Escherichia coli Resistance to Nonbiocidal Antibiofilm Polysaccharides Is Rare and Mediated by Multiple Mutations Leading to Surface Physicochemical Modifications

Antivirulence strategies targeting bacterial behavior, such as adhesion and biofilm formation, are expected to exert low selective pressure and have been proposed as alternatives to biocidal antibiotic treatments to avoid the rapid occurrence of bacterial resistance. Here, we tested this hypothesis using group 2 capsule polysaccharide (G2cps), a polysaccharidic molecule previously shown to impair bacterium-surface interactions, and we investigated the nature of bacterial resistance to a nonbiocidal antibiofilm strategy. We screened an Escherichia coli mutant library for an increased ability to form biofilm in the presence of G2cps, and we identified several mutants displaying partial but not total resistance to this antibiofilm polysaccharide. Our genetic analysis showed that partial resistance to G2cps results from multiple unrelated mutations leading to modifications in surface physicochemical properties that counteract the changes in ionic charge and Lewis base properties induced by G2cps. Moreover, some of the identified mutants harboring improved biofilm formation in the presence of G2cps were also partially resistant to other antibiofilm molecules. This study therefore shows that alterations of bacterial surface properties mediate only partial resistance to G2cps. It also experimentally validates the potential value of nonbiocidal antibiofilm strategies, since full resistance to antibiofilm compounds is rare and potentially unlikely to arise in clinical settings.     

Alcohol intake and diet in France, the prominent role of lifestyle.

AIM: Moderate alcohol intake is related to a decrease of coronary heart disease. This protective effect may be attributed to ethanol but may also depend on the type of alcoholic beverages. However, these differences may be confounded by lifestyle and diet. We investigated the relationships between alcohol consumption, beverage type preference and socio-economic status, diet and lifestyle. METHODS AND RESULTS: A cross-sectional survey on cardiovascular risk factors and nutrition was carried out from 1995 to 1997 by the French MONICA Centres. A sample of 1110 middle-aged men (45-64 years) was randomly recruited; 12.8% of men were abstainers and 16.3% reported a consumption of #10878;60 g/d alcohol. Smoking, waist-to-hip ratio and hypertension increased along with the amount of alcohol intake. Physical activity (from 40.9% in abstainers to 23.8% in heavy drinkers, p=0.0025), educational level (from 11.9+/-4.4 to 11.1+/-3.8 years, p=0.01), socio-economic status and diet quality index (from 7.1+/-2.3 to 6.3+/-2.0, p<0.0001 after multivariate adjustment) decreased along with the increase of alcohol consumption and were higher among wine drinkers than among beer or mixed drinkers. Diet quality index was 7.1+/-1.9, 6.4+/-1.8 and 6.6+/-1.9 among wine, beer and mixed drinkers, respectively (p=0.007 after multivariate adjustment). CONCLUSION: Moderate alcohol drinkers or wine drinkers have healthy diet and behaviours compared to other drinkers or abstainers. The living area plays a significant role in the dieting behaviours.     

Enhanced release of atrial natriuretic factor during exercise-induced myocardial ischaemia in patients after acute myocardial infarction.

To determine whether acute myocardial ischaemia induced by dynamic exercise can lead to changes in plasma levels of atrial natriuretic factor, we performed symptom-limited bicycle electrocardiographic tests in 20 males with recent acute myocardial infarction and in 8 control males. Ten patients developed exercise-induced myocardial ischaemia and 10 patients did not. There were no significant differences between the two groups with regard to age, site of myocardial infarction, urinary sodium, atrial sizes, radionuclide left ventricular ejection fraction, workload, baseline and peak-exercise heart rate, baseline and peak-exercise rate-pressure product, duration of exercise. Also baseline atrial natriuretic factor concentrations were similar in both groups (ischaemic patients: 34.51 +/- 15.73 pg/ml; nonischaemic patients: 27.17 +/- 8.74 pg/ml, NS), while peak-exercise atrial natriuretic factor concentrations were higher in patients with exercise-induced myocardial ischaemia (112.31 +/- 35.5 pg/ml) than in the others (80.46 +/- 23.43 pg/ml) (P less than 0.05). After 15 minutes of recovery, plasma atrial natriuretic factor levels were still raised only in the ischaemic patients (63.3 +/- 15.44 pg/ml, P less than 0.01), returning to baseline after 30 minutes in both groups. In control subjects, the behaviour of atrial natriuretic factor resembled that of the patients without exercise-induced ischaemia, with a significant increase at peak-exercise (from baseline levels of 23.1 +/- 10.5 pg/ml to peak-exercise levels of 91.3 +/- 14.5 pg/ml, P less than 0.0005) and a rapid return to baseline levels after 15 minutes of recovery (28.5 +/- 10.6 pg/ml, NS).(ABSTRACT TRUNCATED AT 250 WORDS)     

Congenital defects of the aortic system]

The authors give a basic embriological classification of congenital arterial defects. Congenital abnormalities of the arterial system (arising in an embryo of 12 to 30 mm) affect the primary segments, and comprise excessive involution of the antibrachial trunk, of the popliteal artery, of the tibio-peroneal trunk and peroneal artery, abnormal or persistence of the interosseus artery, of the artery of sciatic nerve, and of the peroneal artery, a high axillary origin of the radial or antecubital artery, renal polar arteries arising directly from the aorta, and agenesis of the palmar or plantar arches. In the second generation arteries, they comprise agenesis or hypogenesis of the radial, antecubital or tibial arteries, and gross hypogenesis of the trunk of the renal artery with an immature kidney. Arrested or mal-development in the foetus can give rise to coarctation and stenosis of the thoracic aorta and large vessels, to segmental agenesis with huge collaterals, to imperforate osita, especially in the mesenteric arteries, to sudden variations in diameter of the renal arteries, and to parietal dyplasia and aneurysms in vessels in the residual undifferentiated mesenchymatous tissue, and diffuse dilatation or stenosis. The authors give their experience for a cardiological clinic, adding arterial hypertension and arterioparenchymatous dysplasia of the kidneys, Raynaud's, Takayasbu's and Burger's disease, and intermittent claudication of the lower limbs; they indicate the areas which they are currently studying.     

Association of hypertensive status and its drug treatment with lipid and haemostatic factors in middle-aged men: the PRIME study

Aims: To assess the association of hypertensive status and antihypertensive drug treatment with lipid and haemostatic levels in middle-aged men.Methods and results: Hypertensive status, antihypertensive drug treatment, total and high-density lipoprotein (HDL) cholesterol, triglyceride, apoproteins A-I and B, lipoparticles LpA-I, LpE:B and Lp(a), fibrinogen, plasminogen activator inhibitor-1 (PAI-1) activity and factor VII were assessed in a sample of men 50-59 years living in France (n = 7050) and Northern Ireland (n = 2374). After adjustment for age, body mass index, smoking status, educational level, country, alcohol drinking and hypolipidaemic drug treatment, untreated hypertensive subjects had higher levels of total cholesterol, triglyceride, apoproteins A-I and B and PAI-I activity than normotensive subjects. On univariate analysis, diuretics decreased total and HDL-cholesterol and apoproteins A-I and B; those differences remained after multivariate adjustment. Treatment with beta-blockers decreased total and HDL-cholesterol, apoprotein A-I and LpA-I, and this effect remained after multivariate adjustment. Calcium channel blockers decreased total cholesterol and apoproteins A-I and B; those differences remained significant after multivariate adjustment. ACE inhibitors decreased total cholesterol, triglycerides, apoprotein B and LpE:B; and this effect remained after multivariate adjustment. Analysis of the subjects on monotherapy showed beta-blockers to decrease total cholesterol and HDL parameters and angiotensin-converting enzyme (ACE) inhibitors to decrease low-density lipoprotein (LDL)-related parameters, while no effect was found for the other antihypertensive drugs.Conclusions: Hypertensive status is associated with an unfavourable lipid and haemostatic profile in middle-aged men. Antihypertensive treatment with beta-blockers decreases HDL parameters, whereas treatment with ACE inhibitors appears to decrease total cholesterol and LDL-related parameters.     

Myocardial dysfunction and abnormal left ventricular exercise response in autonomic diabetic patients

In diabetic patients, the pathophysiologic mechanisms of exercise-induced left ventricular (LV) dysfunction remain controversial. In this study, the role of myocardial contractility recruitment in determining an abnormal LV response to isometric or dynamic exercise has been investigated in 14 diabetic patients with autonomic dysfunction. Ischemic heat disease was excluded by the absence of LV wall motion abnormalities induced by isotonic and isometric exercise and by coronary angiography. Left ventricular and myocardial function were studied at rest, and during isometric and isotonic exercise, by two-dimensional echocardiography; moreover, recruitment of an inotropic reserve was assessed by postextra-systolic potentiation at rest and at peak handgrip. An abnormal response of LV ejection fraction to isometric (9/14) or to dynamic (8/14) exercise was frequent in study patients. In these patients, baseline myocardial contractility was normal, and the significant increase in ejection fraction by postextrasystolic potentiation indicated a normal contractile reserve (65 ± 7% vs. 74 ± 6%, p=0.001). Nevertheless, the downward displacement of LV ejection fraction-systolic wall stress relationships during exercise suggests an inadequate increase in myocardial contractility. However, the abnormal ejection fraction at peak handgrip was completely reversed by postextrasystolic potentiation (67 ± 6% vs. 58.1 ± 10%, p=0.008), a potent inotropic stimulation independent of the integrity of adrenergic cardiac receptors. A defective inotropic recruitment, despite the presence of a normal LV contractile reserve, plays an important role in deexercise LV dysfunction in diabetic patients with autonomic neuropathy.     

Inadequate management of dyslipidaemic patients in France. Results of the Odyssée study

The objective of this study was to compare the results of the management of dyslipidaemic patients in the community with the objectives fixed by the AFSSAPS recommendations. An observational epidemiological study was set up among 4 000 general practitioners and 527 cardiologists. This study included 22 323 patients (average age 60.6 years) affected by a documented primary dyslipidaemia. The average number of associated risk factors, according to the AFSSAPS criteria, was 1.8. The prevalence of secondary prevention in patients was 17.5%. More than 80% of patients were being treated by a lipid lowering agent (fibrate or statin) combined or not with lifestyle guidelines. In primary prevention, although the target levels of LDL-C fixed by the AFSSAPS were attained in 94.4% and 82.6% respectively for patients with no other risk factor or with one associated risk factor, the objectives were reached in only 55.4% of patients with two other risk factors and in 29.6% of patients with more than two other risk factors. In secondary prevention, the AFSSAPS objectives were attained in only 45.2% of patients. Following this lipid result, 34.8% of patients underwent therapeutic adjustment, principally the use of medication in the patients receiving lifestyle advice or reinforcement of pharmacological treatment. This study underlines the inadequate management in France of dyslipidaemic patients in the community.     

Nerve stimulator for regional anaesthesia procedures with automatic interactive closed-loop control

Abstract

Peripheral nerve stimulators have widespread among anaesthesiologists and remain a popular technique. However, in commercial devices, the user has to manually adjust stimulus intensity. Thus, the aim of this study is to propose a method that allows automating the current intensity control. An earlier nerve stimulator prototype was modified to add an accelerometer and an sEMG module. The choice of these two sensors is aimed at the possibility of observing the mechanical and electrical responses of the muscle contraction evoked by the stimulation. The tests were performed in two steps. The first step was to observe how the sensors behave during stimulation and muscle contraction. The second step was to implement a control algorithm and to validate the automation technique. Comparing the two methods, no significant differences were found on procedure time (manual: 12.5?±?2.3; automatic: 11.6?±?1.9; ρ?=0.380) and blockade latency time (manual: 11.6?±?1.1; automatic: 11.9?±?1.2; ρ?=0.524). Comparing needle-nerve distance in manual or automatic mode, no significant differences were found for 1.0?mA, 0.8?mA, 0.5?mA and 0.3?mA. We conclude that the technique for automating the current intensity update, using accelerometer and/or electromyography, is satisfactory. Furthermore, we conclude that the use of the accelerometer alone is sufficient for detection of muscle contraction.