Highlights • Prevalence of genitourinary syndrome of menopause (GSM) was investigated in a multicentric national study. • Prevalence ranged from 65% to 84% in women 1–6 years after menopause. • ...Vaginal dryness and objective assessment of dry vagina were the most common findings. • Most of the women did not have a previous diagnosis of GSM. • Most of the women with a previous diagnosis received some kind of treatment but almost all still had GSM.
•Static and dynamic long-term structural monitoring data of a monumental building are analyzed.•Their correlation with environmental data is explored and physical meanings are proposed.•The findings ...are applied in a structural health monitoring and damage detection scenario.
Within the context of civil structures, a monitoring system supported by an intelligent diagnostic features extraction allows to keep under observation the overall health state of a building. In most cases, the diagnostic features are influenced by Environmental and Operational Variations (EOVs) which cause fluctuations that can be confused with the appearance of damage, or worse, hide it. A useful strategy to get rid of those confounding effects consists in modelling the structural behaviour of the system, considering and predicting these harmless and reversible fluctuations. However, a model approximates a much more complex reality and therefore it is based on a reasonable number of components whose selection might turn out complicated. In this research, a large amount of heterogeneous field data is systematically analysed to investigate which have the greatest influence on structural behavior and therefore, could contribute for modelling the behaviour of a historic building for Structural Health Monitoring (SHM) purpose. Environmental data, measurements of static sensors and modal natural frequencies collected in more than 10 years are scanned and crossed in order to discover any correlations. The analysis of these time series, treated with mathematical and statistical tools, has led to some mechanical interpretations of the observed behaviour of the system, i.e. the Sanctuary of Vicoforte, a monumental Italian church which houses the largest masonry oval dome in the world. The results obtained, especially in terms of correlations between different factors affecting measurements, are deemed relevant in the practice of long-term monitoring of cultural heritage and existing buildings in general.
Background
Cow's milk allergy (CMA) is one of the most common food allergies in children. Epigenetic mechanisms have been suggested to play a role in CMA pathogenesis. We have shown that DNA ...methylation of Th1/Th2 cytokine genes and FoxP3 affects CMA disease course. Preliminary evidence suggests that also the miRNome could be implicated in the pathogenesis of allergy. Main study outcome was to comparatively evaluate miRNome in children with CMA and in healthy controls.
Methods
Peripheral blood mononuclear cells were obtained from children aged 4‐18 months: 10 CMA patients, 9 CMA patients who outgrew CMA, and 11 healthy controls. Small RNA libraries were sequenced using a next‐generation sequencing‐based approach. Functional assessment of IL‐4 expression was also performed.
Results
Among the miRNAs differently expressed, 2 were upregulated and 14 were downregulated in children with active CMA compared to healthy controls. miR‐193a‐5p resulted the most downregulated miRNA in children with active CMA compared to healthy controls. The predicted targets of miR‐193a‐5p resulted upregulated in CMA patients compared to healthy controls. Peripheral blood CD4+ T cells transfected with a miR193a‐5 inhibitor showed a significant upregulation of IL‐4 mRNA and its protein expression. Children who outgrew CMA showed miRNA‐193a‐5p level, and its related targets expression, similar to that observed in healthy controls.
Conclusions
Our results suggest that miR‐193a‐5p is a post‐transcriptional regulator of IL‐4 expression and could have a role in IgE‐mediated CMA. This miRNA could be a novel diagnostic and therapeutic target for this common form of food allergy in childhood.
Zucchini fruit is susceptible to develop chilling injuries (CI) when stored at low temperature. In this study, the effects of a preconditioning treatment during cold storage and its relation with the ...physiological response to chilling tolerance have been investigated. The commercial variety Sinatra, whose fruit are very sensitive to cold storage, has been used. After harvest, fruit were kept at 4°C or preconditioned during 48 h at 15°C before cold storage. Weight loss, electrolyte leakage and lipid peroxidation were lower in preconditioned at the end of storage time, and CI index was significantly reduced in preconditioned compared to control fruit. The preconditioning treatment improved the energy status of the fruit increasing the pool of ATP, and maintaining the energy charge. The preconditioned fruit improved their antioxidant status with lower H2O2 content and induction of ascorbate peroxidase (APX) and catalase (CAT) activities. A reduction in putrescine was detected in preconditioned fruit along with a lower expression of arginine decarboxylase (ADC) and ornithine decarboxylase (ODC) and a rise in activity of diamine oxidase (DAO). The concentrations of glutamate and γ‐aminobutyrate (GABA) were lower during preconditioning, while that of proline was higher. In summary, preconditioning treatment induces chilling tolerance in zucchini fruit triggering a defence‐response against oxidative stress and increasing ATP pool and proline content.
The potential to accurately quantify epidermal growth factor receptor (EGFR) mutations in plasma from non–small-cell lung cancer patients would enable more rapid and more frequent analyses to assess ...disease status; however, the utility of such analyses for clinical purposes has only recently started to explore.
Plasma samples were obtained from 69 patients with EGFR-mutated tumors and 21 negative control cases. EGFR mutations in plasma were analyzed by a standardized allele-specific polymerase chain reaction (PCR) test and ultra-deep next-generation sequencing (NGS). A semiquantitative index (SQI) was derived from dilutions of known EGFR mutation copy numbers. Clinical responses were evaluated by Response Evaluation Criteria in Solid Tumors 1.1 criteria and expressed as percent tumor shrinkage.
The sensitivity and specificity of the PCR test and NGS assay in plasma versus tissue were 72% versus 100% and 74% versus 100%, respectively. Quantitative indices by the PCR test and NGS were significantly correlated (p < 0.001). EGFR testing at baseline and serially at 4 to 60 days during tyrosine kinase inhibitor therapy revealed a progressive decrease in SQI, starting from day 4, in 95% of cases. The rate of SQI decrease correlated with percent tumor shrinkage at 2 months (p < 0.0001); at 14 days, it was more than 50% in 70% of patients (rapid responders). In two patients with slow response, an early increase in the circulating levels of the T790M mutation was observed. No early T790M mutations were seen in plasma samples of rapid responders.
Quantification of EGFR mutations from plasma with a standardized PCR test is feasible. To our knowledge, this is the first study showing a strong correlation between the EGFR SQI in the first days of treatment and clinical response with relevant implications for patient management.
•Exogenous SA alleviates salt stress in M. sativa–S. meliloti symbiosis.•SA improves growth and photosynthesis of alfalfa plants under salt stress.•Negative effect of NaCl on nitrogen fixation and ...nodule biomass was reduced by SA.•Antioxidants enzymes were induced by SA pretreatments in nodules of M. sativa.•The accumulation of polyamines in response to salinity was prevented by SA.
In this work we have investigated the contribution of pretreatment with 0.1 and 0.5mM salicylic acid (SA) to the protection against salt stress in root nodules of Medicago sativa in symbiosis with Sinorhizobium meliloti. SA alleviated the inhibition induced by salinity in the plant growth and photosynthetic capacity of M. sativa–S. meliloti symbiosis. In addition, SA prevented the inhibition of the nitrogen fixation capacity under salt stress since nodule biomass was not affected by salinity in SA pretreated plants. Antioxidant enzymes peroxidase (POX), superoxide dismutase (SOD), ascorbate peroxidase (APX), dehidroascorbate reductase (DHAR) and glutathione reductase (GR), key in the main pathway that scavenges H2O2 in plants, were induced by SA pretreatments which suggest that SA may participate in the redox balance in root nodules under salt stress. Catalase activity (CAT) was inhibited around 40% by SA which could be behind the increase of H2O2 detected in nodules of plants pretreated with SA. The accumulation of polyamines (PAs) synthesized in response to salinity was prevented by SA which together with the induction of 1-aminocyclopropane-l-carboxylic acid (ACC) content suggest the prevalence of the ethylene signaling pathway induced by SA in detriment of the synthesis of PAs. In conclusion, SA alleviated the negative effect of salt stress in the M. sativa–S. meliloti symbiosis through the increased level of nodule biomass and the induction of the nodular antioxidant metabolism under salt stress. The H2O2 accumulation and the PAs inhibition induced by SA in nodules of M. sativa suggest that SA activates a hypersensitive response dependent on ethylene.
•NO exogenous improved zucchini fruit quality during postharvest cold storage.•NO enhanced the antioxidant capacity during cold storage in Zucchini fruit.•NO treatment increased S-nitrosylation of ...proteins in zucchini fruit exocarp.
Nitric oxide (NO), a major signalling molecule with various physiological functions in plants, participates in many responses to abiotic disorders such as cold stress. Chilling injury (CI) is the most costly postharvest problem in zucchini fruit (Cucurbita pepo L.), since it diminishes market acceptability and shelf life. This study investigates the effect of NO treatment on zucchini fruit during postharvest cold storage. Fruit were dipped in an aqueous solution of sodium nitroprusside (SNP; 25, 100, and 500 μM) as a NO donor and in potassium ferricyanide (a structural analogue of SNP) and distilled water, both used as controls and responding the same during postharvest cold storage. The results showed that the application of 25 μM SNP treatment reduced weight loss and CI in zucchini fruit during cold storage. S-nitrosylated proteins detected in the exocarp of NO-treated fruit were more abundant than in non-treated fruit. The application of SNP improved the quality of zucchini fruit stored at 4 °C, with a reduction of weight loss, electrolyte leakage, content of malondialdehyde and H2O2, and delayed loss of firmness during cold storage. NO-treated fruit showed a higher activity of superoxide dismutase, ascorbate peroxidase, glutathione reductase, and phenylalanine ammonia lyase during the first days of cold storage. Total antioxidant capacity was higher in the NO-treated fruit during the first days of cold storage, supported also by higher concentrations of phenols. NO appeared to play a regulatory role in the antioxidant balance in zucchini fruit, maintaining the cellular redox homeostasis and thus modulating ROS toxicity, thereby improving fruit quality during cold conservation.
ABSTRACT We present results from γ-ray observations of the Coma cluster incorporating six years of Fermi-LAT data and the newly released "Pass 8" event-level analysis. Our analysis of the region ...reveals low-significance residual structures within the virial radius of the cluster that are too faint for a detailed investigation with the current data. Using a likelihood approach that is free of assumptions on the spectral shape we derive upper limits on the γ-ray flux that is expected from energetic particle interactions in the cluster. We also consider a benchmark spatial and spectral template motivated by models in which the observed radio halo is mostly emission by secondary electrons. In this case, the median expected and observed upper limits for the flux above 100 are 1.7 × 10−9 ph cm−2 s−1 and 5.2 × 10−9 ph cm−2 s−1 respectively (the latter corresponds to residual emission at the level of 1.8 ). These bounds are comparable to or higher than predicted levels of hadronic gamma-ray emission in cosmic-ray (CR) models with or without reacceleration of secondary electrons, although direct comparisons are sensitive to assumptions regarding the origin and propagation mode of CRs and magnetic field properties. The minimal expected γ-ray flux from radio and star-forming galaxies within the Coma cluster is roughly an order of magnitude below the median sensitivity of our analysis.
15-40% of non-small cell lung cancer (NSCLC) patients harbor epidermal growth factor receptor (EGFR)-sensitizing mutations. Tyrosine kinase inhibitors (TKIs) provide significant clinical benefit in ...this population, yet all patients will ultimately progress. Liquid biopsy can reliably identify somatic tumor-associated EGFR mutations in plasma. This study aimed to assess the feasibility and value of the quantitative assessment of EGFR driver mutations in plasma in EGFR-mutated NSCLC patients treated with EGFR-TKIs as a tool to evaluate therapeutic response to TKIs and monitor for disease progression. The study included 136 patients with tissue biopsy-confirmed EGFR-sensitizing, mutation-positive lung adenocarcinoma with plasma collected prior to TKI treatment and at least two post-initiation TKI treatment/follow-up blood samples. Plasma samples were tested with the cobas® EGFR Mutation Test v2 (cobas EGFR Test), and semi-quantitative index (SQI) values for each identified mutation were reported by the assay software. The most common baseline EGFR mutations detected in tissue were L858R (53.7%) and exon 19 deletion (39.7%). Plasma cell-free DNA analysis detected EGFR mutations in 74% of the baseline samples. Objective response rate by RECIST 1.1 was achieved in 72% of patients, while 93% had a molecular response (defined as disappearance of the EGFR mutation from plasma). 83% of patients had molecular progression (MP; 1.5X SQI increase or new T790M mutation), and 82% who had a clinical response had clinical progression. On average, MP occurred 42 days prior to clinical progression. Patients who progressed while on first-line TKI showed MP of the original EGFR-sensitizing mutations prior to the emergence of a T790M mutation, which was detected in 27% of the EGFR plasma-positive patients. Longitudinal monitoring of EGFR mutational load in plasma is feasible and can predict both response and clinical progression in EGFR-mutated NSCLC patients treated with EGFR-TKIs, as well as detect treatment-emergent EGFR mutations.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK