20, 55.9 ± 20, and 105.6 ± 31, respectively, postoperatively. The lung volumes measured by computed tomography when corrected for age do not increase significantly postoperatively. The mean Cobb measurement for the preoperative major curves was 64.7° and postoperatively was 46.1° for those curves measured preoperatively, for a 29% curve improvement. All postoperative curves had a mean of 56.4° and 58.1° at final follow-up, a 3% curve increase. The SRS scores for patients remained unchanged and no statistical difference was seen from preoperative to postoperative values. No statistically significant difference was seen in complications, PFT (forced expiratory volume in 1 second, forced vital capacity, RV), lung volumes, scoliosis angles, and SRS scores between sex, age, and disease categories.Conclusion
There was mild improvement in scoliosis angles but no improvement in lung function and volume. Scoliosis Research Society scores indicate that the children have near normal function both before and after VEPTR placement. Pulmonary function, lung volume, and patient subjective assessments did not increase dramatically after VEPTR placement, although scoliosis angles improved. 相似文献937.
Abdelzaher AM Wright ME Ortega C Hasan AR Shibata T Solo-Gabriele HM Kish J Withum K He G Elmir SM Bonilla JA Bonilla TD Palmer CJ Scott TM Lukasik J Harwood VJ McQuaig S Sinigalliano CD Gidley ML Wanless D Plano LR Garza AC Zhu X Stewart JR Dickerson JW Yampara-Iquise H Carson C Fleisher JM Fleming LE 《Journal of water and health》2011,9(3):443-457
Studies evaluating the relationship between microbes and human health at non-point source beaches are necessary for establishing criteria which would protect public health while minimizing economic burdens. The objective of this study was to evaluate water quality and daily cumulative health effects (gastrointestinal, skin, and respiratory illnesses) for bathers at a non-point source subtropical marine recreational beach in order to better understand the inter-relationships between these factors and hence improve monitoring and pollution prevention techniques. Daily composite samples were collected, during the Oceans and Human Health Beach Exposure Assessment and Characterization Health Epidemiologic Study conducted in Miami (Florida, USA) at a non-point source beach, and analyzed for several pathogens, microbial source tracking markers, indicator microbes, and environmental parameters. Analysis demonstrated that rainfall and tide were more influential, when compared to other environmental factors and source tracking markers, in determining the presence of both indicator microbes and pathogens. Antecedent rainfall and F+ coliphage detection in water should be further assessed to confirm their possible association with skin and gastrointestinal (GI) illness outcomes, respectively. The results of this research illustrate the potential complexity of beach systems characterized by non-point sources, and how more novel and comprehensive approaches are needed to assess beach water quality for the purpose of protecting bather health. 相似文献
938.
939.
Objective
Rare diseases may be difficult to study through conventional research methods, but are amenable to study through certain uncommonly used designs. We sought to explain these designs and to provide a framework to assist researchers in identifying the most appropriate design for a given research question.Study Design and Setting
We systematically searched for literature describing rare disease research frameworks, trial designs, and trials that applied them. We present the advantages and disadvantages of each approach using these published examples, and a practical framework to help researchers in selecting between design choices.Results
When research participants are limited, researchers should consider using: 1) a crossover design; 2) n-of-1 trials; or 3) one of the following adaptive designs: a) a response-adaptive randomization design, b) a ranking and selection design, c) an internal pilot design, or d) a sequential design. Bayesian analysis may be applied to conventional designs, or to any of these uncommon designs. Several of these approaches may also be used in combination. The choice between methods should be guided by factors related to the intervention, disease, anticipated recruitment duration and success, and current state of knowledge about the treatment.Conclusion
These techniques may facilitate research in rare diseases. 相似文献940.
Eshaghi A Patel SN Sarabia A Higgins RR Savchenko A Stojios PJ Li Y Bastien N Alexander DC Low DE Gubbay JB 《Emerging infectious diseases》2011,17(8):1472-1474
Recent case reports describe multidrug-resistant influenza A pandemic (H1N1) 2009 virus infection in immunocompromised patients exposed to neuraminidase inhibitors because of an I223R neuraminidase mutation. We report a case of multidrug-resistant pandemic (H1N1) 2009 bearing the I223R mutation in an ambulatory child with no previous exposure to neuraminidase inhibitors. 相似文献