87 research outputs found
Trends in yearly prevalence of third-generation cephalosporin and fluoroquinolone resistant Enterobacteriaceae infections and antimicrobial use in Spanish hospitals, Spain, 1999 to 2010
Escherichia coli, Klebsiella pneumoniae, and
Enterobacter spp. are a major cause of infections in
hospitalised patients. The aim of our study was to
evaluate rates and trends of resistance to third-generation
cephalosporins and fluoroquinolones in infected
patients, the trends in use for these antimicrobials,
and to assess the potential correlation between both
trends. The database of national point prevalence
study series of infections and antimicrobial use among
patients hospitalised in Spain over the period from
1999 to 2010 was analysed. On average 265 hospitals
and 60,000 patients were surveyed per year yielding
a total of 19,801 E. coli, 3,004 K. pneumoniae and
3,205 Enterobacter isolates. During the twelve years
period, we observed significant increases for the
use of fluoroquinolones (5.8%â10.2%, p<0.001), but
not for third-generation cephalosporins (6.4%â5.9%,
p=NS). Resistance to third-generation cephalosporins
increased significantly for E. coli (5%â15%, p<0.01)
and for K. pneumoniae infections (4%â21%, p<0.01)
but not for Enterobacter spp. (24%). Resistance to fluoroquinolones
increased significantly for E. coli (16%â
30%, p<0.01), for K. pneumoniae (5%â22%, p<0.01),
and for Enterobacter spp. (6%â15%, p<0.01). We found
strong correlations between the rate of fluoroquinolone
use and the resistance to fluoroquinolones,
third-generation cephalosporins, or co-resistance to
both, for E. coli (R=0.97, p<0.01, R=0.94, p<0.01, and
R=0.96, p<0.01, respectively), and for K. pneumoniae
(R=0.92, p<0.01, R=0.91, p<0.01, and R=0.92, p<0.01,
the use of third-generation cephalosporins and resistance
to any of the latter antimicrobials. No significant
correlations could be found for Enterobacter spp..
Knowledge of the trends in antimicrobial resistance
and use of antimicrobials in the hospitalised population
at the national level can help to develop prevention
strategiesSupported by the Fondo para la investigaciĂłn, Spanish
Ministry of Health, grant PI07/90255
Maximum Flux Transition Paths of Conformational Change
Given two metastable states A and B of a biomolecular system, the problem is
to calculate the likely paths of the transition from A to B. Such a calculation
is more informative and more manageable if done for a reduced set of collective
variables chosen so that paths cluster in collective variable space. The
computational task becomes that of computing the "center" of such a cluster. A
good way to define the center employs the concept of a committor, whose value
at a point in collective variable space is the probability that a trajectory at
that point will reach B before A. The committor "foliates" the transition
region into a set of isocommittors. The maximum flux transition path is defined
as a path that crosses each isocommittor at a point which (locally) has the
highest crossing rate of distinct reactive trajectories. (This path is
different from that of the MaxFlux method of Huo and Straub.) It is argued that
such a path is nearer to an ideal path than others that have been proposed with
the possible exception of the finite-temperature string method path. To make
the calculation tractable, three approximations are introduced, yielding a path
that is the solution of a nonsingular two-point boundary-value problem. For
such a problem, one can construct a simple and robust algorithm. One such
algorithm and its performance is discussed.Comment: 7 figure
Dietary inflammatory index and anthropometric measures of obesity in a population sample at high cardiovascular risk from the PREDIMED (PREvenciĂłn con DIeta MEDiterrĂĄnea) trial
The dietary inflammatory index (DII) is a new tool to assess the inflammatory potential of the diet. In the present study, we aimed to determine the association between the DII and BMI, waist circumference and waist:height ratio (WHtR). We conducted a cross-sectional study of 7236 participants recruited into the PREvención con DIeta MEDiterrånea trial. Information from a validated 137-item FFQ was used to calculate energy, food and nutrient intakes. A fourteen-item dietary screener was used to assess adherence to the Mediterranean diet (MeDiet). Sex-specific multivariable linear regression models were fitted to estimate differences (and 95 % CI) in BMI, waist circumference and WHtR across the quintiles of the DII. All nutrient intakes, healthy foods and adherence to the MeDiet were higher in the quintile with the lowest DII score (more anti-inflammatory values) except for intakes of animal protein, saturated fat and monounsaturated fat. Although an inverse association between the DII and total energy was apparent, the DII was associated with higher average BMI, waist circumference and WHtR after adjusting for known risk factors. The adjusted difference in the WHtR for women and men between the highest and lowest quintiles of the DII was 1·60 % (95 % CI 0·87, 2·33) and 1·04 % (95 % CI 0·35, 1·74), respectively. Pro-inflammatory scores remained associated with obesity after controlling for the effect that adherence to a MeDiet had on inflammation. In conclusion, the present study shows a direct association between the DII and indices of obesity, and supports the hypothesis that diet may have a role in the development of obesity through inflammatory modulation mechanisms
Dietary inflammatory index and anthropometric measures of obesity in a population sample at high cardiovascular risk from the PREDIMED trial
The dietary inflammatory index (DII) is a new tool to assess the inflammatory potential of diet. We aimed to determine the association between the DII and body mass index (BMI), waist circumference and waist to height ratio (WHtR). We conducted a cross-sectional study of 7,236 participants recruited into the PREDIMED trial (PREvenciĂłn con DIeta MEDiterrĂĄnea). Information from a validated 137-item food frequency questionnaire was used to calculate energy, foods and nutrients. A 14-item dietary screener was used to assess adherence to the Mediterranean diet (MeDiet). Sex-specific multivariable linear regression models were fitted to estimate differences (and 95% confidence intervals) in BMI, waist circumference and WHtR across quintiles of the DII. All nutrient intakes, healthy foods and adherence to the MeDiet were higher in the quintile with lowest DII score (more anti-inflammatory values) except for animal protein, saturated and monounsaturated fat. Though an inverse association between DII and total energy was apparent, the DII was associated with higher average BMI, waist circumference and WHtR after adjusting for known risk factors. The adjusted difference in WHtR for women and men between the highest and lowest quintile of DII was 1.60% (95% CI 0.87-2.33) and 1.04% (95% CI 0.35-1.74), respectively. Pro-inflammatory scores remained associated with obesity after controlling for the effect that adherence to a MeDiet had on inflammation. In conclusion, this study shows a direct association between the DII and indices of obesity and supports the hypothesis that diet may have a role in the development of obesity through inflammatory modulation mechanisms
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Dietary αâLinolenic Acid, Marine Ïâ3 Fatty Acids, and Mortality in a Population With High Fish Consumption: Findings From the PREvenciĂłn con DIeta MEDiterrĂĄnea (PREDIMED) Study
Background: Epidemiological evidence suggests a cardioprotective role of αâlinolenic acid (ALA), a plantâderived Ïâ3 fatty acid. It is unclear whether ALA is beneficial in a background of high marine Ïâ3 fatty acids (longâchain nâ3 polyunsaturated fatty acids) intake. In persons at high cardiovascular risk from Spain, a country in which fish consumption is customarily high, we investigated whether meeting the International Society for the Study of Fatty Acids and Lipids recommendation for dietary ALA (0.7% of total energy) at baseline was related to allâcause and cardiovascular disease mortality. We also examined the effect of meeting the society's recommendation for longâchain nâ3 polyunsaturated fatty acids (â„500 mg/day). Methods and Results: We longitudinally evaluated 7202 participants in the PREvenciĂłn con DIeta MEDiterrĂĄnea (PREDIMED) trial. Multivariableâadjusted Cox regression models were fitted to estimate hazard ratios. ALA intake correlated to walnut consumption (r=0.94). During a 5.9ây followâup, 431 deaths occurred (104 cardiovascular disease, 55 coronary heart disease, 32 sudden cardiac death, 25 stroke). The hazard ratios for meeting ALA recommendation (n=1615, 22.4%) were 0.72 (95% CI 0.56â0.92) for allâcause mortality and 0.95 (95% CI 0.58â1.57) for fatal cardiovascular disease. The hazard ratios for meeting the recommendation for longâchain nâ3 polyunsaturated fatty acids (n=5452, 75.7%) were 0.84 (95% CI 0.67â1.05) for allâcause mortality, 0.61 (95% CI 0.39â0.96) for fatal cardiovascular disease, 0.54 (95% CI 0.29â0.99) for fatal coronary heart disease, and 0.49 (95% CI 0.22â1.01) for sudden cardiac death. The highest reduction in allâcause mortality occurred in participants meeting both recommendations (hazard ratio 0.63 [95% CI 0.45â0.87]). Conclusions: In participants without prior cardiovascular disease and high fish consumption, dietary ALA, supplied mainly by walnuts and olive oil, relates inversely to allâcause mortality, whereas protection from cardiac mortality is limited to fishâderived longâchain nâ3 polyunsaturated fatty acids. Clinical Trial Registration URL: http://www.Controlled-trials.com/. Unique identifier: ISRCTN35739639
Exploring PAZ/3âČ-overhang interaction to improve siRNA specificity: a combined experimental and modeling study
The understanding of the dynamical and mechanistic aspects that lie behind siRNA-based gene regulation is a requisite to boost the performance of siRNA therapeutics. A systematic experimental and computational study on the 3âČ-overhang structural requirements for the design of more specific and potent siRNA molecules was carried out using nucleotide analogues differing in structural parameters, such as sugar constraint, lack of nucleobase, distance between the phosphodiester backbone and nucleobase, enantioselectivity, and steric hindrance. The results established a set of rules governing the siRNA-mediated silencing, indicating that the thermodynamic stability of the 5âČ-end is a crucial determinant for antisense-mediated silencing but is not sufficient to avoid sense-mediated silencing. Both theoretical and experimental approaches consistently evidence the existence of a direct connection between the PAZ/3âČ-overhang binding affinity and siRNAâs potency and specificity. An overall description of the systems is thus achieved by atomistic simulations and free energy calculations that allow us to propose a robust and self-contained procedure for studying the factors implied in PAZ/3âČ-overhang siRNA interactions. A higher RNAi activity is associated with a moderate-to-strong PAZ/3âČ-overhang binding. Contrarily, lower binding energies compromise siRNA potency, increase specificity, and favor siRNA downregulation by Ago2-independent mechanisms. This work provides in-depth details for the design of powerful and safe synthetic nucleotide analogues for substitution at the 3âČ-overhang, enabling some of the intrinsic siRNA disadvantages to be overcome
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