Broad-spectrum antimicrobial activity of quaternary ammonium surfactants (QAS) makes them attractive and cheap topical prophylactic options for sexually transmitted infections and perinatal ...vertically transmitted urogenital infections. Although attributed to their high affinity for biological membranes, the mechanisms behind QAS microbicidal activity are not fully understood. We evaluated how QAS structure affects antimicrobial activity and whether this can be exploited for use in prophylaxis of bacterial infections.
Acute toxicity of QAS to in vitro models of human epithelial cells and bacteria were compared to identify selective and potent bactericidal agents. Bacterial cell viability, membrane integrity, cell cycle and metabolism were evaluated to establish the mechanisms involved in selective toxicity of QAS.
QAS toxicity normalized relative to surfactant critical micelle concentration showed n-dodecylpyridinium bromide (C12PB) to be the most effective, with a therapeutic index of ∼10 for an MDR strain of Escherichia coli and >20 for Neisseria gonorrhoeae after 1 h of exposure. Three modes of QAS antibacterial action were identified: impairment of bacterial energetics and cell division at low concentrations; membrane permeabilization and electron transport inhibition at intermediate doses; and disruption of bacterial membranes and cell lysis at concentrations close to the critical micelle concentration. In contrast, toxicity to mammalian cells occurs at higher concentrations and, as we previously reported, results primarily from mitochondrial dysfunction and apoptotic cell death.
Our data show that short chain (C12) n-alkyl pyridinium bromides have a sufficiently large therapeutic window to be good microbicide candidates.
The influence of climate variation on the availability of water resources was analyzed in the headwaters of the Tagus River basin using two drought indices, the standardized precipitation index (SPI) ...and the standardized precipitation evapotranspiration index (SPEI). This basin is highly regulated and strategic, and contains two hyperannual reservoirs that are the origin of the water supply system for Mediterranean areas of southeast Spain. The indices confirmed that drought conditions have prevailed in the headwaters of the Tagus River since the 1970s. The responses in river discharge and reservoir storage were slightly higher when based on the SPEI rather than the SPI, which indicates that although precipitation had a major role in explaining temporal variability in the analyzed parameters, the influence of temperature was not negligible. Moreover, the greatest response in hydrological variables was evident over longer timescales of the climatic drought indices. Although the effect of climate variability on water resources was substantial during the analyzed period, we also showed a major change in hydrological–climatic relationships in regulated systems including reservoir storage and outflow. These were closely related to changes in external demand following commencement of the water transfer system to the Júcar and Segura basins after the 1980s. The marked reduction in water availability in the basin, which is related to more frequent droughts, contrasts with the amount of water transferred, which shows a clear upward trend associated with increasing water demand in the Mediterranean basin.
•Fermentative strategy and varietal factors modulated the chemical profile of wines.•The chemometric approach identified potential markers for each fermentative strategy.•EBBAs and cinnamates ...highlighted as markers of sequential fermentations.•2-Phenyl acetate and stone fruit highlighted as markers of spontaneous fermentations.•The fermentative strategies contributed to variability and quality of white wines.
This study evaluates the impact on two varietal white wines from ‘Chardonnay’ and ‘Verdejo’ cultivars of different fermentative strategies: inoculation with Saccharomyces cerevisiae yeast (CT), sequential inoculation (Torulaspora delbrueckii/Saccharomyces cerevisiae) (SI), and spontaneous fermentation (SP). The wines’ chemical composition was characterized by oenological parameters, organic acids, metals, major volatile compounds, ester compounds and sensory analyses. The fermentative strategy (CT, SI and SP) was found to be a key factor for assessing different styles of white wines. SI wines showed enhanced ‘mature fruit’ nuances and a chemical profile characterized by higher content of ethyl propanoate, ethyl isobutyrate and ethyl dihydrocinnamate. Meanwhile, the SP wines presented enhanced “stone fruit” nuances possible related to the higher contents of 2-phenyl acetate and isobutyl acetate. After a chemometric approach the above esters were identified as the markers of each fermentative strategy, independently of the variety.
Lipopolysaccharide-binding protein (LBP) is a 65-kDa acute-phase protein present in blood at high concentrations, known to be derived from the liver. We aimed to gain insights into the association of ...circulating LBP with insulin resistance in humans and mice. METHODS, DESIGN AND MEASUREMENTS: We studied the cross-sectional (n=222) and weight loss-induced (n=34) associations of LBP (enzyme-linked immunosorbent assay) with inflammatory and metabolic parameters (including minimal model-measured insulin sensitivity), and the effects of high-fat diet (HFD), metformin and genetic insulin sensitization (glucagon-like peptide 1 receptor knockout model) in mice.
Circulating LBP concentration was significantly increased in subjects with type 2 diabetes and dramatically increased in subjects with morbid obesity. LBP was significantly associated with insulin sensitivity and different inflammatory markers and decreased after weight loss (22.2 ± 5.8 vs 16.2 ± 9.3 μg ml(-1), P<0.0001) in association with changes in body mass index and insulin sensitivity. Circulating LBP concentration was increased in HFD mice, whereas decreased in glucagon-like peptide 1 receptor knockout mice (significantly more insulin sensitive than wild-type mice) and after metformin administration.
LBP is an inflammatory marker associated with obesity-related insulin resistance.
Continuous Fibre Reinforced Thermoplastic Composites (CFRTPCs) are becoming alternative materials to replace the conventional thermosetting polymers and metals due to excellent mechanical ...performance, recycling and potential used in lightweight structures. Fused deposition modelling (FDM) is a promising additive manufacturing technology and an alternative of conventional processes for the fabrication of CFRTPCs due to its ability to build functional parts having complex geometries. The mechanical properties of a built part depend on several process parameters. The aim of this study is to characterize the effect of build orientation, layer thickness and fibre volume content on the mechanical performance of 3D printed continuous fibre reinforced composites components manufactured by a desktop 3D printer. Tensile and three-point bending tests are carried out to determine the mechanical response of the printed specimens. SEM images of fractured surfaces are evaluated to determine the effects of process parameters on failure modes.
It is observed that the effect of layer thickness of nylon samples on the mechanical performance is marginally significant. In addition, continuous fibre reinforced samples show higher strength and stiffness values than unreinforced ones. The results show that carbon fibre reinforced composites exhibit the best mechanical performance with higher stiffness and flat samples exhibit higher values of strength and stiffness than on-edge samples. Additionally, the results show that strength and stiffness increase as fibre volume content increases in most cases but, conversely, the level of increment in mechanical performance is moderate with continued rise in fibre content, particularly in the case of Kevlar® and glass fibres, due to weak bonding between the fibre/nylon layers as well as the presence of increased levels of defects. Finally, the practicality of the results is assessed by testing an evaluation structure.
BACKGROUNDSpain has been one of the countries most affected by the COVID-19 pandemic. OBJECTIVETo create a registry of patients with COVID-19 hospitalized in Spain, in order to improve our knowledge ...of the clinical, diagnostic, therapeutic, and prognostic aspects of this disease. METHODSA multicentre retrospective cohort study, including consecutive patients hospitalized with confirmed COVID-19 throughout Spain. Epidemiological and clinical data, additional tests at admission and at seven days, treatments administered, and progress at 30 days of hospitalization were collected from electronic medical records. RESULTSUp to June 30th 2020, 15,111 patients from 150 hospitals were included. Their median age was 69.4 years (range: 18-102 years) and 57.2% were male. Prevalences of hypertension, dyslipidemia, and diabetes mellitus were 50.9%, 39.7%, and 19.4%, respectively. The most frequent symptoms were fever (84.2%) and cough (73.5%). High values of ferritin (73.5%), lactate dehydrogenase (73.9%), and D-dimer (63.8%), as well as lymphopenia (52.8%), were frequent. The most used antiviral drugs were hydroxychloroquine (85.6%) and lopinavir/ritonavir (61.4%); 33.1% developed respiratory distress. Overall mortality rate was 21.0%, with a marked increase with age (50-59 years: 4.7%, 60-69 years: 10.5%, 70-79 years: 26.9%, ≥80 years: 46.0%). CONCLUSIONSThe SEMI-COVID-19 Network provides data on the clinical characteristics of patients with COVID-19 hospitalized in Spain. Patients with COVID-19 hospitalized in Spain are mostly severe cases, as one in three patients developed respiratory distress and one in five patients died. These findings confirm a close relationship between advanced age and mortality.
We present the ioChem-BD platform (www.iochem-bd.org) as a multiheaded tool aimed to manage large volumes of quantum chemistry results from a diverse group of already common simulation packages. The ...platform has an extensible structure. The key modules managing the main tasks are to (i) upload of output files from common computational chemistry packages, (ii) extract meaningful data from the results, and (iii) generate output summaries in user-friendly formats. A heavy use of the Chemical Mark-up Language (CML) is made in the intermediate files used by ioChem-BD. From them and using XSL techniques, we manipulate and transform such chemical data sets to fulfill researchers’ needs in the form of HTML5 reports, supporting information, and other research media.
Continuous fibre reinforced thermoplastic composites (CFRTPCs) are becoming more significant in industrial applications due to their inherit advantages such as excellent mechanical performance, ...potential use in lightweight structures and being recyclable. Fused deposition modelling (FDM) is a promising additive manufacturing technology and an alternative to conventional processes for the fabrication of CFRTPCs due to its ability to build functional parts having complex geometries. However, a major concern affecting the efficient use of 3D printed composites is their weak interlaminar bonding performance compared to conventional pre-preg composites. The aim of this study is to evaluate the effect of layer thickness and fibre volume content on the interlaminar bonding performance of 3D printed continuous carbon, glass and Kevlar® fibre reinforced nylon composites manufactured by FDM technique. Short beam shear tests were carried out to determine interlaminar shear strength (ILSS). SEM images and cross-sectional micrographs were examined to assess failure mechanics of the different configurations.
It was observed that the effect of layer thickness of nylon samples on the interlaminar shear performance was marginally significance. ILSS values decrease as layer thickness increase due to higher porosity. In addition, continuous fibre reinforced samples show higher ILSS values than unreinforced ones but, conversely, the level of increase in ILSS is moderate with continued increase in fibre content, particularly in the case of Kevlar® fibre. Carbon fibre reinforced composites exhibit the best interlaminar shear performance with higher stiffness. On the other hand, Kevlar® fibre reinforced composites have the lowest interlaminar shear performance due to poor wettability of Kevlar® fibre bundles by the nylon, leading to extensive delamination. Finally, the results obtained demonstrate that it is still a challenge to increase shear performance of 3D printed composites with respect to common pre-preg materials. Nevertheless, ILSS values exhibited by 3D printed composites are significantly higher than the usual 3D printed thermoplastics.
•The effect of process parameters on the ILSS performance of continuous fibre reinforced composites is investigated.•Short beam shear tests are performed to obtain interlaminar shear strength (ILSS).•In the case of nylon samples, ILSS values decrease as layer thickness increases due to higher porosity.•Reinforced samples show higher ILSS values than nylon ones, but the level of increase is moderate with fibre content.•Carbon fibre reinforced samples exhibit the best interlaminar shear performance with higher stiffness.
Many controversies regarding the association of liver miRNAs with obesity and nonalcoholic fatty liver diseases (NAFLD) call for additional validations. This study sought to investigate variations in ...genes and hepatic miRNAs in a sample of obese patients with or without NAFLD and human hepatocytes (HH).
A total of 60 non-consecutive obese women following bariatric surgery were recruited. Subjects were classified as NAFLD (n=17), borderline (n=24) and controls (n=19) with normal enzymatic profile, liver histology and ultrasound assessments. Profiling of 744 miRNAs was performed in 8 obese women with no sign of hepatic disease and 11 NAFLD patients. Additional validation and expression of genes related to de novo fatty acid (FA) biosynthesis, uptake, transport and β-oxidation; glucose metabolism, and inflammation was tested in the extended sample. Induction of NAFLD-related genes and miRNAs was examined in HepG2 cells and primary HH treated with palmitic acid (PA), a combination of palmitate and oleic acid, or high glucose, and insulin (HG) mimicking insulin resistance in NAFLD.
In the discovery sample, 14 miRNAs were associated with NAFLD. Analyses in the extended sample confirmed decreased miR-139-5p, miR-30b-5p, miR-122-5p and miR-422a, and increased miR-146b-5p in obese subjects with NAFLD. Multiple linear regression analyses disclosed that NAFLD contributed independently to explain miR-139-5p (P=0.005), miR-30b-5p (P=0.005), miR-122-5p (P=0.021), miR-422a (P=0.007) and miR-146a (P=0.033) expression variance after controlling for confounders. Decreased miR-122-5p in liver was associated with impaired FA usage. Expression of inflammatory and macrophage-related genes was opposite to decreased miR-30b-5p, miR-139-5p and miR-422a, whereas increased miR-146b-5p was associated with FABP4 and decreased glucose metabolism and FA mobilization. In partial agreement, PA (but not HG) led to decreased miR-139-5p, miR-30b-5p, miR-422a and miR-146a in vitro, in parallel with increased lipogenesis and FA transport, decreased glucose metabolism and diminished FA oxidation.
This study confirms decreased liver glucose and lipid metabolism but increased FA biosynthesis coupled with changes in five unique miRNAs in obese patients with NAFLD.
Context. During the period between 15 September 2014 and 4 February 2015, the Rosetta spacecraft accomplished the circular orbit phase around the nucleus of comet 67P/Churyumov-Gerasimenko (67P). The ...Grain Impact Analyzer and Dust Accumulator (GIADA) onboard Rosetta monitored the 67P coma dust environment for the entire period. Aims. We aim to describe the dust spatial distribution in the coma of comet 67P by means of in situ measurements. We determine dynamical and physical properties of cometary dust particles to support the study of the production process and dust environment modification. Methods. We analyzed GIADA data with respect to the observation geometry and heliocentric distance to describe the coma dust spatial distribution of 67P, to monitor its activity, and to retrieve information on active areas present on its nucleus. We combined GIADA detection information with calibration activity to distinguish different types of particles that populate the coma of 67P: compact particles and fluffy porous aggregates. By means of particle dynamical parameters measured by GIADA, we studied the dust acceleration region. Results. GIADA was able to distinguish different types of particles populating the coma of 67P: compact particles and fluffy porous aggregates. Most of the compact particle detections occurred at latitudes and longitudes where the spacecraft was in view of the comet’s neck region of the nucleus, the so-called Hapi region. This resulted in an oscillation of the compact particle abundance with respect to the spacecraft position and a global increase as the comet moved from 3.36 to 2.43 AU heliocentric distance. The speed of these particles, having masses from 10-10 to 10-7 kg, ranged from 0.3 to 12.2 m s-1. The variation of particle mass and speed distribution with respect to the distance from the nucleus gave indications of the dust acceleration region. The influence of solar radiation pressure on micron and submicron particles was studied. The integrated dust mass flux collected from the Sun direction, that is, particles reflected by solar radiation pressure, was three times higher than the flux coming directly from the comet nucleus. The awakening 67P comet shows a strong dust flux anisotropy, confirming what was suggested by on-ground dust coma observations performed in 2008.
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