Temporal σB stress-response profiles impact Bacillus subtilis fitness.

The Gram-positive model organism Bacillus subtilis responds to environmental stressors by activating the alternative sigma factor σB. The sensing apparatus upstream of σB activation is thought to consist of cytoplasmic stressosomes-megadalton-sized protein complexes that include five paralogous proteins known as RsbRs. The RsbRs are presumed to be involved in stress sensing and the subsequent response. Perturbations to the RsbR complement in stressosomes by engineering cells that produce only one of the RsbR paralogs ("single-RsbR strains") lead to altered σB response dynamics with respect to timing and magnitude. Here, we asked whether such changes to σB response dynamics impact the relative fitness of a strain. We competed strain pairs with different RsbR complements under ethanol and sodium chloride stress and found not only differences in relative fitness among wild-type and single-RsbR strains but also different relative fitness values in the two different stressors. We found that the presence of RsbRA, which dominates the wild-type σB response, enhances fitness in ethanol but is detrimental to fitness in NaCl. Meanwhile, RsbRD-only cells were among the most fit in NaCl. Strains producing hybrid RsbR fusion proteins displayed different fitness values that depended on the RsbR proteins from which they were derived. Our results here suggest that σB response dynamics can impact fitness, highlighting the physiological importance of the unusual stressosome-based general stress response system of B. subtilis. IMPORTANCE: The model bacterium Bacillus subtilis uses cytoplasmic multiprotein complexes, termed stressosomes, to activate the alternative sigma factor σB when facing environmental stresses. We have previously shown that genetically manipulating the complement of putative sensor proteins in stressosomes can alter the dynamics of the σB response in terms of its magnitude and timing. However, it is unknown whether these response dynamics impact the fitness of cells challenged by environmental stressors. Here, we examine the fitness of strains with different σB responses by competing strain pairs in exponential-phase co-cultures under environmental stress. We find that strains with different response dynamics show different competitive indices that differ by stressor. These results suggest that the dynamics of the σB response can affect the fitness of cells facing environmental stress, highlighting the relevance of different σB dynamics.

Long-term outcomes and factors influencing late survival following elective abdominal aortic aneurysm repair: A 24-year experience.

BACKGROUND: Abdominal aortic aneurysms can be either treated by an open abdominal aortic aneurysm repair or an endovascular repair. Comparing clinical predictors of outcomes and those which influence survival rates in the long term is important in determining the choice of treatment offered and the decision-making process with patients. AIMS: To determine the influence of pre-existing clinical predictors and perioperative determinants on late survival of elective open abdominal aortic aneurysm repair and endovascular repair at a tertiary hospital. METHODS: Consecutive patients undergoing elective abdominal aortic aneurysm repair from 1990 to 2013 were included. Data were collected from a prospectively acquired database and death data were gathered from the Queensland state death registry. Pre-existing risks and perioperative factors were assessed independently. Kaplan-Meier and Cox regression modeling were performed. RESULTS: During the study period, 1340 abdominal aortic aneurysms were repaired electively, of which 982 were open abdominal aortic aneurysm repair. The average age was 72.4 years old and 81.7% were males. The cumulative percentage survival rates for open abdominal aortic aneurysms repair at 5, 10, 15 and 20 years were 79, 49, 31 and 22, respectively. The corresponding 5-, 10- and 15-year survival rates for endovascular repair were not significantly different at 75, 49 and 33%, respectively (P = 0.75). Predictors of reduced survival were advanced age, American Society of Anaesthesiology scores, chronic obstructive pulmonary disease, renal impairment, bifurcated grafts, peripheral vascular disease and congestive heart failure. CONCLUSIONS: Open repair offers a good long-term treatment option for patients with an abdominal aortic aneurysm and in our experience there is no significant difference in late survival between open abdominal aortic aneurysms repair and endovascular repair. Consideration of the factors identified in this study that predict reduced long-term survival for open abdominal aortic aneurysms repair and endovascular repair should be considered when deciding repair of abdominal aortic aneurysm.

Important observations made managing carotid body tumors during a 25-year experience.

OBJECTIVES: Our objective was to assess the short- and long-term outcome for patients after carotid body tumor (CBT) resection and discuss the potential pitfalls of the treatment. METHODS: An analysis was undertaken of all patients who underwent CBT resection at Royal Brisbane and Women's Hospital and Greenslopes Private Hospital between 1982 and 2007. Primary tumor characteristics, surgical technique, and outcomes were recorded and analyzed. RESULTS: A total of 49 consecutive CBT resections (2 recurrent tumors) were carried out in 39 patients (26 women [56%]) who were a mean age of 49 years (range, 17-75 years). A nontender neck mass was the presenting complaint in 85%, followed by screening in familial or contralateral tumors in 26%. Familial cases occurred in 11 patients (28%). There were no operative deaths. Complications occurred in 13 of the 49 operations (27%), predominantly temporary nerve palsies and were more likely to occur in tumors of large volume or in cases of removal of coexisting vagal tumors. Malignant disease was present in seven cases (15%). All patients have been followed-up postoperatively for a mean of 11 years (range, 2-26 years). Metachronous paragangliomas have been discovered in six patients, all with familial disease. CONCLUSIONS: Early resection of carotid body tumors should be undertaken while still small to minimize the risk of neural injury, which increases with tumor size. In cases of bilateral CBT, we recommend that the smaller tumor be resected first, before the staged resection of the larger contralateral tumor. In familial or bilateral tumor cases, other synchronous and metachronous paragangliomas should be excluded. Mandatory lifelong follow-up is essential.

Open surgery for atherosclerotic chronic mesenteric ischemia.

BACKGROUND: This study was undertaken to document the results of our current practice of open mesenteric revascularization to enable comparison with the recent trend of percutaneous endovascular therapy for the treatment of chronic mesenteric ischemia. METHODS: Patients were identified via operation code data as well ongoing audit data from 1992 until 2006. Only patients with a history of chronic mesenteric ischemia secondary to atherosclerosis for 3 months or longer were included in the study. Follow-up data have been collected prospectively and include clinical examination and history, as well as graft surveillance consisting of mesenteric duplex ultrasonography, computed tomography, and/or angiography every 6 months for 3 years and then yearly thereafter. RESULTS: Thirty-nine consecutive patients underwent 41 open revascularization procedures for chronic mesenteric ischemia, comprising 67 bypass grafts. The mean patient age was 65 years (range, 45-85 years), and 44% (n = 17) were male. Symptoms were present on average for 11 months (range, 4-48 months) before treatment. The average weight loss was 11.4 kg, and three patients (7.6%) also had evidence of ischemic enteritis. There was one perioperative death, thus giving a perioperative mortality rate of 2.5%. Perioperative morbidity occurred in five patients (12.2%). Primary graft patency was 92% at 5 years. Seven patients died during follow-up, which ranged from 4 to 161 months (mean, 39 months)-one (2.5%) from mesenteric ischemia. Two (5%) other patients have had recurrent mesenteric ischemic symptoms. CONCLUSIONS: Open surgical mesenteric revascularization by bypass grafting for atherosclerotic-induced chronic mesenteric ischemia can be performed with low mortality and morbidity and provides excellent long-term primary patency rates and symptom-free outcomes. Pending more data on the acute and long-term results of endovascular techniques, open mesenteric revascularization remains the gold standard for most patients with chronic mesenteric ischemia.