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.
•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.
Aims
To test in an outpatient setting the safety and efficacy of continuous subcutaneous insulin infusion (CSII) driven by a modular model predictive control (MMPC) algorithm informed by continuous ...glucose monitoring (CGM) measurement.
Methods
13 patients affected by type 1 diabetes participated to a non‐randomized outpatient 42‐h experiment that included two evening meals and overnight periods (in short, dinner & night periods). CSII was patient‐driven during dinner & night period 1 and MMPC‐driven during dinner&night period 2. The study was conducted in hotels, where patients could move around freely. A CGM system (G4 Platinum; Dexcom Inc., San Diego, CA, USA) and insulin pump (AccuChek Combo; Roche Diagnostics, Mannheim, Germany) were connected wirelessly to a smartphone‐based platform (DiAs, Diabetes Assistant; University of Virginia, Charlottesville, VA, USA) during both periods.
Results
A significantly lower percentage of time spent with glucose levels <3.9 mmol/l was achieved in period 2 compared with period 1: 1.96 ± 4.56% vs 12.76 ± 15.84% (mean ± standard deviation, p < 0.01), together with a greater percentage of time spent in the 3.9–10 mmol/l target range: 83.56 ± 14.02% vs 62.43 ± 29.03% (p = 0.04). In addition, restricting the analysis to the overnight phases, a lower percentage of time spent with glucose levels <3.9 mmol/l (1.92 ± 4.89% vs 12.7 ± 19.75%; p = 0.03) was combined with a greater percentage of time spent in 3.9–10 mmol/l target range in period 2 compared with period 1 (92.16 ± 8.03% vs 63.97 ± 2.73%; p = 0.01). Average glucose levels were similar during both periods.
Conclusions
The results suggest that MMPC managed by a wearable system is safe and effective during evening meal and overnight. Its sustained use during this period is currently being tested in an ongoing randomized 2‐month study.
Zucchini fruit is susceptible to chilling injury (CI), but the response to low storage temperature is cultivar dependent. Previous reports about the response of zucchini fruit to chilling storage ...have been focused on the physiology and biochemistry of this process, with little information about the molecular mechanisms underlying it. In this work, we present a comprehensive analysis of transcriptomic changes that take place after cold storage in zucchini fruit of two commercial cultivars with contrasting response to chilling stress.
RNA-Seq analysis was conducted in exocarp of fruit at harvest and after 14 days of storage at 4 and 20 °C. Differential expressed genes (DEGs) were obtained comparing fruit stored at 4 °C with their control at 20 °C, and then specific and common up and down-regulated DEGs of each cultivar were identified. Functional analysis of these DEGs identified similarities between the response of zucchini fruit to low temperature and other stresses, with an important number of GO terms related to biotic and abiotic stresses overrepresented in both cultivars. This study also revealed several molecular mechanisms that could be related to chilling tolerance, since they were up-regulated in cv. Natura (CI tolerant) or down-regulated in cv. Sinatra (CI sensitive). These mechanisms were mainly those related to carbohydrate and energy metabolism, transcription, signal transduction, and protein transport and degradation. Among DEGs belonging to these pathways, we selected candidate genes that could regulate or promote chilling tolerance in zucchini fruit including the transcription factors MYB76-like, ZAT10-like, DELLA protein GAIP, and AP2/ERF domain-containing protein.
This study provides a broader understanding of the important mechanisms and processes related to coping with low temperature stress in zucchini fruit and allowed the identification of some candidate genes that may be involved in the acquisition of chilling tolerance in this crop. These genes will be the basis of future studies aimed to identify markers involved in cold tolerance and aid in zucchini breeding programs.
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