Agronomic, nutritional and nutraceutical aspects of durum wheat (Triticum durum Desf.) cultivars under low input agricultural management

Among cereals, durum wheat has a central role in the Italian diet and economy, where there is a historical tradition of pasta making. In the present study, we evaluated the nutrient and nutraceutical properties of 2 old and 6 modern durum wheat varieties grown under low input agricultural management. Considering the lack of available data on the adaptability of existing durum wheat varieties to the low input and organic sectors, the research aimed at providing a complete description of the investigated genotypes, considering the agronomic performance as well as the nutrient and phytochemical composition. The experimental trials were carried out at the same location (Bologna, Northern Italy) for two consecutive growing seasons (2006/2007, 2007/2008). No clear distinction between old and modern varieties was observed in terms of grain yield (mean values ranging from 2.5 to 4.0 t/ha), highlighting that the divergence in productivity, normally found between dwarf and non-dwarf genotypes, is strongly reduced when they are cropped under low input management. All durum wheat varieties presented high protein levels and, in addition, provided remarkable amounts of phytochemicals such as dietary fibre, polyphenols, flavonoids and carotenoids. Some of the investigated genotypes, such as Senatore Cappelli, Solex, Svevo and Orobel, emerged with intriguing nutritional and phytochemical profiles, with the highest levels of dietary fibre and antioxidant compounds. The study provided the basis for further investigations into the adaptability of the durum wheat genotypes to low input management, for the selection of genotypes characterised by higher yield and valuable nutrient and nutraceutical quality

Using salinity to improve nutritional and market value of strawberries

Plants respond to salinity by producing antioxidants and osmolytes; some of these are nutritionally useful to humans (e.g. phenolics), or may improve the sensory quality of produce (e.g. sugars). For the current study, strawberries were irrigated with 0, 10, 20 or 40 mM NaCl, and the responses in antioxidants, phenolics, and flavour attributes were measured. A linear positive relationship was observed between salt stress and antioxidant concentrations, and the DPPH antioxidant assay responded more clearly than the FRAP assay. Phenolics were increased with statistical significance by salinity at all treatment levels, although trends differed between total phenolics and the subclasses anthocyanins and total flavonoids. It was seen that mild salinity (10 mM) with a low impact on yield could be used to increase antioxidants (6-10% above control) and total phenolics (11-16% above control). However differences between cultivars outweighed differences due to salinity in treatments below 20 mM NaCl. We found that sugars in strawberries (unlike other fruits) weren’t increased by salinity treatment. The lack of sugar increase can be explained by suggesting that organic acids are more important osmolytes than sugars for strawberries under salinity. However it was also determined that the failure of strawberries to increase their soluble sugars during salt stress can be explained by the lean nutrient regimes used by researchers, which don’t represent commercial production practices. Practically, mild salinity (≤20 mM) can be used to increase strawberry fruit value, but should be combined with an appropriate nutrient regime to avoid harm to flavour quality. The varieties Elsanta and Elsinore are both suitable for salt treatment, but Elsanta is better for antioxidant and phenolic production, as well as being more salt tolerant

Decay control of cold stored Citrus clementina Hort. ex Tan. fruit by pre- and postharvest application of potassium phosphite

The effectiveness of pre- and postharvest application of potassium phosphite against naturally occuring postharvest decay and storage disorders on clementine Monreal fruit (Citrus clementina Hort. ex Tan.) was investigated. Phosphite solutions were applied according to the following experimental protocol: by spraying fruit on the trees (2.5 g/L), at fruit colour breaking and 15 days before harvest; by the combination of preharvest (2.5 g/L) and postharvest dipping application (4 g of a.i./L). Preharvest applications were compared to Phosethyl-Al solution (2.5 g/L) and water control. Decay and disorders were assessed after 30 days of cold storage at 6±1°C and 90-95% RH, followed by 7 days of shelf life at 20±2°C. The combination of pre- and postharvest application of phosphite was more effective in reducing green (Penicillium digitatum Sacc.) and blue mould (P. italicum Weh.) incidence, as compared to water control, but it was not so effective in reducing the incidence of minor decay. Potassium phosphite treatments, before harvest and in pre-postharvest combination, significantly reduced chilling injury and aging with respect to water control. Based on these results, pre and postharvest application of potassium phosphite can be considered a useful strategy to be included in an integrated approach for controlling green and blue mould of citrus fruit in storage

Long-Term Prognostic Impact of Right Ventricular Dysfunction in Patients with COVID-19

The characteristics and clinical course of hospitalized patients with coronavirus disease 2019 (COVID-19) have been widely described, while long-term data are still poor. The aim of this study was to evaluate the long-term clinical outcome and its association with right ventricular (RV) dysfunction in hospitalized patients with COVID-19. This was a prospective multicenter study of consecutive COVID-19 patients hospitalized at seven Italian Hospitals from 28 February to 20 April 2020. The study population was divided into two groups according to echocardiographic evidence of RV dysfunction. The primary study outcome was 1-year mortality. The propensity score matching was performed to balance for potential baseline confounders. The study population consisted of 224 patients (mean age 69 \ub1 14, male sex 62%); RV dysfunction was diagnosed in 63 cases (28%). Patients with RV dysfunction were older (75 vs. 67 years, p < 0.001), had higher prevenance of coronary artery disease (27% vs. 11%, p = 0.003), and lower left ventricular ejection fraction (50% vs. 55%, p <0.001). The rate of 1-year mortality (67% vs. 28%; p 64 0.001) was significantly higher in patients with RV dysfunction compared with patients without. After propensity score matching, patients with RV dysfunction showed a worse long-term survival (62% vs. 29%, p <0.001). The multivariable Cox regression model showed an independent association of RV dysfunction with 1-year mortality. RV dysfunction is a relatively common finding in hospitalized COVID-19 patients, and it is independently associated with an increased risk of 1-year mortality

Phase 1/2 study of valproic acid and short-course radiotherapy plus capecitabine as preoperative treatment in low-moderate risk rectal cancer-V-shoRT-R3 (Valproic acid--short Radiotherapy--rectum 3rd trial).

BACKGROUND: Locally advanced rectal cancer (LARC) is a heterogeneous group of tumors where a risk-adapted therapeutic strategy is needed. Short-course radiotherapy (SCRT) is a more convenient option for LARC patients than preoperative long-course RT plus capecitabine. Histone-deacetylase inhibitors (HDACi) have shown activity in combination with RT and chemotherapy in the treatment of solid tumors. Valproic acid (VPA) is an anti-epileptic drug with HDACi and anticancer activity. In preclinical studies, our group showed that the addition of HDACi, including VPA, to capecitabine produces synergistic antitumour effects by up-regulating thymidine phosphorylase (TP), the key enzyme converting capecitabine to 5-FU, and by downregulating thymidylate synthase (TS), the 5-FU target. METHODS/DESIGN: Two parallel phase-1 studies will assess the safety of preoperative SCRT (5 fractions each of 5 Gy, on days 1 to 5) combined with (a) capecitabine alone (increasing dose levels: 500-825 mg/m2/bid), on days 1-21, or (b) capecitabine as above plus VPA (oral daily day -14 to 21, with an intra-patient titration for a target serum level of 50-100 microg/ml) followed by surgery 8 weeks after the end of SCRT, in low-moderate risk RC patients. Also, a randomized phase-2 study will be performed to explore whether the addition of VPA and/or capecitabine to preoperative SCRT might increase pathologic complete tumor regression (TRG1) rate. A sample size of 86 patients (21-22/arm) was calculated under the hypothesis that the addition of capecitabine or VPA to SCRT can improve the TRG1 rate from 5% to 20%, with one-sided alpha = 0.10 and 80% power.Several biomarkers will be evaluated comparing normal mucosa with tumor (TP, TS, VEGF, RAD51, XRCC1, Histones/proteins acetylation, HDAC isoforms) and on blood samples (polymorphisms of DPD, TS, XRCC1, GSTP1, RAD51 and XRCC3, circulating endothelial and progenitors cells; PBMCs-Histones/proteins acetylation). Tumor metabolism will be measured by 18FDG-PET at baseline and 15 days after the beginning of SCRT. DISCUSSION: This project aims to improve the efficacy of preoperative treatment of LARC and to decrease the inconvenience and the cost of standard long-course RT. Correlative studies could identify both prognostic and predictive biomarkers and could add new insight in the mechanism of interaction between VPA, capecitabine and RT.EudraCT Number: 2012-002831-28. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT01898104

Vinorelbine plus 3-weekly trastuzumab in metastatic breast cancer: a single-centre phase 2 trial

BACKGROUND: After two studies reporting response rates higher than 70% in HER2-positive metastatic breast cancer with weekly trastuzumab and vinorelbine, we planned a phase 2 study to test activity of the same combination, with trastuzumab given every 3 weeks. METHODS: Patients with HER2-positive metastatic breast cancer (3+ at immunohistochemistry or positive at fluorescence in situ hybridization), PS ≤2, normal left-ventricular ejection fraction (LVEF) and no more than one chemotherapy line for metastatic disease were eligible. Vinorelbine (30 mg/m(2)) was given on days 1&8 every 21 and trastuzumab (8 mg/kg day 1, then 6 mg/kg) every 21 days). A single-stage phase 2 design, with p(0 )= 0.45, p(1 )= 0.65, type I and II error = 0.10, was applied; 22 objective responses were required in 39 patients. RESULTS: From Nov 2002 to May 2005, 50 patients were enrolled, with a median age of 54 years (range 31–81). Among 40 patients eligible for response assessment, there were 7 complete and 13 partial responses (overall response rate 50%; 95% exact CI 33.8–66.2); 11 patients had disease stabilization, lasting more than 6 months in 10 cases. Response rate did not vary according to patients and tumor characteristics, type and amount of previous chemotherapy. Within the whole series, median progression-free survival was 9.6 months (95% CI 7.3–12.3), median overall survival 22.7 months (95% CI 19.5-NA). Fifteen patients (30%) developed brain metastases at a median time of 12 months (range 1–25). There was one toxic death due to renal failure in a patient receiving concomitant pamidronate. Twenty-three patients (46%) had grade 3–4 neutropenia, 2 (4%) grade 3 anemia, 4 (8%) febrile neutropenia. Two patients stopped treatment because of grade 2 decline of LVEF and one patient because of grade 2 liver toxicity concomitant with a grade 1 decline of LVEF. One patient stopped trastuzumab after 50 cycles because of grade 1 decline of LVEF. CONCLUSION: Although lower than in initial studies, activity of 3-weekly trastuzumab plus vinorelbine fell within the range of results reported with weekly schedules. Toxicity was prevalently manageable. This combination is safe and active for metastatic breast cancer patients who received adjuvant taxanes with anthracyclines

Toward an international consensus-Integrating lipoprotein apheresis and new lipid-lowering drugs

Background: Despite advances in pharmacotherapy of lipid disorders, many dyslipidemic patients do not attain sufficient lipid lowering to mitigate risk of atherosclerotic cardiovascular disease. Several classes of novel lipid-lowering agents are being evaluated to reduce atherosclerotic cardiovascular disease risk. Lipoprotein apheresis (LA) is effective in acutely lowering the plasma concentrations of atherogenic lipoproteins including low-density lipoprotein cholesterol and lipoprotein(a), and novel lipid-lowering drugs may dampen the lipid rebound effect of LA, with the possibility that LA frequency may be decreased, in some cases even be discontinued. Sources of material: This document builds on current American Society for Apheresis guidelines and, for the first time, makes recommendations from summarized data of the emerging lipid-lowering drug classes (inhibitors of proprotein convertase subtilisin/kexin type 9 or microsomal triglyceride transfer protein, high-density lipoprotein mimetic), including the available evidence on combination therapy with LA with respect to the management of patients with dyslipidemia. Abstract of findings: Recommendations for different indications are given based on the latest evidence. However, except for lomitapide in homozygous familial hypercholesterolemia and alirocumab/evolocumab in heterozygous familial hypercholesterolemia subjects, limited data are available on the effectiveness and safety of combination therapy. More studies on combining LA with novel lipid-lowering drugs are needed. Conclusion: Novel lipid-lowering agents have potential to improve the performance of LA, but more evidence is needed. The Multidisciplinary International Group for Hemapheresis TherapY and Metabolic DIsturbances Contrast scientific society aims to establish an international registry of clinical experience on LA combination therapy to expand the evidence on this treatment in individuals at high cardiovascular disease risk

The DREAMS experiment flown on the ExoMars 2016 mission for the study of Martian environment during the dust storm season

The DREAMS (Dust characterization, Risk assessment and Environment Analyser on the Martian Surface) instrument on Schiaparelli lander of ExoMars 2016 mission was an autonomous meteorological station designed to completely characterize the Martian atmosphere on surface, acquiring data not only on temperature, pressure, humidity, wind speed and its direction, but also on solar irradiance, dust opacity and atmospheric electrification; this comprehensive set of parameters would assist the quantification of risks and hazards for future manned exploration missions mainly related to the presence of airborne dust. Schiaparelli landing on Mars was in fact scheduled during the foreseen dust storm season (October 2016 in Meridiani Planum) allowing DREAMS to directly measure the characteristics of such extremely harsh environment. DREAMS instrument’s architecture was based on a modular design developing custom boards for analog and digital channel conditioning, power distribution, on board data handling and communication with the lander. The boards, connected through a common backbone, were hosted in a central electronic unit assembly and connected to the external sensors with dedicated harness. Designed with very limited mass and an optimized energy consumption, DREAMS was successfully tested to operate autonomously, relying on its own power supply, for at least two Martian days (sols) after landing on the planet. A total of three flight models were fully qualified before launch through an extensive test campaign comprising electrical and functional testing, EMC verification and mechanical and thermal vacuum cycling; furthermore following the requirements for planetary protection, contamination control activities and assay sampling were conducted before model delivery for final integration on spacecraft. During the six months cruise to Mars following the successful launch of ExoMars on 14th March 2016, periodic check outs were conducted to verify instrument health check and update mission timelines for operation. Elaboration of housekeeping data showed that the behaviour of the whole instrument was nominal during the whole cruise. Unfortunately DREAMS was not able to operate on the surface of Mars, due to the known guidance anomaly during the descent that caused Schiaparelli to crash at landing. The adverse sequence of events at 4 km altitude anyway triggered the transition of the lander in surface operative mode, commanding switch on the DREAMS instrument, which was therefore able to correctly power on and send back housekeeping data. This proved the nominal performance of all DREAMS hardware before touchdown demonstrating the highest TRL of the unit for future missions. The spare models of DREAMS are currently in use at university premises for the development of autonomous units to be used in cubesat mission and in probes for stratospheric balloons launches in collaboration with Italian Space Agency

Outcomes of pregnancies after kidney transplantation: lessons learned from CKD. A comparison of transplanted, nontransplanted chronic kidney disease patients and low-risk pregnancies: a multicenter nationwide analysis.

BACKGROUND: Kidney transplantation (KT) may restore fertility in CKD. The reasons why materno-foetal outcomes are still inferior to the overall population are only partially known. Comparison with the CKD population may offer some useful insights for management and counselling.Aim of this study was to analyse the outcomes of pregnancy after KT, compared with a large population of non-transplanted CKD patients and with low-risk control pregnancies, observed in Italy the new millennium. METHODS: We selected 121 live-born singletons after KT (Italian study group of kidney in pregnancy, national coverage about 75%), 610 live-born singletons in CKD and 1418 low-risk controls recruited in 2 large Italian Units, in the same period (2000-2014). The following outcomes were considered: maternal and foetal death; malformations; preterm delivery; small for gestational age baby (SGA); need for the neonatal intensive care unit (NICU); doubling of serum creatinine or increase in CKD stage. Data were analysed according to kidney diseases, renal function (staging according to CKD-EPI), hypertension, maternal age, partity, ethnicity. RESULTS: Materno-foetal outcomes are less favourable in CKD and KT as compared with the low-risk population. CKD stage and hypertension are important determinants of results. KT patients with e-GFR >90 have worse outcomes compared with CKD stage 1 patients; the differences level off when only CKD patients affected by glomerulonephritis or systemic diseases ('progressive CKD') are compared with KT. In the multivariate analysis, risk for preterm and early-preterm delivery was linked to CKD stage (2-5 versus 1: RR 3.42 and 3.78) and hypertension (RR 3.68 and 3.16) while no difference was associated with being a KT or a CKD patient. CONCLUSIONS: The materno-foetal outcomes in patients with kidney transplantation are comparable with those of nontransplanted CKD patients with similar levels of kidney function impairment and progressive and/or immunologic kidney diseas