Candida auris is an emerging multidrug-resistant fungus that causes a wide range of symptoms. We report finding 17 cases of C. auris infection that were originally misclassified but correctly ...identified 27.5 days later on average. Patients with a delayed diagnosis of C. auris had a 30-day mortality rate of 35.2%.
There are few prospective studies with sufficient duration in time to evaluate clinical and antibiotic resistance impact of antibiotic stewardship programs (ASP). This is a descriptive study between ...January 2012 and December 2017, pre-post intervention. A meropenem ASP was initiated in January 2015; in patients who started treatment with meropenem, an infectious disease physician performed treatment recommendations to prescribers. Prospective information was collected to evaluate adequacy of meropenem prescription to local guidelines and to compare results between cases with accepted or rejected intervention. Analysis was performed to verify variables associated with intervention acceptance and with any significant change in meropenem consumption, hospital-acquired multidrug-resistant (MDR) bloodstream infections (BSIs), and 30-day all-cause crude death in MDR BSIs. Adequacy of meropenem prescription and de-escalation from meropenem treatment to narrower-spectrum antibiotic improved progressively over time, after ASP implementation (
p
< 0.001). Interventions on prescription were performed in 330 (38.7%) patients without meropenem justified treatment; in 269, intervention was accepted and in 61 not. Intervention acceptance was associated with shorter duration of treatment, cost, and inpatient days (
p
< 0.05); intervention rejection was not associated with severity of patient. During the period 2015–2017, meropenem consumption decreased compared with 2012–2014 (rate ratio RR 0.67; 95% CI 0.58–0.77,
p
< 0.001). Also decreased were hospital-acquired MDR BSI rate (RR 0.63; 95% CI 0.38–1.02,
p
= 0,048) and 30-day all-cause crude death in MDR BSIs (RR 0.45; 95% CI 0.14–1.24,
p
= 0.096), coinciding in time with ASP start-up. The decrease and better use of meropenem achieved had a sustained clinical, economic, and ecological impact, reducing costs and mortality of hospital-acquired MDR BSIs.
Background and purpose
Cytomegalovirus (CMV) infection has recently been associated with a lower multiple sclerosis (MS) susceptibility, although it remains controversial whether it has a protective ...role or is merely an epiphenomenon related to westernization and early‐life viral infections. We aimed to evaluate whether CMV serostatus may differ in patients with early MS as compared with patients with non‐early MS, analyzing the putative association of this virus with MS clinical course and humoral immune responses against other herpesviruses.
Methods
Multicentric analysis was undertaken of 310 patients with MS (early MS, disease duration ≤5 years, n = 127) and controls (n = 155), evaluating specific humoral responses to CMV, Epstein–Barr virus and human herpesvirus‐6, as well as T‐cell and natural killer (NK)‐cell immunophenotypes.
Results
Cytomegalovirus seroprevalence in early MS was lower than in non‐early MS or controls (P < 0.01), being independently associated with disease duration (odds ratio, 1.04; 95% confidence interval, 1.01–1.08, P < 0.05). CMV+ patients with MS displayed increased proportions of differentiated T‐cells (CD27−CD28−, CD57+, LILRB1+) and NKG2C+ NK‐cells, which were associated with a lower disability in early MS (P < 0.05). CMV+ patients with early MS had an age‐related decline in serum anti‐EBNA‐1 antibodies (P < 0.01), but no CMV‐related differences in anti‐human herpesvirus‐6 humoral responses.
Conclusions
Low CMV seroprevalence was observed in patients with early MS. Modification of MS risk attributed to CMV might be related to the induction of differentiated T‐cell and NK‐cell subsets and/or modulation of Epstein–Barr virus‐specific immune responses at early stages of the disease.
Aims
To investigate the cytotoxicity and bioactivity of several pulpotomy materials: Biodentine (Septodont, Saint‐Maur‐des‐Fosses, France) MTA (Angelus, Londrina, PR, Brazil), Theracal LC (Bisco ...Inc., Schamburg, IL, USA) and IRM (Dentsply DeTrey GmbH, Konstanz, Germany), after contact with stem cells isolated from human exfoliated primary teeth (SHEDs).
Methodology
SHEDs were cultured in the presence of the eluates of various pulpotomy materials for 24, 48 and 72 h. Cell viability was determined by mitochondrial dehydrogenase enzymatic (MTT) assay. Apoptosis and changes in cell phenotype were evaluated by flow cytometry. Also, an in vitro scratch wound‐healing assay was used to determine their effects on cell migration. To assess cell morphology and attachment to the different pulpotomy materials, SHEDs were directly seeded onto the material surfaces and analysed by scanning electron microscopy (SEM). Finally, the deposition of a calcified matrix in presence of these materials was verified by Alizarin Red staining. Statistical analysis was performed with analysis of variance and Bonferroni or Tukey post‐test (α = 0.05).
Results
Cell viability in the presence of Biodentine eluates was significantly higher to that obtained using complete medium alone (control; P < 0.01) and was also significantly higher than using MTA Angelus from 48 h of incubation (P < 0.01). However, Theracal LC and IRM were associated with low rates of cell viability (P < 0.001). Similar results were obtained in an apoptosis assay. In addition, SHEDs maintained their mesenchymal phenotype in all conditions although their capacity to migrate was higher in the presence of Biodentine. SEM studies revealed a suitable proliferation rate, cell spreading and attachment, especially when using Biodentine and MTA Angelus discs. Finally, Biodentine eluates significantly induced calcified matrix deposition from 7 days of culture (P < 0.01).
Conclusions
Biodentine exhibited better cytocompatibility and bioactivity than MTA Angelus, Theracal LC and IRM.
Summary
Background
Vascular malformations are a complex pathology with few treatment options. In previously published studies, oral sirolimus (rapamycin) has shown promising results in the treatment ...of low‐flow vascular malformations, but its usefulness in high‐flow vascular malformations is controversial.
Aim
To evaluate the efficacy and safety of sirolimus for the treatment of high‐flow vascular malformations in real‐life practice.
Methods
In a unit specializing in vascular anomalies, patients treated with oral sirolimus for high‐flow vascular malformations were located by consulting the drug dispensations. Reviewing the electronic medical records, data on patient demographics, vascular malformation characteristics, treatments, toxicity and clinical course were collected and statistically analysed.
Results
Nine patients with vascular malformations were included: eight had arteriovenous malformation and one had arteriovenous fistula. Six of these malformations were isolated while three were part of a syndrome. Sirolimus was initiated at a dosage of 1–4 mg/day to be taken as a single dose. Partial response was observed in eight of the nine patients (88.9%) with high‐flow vascular malformation, while worsening was observed in the remaining patient. The treatment was well tolerated and at the most recent follow‐up, five patients remained on treatment with oral sirolimus.
Conclusion
Our results show that oral sirolimus is a well‐tolerated therapeutic option, with an excellent safety profile, which can be useful in the long‐term stabilization of patients with high‐flow vascular malformations. Single‐daily dosage may improve long‐term adherence to treatment without worsening its effectiveness.
Edging closer towards developing air and moisture compatible polar organometallic chemistry, the chemoselective and ultrafast addition of a range of aryllithium reagents to nitriles has been ...accomplished by using glycerol as a solvent, at ambient temperature in the presence of air, establishing a novel sustainable access to aromatic ketones. Addition reactions occur heterogeneously (“on glycerol conditions”), where the lack of solubility of the nitriles in glycerol and the ability of the latter to form strong intermolecular hydrogen bonds seem key to favouring nucleophilic addition over competitive hydrolysis. Remarkably, PhLi exhibits a greater resistance to hydrolysis working “on glycerol” conditions than “on water”. Introducing glycerol as a new solvent in organolithium chemistry unlocks a myriad of opportunities for developing more sustainable, air and moisture tolerant main‐group‐metal‐mediated organic synthesis.
Hooked on glycerol! Using glycerol as a sustainable and green reaction medium enables the efficient chemoselective addition of aryllithium reagents to nitriles at room temperature in air, edging closer towards reaching air and moisture compatible polar organometallic chemistry.
The aim of this work was to determine the role of saliva in wine aroma release by using static and dynamic headspace conditions. In the latter conditions, two different sampling points (t = 0 and t = ...10 min) corresponding with oral (25.5 °C) and postoral phases (36 °C) were monitored. Both methodologies were applied to reconstituted dearomatized white and red wines with different nonvolatile wine matrix compositions and a synthetic wine (without matrix effect). All of the wines had the same ethanol concentration and were spiked with a mixture of 45 aroma compounds covering a wide range of physicochemical characteristics at typical wine concentrations. Two types of saliva (human and artificial) or control samples (water) were added to the wines. The adequacy of the two headspace methodologies for the purposes of the study (repeatability, linear ranges, determination coefficients, etc.) was previously determined. After application of different chemometric analysis (ANOVA, LSD, PCA), results showed a significant effect of saliva on aroma release dependent on saliva type (differences between artificial and human) and on wine matrix using static headspace conditions. Red wines were more affected than white and synthetic wines by saliva, specifically human saliva, which provoked a reduction in aroma release for most of the assayed aroma compounds independent of their chemical structure. The application of dynamic headspace conditions using a saliva bioreactor at the two different sampling points (t = 0 and t = 10 min) showed a lesser but significant effect of saliva than matrix composition and a high influence of temperature (oral and postoral phases) on aroma release.
A new method to tag the barium daughter in the double-beta decay of ^{136}Xe is reported. Using the technique of single molecule fluorescent imaging (SMFI), individual barium dication (Ba^{++}) ...resolution at a transparent scanning surface is demonstrated. A single-step photobleach confirms the single ion interpretation. Individual ions are localized with superresolution (∼2 nm), and detected with a statistical significance of 12.9σ over backgrounds. This lays the foundation for a new and potentially background-free neutrinoless double-beta decay technology, based on SMFI coupled to high pressure xenon gas time projection chambers.
Summary
Light is pervasive in the leaf environment, creating opportunities for both plants and pathogens to cue into light as a signal to regulate plant‐microbe interactions. Light enhances plant ...defences and regulates opening of stomata, an entry point for foliar bacterial pathogens such as Pseudomonas syringae pv. tomato DC3000 (PsPto). The effect of light perception on gene expression and virulence was investigated in PsPto. Light induced genetic reprogramming in PsPto that entailed significant changes in stress tolerance and virulence. Blue light‐mediated up‐regulation of type three secretion system genes and red light‐mediated down‐regulation of coronatine biosynthesis genes. Cells exposed to white light, blue light or darkness before inoculation were more virulent when inoculated at dawn than dusk probably due to an enhanced entry through open stomata. Exposure to red light repressed coronatine biosynthesis genes which could lead to a reduced stomatal re‐opening and PsPto entry. Photoreceptor were required for the greater virulence of light‐treated and dark‐treated PsPto inoculated at dawn as compared to dusk, indicating that these proteins sense the absence of light and contribute to priming of virulence in the dark. These results support a model in which PsPto exploits light changes to maximize survival, entry and virulence on plants.
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