Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) allows a fast and reliable bacterial identification from culture plates. Direct analysis of clinical ...samples may increase its usefulness in samples in which a fast identification of microorganisms can guide empirical treatment, such as blood cultures (BC). Three hundred and thirty BC, reported as positive by the automated BC incubation device, were processed by conventional methods for BC processing, and by a fast method based on direct MALDI-TOF MS. Three hundred and eighteen of them yield growth on culture plates, and 12 were false positive. The MALDI-TOF MS-based method reported that no peaks were found, or the absence of a reliable identification profile, in all these false positive BC. No mixed cultures were found. Among these 318 BC, we isolated 61 Gram-negatives (GN), 239 Gram-positives (GP) and 18 fungi. Microorganism identifications in GN were coincident with conventional identification, at the species level, in 83.3% of BC and, at the genus level, in 96.6%. In GP, identifications were coincident with conventional identification in 31.8% of BC at the species level, and in 64.8% at the genus level. Fungaemia was not reliably detected by MALDI-TOF. In 18 BC positive for Candida species (eight C. albicans, nine C. parapsilosis and one C. tropicalis), no microorganisms were identified at the species level, and only one (5.6%) was detected at the genus level. The results of the present study show that this fast, MALDI-TOF MS-based method allows bacterial identification directly from presumptively positive BC in a short time (<30 min), with a high accuracy, especially when GN bacteria are involved.
Palbociclib plus endocrine therapy (ET) is the standard treatment of hormone receptor-positive and human epidermal growth factor receptor 2-negative, metastatic breast cancer (MBC). However, its ...efficacy has not been compared with that of chemotherapy in a phase III trial.
PEARL is a multicentre, phase III randomised study in which patients with aromatase inhibitor (AI)-resistant MBC were included in two consecutive cohorts. In cohort 1, patients were randomised 1 : 1 to palbociclib plus exemestane or capecitabine. On discovering new evidence about estrogen receptor-1 (ESR1) mutations inducing resistance to AIs, the trial was amended to include cohort 2, in which patients were randomised 1 : 1 between palbociclib plus fulvestrant and capecitabine. The stratification criteria were disease site, prior sensitivity to ET, prior chemotherapy for MBC, and country of origin. Co-primary endpoints were progression-free survival (PFS) in cohort 2 and in wild-type ESR1 patients (cohort 1 + cohort 2). ESR1 hotspot mutations were analysed in baseline circulating tumour DNA.
From March 2014 to July 2018, 296 and 305 patients were included in cohort 1 and cohort 2, respectively. Palbociclib plus ET was not superior to capecitabine in both cohort 2 median PFS: 7.5 versus 10.0 months; adjusted hazard ratio (aHR): 1.13; 95% confidence interval (CI): 0.85-1.50 and wild-type ESR1 patients (median PFS: 8.0 versus 10.6 months; aHR: 1.11; 95% CI: 0.87-1.41). The most frequent grade 3-4 toxicities with palbociclib plus exemestane, palbociclib plus fulvestrant and capecitabine, respectively, were neutropenia (57.4%, 55.7% and 5.5%), hand/foot syndrome (0%, 0% and 23.5%), and diarrhoea (1.3%, 1.3% and 7.6%). Palbociclib plus ET offered better quality of life (aHR for time to deterioration of global health status: 0.67; 95% CI: 0.53-0.85).
There was no statistical superiority of palbociclib plus ET over capecitabine with respect to PFS in MBC patients resistant to AIs. Palbociclib plus ET showed a better safety profile and improved quality of life.
•Palbociclib plus fulvestrant did not provide evidence of PFS superiority over capecitabine in MBC patients resistant to AIs.•Palbociclib plus ET did not show PFS superiority over capecitabine in wild-type ESR1 MBC patients resistant to AIs.•Palbociclib plus ET was better tolerated and offered better quality of life than capecitabine.
► Wine is associated with reduced chronic diseases. ► Resveratrol, hydroxytyrosol and melatonin are compounds naturally present in wine. ► The effect of these molecules on health is reviewed.
Regular ...moderate wine consumption is often associated with reduced morbidity and mortality from a variety of chronic diseases in which inflammation is the root cause. This review is focused on three of the numerous bioactive compounds present in wine: resveratrol, hydroxytyrosol and melatonin. Resveratrol and hydroxytyrosol are polyphenols. Melatonin, recently described in wine, is an indoleamine. Their structures, concentrations in wine, bioavailability, pharmacokinetic and health promoting properties are reviewed. Resveratrol seems to be one of the most promising compounds due to its bioactivity, with wine being the main source of resveratrol in diet. Hydroxytyrosol, which its main source in diet is olive oil has been also found in both red and white wine in considerable amounts. Melatonin has been found in wine in low amounts. However, both high bioactivity and bioavailability have been attributed to it. They show antioxidant, cardioprotective, anticancer, antidiabetic, neuroprotective and antiaging activities. However, human studies are still in the initial stages and therefore further studies are needed.
An evaluation of a multiplex PCR assay (Bruce-ladder) was performed in seven laboratories using 625 Brucella strains from different animal and geographical origins. This robust test can differentiate ...in a single step all of the classical Brucella species, including those found in marine mammals and the S19, RB51, and Rev.1 vaccine strains.
The rising costs of fishmeal worldwide promote great research effort aimed to find alternative and renewable ingredients for aquafeeds. In the last years considerable attention has been paid to the ...use of algae as a potential ingredient for fish feeds. The objective of this work was to evaluate the effects of the microalgae Scenedesmus almeriensis incorporated to diets intended to feed sea bream (Sparus aurata) juveniles in a 45-day trial. Growth, body composition, and intestinal functionality of fish were studied. Microalgae meal was tested in triplicate at different inclusion levels (0%, 12%, 20%, 25% and 39%). At the end of the trial, individual body weight was recorded for evaluation of growth and nutrient utilization, and biological samples were obtained for proximate analysis, determination of digestive enzyme activities, intestinal histology, and microvilli morphological evaluation. Results indicated that S. almeriensis did not cause negative effects on fish growth or nutrient utilization efficiency. Growth rate and protein utilization in fish fed on a diet with 20% Scenedesmus meal tended to be higher, although not significantly different from those fed on control diet. None of the treatments caused adverse effects on body composition. Fish fed 12% S. almeriensis showed higher trypsin than animals fed on control diet. Leucine-aminopeptidase and alkaline phosphatase activities showed a quadratic response with increasing levels of Scenedesmus biomass. Ultrastructural study revealed that the dietary inclusion of algal biomass, especially at 20% level, significantly increased the absorptive capacity of intestinal mucosa in both the anterior and posterior intestinal regions. This study confirmed the usefulness of S. almeriensis to partially replace fishmeal in practical diets for gilthead sea bream juveniles.
•The use of Scenedesmus meal did not affect fish growth and nutrient utilization.•The dietary inclusion of Scenedesmus biomass did not affect muscle composition.•The level of intestinal enzyme activities was increased in Scenedesmus-fed sea bream.•Scenedesmus almeriensis biomass may be useful to enhance gut functionality in fish.•S. almeriensis can partially replace fishmeal in diets for sea bream juveniles.
Abstract
We present a detailed prompt emission and early optical afterglow analysis of the two very-high-energy (VHE) detected bursts GRB 201015A and GRB 201216C, and their comparison with a subset ...of similar bursts. Time-resolved spectral analysis of multistructured GRB 201216C using the Bayesian binning algorithm revealed that during the entire duration of the burst, the low-energy spectral index (
α
pt
) remained below the limit of the synchrotron line of death. However, statistically some of the bins supported the additional thermal component. Additionally, the evolution of spectral parameters showed that both the peak energy (
E
p
) and
α
pt
tracked the flux. These results were further strengthened using the values of the physical parameters obtained by synchrotron modeling of the data. Our earliest optical observations of both bursts using the F/Photometric Robotic Atmospheric Monitor Observatorio del Roque de los Muchachos and Burst Observer and Optical Transient Exploring System robotic telescopes displayed a smooth bump in their early optical light curves, consistent with the onset of the afterglow due to synchrotron emission from an external forward shock. Using the observed optical peak, we constrained the initial bulk Lorentz factors of GRB 201015A and GRB 201216C to Γ
0
= 204 and Γ
0
= 310, respectively. The present early optical observations are the earliest known observations constraining outflow parameters and our analysis indicate that VHE detected bursts could have a diverse range of observed luminosity within the detectable redshift range of present VHE facilities.
Summary
Background
We have observed an increase in hepatotoxicity (DILI) reporting related to the use of anabolic androgenic steroids (AAS) for bodybuilding.
Aim
To characterise phenotype ...presentation, outcome and severity of AAS DILI.
Methods
Data on 25 cases of AAS DILI reported to the Spanish (20) and Latin‐American (5) DILI Registries were collated and compared with previously published cases.
Results
AAS DILI increased from representing less than 1% of the total cases in the Spanish DILI Registry in the period 2001–2009 to 8% in 2010–2013. Young men (mean age 32 years), requiring hospitalisation, hepatocellular injury and jaundice were predominating features among the AAS cases. AAS DILI caused significantly higher bilirubin values independent of type of damage when compared to other drug classes (P = 0.001). Furthermore, the cholestatic AAS cases presented significantly higher mean peak bilirubin (P = 0.029) and serum creatinine values (P = 0.0002), compared to the hepatocellular cases. In a logistic regression model, the interaction between peak bilirubin values and cholestatic damage was associated with the development of AAS‐induced acute kidney impairment (AKI) OR 1.26 (95% CI: 1.035–1.526); P = 0.021, with 21.5 ×ULN being the best bilirubin cut‐off point for predicting AKI risk (AUCROC 0.92). No fatalities occurred.
Conclusions
Illicit recreational AAS use is a growing cause of reported DILI that can lead to severe hepatic and renal injury. AAS DILI is associated with a distinct phenotype, characterised by considerable bilirubin elevations independent of type of damage. Although hepatocellular injury predominates, acute kidney injury develops in cholestatic cases with pronounced jaundice.
Boltzmann showed that in spite of momentum and energy redistribution through collisions, a rarefied gas confined in a isotropic harmonic trapping potential does not reach equilibrium; it evolves ...instead into a breathing mode where density, velocity, and temperature oscillate. This counterintuitive prediction is upheld by cold atoms experiments. Yet, are the breathers eternal solutions of the dynamics even in an idealized and isolated system? We show by a combination of hydrodynamic arguments and molecular dynamics simulations that an original dissipative mechanism is at work, where the minute and often neglected bulk viscosity eventually thermalizes the system, which thus reaches equilibrium.
Improvements in magnetic resonance imaging (MRI), total mesorectal excision (TME) surgery, and the use of (chemo)radiotherapy (CRT) have improved local control of rectal cancer; however, we have been ...unable to eradicate local recurrence (LR). Even in the face of TME and negative resection margins (R0), a significant proportion of patients with enlarged lateral lymph nodes (LLNs) suffer from lateral LR (LLR). Japanese studies suggest that the addition of an LLN dissection (LLND) could reduce LLR. This multicenter pooled analysis aims to ascertain whether LLNs actually pose a problem and whether LLND results in fewer LLRs.
Data from 1,216 consecutive patients with cT3/T4 rectal cancers up to 8 cm from the anal verge who underwent surgery in a 5-year period were collected. LLND was performed in 142 patients (12%). MRIs were re-evaluated with a standardized protocol to assess LLN features.
On pretreatment MRI, 703 patients (58%) had visible LLN, and 192 (16%) had a short axis of at least 7 mm. One hundred eight patients developed LR (5-year LR rate, 10.0%), of which 59 (54%) were LLRs (5-year LLR rate, 5.5%). After multivariable analyses, LLNs with a short axis of at least 7 mm resulted in a significantly higher risk of LLR (hazard ratio, 2.060; P = .045) compared with LLNs of less than 7 mm. In patients with LLNs at least 7 mm, (C)RT plus TME plus LLND resulted in a 5-year LLR of 5.7%, which was significantly lower than that in patients who underwent (C)RT plus TME (5-year LLR, 19.5%; P = .042).
LLR is still a significant problem after (C)RT plus TME in LLNs with a short axis at least 7 mm on pretreatment MRI. The addition of LLND results in a significantly lower LLR rate.
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