Malaria PCR Detection in Cambodian Low-Transmission Settings: Dried Blood Spots versus Venous Blood Samples

In the context of malaria elimination, novel strategies for detecting very low malaria parasite densities in asymptomatic individuals are needed. One of the major limitations of the malaria parasite detection methods is the volume of blood samples being analyzed. The objective of the study was to compare the diagnostic accuracy of a malaria polymerase chain reaction assay, from dried blood spots (DBS, 5 μL) and different volumes of venous blood (50 μL, 200 μL, and 1 mL). The limit of detection of the polymerase chain reaction assay, using calibrated Plasmodium falciparum blood dilutions, showed that venous blood samples (50 μL, 200 μL, 1 mL) combined with Qiagen extraction methods gave a similar threshold of 100 parasites/mL, ∼100-fold lower than 5 μL DBS/Instagene method. On a set of 521 field samples, collected in two different transmission areas in northern Cambodia, no significant difference in the proportion of parasite carriers, regardless of the methods used was found. The 5 μL DBS method missed 27% of the samples detected by the 1 mL venous blood method, but most of the missed parasites carriers were infected by Plasmodium vivax (84%). The remaining missed P. falciparum parasite carriers (N = 3) were only detected in high-transmission areas.     

Activity of Ceftaroline against Enterococcus faecium PBP5

The opportunistic human pathogen Enterococcus faecium overproduces the low-affinity PBP5. In clinical strains, mutations in PBP5 further reduce its acylation rate by β-lactams. Previous studies have reported that ceftaroline had poor inhibitory activity against β-lactam-resistant E. faecium strains. In this study, we show that ceftaroline exhibits killing activity against our laboratory-derived ampicillin-resistant E. faecium mutant that overproduces a wild-type PBP5 and that ceftaroline inactivates PBP5 much faster than benzylpenicillin and faster than ceftobiprole.     

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.     

Effect of the linolenic acid content of the mother's diet on the polyunsaturated fatty acid composition of subcellular fractions in brain development in the rat

In order to determine precisely the respective roles of linolenic acid and linoleic acid in the maternal diet on rat brain subcellular fractions during development, we used two diets with different percentages of linolenic acid (18:3 n-3). The animals were fed peanut oil (group A) or soybean oil (group B) during pregnancy and throughout lactation. Nature and amount of essential fatty acids had no incidence on saturated and monounsaturated fatty acid distributions in myelin, synaptosomal, mitochondrial and microsomal fractions. In adult rats, all subcellular fractions are marked by an increase of n-3 fatty acid and a decrease of n-6 fatty acid levels in group B compared to group A. In 15-day-old animals, on the contrary, only the synaptosomal fractions are significantly affected by the diet. Independent of diet, brain development is marked by a decrease of n-6 fatty acids in all subcellular fractions; on the other hand, the n-3 fatty acid level is increased in the synaptosomal and mitochondrial fractions, and decrease in the myelin and microsomal fractions. The sum of (n-3 + n-6) fatty acids remains constant in group B and in group A in all subcellular fractions. Finally, under our experimental conditions, we found no marked effect of diet composition upon linoleic acid conversion to arachidonic acid; only the delta 4-7-10-13-16-docosapentaenoic acid (22:5 n-6) level decreased in group B. delta 7-10-13-16-19-Docosapentaenoic acid (22:5 n-3) seemed to be a better substrate for delta 4 desaturase than delta 7-10-13-16-docosatetraenoic acid (22:4 n-6).     

Pooled analysis of higher versus lower blood pressure targets for vasopressor therapy septic and vasodilatory shock

Purpose

Guidelines for shock recommend mean arterial pressure (MAP) targets for vasopressor therapy of at least 65 mmHg and, until recently, suggested that patients with underlying chronic hypertension and atherosclerosis may benefit from higher targets. We conducted an individual patient-data meta-analysis of recent trials to determine if patient variables modify the effect of different MAP targets.

Methods

We searched the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials for randomized controlled trials of higher versus lower blood pressure targets for vasopressor therapy in adult patients in shock (until November 2017). After obtaining individual patient data from both eligible trials, we used a modified version of the Cochrane Collaboration’s instrument to assess the risk of bias of included trials. The primary outcome was 28-day mortality.

Results

Included trials enrolled 894 patients. Controlling for trial and site, the OR for 28-day mortality for the higher versus lower MAP targets was 1.15 (95% CI 0.87–1.52). Treatment effect varied by duration of vasopressors before randomization (interaction p = 0.017), but not by chronic hypertension, congestive heart failure or age. Risk of death increased in higher MAP groups among patients on vasopressors > 6 h before randomization (OR 3.00, 95% CI 1.33–6.74).

Conclusions

Targeting higher blood pressure targets may increase mortality in patients who have been treated with vasopressors for more than 6 h. Lower blood pressure targets were not associated with patient-important adverse events in any subgroup, including chronically hypertensive patients.

     

Design of melt-recyclable poly(ε-caprolactone)-based supramolecular shape-memory nanocomposites

A novel poly(epsilon-caprolactone) (PCL) supramolecular network exhibiting shape-memory behavior was successfully constructed with pendant UPy units that are highly able to dimerize. The dynamic network was obtained by a simple and versatile strategy consisting of chain-extension reaction between α,ω-dihydroxyoligoPCL and hydroxylated UPy units in the presence of hexamethylene diisocyanate as a coupling agent and further intermolecular dimerization of the UPy along the polyurethane backbone. ¹H NMR analyses confirmed the dynamic features of the system, and DMTA in tensile mode was investigated to assess the SMP properties. Recyclability was also assessed by taking advantage of these supramolecular networks. Further addition of cellulose nanocrystals into the polymer network enabled adjustment of the extent of the net-points and therefore the SMP features. As confirmed by dispersion tests in solution and SEM observations, these bio-based nanofillers were homogeneously distributed in the network via supramolecular interaction between the hydroxyl groups present on their surface and UPy moieties along the polyurethane backbone. Thus, the here developed nanomaterials might reveal applicability in areas where a combination of SMP and biocompatibility is needed.

Novel melt-recyclable poly(ε-caprolactone)/cellulose nanocrystals supramolecular nanocomposite networks with shape-memory behavior have been successfully constructed by playing with UPy chemistry.