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INTRODUCTION: Olive oil is a widely recognized and appreciated food commodity, its quality and health benefits can be compromised when the oil goes through oxidative processes that may occur during production and storage. This study aimed to investigate the effects of the olive genotype on polar phenolic content after seven months of storage. METHODS: Oil produced from eight different olive cultivars (Leccino, Leccio del Corno, Moraiolo, Frantoio, Bianchera, Pendolino, Maurino, and Caninese) grown in southern Tuscany, Italy, were subjected to chemical analysis such as free fatty acids, peroxide value, K232 and K268, phenolics and UPLC-DAD at the beginning of the trial (Control) and seven months later (Stored). RESULTS AND CONCLUSIONS: Free fatty acids, peroxide values, K232 and K268, significantly increased, suggesting heightened hydrolysis and oxidation after storage. A cultivar effect was observed, with Leccino, Moraiolo, and Pendolino showing less susceptibility to oxidation (low differences between Control and Stored). In contrast, others (Bianchera and Caninese) are more affected (higher differences between Control and Stored). Phenolics analysis supports this observation, revealing that samples with higher resistance to oxidation exhibit elevated levels of hydroxytyrosol, tyrosol, vanillic acid, caffeic acid, p-coumaric acid, and ferulic acid. Principal Component Analysis highlights that Bianchera and Caninese cultivars correlate with rutin, tyrosol, and pinoresinol. As this research delves into the intricate relationship between genotype diversity, phenolic composition, and oxidative stability, a nuanced understanding emerges, shedding light on how different cultivars may present varying compositions and concentrations of phenols, ultimately influencing the oils resistance to the oxidation that occurred during storage.

Ozone (O3) is currently employed in wineries as a sanitizing agent and is used to control microbial growth and infection. This molecule decomposes spontaneously to oxygen upon application and the use of ozonated water can represent an alternative for the control of pathogens in the vineyard. Entire canopies of Vitis vinifera (cv Vermentino) plants have been sprayed throughout the vegetative growth with water saturated with O3 to assess the effects of these treatments in reducing the microorganism population, and to evaluate if and how the oxidative stress, induced in the plant by this strong oxidizing agent, affects fruit development, the activity of the cellular antioxidant system, and the production of aromas by the grape berries at ripening. Ozonated water treatments resulted in a partial control of microorganism population, especially considering fungi. Furthermore, the treatments induced a slight delay in the technological maturity of grapes, a significant increase in antioxidant capacity and changes of aroma profile of the grapes at harvest, with an accumulation of monoterpenes. In general, ozonized water treatments showed promising results and seem to be a feasible protocol to be applied in the vineyard in order to reduce the use of chemicals.

Some physiological processes in reproductive organs, if not controlled, can lead to crop loss even in the absence of environmental stress. These processes may occur pre- or post- harvest, and in diverse species and include abscission processes in cereal grain, e.g., shattering and in immature fruit, e.g., preharvest drop, preharvest sprouting of cereals, and postharvest senescence in fruit. Some of the molecular mechanisms and genetic determinants underlying these processes are now better detailed, making it possible to refine them by gene editing. Here, we discuss using advanced genomics to identify genetic determinants underlying crop physiological traits. Examples of improved phenotypes developed for preharvest problems are provided, and suggestions for reducing postharvest fruit losses by gene and promoter editing were made.

Objective Systemic sclerosis (SSc) is associated with an increased risk of cancer. We aimed to assess the prevalence of cancer in our cohort and to explore possible associations with clinical, immunological and treatment characteristics.Methods Our retrospective monocentric cohort study of patients with SSc recorded prevalent and incident cases of malignancy, including those diagnosed within 3 years of the SSc onset (defined as cancer-associated scleroderma) and sought associations with the clinical characteristics and the serum autoantibody profiling performed using RNA and protein immunoprecipitation, Western-blot, immunoblot and ELISA at the time of SSc diagnosis, prior to any specific treatment.Results Among 290 patients with SSc, the overall prevalence of cancer was 20%, with 8% of cases being cancer-associated scleroderma. Both conditions were more frequent in elderly patients and in patients with positive anti-Ro52 or anti-U3-RNP. Cancer-associated scleroderma was significantly more prevalent among patients negative for both anti-centromere (ACA) and anti-topoisomerase-1 (TOPO1) antibodies, especially in the case of diffuse SSc. Immunosuppressants were not significantly associated with cancer. Patients triple negative for ACA, TOPO1 and anti-RNA polymerase III antibodies had a significantly higher risk of breast cancer.Conclusions Cancer surveillance should be particularly careful in patients with diffuse SSc, increased age at disease onset and without classical SSc-related autoantibodies.

IntroductionOlive oil is a widely recognized and appreciated food commodity, its quality and health benefits can be compromised when the oil goes through oxidative processes that may occur during production and storage. This study aimed to investigate the effects of the olive genotype on polar phenolic content after seven months of storage.MethodsOil produced from eight different olive cultivars (Leccino, Leccio del Corno, Moraiolo, Frantoio, Bianchera, Pendolino, Maurino, and Caninese) grown in southern Tuscany, Italy, were subjected to chemical analysis such as free fatty acids, peroxide value, K232 and K268, phenolics and UPLC-DAD at the beginning of the trial (Control) and seven months later (Stored).Results and ConclusionsFree fatty acids, peroxide values, K232 and K268, significantly increased, suggesting heightened hydrolysis and oxidation after storage. A cultivar effect was observed, with Leccino, Moraiolo, and Pendolino showing less susceptibility to oxidation (low differences between Control and Stored). In contrast, others (Bianchera and Caninese) are more affected (higher differences between Control and Stored). Phenolics analysis supports this observation, revealing that samples with higher resistance to oxidation exhibit elevated levels of hydroxytyrosol, tyrosol, vanillic acid, caffeic acid, p-coumaric acid, and ferulic acid. Principal Component Analysis highlights that Bianchera and Caninese cultivars correlate with rutin, tyrosol, and pinoresinol. As this research delves into the intricate relationship between genotype diversity, phenolic composition, and oxidative stability, a nuanced understanding emerges, shedding light on how different cultivars may present varying compositions and concentrations of phenols, ultimately influencing the oil’s resistance to the oxidation that occurred during storage.

Objectives Vasoactive drugs have exhibited clinical efficacy in addressing pulmonary arterial hypertension, manifesting a significant reduction in morbidity and mortality. Pulmonary hypertension may complicate advanced interstitial lung disease (PH-ILD) and is associated with high rates of disability, hospitalisation due to cardiac and respiratory illnesses, and mortality. Prior management hinged on treating the underlying lung disease and comorbidities. However, the INCREASE trial of inhaled treprostinil in PH-ILD has demonstrated that PH-ILD can be effectively treated with vasoactive drugs.Methods This comprehensive systematic review examines the evidence for vasoactive drugs in the management of PH-ILD.Results A total of 1442 pubblications were screened, 11 RCTs were considered for quantitative synthesis. Unfortunately, the salient studies are limited by population heterogeneity, short-term follow-up and the selection of outcomes with uncertain clinical significance.Conclusions This systematic review underscores the necessity of establishing a precision medicine-oriented strategy, directed at uncovering and addressing the intricate cellular and molecular mechanisms that underlie the pathophysiology of PH-ILD.PROSPERO registration number CRD42023457482.

Abstract Background Olea europaea L. is a traditional tree crop of the Mediterranean basin with a worldwide economical high impact. Differently from other fruit tree species, little is known about the physiological and molecular basis of the olive fruit development and a few sequences of genes and gene products are available for olive in public databases. This study deals with the identification of large sets of differentially expressed genes in developing olive fruits and the subsequent computational annotation by means of different software. Results mRNA from fruits of the cv. Leccino sampled at three different stages [i.e., initial fruit set (stage 1), completed pit hardening (stage 2) and veraison (stage 3)] was used for the identification of differentially expressed genes putatively involved in main processes along fruit development. Four subtractive hybridization libraries were constructed: forward and reverse between stage 1 and 2 (libraries A and B), and 2 and 3 (libraries C and D). All sequenced clones (1,132 in total) were analyzed through BlastX against non-redundant NCBI databases and about 60% of them showed similarity to known proteins. A total of 89 out of 642 differentially expressed unique sequences was further investigated by Real-Time PCR, showing a validation of the SSH results as high as 69%. Library-specific cDNA repertories were annotated according to the three main vocabularies of the gene ontology (GO): cellular component, biological process and molecular function. BlastX analysis, GO terms mapping and annotation analysis were performed using the Blast2GO software, a research tool designed with the main purpose of enabling GO based data mining on sequence sets for which no GO annotation is yet available. Bioinformatic analysis pointed out a significantly different distribution of the annotated sequences for each GO category, when comparing the three fruit developmental stages. The olive fruit-specific transcriptome dataset was used to query all known KEGG (Kyoto Encyclopaedia of Genes and Genomes) metabolic pathways for characterizing and positioning retrieved EST records. The integration of the olive sequence datasets within the MapMan platform for microarray analysis allowed the identification of specific biosynthetic pathways useful for the definition of key functional categories in time course analyses for gene groups. Conclusion The bioinformatic annotation of all gene sequences was useful to shed light on metabolic pathways and transcriptional aspects related to carbohydrates, fatty acids, secondary metabolites, transcription factors and hormones as well as response to biotic and abiotic stresses throughout olive drupe development. These results represent a first step toward both functional genomics and systems biology research for understanding the gene functions and regulatory networks in olive fruit growth and ripening.

Vaccine hesitancy has been included among the top ten threats to global health by the World Health Organization. Pharmacists can play a pivotal role in removing the individual barrier to vaccination, because of the relationship of trust they have with citizens and their ease of access. The aim of this study was to examine the impact of a pharmacy-based intervention to support the 2019 influenza vaccination campaign conducted in the Carnia district through one-to-one counseling. We analyzed data collected by pharmacists between 22 October 2019 and 20 January 2020, and trends in vaccination adherence in the context of the Local Health Authority and the entire province of Udine since 2016. The results showed that 77.2% of people who had not received an influenza vaccination in the previous year changed their minds about vaccination after receiving counseling. The pharmacy-based intervention improved influenza vaccination adherence in the target district (+13.4%), even when compared to the neighboring district of Gemona or considering the data in the broader local and provincial context, and this effect was particularly pronounced among those aged 65 to 74 years (p < 0.01). Considering these findings, pharmacies should be more effectively involved in the provision of public health services aimed at improving accessibility, timeliness, and equity.

Consumers are more and more oriented towards the purchase of safer food and beverages, which is pushing the wine sector to find alternatives to the use of sulfur dioxide. Ozone (O3) is already applied in the wine industry to produce sulfur dioxide-free wines through the patented method Purovino®. The aim of this two-year study was that of evaluating whether the postharvest treatment of grapes with ozone affects volatile organic compounds (VOCs) and polyphenol profile in berries, and in turn, wine composition. Grape bunches (Vitis vinifera L.) of cv Sangiovese were fumigated overnight with gaseous ozone (max 20 g·h−1 with 6% w.w−1 of ozone) in a cold room at 4°C (±0.5). After treatment, grapes were processed into wine. In grapes, ozone treatments increased total polyphenol and flavonoid content and upregulated specific genes (phenylalanine ammonia lyase, VvPAL, flavanol synthase 1, and VvFLS1) involved in polyphenol biosynthesis. Wine obtained from ozone-treated grapes had higher flavanol content than the control. Fumigation only slightly affected the different VOC classes of grapes and wine, including aroma compounds derived from the lipoxygenase (LOX) pathway. Although a season-dependent effect was observed, results showed that postharvest ozone treatments applied to avoid the use of sulfur dioxide introduced limited but, in general, positive modifications to grape and wine composition. This information provides assurance to winemakers that the maintenance of wine quality and typicity will be guaranteed when using ozone treatments.

Abstract Introduction Determining the optimal timing for extubation can be challenging in the intensive care. In this study, we aim to identify predictors for extubation failure in critically ill patients with COVID-19. Methods We used highly granular data from 3464 adult critically ill COVID patients in the multicenter Dutch Data Warehouse, including demographics, clinical observations, medications, fluid balance, laboratory values, vital signs, and data from life support devices. All intubated patients with at least one extubation attempt were eligible for analysis. Transferred patients, patients admitted for less than 24 h, and patients still admitted at the time of data extraction were excluded. Potential predictors were selected by a team of intensive care physicians. The primary and secondary outcomes were extubation without reintubation or death within the next 7 days and within 48 h, respectively. We trained and validated multiple machine learning algorithms using fivefold nested cross-validation. Predictor importance was estimated using Shapley additive explanations, while cutoff values for the relative probability of failed extubation were estimated through partial dependence plots. Results A total of 883 patients were included in the model derivation. The reintubation rate was 13.4% within 48 h and 18.9% at day 7, with a mortality rate of 0.6% and 1.0% respectively. The grandient-boost model performed best (area under the curve of 0.70) and was used to calculate predictor importance. Ventilatory characteristics and settings were the most important predictors. More specifically, a controlled mode duration longer than 4 days, a last fraction of inspired oxygen higher than 35%, a mean tidal volume per kg ideal body weight above 8 ml/kg in the day before extubation, and a shorter duration in assisted mode (

Abstract Male breast cancer (MBC) is a rare disease. The few studies on MBC reported conflicting data regarding survival outcomes compared to women. This study has two objectives: to describe the characteristics of a single-cohort of MBC and to compare overall survival (OS) and disease-free survival (DFS) between men and women using the propensity score matching (PSM) analysis. We considered MBC patients (n = 40) diagnosed between January 2004 and May 2019. Clinical, pathological, oncological and follow-up data were analyzed. Univariate analysis was performed to determine the prognostic factors on OS and DFS for MBC. We selected female patients with BC (n = 2678). To minimize the effect of the imbalance of the prognostic factors between the two cohorts, the PSM method (1:3 ratio) was applied and differences in survival between the two groups were assessed. The average age of MBC patients was 73 years. The 5-year OS and DFS rates were 76.7% and 72.2% respectively. The prognostic factors that significantly influenced OS and DFS were tumor size and lymph node status. After the PSM, 5 year-OS was similar between MBC and FBC (72.9% vs 72.3%, p = 0.70) while we found a worse DFS for MBC (72.2% vs 91.4%, p = 0.03). Our data confirmed previous reported MBC characteristics: we found a higher risk of recurrence in MBC compared to FMC but similar OS. MBC and FMC are different entities and studies are needed to understand its epidemiology and guide its management.

The European Community has recently imposed considerable restrictions on the use of pesticides, with the establishment of a regulatory framework for the sustainable use of agro-chemicals. However, in the viticulture sector, the intensive use of chemical pesticides, as well as sulfur and copper, is often required. Recently, ozone has been proposed as a possible environmentally friendly tool for controlling the development of pests on vines. However, little is known about the parameters linked to the practical application of ozone for controlling grapevine pests and how it triggers plant defence mechanisms. The main aim of this preliminary study was to determine the concentration of ozone and exposure duration in a treatment for stimulating the expression of systemic acquired resistance (SAR)-related genes, without inducing toxic effects and affecting vine health. In the first trial, three different combinations of ozone concentration and duration of treatment were tested on potted grapevines: i) gaseous ozone at 300 ppb for 12 hours, ii) gaseous ozone at 100 ppb for 6 hours, and iii) gaseous ozone at 100 ppb for 3 hours. Based on the results of the first trial, the potted vines were treated with just 100 ppb for 3 hours in a second trial. Leaves at different developmental stages were sampled. The expression level of systemic acquired resistance-related genes was analysed 12 hours and 7 days after each treatment. Furthermore, physiological parameters and NIR spectra were analysed. Ozone induced a transient up-regulation (limited to 12 hours after the treatments) of chitinases, β-1,3-glucanase and glutathione-S-transferase. On the other hand, pathogen-related (PR) genes showed a more persistent over-expression. The ozone treatment selectively affected the stomatal conductance depending on the different ozone concentrations. Detected NIR spectra revealed significant structural changes in ozone-treated plants, especially in leaves exposed to higher concentrations of ozone. These results suggest that ozone is able to transiently stimulate the expression of some resistance-related genes even at low and non-toxic doses for the vine leaves.

Due to the greenhouse gas increase, grapes are often exposed to high temperatures in several growing areas especially during the final developmental stages, and this is particularly true when early ripening cultivars are harvested. This may cause undesirable effects on berry metabolism and composition and wine quality, particularly concerning the aroma profile. Harvesting at night or keeping the harvested grapes in cold rooms before vinification are empirical protocols applied in specific viticultural areas. To study the effects of decreasing berry temperature after harvest, white-skinned berries (cv Vermentino) were maintained at 4 or 10°C for 24 or 48 h before processing (pre-cooling). Control grapes were kept at 22°C. Grapes cooled at 10°C for 24 and 48 h resulted richer in polyphenols and showed a significant up-regulation of genes involved in polyphenols biosynthesis (i.e., VvPAL, VvSTS2, and VvFLS1). Similar behavior was observed in samples kept at 4°C for 48 h. Pre-cooling induced specific changes in the volatile organic compound (VOC) profiles. In particular, higher amounts of a specific subcategory of terpenes, namely sesquiterpenes, were detected in cooled samples. The induction of the expression of key genes involved in terpenoids biosynthesis (VvHDR, VvDX3, VvTER, VvGT14) was detected in cooled grapes, with variable effects depending on temperature and treatment duration. In both cooled samples, the evolution of alcoholic fermentation followed a regular trend but ended earlier. Higher phenolic content was detected in wines obtained from the 10°C-treated grapes. Higher residual concentration of malic acid at the end of fermentation was detected in wine samples from grapes pre-cooled at 4°C. Sesquiterpenes also showed a general increase in wines from cooled grapes, especially after pre-cooling at 10°C for 48 h. Different sensory profiles characterized the wine samples, with the best scores in terms of general pleasantness obtained by the wine produced from grapes pre-cooled at 4°C for 24 h. These results demonstrate that pre-cooling harvested grapes induces specific effect on the VOC profile and other quality parameters of Vermentino wine, and this appears to be the result of specific metabolic and compositional changes occurring in the berries.

OBJECTIVES:. As coronavirus disease 2019 is a novel disease, treatment strategies continue to be debated. This provides the intensive care community with a unique opportunity as the population of coronavirus disease 2019 patients requiring invasive mechanical ventilation is relatively homogeneous compared with other ICU populations. We hypothesize that the novelty of coronavirus disease 2019 and the uncertainty over its similarity with noncoronavirus disease 2019 acute respiratory distress syndrome resulted in substantial practice variation between hospitals during the first and second waves of coronavirus disease 2019 patients. DESIGN:. Multicenter retrospective cohort study. SETTING:. Twenty-five hospitals in the Netherlands from February 2020 to July 2020, and 14 hospitals from August 2020 to December 2020. PATIENTS:. One thousand two hundred ninety-four critically ill intubated adult ICU patients with coronavirus disease 2019 were selected from the Dutch Data Warehouse. Patients intubated for less than 24 hours, transferred patients, and patients still admitted at the time of data extraction were excluded. MEASUREMENTS AND MAIN RESULTS:. We aimed to estimate between-ICU practice variation in selected ventilation parameters (positive end-expiratory pressure, Fio2, set respiratory rate, tidal volume, minute volume, and percentage of time spent in a prone position) on days 1, 2, 3, and 7 of intubation, adjusted for patient characteristics as well as severity of illness based on Pao2/Fio2 ratio, pH, ventilatory ratio, and dynamic respiratory system compliance during controlled ventilation. Using multilevel linear mixed-effects modeling, we found significant (p ≤ 0.001) variation between ICUs in all ventilation parameters on days 1, 2, 3, and 7 of intubation for both waves. CONCLUSIONS:. This is the first study to clearly demonstrate significant practice variation between ICUs related to mechanical ventilation parameters that are under direct control by intensivists. Their effect on clinical outcomes for both coronavirus disease 2019 and other critically ill mechanically ventilated patients could have widespread implications for the practice of intensive care medicine and should be investigated further by causal inference models and clinical trials.

High CO2 concentrations applied to harvested horticultural products can modify primary and secondary metabolism. This work reports the metabolic responses to short-term CO2 treatments of white-skinned grapes (cv Trebbiano) undergoing postharvest partial dehydration. The influence of CO2 treatments on the aroma profile of the derived sweet wine was also assessed. Harvested grapes were treated with gaseous CO2 (30%) or air (control) for 24 h and then dehydrated (about 45% of weight loss) before vinification. Lipophilic and phenolic compounds of grape skin and the wine aroma profile were analyzed. In CO2-treated berries, the lipophilic and phenolic compounds decreased at a reduced and faster rate, respectively, during dehydration. Aroma profile of wine from CO2-treated grapes showed a slight but significantly higher content of glycosylated C13 and terpene compounds, and a decrease/absence of free acids, vanillin derivates and other phenol volatiles. The higher content of volatile alcohols in wine from treated berries suggests that the alcoholic fermentation was triggered. CO2 application before the withering process of Trebbiano grapes affects the aroma profile of the resulting wine by altering the free:glycosylated volatiles ratio. This study provides information on the possible use of CO2 as metabolic elicitor to modulate the aroma profile of the resulting wines obtained after grape dehydration.

Background: Diabetes is a significant health problem in Italy as in other western countries. Objective: To review available epidemiological data and the legislative framework for diabetes care in Italy. Methods: Review of Italian Health Ministry's official documents and analysis of epidemiological data published by Italian Scientific Societies. Findings: Diabetes affects more than 5% of the Italian population. The expenditures for the care of people with diabetes are about €10 billion ($US 11 billion) a year and are increasing over time. Italian law regulates the clinical care of people with diabetes and creates a clinical framework involving medical organizations, prevention programs, personnel training, and legal protection. The National Health Program is structured in essential levels of assistance that can be defined differently in the various regions. In 2013, the “National Diabetes Plan,” defining priority areas for intervention, was approved and represents the main regulatory tool for the management of diabetes within the Italian National Health Service. In Italy, the status of diabetes care is being monitored using the data from 2 permanent observatories: the ARNO Observatory Diabetes and the Associazione Medici Diabetologi Annals. Conclusions: A comprehensive approach to diabetes is offered to all citizens, consonant with the constitutionally guaranteed right to health. However, this important effort translates into a relevant financial burden for the National Health Service.

Background: Pasta is a refined carbohydrate with a low glycemic index. Whether pasta shares the metabolic advantages of other low glycemic index foods has not really been investigated. The aim of this study is to document, in people with type-2 diabetes, the consumption of pasta, the connected dietary habits, and the association with glucose control, measures of adiposity, and major cardiovascular risk factors. Methods: We studied 2562 participants. The dietary habits were assessed with the European Prospective Investigation into Cancer and Nutrition (EPIC) questionnaire. Sex-specific quartiles of pasta consumption were created in order to explore the study aims. Results: A higher pasta consumption was associated with a lower intake of proteins, total and saturated fat, cholesterol, added sugar, and fiber. Glucose control, body mass index, prevalence of obesity, and visceral obesity were not significantly different across the quartiles of pasta intake. No relation was found with LDL cholesterol and triglycerides, but there was an inverse relation with HDL-cholesterol. Systolic blood pressure increased with pasta consumption; but this relation was not confirmed after correction for confounders. Conclusions: In people with type-2 diabetes, the consumption of pasta, within the limits recommended for total carbohydrates intake, is not associated with worsening of glucose control, measures of adiposity, and major cardiovascular risk factors.