Strain- and host species-specific inflammasome activation, IL-1β release, and cell death in macrophages infected with uropathogenic Escherichia coli

Uropathogenic Escherichia coli (UPEC) is the main etiological agent of urinary tract infections (UTIs). Little is known about interactions between UPEC and the inflammasome, a key innate immune pathway. Here we show that UPEC strains CFT073 and UTI89 trigger inflammasome activation and lytic cell death in human macrophages. Several other UPEC strains, including two multidrug-resistant ST131 isolates, did not kill macrophages. In mouse macrophages, UTI89 triggered cell death only at a high multiplicity of infection, and CFT073-mediated inflammasome responses were completely NLRP3-dependent. Surprisingly, CFT073- and UTI89-mediated responses only partially depended on NLRP3 in human macrophages. In these cells, NLRP3 was required for interleukin-1β (IL-1β) maturation, but contributed only marginally to cell death. Similarly, caspase-1 inhibition did not block cell death in human macrophages. In keeping with such differences, the pore-forming toxin α-hemolysin mediated a substantial proportion of CFT073-triggered IL-1β secretion in mouse but not human macrophages. There was also a more substantial α-hemolysin-independent cell death response in human vs. mouse macrophages. Thus, in mouse macrophages, CFT073-triggered inflammasome responses are completely NLRP3-dependent, and largely α-hemolysin-dependent. In contrast, UPEC activates an NLRP3-independent cell death pathway and an α-hemolysin-independent IL-1β secretion pathway in human macrophages. This has important implications for understanding UTI in humans.

Experimental studies of lipped channel beams subject to web crippling under ETF and ITF load cases

Lipped channel beams (LCBs) are commonly used as floor joists and bearers in buildings. However, they are subjected to specific failure modes such as web crippling. Despite considerable web crippling research, recent studies [1-6] have shown that the current web crippling design rules are unable to predict the test capacities under ETF and ITF load cases. In many instances, the predictions by the available design standards such as AISI S100, AS/NZS 4600 and Eurocode 3 Part 1-3 [7-9] are inconsistent. Hence thirty-six tests were conducted to assess the web crippling behaviour and strengths of LCBs under two flange load cases. Experimental web crippling capacities were then compared with the predictions from the current design rules. These comparisons showed that AS/NZS 4600 and AISI S100 design equations are very unconservative for LCB sections under ETF load case and are conservative for ITF load case. Hence improved equations were proposed to determine the web crippling capacities of LCBs. Suitable design rules were also developed using the direct strength method. This paper presents the details of this study and the results including improved design rules.

Impact of ethnicity upon body composition assessment in Sri Lankan Australian children

Objectives: Obesity is a disease with excess body fat where health is adversely affected. Therefore it is prudent to make the diagnosis of obesity based on the measure of percentage body fat. Body composition of a group of Australian children of Sri Lankan origin were studied to evaluate the applicability of some bedside techniques in the measurement of percentage body fat. Methods: Height (H) and weight (W) was measured and BMI (W/H2) calculated. Bioelectrical impedance analysis (BIA) was measured using tetra polar technique with an 800 μA current of 50 Hz frequency. Total body water was used as a reference method and was determined by deuterium dilution and fat free mass and hence fat mass (FM) derived using age and gender specific constants. Percentage FM was estimated using four predictive equations, which used BIA and anthropometric measurements. Results: Twenty-seven boys and 15 girls were studied with mean ages being 9.1 years and 9.6 years, respectively. Girls had a significantly higher FM compared to boys. The mean percentage FM of boys (22.9 ± 8.7%) was higher than the limit for obesity and for girls (29.0 ± 6.0%) it was just below the cut-off. BMI was comparatively low. All but BIA equation in boys under estimated the percentage FM. The impedance index and weight showed a strong association with total body water (r 2 = 0.96, P < 0.001). Except for BIA in boys all other techniques under diagnosed obesity. Conclusions: Sri Lankan Australian children appear to have a high percentage of fat with a low BMI and some of the available indirect techniques are not helpful in the assessment of body composition. Therefore ethnic and/or population specific predictive equations have to be developed for the assessment of body composition, especially in a multicultural society using indirect methods such as BIA or anthropometry.

Seasonal variations in the body composition of lightweight rowers

OBJECTIVE To monitor the seasonal body composition alterations in 18 lightweight rowers (six females, 12 males) across a rowing season incorporating preseason, early competition, competition, and postseason. METHODS Subject age was 23.1 (SD 4.5) years, height 170.8 (5.6) cm (female, 23.5 (3.5) years, 180.5 (2.7) cm (male). Body weight, fat mass, and fat-free mass (FFM) were assessed using dual energy x ray absorptiometry (DXA-L Lunar) and skinfold techniques. Weight control techniques were documented before major regattas by a questionnaire. RESULTS Female body weight was reduced from 61.3 (2.9) to 57.0 (1.1) kg (5.9%), while male body weight was reduced from 75.6 (3.1) to 69.8 (1.6) kg (7.8%) preseason to competition season respectively. These body weight reductions were mirrored by a significant reduction in fat mass as indicated by the sum of skinfolds [female seven sites: 80.9 (8.1) to 68.2 (11.8) mm; male eight sites: 54.2 (8.7) to 41.8 (4.8) mm], percentage body fat [female 22.1 (1.0) to 19.7 (2.4)%; male 10.0 (0.9) to 7.8 (0.8)%], and total fat [female 12.5 (5.2) to 10.9 (1.4) kg; male 7.3 (1.9) to 5.6 (1.8) kg] (DXA). In contrast, no changes were observed in FFM despite a season of intensive rowing training. Seasonal body weight control was achieved through reduced total energy and dietary fat intakes. Acute body weight reductions were achieved by exercise in 73.3% of participants, food restriction in 71.4%, and fluid restrictions in 62.9%. CONCLUSIONS Seasonal body weight alterations in lightweight rowers are in response to a significant reduction in fat mass. However, the weight restrictions appear to be limiting an increase in FFM which could be beneficial to rowing performance.