Publications by authors named "Marco Trevisan"

117 Publications

Pharmacoepidemiology for nephrologists (part 1): concept, applications and considerations for study design.

Clin Kidney J 2021 May 14;14(5):1307-1316. Epub 2020 Dec 14.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden.

Randomized controlled trials on drug safety and effectiveness are the foundation of medical evidence, but they may have limited generalizability and be unpowered to detect rare and long-term kidney outcomes. Observational studies in routine care data can complement and expand trial evidence on the use, safety and effectiveness of medications and aid with clinical decisions in areas where evidence is lacking. Access to routinely collected large healthcare data has resulted in the proliferation of studies addressing the effect of medications in patients with kidney diseases and this review provides an introduction to the science of pharmacoepidemiology to critically appraise them. In this first review we discuss the concept and applications of pharmacoepidemiology, describing methods for drug-utilization research and discussing the strengths and caveats of the most commonly used study designs to evaluate comparative drug safety and effectiveness.
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http://dx.doi.org/10.1093/ckj/sfaa244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8247736PMC
May 2021

Stopping mineralocorticoid receptor antagonists after hyperkalaemia: trial emulation in data from routine care.

Eur J Heart Fail 2021 Jul 1. Epub 2021 Jul 1.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

Aims: Whether to continue or stop mineralocorticoid receptor antagonists (MRA) after an episode of hyperkalaemia is a challenge in clinical practice. While stopping MRA may prevent recurrent hyperkalaemias, it deprives patients of their cardioprotection. We here assessed the association between stopping vs. continuing MRA therapy after hyperkalaemia and the subsequent risks of adverse health events.

Methods And Results: Observational study from the Stockholm CREAtinine Measurements (SCREAM) project 2006-2018. We identified patients initiating MRA and surviving a first-detected episode of hyperkalaemia (plasma potassium >5.0 mmol/L). Using target trial emulation methods, we assessed the association between stopping vs. continuing MRA within 6 months after hyperkalaemia and subsequent outcomes. The primary outcome was the composite of hospital admission with heart failure, stroke, myocardial infarction, or death. The secondary outcome was occurrence of another hyperkalaemia event. Among 39 518 patients initiating MRA, we identified 7366 who developed hyperkalaemia. Median age was 76 years, 45% were women and 69% had a history of heart failure. Following hyperkalaemia, 2222 (30%) discontinued treatment. Compared with continuing MRA, stopping therapy was associated with a lower 2-year risk of recurrent hyperkalaemia [hazard ratio (HR) 0.75, 95% confidence interval (CI) 0.72-0.79], but a higher risk of the primary outcome (HR 1.10, 95% CI 1.06-1.14). Similar results were observed in patients with heart failure, after censoring when treatment decision was changed, and across pre-specified subgroups.

Conclusions: Stopping MRA after an episode of hyperkalaemia was associated with reduced risk for recurrent hyperkalaemia, but higher risk of death or cardiovascular events. Recurrent hyperkalaemia was common in either strategy.
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http://dx.doi.org/10.1002/ejhf.2287DOI Listing
July 2021

Alpha-1 adrenergic receptor antagonists to prevent hyperinflammation and death from lower respiratory tract infection.

Elife 2021 06 11;10. Epub 2021 Jun 11.

Stanford Graduate School of Business, Stanford University, Stanford, United States.

In severe viral pneumonia, including Coronavirus disease 2019 (COVID-19), the viral replication phase is often followed by hyperinflammation, which can lead to acute respiratory distress syndrome, multi-organ failure, and death. We previously demonstrated that alpha-1 adrenergic receptor (⍺-AR) antagonists can prevent hyperinflammation and death in mice. Here, we conducted retrospective analyses in two cohorts of patients with acute respiratory distress (ARD, n = 18,547) and three cohorts with pneumonia (n = 400,907). Federated across two ARD cohorts, we find that patients exposed to ⍺-AR antagonists, as compared to unexposed patients, had a 34% relative risk reduction for mechanical ventilation and death (OR = 0.70, p = 0.021). We replicated these methods on three pneumonia cohorts, all with similar effects on both outcomes. All results were robust to sensitivity analyses. These results highlight the urgent need for prospective trials testing whether prophylactic use of ⍺-AR antagonists ameliorates lower respiratory tract infection-associated hyperinflammation and death, as observed in COVID-19.
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http://dx.doi.org/10.7554/eLife.61700DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8195605PMC
June 2021

Changes in the chemical and sensory profile of ripened Italian salami following the addition of different microbial starters.

Meat Sci 2021 Oct 29;180:108584. Epub 2021 May 29.

Department for Sustainable Food Process, Università Cattolica del Sacro Cuore, Via Emilia Parmense 84, 29122 Piacenza, Italy.

In this work, Italian salami were produced using microbial starters (Pediococcus pentosaceus, Lactobacillus sakei, and Staphylococcus xylosus) and compared to a control sample (without starter). Metabolomics in combination with microbiological and sensory analyses were used to investigate the overall quality. Samples were analyzed immediately after stuffing, following 7, 30, and 45 days of ripening. Each microbial starter imposed distinctive metabolomic signatures at the end of ripening. The accumulated discriminant compounds were mainly related to lipid oxidation (including hydroxy- and epoxy derivatives of fatty acids) following the inoculation with L. sakei. However, the inoculation with P. pentosaceus resulted in the accumulation of γ-glutamyl peptides, compounds driving a kokumi-related taste. Noteworthy, our findings supported the involvement of the chemical compounds profiled in the definition of final taste and aroma. This information paves the way towards the definition of more objective and tailored starters-related flavours enhancement approaches in the sector of cured meat.
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http://dx.doi.org/10.1016/j.meatsci.2021.108584DOI Listing
October 2021

Biogenic ZnO Nanoparticles Synthesized Using a Novel Plant Extract: Application to Enhance Physiological and Biochemical Traits in Maize.

Nanomaterials (Basel) 2021 May 12;11(5). Epub 2021 May 12.

Department for Sustainable Food Process, Università Cattolica del Sacro Cuore, 29122 Piacenza, Italy.

The need to increase crop productivity and resistance directs interest in nanotechnology. Indeed, biogenic metal oxide nanoparticles can promote beneficial effects in plants, while their synthesis avoids the environmental impacts of conventional synthetic procedures. In this context, this research aimed to synthesize biogenic zinc oxide nanoparticles (ZnO-NPs) using, for the first time, an extract of a wild and spontaneous aquatic species, (duckweed). The effectiveness of this biogenic synthesis was evidenced for comparison with non-biogenic ZnO-NPs (obtained without using the plant extract), which have been synthesized in this research. XRD (X-ray diffraction), FE-SEM (field emission gun electron scanning microscopy), EDX (energy dispersive x-ray spectroscopy), TEM (transmission electron microscope) and UV-vis (ultraviolet-visible spectrophotometry) showed the biogenic approach effectiveness. The duckweed extract was subjected to UHPLC-ESI/QTOF-MS (ultra high-pressure liquid chromatography quadrupole time of flight mass spectrometry) phenolic profiling. This untargeted characterization highlighted a high and chemically diverse content in the duckweed extract of compounds potentially implicated in nanoparticulation. From an application standpoint, the effect of biogenic nanoparticles was investigated on some traits of maize subjected to seed priming with a wide range of biogenic ZnO-NPs concentrations. Inductive effects on the shoot and root biomass development were ascertained concerning the applied dosage. Furthermore, the biogenic ZnO-NPs stimulated the content of chlorophylls, carotenoids, and anthocyanin. Finally, the study of malondialdehyde content (MDA) as a marker of the oxidative status further highlighted the beneficial and positive action of the biogenic ZnO-NPs on maize.
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http://dx.doi.org/10.3390/nano11051270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151215PMC
May 2021

Pharmacoepidemiology for nephrologists (part 2): potential biases and how to overcome them.

Clin Kidney J 2021 May 14;14(5):1317-1326. Epub 2020 Dec 14.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden.

Observational pharmacoepidemiological studies using routinely collected healthcare data are increasingly being used in the field of nephrology to answer questions on the effectiveness and safety of medications. This review discusses a number of biases that may arise in such studies and proposes solutions to minimize them during the design or statistical analysis phase. We first describe designs to handle confounding by indication (e.g. active comparator design) and methods to investigate the influence of unmeasured confounding, such as the E-value, the use of negative control outcomes and control cohorts. We next discuss prevalent user and immortal time biases in pharmacoepidemiology research and how these can be prevented by focussing on incident users and applying either landmarking, using a time-varying exposure, or the cloning, censoring and weighting method. Lastly, we briefly discuss the common issues with missing data and misclassification bias. When these biases are properly accounted for, pharmacoepidemiological observational studies can provide valuable information for clinical practice.
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http://dx.doi.org/10.1093/ckj/sfaa242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087121PMC
May 2021

Kidney Function, Kidney Function Decline, and the Risk of Dementia in Older Adults: A Registry-Based Study.

Neurology 2021 May 5. Epub 2021 May 5.

Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet, Stockholm, Sweden.

Objective: Community-based reports regarding the association between the estimated glomerular filtration rate (eGFR) and dementia risk show conflicting results. This study aims is to investigate the links between kidney function, kidney function decline and dementia incidence.

Methods: We analyzed the association of eGFR with the risk of dementia (defined as a new dementia diagnosis or initiation of dementia treatments) among 329,822 residents of Stockholm who accessed healthcare during 2006-2011, were ≥65 years, had no history of dementia or underwent kidney replacement therapy. We also estimated the rate of eGFR decline among 205,622 residents with repeated eGFR measurements during the first-year of observation and investigated its association with subsequent dementia risk.

Results: 18,983 cases of dementia (5.8% of participants) were detected over a median follow-up of 5 years. Dementia incidence rates (IR) were progressively higher with lower eGFR: from 6.56/1000 person-years in persons with eGFR 90-104ml/min to 30.28/1000 person-years in those with eGFR<30ml/min. After multivariable adjustment, lower eGFR was associated with a higher dementia risk [hazard ratio(HR), 1.71; 95% confidence interval(CI), 1.54-1.91 in eGFR 30-59ml/min and HR 2.62, 1.91-3.58 in eGFR<30ml/min] compared with eGFR of 90-104ml/min. A steeper decline in eGFR (decline>2ml/min/1.73m/year) within one year was associated with higher dementia risk. Risk magnitudes were stronger for vascular dementia than for Alzheimer. As many as 10% (95% CI 6-14%) of dementia cases could be attributed to eGFR<60ml/min/1.73m, a proportion higher than that attributed to other dementia risk factors such as cardiovascular disease and diabetes.

Conclusions: Both lower kidney function and steeper kidney function decline are associated with the development of dementia.
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http://dx.doi.org/10.1212/WNL.0000000000012113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253567PMC
May 2021

Integrated Genomic and Greenhouse Assessment of a Novel Plant Growth-Promoting Rhizobacterium for Tomato Plant.

Front Plant Sci 2021 30;12:660620. Epub 2021 Mar 30.

Department for Sustainable Food Process, Università Cattolica del Sacro Cuore, Piacenza, Italy.

Plant growth promoting rhizobacteria (PGPR) can display several plant-beneficial properties, including support to plant nutrition, regulation of plant growth, and biocontrol of pests. Mechanisms behind these effects are directly related to the presence and expression of specific genes, and different PGPR strains can be differentiated by the presence of different genes. In this study we reported a comprehensive evaluation of a novel PGPR UC4115 from the field to the lab, and from the lab to the plant. The isolate from tomato field was screened for different activities related to plant nutrition and growth regulation as well as for antifungal traits. We performed a functional annotation of genes contributing to plant-beneficial functions previously tested . Furthermore, the characterization, the whole genome sequencing and annotation of UC4115, were compared with the well-known PGPR strain Sp7. This novel comparative analysis revealed different accumulation of plant-beneficial functions contributing genes, and the presence of different genes that accomplished the same functions. Greenhouse assays on tomato seedlings from BBCH 11-12 to BBCH > 14 were performed under either organic or conventional management. In each of them, three PGPR inoculations (control, UC4115, Sp7) were applied at either seed-, root-, and seed plus root level. Results confirmed the PGP potential of UC4115; in particular, its high value potential as indole-3-acetic acid producer was observed in increasing of root length density and diameter class length parameters. While, in general, Sp7 had a greater effect on biomass, probably due to its high ability as nitrogen-fixing bacteria. For UC4115, the most consistent data were noticed under organic management, with application at seed level. While, Sp7 showed the greatest performance under conventional management. Our data highlight the necessity to tailor the selected PGPR, with the mode of inoculation and the crop-soil combination.
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http://dx.doi.org/10.3389/fpls.2021.660620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042378PMC
March 2021

Validation of risk scores for ischaemic stroke in atrial fibrillation across the spectrum of kidney function.

Eur Heart J 2021 04;42(15):1476-1485

Department of Clinical Epidemiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, the Netherlands.

Aims: The increasing prevalence of ischaemic stroke (IS) can partly be explained by the likewise growing number of patients with chronic kidney disease (CKD). Risk scores have been developed to identify high-risk patients, allowing for personalized anticoagulation therapy. However, predictive performance in CKD is unclear. The aim of this study is to validate six commonly used risk scores for IS in atrial fibrillation (AF) patients across the spectrum of kidney function.

Methods And Results: Overall, 36 004 subjects with newly diagnosed AF from SCREAM (Stockholm CREAtinine Measurements), a healthcare utilization cohort of Stockholm residents, were included. Predictive performance of the AFI, CHADS2, Modified CHADS2, CHA2DS2-VASc, ATRIA, and GARFIELD-AF risk scores was evaluated across three strata of kidney function: normal kidney function [estimated glomerular filtration rate (eGFR) >60 mL/min/1.73 m2], mild CKD (eGFR 30-60 mL/min/1.73 m2), and advanced CKD (eGFR <30 mL/min/1.73 m2). Predictive performance was assessed by discrimination and calibration. During 1.9 years, 3069 (8.5%) patients suffered an IS. Discrimination was dependent on eGFR: the median c-statistic in normal eGFR was 0.75 (range 0.68-0.78), but decreased to 0.68 (0.58-0.73) and 0.68 (0.55-0.74) for mild and advanced CKD, respectively. Calibration was reasonable and largely independent of eGFR. The Modified CHADS2 score showed good performance across kidney function strata, both for discrimination [c-statistic: 0.78 (95% confidence interval 0.77-0.79), 0.73 (0.71-0.74) and 0.74 (0.69-0.79), respectively] and calibration.

Conclusion: In the most clinically relevant stages of CKD, predictive performance of the majority of risk scores was poor, increasing the risk of misclassification and thus of over- or undertreatment. The Modified CHADS2 score performed good and consistently across all kidney function strata, and should therefore be preferred for risk estimation in AF patients.
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http://dx.doi.org/10.1093/eurheartj/ehab059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046502PMC
April 2021

Exogenous application of ZnO nanoparticles and ZnSO distinctly influence the metabolic response in Phaseolus vulgaris L.

Sci Total Environ 2021 Jul 9;778:146331. Epub 2021 Mar 9.

Department for Sustainable Food Process, Università Cattolica del Sacro Cuore, Piacenza, Italy. Electronic address:

Nanomaterials-mediated contamination (including the highly reactive metal oxides ZnO nanoparticles) is becoming one of the most concerning issues worldwide. In this study, the toxic effects of two chemical species of Zn (ZnO nanoparticles and bulk ZnSO) were investigated in bean plants, following either foliar or soil application, at concentrations from 250 to 2000 mg L using biochemical assays, proteomics and metabolomics. The accumulation of Zn in plant tissues depended on the application type, zinc chemical form and concentration, in turn triggering distinctive morphological, physiological, and redox responses. Bean plants were more sensitive to the foliar than to the soil application, and high concentrations of ZnO NP and bulk ZnSO determined the highest plant growth inhibition and stress symptoms. However, low dosages of ZnSO induced a slight plant growth promotion and better physiological and antioxidative response. Low concentration of Zn leaded to increased activity of stress-related proteins and secondary metabolites with antioxidant capacity, while increasing concentration reached the exhausted phase of the plant stress response, reducing the antioxidant defense system. Such high concentrations increased lipids peroxidation, protein degradation and membranes integrity. Oxidative damage occurred at high concentrations of both chemical species of Zn. Foliar spraying impaired photosynthetic efficiency, while soil applications (especially ZnSO) elicited antioxidant metabolites and proteins, and impaired chloroplast-related proteins involved in the electron transport chain and ATP production. Taken together, the results highlighted distinctive and nanoparticles-related toxic effects of ZnO in bean, compared to ionic forms of Zn.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146331DOI Listing
July 2021

Risk-benefit in food safety and nutrition - Outcome of the 2019 Parma Summer School.

Food Res Int 2021 03 5;141:110073. Epub 2021 Jan 5.

University of Parma, Department of Food and Drug, Italy. Electronic address:

Risk-benefit assessment is the comparison of the risk of a situation to its related benefits, i.e. a comparison of scenarios estimating the overall health impact. The risk-benefit analysis paradigm mirrors the classical risk analysis one: risk-benefit assessment goes hand-in-hand with risk-benefit management and risk-benefit communication. The various health effects associated with food consumption, together with the increasing demand for advice on healthy and safe diets, have led to the development of different research disciplines in food safety and nutrition. In this sense, there is a clear need for a holistic approach, including and comparing all of the relevant health risks and benefits. The risk-benefit assessment of foods is a valuable approach to estimate the overall impact of food on health. It aims to assess together the negative and positive health effects associated with food intake by integrating chemical and microbiological risk assessment with risk and benefit assessment in food safety and nutrition. The 2019 Parma Summer School on risk-benefit in food safety and nutrition had the objective was to provide an opportunity to learn from experts in the field of risk-benefit approach in food safety and nutrition, including theory, case studies, and communication of risk-benefit assessments plus identify challenges for the future. It was evident that whereas tools and approaches have been developed, more and more case studies have been performed which can form an inherent validation of the risk-benefit approach. Executed risk-benefit assessment case studies apply the steps and characteristics developed: a problem formulation (with at least 2 scenarios), a tiered approach until a decision can be made, one common currency to describe both beneficial and adverse effects (DALYs in most instances). It was concluded that risk-benefit assessment in food safety and nutrition is gaining more and more momentum, while also many challenges remain for the future. Risk-benefit is on the verge of really enrolling into the risk assessment and risk analysis paradigm. The interaction between risk-benefit assessors and risk-benefit managers is pivotal in this, as is the interaction with risk-benefit communicators.
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http://dx.doi.org/10.1016/j.foodres.2020.110073DOI Listing
March 2021

Gas exchange, vine performance and modulation of secondary metabolism in Vitis vinifera L. cv Barbera following long-term nitrogen deficit.

Planta 2021 Feb 22;253(3):73. Epub 2021 Feb 22.

Department for Sustainable Food Process, Università Cattolica del Sacro Cuore, Via Emilia Parmense 84, 29122, Piacenza, Italy.

Main Conclusion: A reprogramming of secondary metabolism to acclimate to nitrogen deficiency was seen in grapevine eliciting an accumulation of strigolactones and jasmonate. This response links with photosynthetic compensation and enhanced ripening. In addition to the metabolism directly related to nitrogen assimilation, long-term nitrogen depletion may affect plant secondary metabolism, in turn affecting grapevine performance. In this work, the effect of nitrogen deficit was investigated in V. vinifera cv. Barbera potted vines following three years of deprivation, using a combination of morpho-physiological assessments and mass spectrometry-based untargeted metabolomics. Plants grown under nitrogen limitation showed reduced growth and even more curtailed yields, lowered SPAD values, and a quite preserved leaf gas exchange, compared to plants grown under non-limiting nitrogen availability. Ripening was decidedly accelerated, and berry composition improved in terms of higher sugar and phenolic contents under nitrogen-limiting conditions. Metabolomics showed the broad involvement of secondary metabolism in acclimation to nitrogen deficiency, including a distinctive modulation of the phytohormone profile. Several nitrogen-containing metabolites were down accumulated under nitrogen-limiting conditions, including alkaloids, glucosinolates, hypoxanthine, and inosine. On the other hand, phenylpropanoids showed an accumulation trend. Concerning the recruitment of hormones, nitrogen deprivation elicited an accumulation of strigolactones and jasmonate. Noteworthy, both strigolactones and jasmonates have been previously related to increased photosynthetic efficiency under abiotic stress. Furthermore, the severe reduction of lateral shoot development we recorded in N-deprived vines is consistent with the accumulation of strigolactones. Overall, our results suggest that nitrogen deprivation induced a rather broad metabolic reprogramming, mainly including secondary metabolism and hormones profile, reflected in the modulation of photosynthetic performance, canopy growth, and possibly fruit quality.
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http://dx.doi.org/10.1007/s00425-021-03590-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897622PMC
February 2021

Concealed metabolic reprogramming induced by different herbicides in tomato.

Plant Sci 2021 Feb 25;303:110727. Epub 2020 Oct 25.

Department for Sustainable Food Process, Università Cattolica del Sacro Cuore, Via Emilia Parmense 84, 29122 Piacenza, Italy.

Herbicide application is a common procedure in agriculture, whose potentially adverse effects are assessed mainly with respect to weeds or in terms of residues and environmental impact. However, recent evidence has highlighted possible effects of pesticide treatments on plant metabolism, with potential implications for fruit quality. Therefore, the goal of this study was to investigate the impact of four different herbicides on the metabolic processes in industrial tomato plants. To this aim, plants were treated either with the selective herbicides metribuzin and rimsulfuron or with the non-selective herbicides glyphosate and pelargonic acid. Thereafter, leaves were analyzed using a metabolomics approach, and 247 differential compounds were selected by multivariate statistics and used to examine the changes at the molecular level. Data interpretation via the PlantCyc Pathway Tool revealed that the tested herbicides induced distinctive responses to the treatments, with the phytohormone profile (gibberellins and jasmonates) and secondary metabolism (including stress-related compounds, such as phenylpropanoids and glucosinolates) showing the largest modulation. Surprisingly, such metabolic reprogramming also affected several aspects of the fruits even though the herbicides were applied several weeks before, thus opening the possibility of effects on food quality. To date, these hidden effects have been largely underestimated even though they deserve to be carefully considered since they may affect the qualitative and quantitative traits of the yield.
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http://dx.doi.org/10.1016/j.plantsci.2020.110727DOI Listing
February 2021

Impact of Climatic Conditions on the Resveratrol Concentration in Blend of L. cvs. Barbera and Croatina Grape Wines.

Molecules 2021 Jan 14;26(2). Epub 2021 Jan 14.

Department of Sustainable Crop Production, Università Cattolica del Sacro Cuore, Via Emilia Parmense 84, 29122 Piacenza, Italy.

The aim of this work was to investigate the effect of meteorological conditions on resveratrol concentration of red wines produced in Piacenza viticultural region (Italy). In this regard, six representative estates producing Colli Piacentini Gutturnio DOC (a blend of L. cvs. Barbera and Croatina) vintage wines were analysed for trans- and cis-resveratrol over an 8-year period (1998-2005). Grapes were taken from the same vineyard in each estate by using the same enological practices over the entire investigated period. The meteorological conditions corresponding to the production areas were recorded, and bioclimatic indices were calculated as well. Overall, cis-resveratrol concentration was negatively correlated to Huglin index and August mean temperature, whilst positive correlation coefficients were found when considering the Selianinov index and the rainfall of September.
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http://dx.doi.org/10.3390/molecules26020401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828720PMC
January 2021

Identification of markers of sensory quality in ground coffee: an untargeted metabolomics approach.

Metabolomics 2020 12 14;16(12):127. Epub 2020 Dec 14.

Department for Sustainable Food Process, Università Cattolica del Sacro Cuore, Via Emilia Parmense 84, 29122, Piacenza, Italy.

Introduction: In the last years, consumers increased the demand for high-quality and healthy beverages, including coffee. To date, among the techniques potentially available to determine the overall quality of coffee beverages, metabolomics is emerging as a valuable tool.

Objective: In this study, 47 ground coffee samples were selected during the 2018 Edition of the "International coffee tasting" (ICT) in order to provide discrimination based on both chemical and sensory profiles. In particular, 20 samples received a gold medal ("high quality" group), while lower sensory scores characterized 27 samples (without medal).

Methods: Untargeted metabolomics based on ultra-high pressure liquid chromatography coupled with quadrupole-time-of-flight (UHPLC-QTOF) and head space-gas chromatography coupled with mass spectrometry platforms followed by multivariate statistical approaches (i.e., both supervised and unsupervised) were used to provide new insight into the searching of potential markers of sensory quality.

Results: Several compounds were identified, including polyphenols, alkaloids, diazines, and Maillard reaction products. Also, the headspace/GC-MS highlighted the most important volatile compounds. Polyphenols were scarcely correlated to the sensory parameters, whilst the OPLS-DA models built using typical coffee metabolites and volatile/Maillard compounds possessed prediction values > 0.7. The "high quality" group showed specific metabolomic signatures, thus corroborating the results from the sensory analysis. Overall, methyl pentanoate (ROC value = 0.78), 2-furfurylthiol (ROC value = 0.75), and L-Homoserine (ROC value = 0.74) established the higher number of significant (p < 0.05) correlations with the sensory parameters.

Conclusion: Although ad-hoc studies are advisable to further confirm the proposed markers, this study demonstrates the suitability of untargeted metabolomics for evaluating coffee quality and the potential correlations with the sensory attributes.
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http://dx.doi.org/10.1007/s11306-020-01751-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736008PMC
December 2020

Nutraceutical Profiles of Two Hydroponically Grown Sweet Basil Cultivars as Affected by the Composition of the Nutrient Solution and the Inoculation With .

Front Plant Sci 2020 5;11:596000. Epub 2020 Nov 5.

Faculty of Science and Technology, Free University of Bozen-Bolzano, Bolzano, Italy.

Sweet basil ( L.) is one of the most produced aromatic herbs in the world, exploiting hydroponic systems. It has been widely assessed that macronutrients, like nitrogen (N) and sulfur (S), can strongly affect the organoleptic qualities of agricultural products, thus influencing their nutraceutical value. In addition, plant-growth-promoting rhizobacteria (PGPR) have been shown to affect plant growth and quality. is a PGPR able to colonize the root system of different crops, promoting their growth and development and influencing the acquisition of mineral nutrients. On the bases of these observations, we aimed at investigating the impact of both mineral nutrients supply and rhizobacteria inoculation on the nutraceutical value on two different sweet basil varieties, i.e., and . To these objectives, basil plants have been grown in hydroponics, with nutrient solutions fortified for the concentration of either S or N, supplied as SO or NO , respectively. In addition, plants were either non-inoculated or inoculated with . At harvest, basil plants were assessed for the yield and the nutraceutical properties of the edible parts. The cultivation of basil plants in the fortified nutrient solutions showed a general increasing trend in the accumulation of the fresh biomass, albeit the inoculation with did not further promote the growth. The metabolomic analyses disclosed a strong effect of treatments on the differential accumulation of metabolites in basil leaves, producing the modulation of more than 400 compounds belonging to the secondary metabolism, as phenylpropanoids, isoprenoids, alkaloids, several flavonoids, and terpenoids. The primary metabolism that resulted was also influenced by the treatments showing changes in the fatty acid, carbohydrates, and amino acids metabolism. The amino acid analysis revealed that the treatments induced an increase in arginine (Arg) content in the leaves, which has been shown to have beneficial effects on human health. In conclusion, between the two cultivars studied, displayed the most positive effect in terms of nutritional value, which was further enhanced following inoculation.
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http://dx.doi.org/10.3389/fpls.2020.596000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674207PMC
November 2020

Impact of a Pitanga Leaf Extract to Prevent Lipid Oxidation Processes during Shelf Life of Packaged Pork Burgers: An Untargeted Metabolomic Approach.

Foods 2020 Nov 15;9(11). Epub 2020 Nov 15.

Department for Sustainable Food Process (DiSTAS), Università Cattolica del Sacro Cuore, Via Emilia Parmense 84, 29122 Piacenza, Italy.

In this work, the comprehensive metabolomic changes in pork burgers treated with different antioxidants, namely, (a) a control without antioxidants, (b) 200 mg/kg butylated hydroxytoluene (BHT), and (c) 250 mg/kg pitanga leaf extract (PLE, from L.), each one packaged under modified atmosphere (80% O and 20% CO) for 18 days storage at 2 ± 1 °C, were deeply studied. In particular, untargeted metabolomics was used to evaluate the impact of the antioxidant extracts on meat quality. The PLE phytochemical profile revealed a wide variety of antioxidant compounds, such as polyphenols, alkaloids, and terpenoids. Multivariate statistics (both unsupervised and supervised) allowed to observe marked differences in BHT and PLE burgers metabolomic profiles during storage. Most of the differences could be attributed to hexanoylcarnitine, 4-hydroxy-2-nonenal, 6-hydroxypentadecanedioic acid, 9S,11S,15S,20-tetrahydroxy-5Z,13E-prostadienoic acid (20-hydroxy-PGF2a), sativic acid, followed by glycerophospholipids. In addition, significant correlations ( < 0.01) were observed between thiobarbituric acid reactive substances and metabolites related to lipid oxidation processes. Therefore, the approach used showed a clear modulation of lipid oxidation, likely promoted by the plant leaf extract, thus confirming the ability of PLE to delay lipid oxidative phenomena during storage.
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http://dx.doi.org/10.3390/foods9111668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7696221PMC
November 2020

Changes in physiological activities and root exudation profile of two grapevine rootstocks reveal common and specific strategies for Fe acquisition.

Sci Rep 2020 11 2;10(1):18839. Epub 2020 Nov 2.

Biotechnology Department, University of Verona, Verona, Italy.

In several cultivation areas, grapevine can suffer from Fe chlorosis due to the calcareous and alkaline nature of soils. This plant species has been described to cope with Fe deficiency by activating Strategy I mechanisms, hence increasing root H extrusion and ferric-chelate reductase activity. The degree of tolerance exhibited by the rootstocks has been reported to depend on both reactions, but to date, little emphasis has been given to the role played by root exudate extrusion. We studied the behaviour of two hydroponically-grown, tolerant grapevine rootstocks (Ramsey and 140R) in response to Fe deficiency. Under these experimental conditions, the two varieties displayed differences in their ability to modulate morpho-physiological parameters, root acidification and ferric chelate reductase activity. The metabolic profiling of root exudates revealed common strategies for Fe acquisition, including ones targeted at reducing microbial competition for this micronutrient by limiting the exudation of amino acids and sugars and increasing instead that of Fe(III)-reducing compounds. Other modifications in exudate composition hint that the two rootstocks cope with Fe shortage via specific adjustments of their exudation patterns. Furthermore, the presence of 3-hydroxymugenic acid in these compounds suggests that the responses of grapevine to Fe availability are rather diverse and much more complex than those usually described for Strategy I plants.
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http://dx.doi.org/10.1038/s41598-020-75317-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606434PMC
November 2020

Kidney function and the risk of heart failure in patients with new-onset atrial fibrillation.

Int J Cardiol 2020 Dec 6;320:101-105. Epub 2020 Aug 6.

Department of Cardiology, Karolinska University Hospital, Solna, Sweden; Department of Medicine Karolinska Institutet, Huddinge, Sweden. Electronic address:

Aims: Heart failure (HF) is the most common complication of patients with atrial fibrillation (AF), but possible risk factors or health consequences are not well described. Low kidney function is a risk factor for both AF and HF. We evaluated estimated glomerular filtration rate (eGFR) as a predictor of HF in patients with AF, and then quantified the adverse health outcomes associated to incident HF.

Methods And Results: This is an observational analysis of 19,662 adults without a previous history of HF who had new-onset AF in Stockholm healthcare (Sweden) during 2007-2011. During a median of 713 (IQR 281-1253) days of follow up, 3342 (16.4%) patients developed HF, with incidence rate of 7.4 per 100-person-years (95% CI 7.2-7.7). In Cox regression, eGFR was linearly associated with subsequent HF risk. Compared to eGFR≥60 ml/min/1.73 m, patients with eGFR 30-59 and eGFR<30 ml/min/1.73 m had 13% (HR 1.13; 95% CI 1.04-1.23) and 53% (HR 1.53; 1.25-1.88) higher risk of HF. Results were consistent across various pre-specified subgroups and after excluding early events. Compared to non-HF, developing HF (as a time-varying exposure) was associated with a 5-fold (HR 5.05; 4.07-6.28) higher risk of subsequent kidney function decline, a 1.5 times higher risk of stroke (HR 1.54; 1.35-1.76), and a doubling in the risk of myocardial infarction (HR 2.21; 1.87-2.62) and death (HR 2.17; 2.01-2.33).

Conclusion: In patients with AF, low kidney function associates with the risk of HF. Developing HF heightened the subsequent risk of kidney function decline, cardiovascular event and death.
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http://dx.doi.org/10.1016/j.ijcard.2020.08.003DOI Listing
December 2020

Acceleration of kidney function decline after incident hospitalization with cardiovascular disease: the Stockholm CREAtinine Measurements (SCREAM) project.

Eur J Heart Fail 2020 10 20;22(10):1790-1799. Epub 2020 Aug 20.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

Aims: The cardiorenal syndrome refers to a bidirectional relationship between the kidney and the heart. However, epidemiological evidence of cardiovascular disease (CVD) as a risk factor for chronic kidney disease (CKD) progression is actually scarce.

Methods And Results: We examined the slopes of estimated glomerular filtration rate (eGFR) decline in the 2 years before vs. after an incident hospitalization with heart failure (HF) (n = 20 420), coronary heart disease (CHD) (n = 18 152), or stroke (n = 1808) using data from a complete laboratory data collection in Stockholm, Sweden between 2006 and 2011. eGFR slopes were estimated using mixed-effect models with unstructured residual correlation. Overall, incident hospitalization with HF and CHD, but not stroke, was significantly associated with a subsequent accelerated decline in eGFR, with a faster eGFR decline and greater slope change after HF than CHD. The pre-event vs. post-event eGFR slopes (mL/min/1.73 m per year) were -1.67 (-1.77 to -1.57) vs. -2.76 (-2.82 to -2.71), with a Δslope of -1.09 (-1.16 to -1.02) for HF; -1.09 (-1.20 to -0.98) vs. -1.87 (-1.92 to -1.81), with a Δslope of -0.78 (-0.85 to -0.70) for CHD; and -1.00 (-1.37 to -0.63) vs. -0.99 (-1.19 to -0.78), with a Δslope of 0.02 (-0.24 to 0.27) for stroke. The accelerated declines in eGFR after HF and CHD were consistent across the spectrum of eGFR, although pre-event eGFR slopes were steeper in lower eGFR (e.g. pre-event eGFR slope for HF -0.64 (-0.76 to -0.53) for eGFR ≥60 mL/min/1.73 m , -1.43 (-1.57 to -1.30) for eGFR 30-59 mL/min/1.73 m , and -2.42 (-2.71 to -2.12) for eGFR <30 mL/min/1.73 m ).

Conclusions: Incident hospitalization with cardiac diseases (i.e. HF and CHD) was significantly associated with a subsequent acceleration of eGFR decline.
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http://dx.doi.org/10.1002/ejhf.1968DOI Listing
October 2020

Isolation and Screening of Extracellular PGPR from the Rhizosphere of Tomato Plants after Long-Term Reduced Tillage and Cover Crops.

Plants (Basel) 2020 May 25;9(5). Epub 2020 May 25.

Department for Sustainable Food Process, Università Cattolica del Sacro Cuore, 29122 Piacenza, Italy.

Plant growth promoting rhizobacteria provide an innovative solution to address challenges in sustainable agro-ecosystems, improving plant growth as well as acting as agents of biocontrol. In this study autochthonous bacteria were isolated from the rhizosphere of processing tomato plants ( L) cultivated with conservation agriculture practices (i.e., reduced tillage and cover crops), and evaluated for both growth-promoting activities (PGPAs), and antagonistic potential against the phytopathogenic pest . Considering the several activities of PGPR, we decided to structure the screening with a hierarchic approach, starting from testing the capability of fixing nitrogen. The obtained bacteria were processed through the molecular typing technique rep-PCR (Repetitive Extragenic Palindromic) in order to discriminate microbial strains with the same profiles, and identified via 16S rDNA sequencing. Thirty-eight selected isolates were screened in vitro for different activities related to plant nutrition and plant growth regulation as well as for antifungal traits. Isolated bacteria were found to exhibit different efficiencies in indoleacetic acid production and siderophore production, phosphate solubilization and biocontrol activity against the widespread soil-borne plant pathogen . All the 38 bacterial isolates showed at least one property tested. With a view to detect the suitable candidates to be developed as biofertilizers, the selected isolates were ranked by their potential ability to function as PGPR. Thus, consortium of native PGPR bacteria inoculants may represent a suitable solution to address the challenges in sustainable agriculture, to ensure crop yield and quality, lowering the application of chemicals input.
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http://dx.doi.org/10.3390/plants9050668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7285081PMC
May 2020

Bisphosphonate utilization across the spectrum of eGFR.

Arch Osteoporos 2020 05 9;15(1):69. Epub 2020 May 9.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

Bisphosphonates are the most common treatment for osteoporosis but there are concerns regarding its use in CKD. We evaluated the frequency of BSP by eGFR categories among patients with osteoporosis from two healthcare systems. Our results show that 56% of patients were treated, with reduced odds in those with lower eGFR.

Introduction: Osteoporosis is common in patients with chronic kidney disease (CKD). Bisphosphonates (BSP) are the most common treatment but there are concerns regarding its efficacy and toxicity in CKD. We evaluated the frequency of BSP use by level of estimated glomerular filtration rate (eGFR) in patients with osteoporosis.

Methods: We assessed BSP use in patients with incident osteoporosis from the SCREAM-Cohort, Stockholm-Sweden, and Geisinger Healthcare, PA, USA. Osteoporosis was defined as the first encountered ICD diagnosis, and BSP use was defined as the dispensation or prescription of any BSP from 6 months prior to 3 years after the diagnosis. Multinomial logistic regression was used to account for the competing risk of death.

Results: A total of 15,719 women and 3011 men in SCREAM and 17,325 women and 3568 men in Geisinger with incident osteoporosis were included. Overall, 56% of individuals used BSP in both studies, with a higher proportion in women. After adjustments, the odds of BSP was lower across lower eGFR in SCREAM, ranging from 0.90 (0.81-0.99) for eGFR 75-89 mL/min/1.73m to 0.56 (0.46-0.68) for eGFR 30-44 mL/min/1.73m in women and from 0.72 (0.54-0.97) for eGFR of 60-74 to 0.42 (0.25-0.70) for eGFR 30-44 mL/min/1.73m in men. In Geisinger, odds were lower for eGFR < 30 mL/min/1.73m in both sexes and the frequency of BSP use dropped over time.

Conclusion: In the two healthcare systems, approximately half of the people diagnosed with osteoporosis received BSP. Practices of prescription in relation to eGFR varied, but those with lower eGFR were less likely to receive BSP.
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http://dx.doi.org/10.1007/s11657-020-0702-2DOI Listing
May 2020

New insights in the allelopathic traits of different barley genotypes: Middle Eastern and Tibetan wild-relative accessions vs. cultivated modern barley.

PLoS One 2020 23;15(4):e0231976. Epub 2020 Apr 23.

Faculty of Science and Technology, Free University of Bozen-Bolzano, Bolzano, Italy.

The two alkaloids gramine and hordenine have been known for playing a role in the allelopathic ability in barley (Hordeum vulgare L.). These allelochemicals can be both found in leaves and roots in some barley cultivars whereas in others one seems to exclude the other. In this study eighteen accessions of barley from the Middle-East area, one accession from Tibet and the modern spring cultivar Barke, already used as parental donor in a nested associated mapping (NAM) population, were screened for their gramine, hordenine and N-methyltyramine (the direct precursor of hordenine) content in leaves, roots and exudates. Moreover, the toxicity of the three allelochemicals on root growth inhibition on lettuce (Lactuca sativa L.) was evaluated. Results of this study showed the preferential production of gramine and hordenine in leaves and roots, respectively, in the nineteen barley accessions. On the other hand, in the modern barley cultivar Barke, the highest content of hordenine in roots and the general lack of gramine suggests a favored biosynthesis of the former. Gramine was not detected in the root exudates. In additions, different metabolomic profiles were observed in wild relatives compared to modern barley genotypes. The results also showed the phytotoxic effects of the three compounds on root growth of lettuce seedlings, with a reduction in root length and an increase of root surface area and diameter. In conclusion, this study highlighted the impact of the domestication effects on the production and distribution of the two allelopathic alkaloids gramine and hordenine in barley.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0231976PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7179892PMC
July 2020

Metabolomic Study to Evaluate the Transformations of Extra-Virgin Olive Oil's Antioxidant Phytochemicals During In Vitro Gastrointestinal Digestion.

Antioxidants (Basel) 2020 Apr 6;9(4). Epub 2020 Apr 6.

Department for Sustainable Food Process, Università Cattolica del Sacro Cuore, Via Emilia Parmense 84, 29122 Piacenza, Italy.

In this work, different commercial extra-virgin olive oils (EVOO) were subjected to in vitro gastrointestinal digestion and the changes in bioactive compounds were evaluated by ultra-high-pressure liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry, using untargeted metabolomics. As expected, raw EVOO samples were abundant in total sterols (on average: 3007.4 mg equivalents/kg) and tyrosol equivalents (on average: 334.1 mg equivalents/kg). However, the UHPLC-QTOF screening allowed us to annotate 310 compounds, with a large abundance of sterols (219 compounds), followed by polyphenols (67 compounds) and terpenoids. The in vitro gastrointestinal digestion was found to affect the phytochemical composition of the different EVOO samples. In particular, both unsupervised and supervised statistics depicted the modifications of the bioactive profile following gastric and pancreatic phases. Overall, the compounds which resulted as the most affected by the in vitro digestion were flavonoids (cyanidin and luteolin equivalents), whilst relatively high % bioaccessibility values were recorded for tyrosol equivalents during the pancreatic phase (on average, 66%). In this regard, oleuropein-aglycone (i.e., the major phenolic compound in EVOO) was converted to hydroxytyrosol, moving from an average value of 1.3 (prior to the in vitro digestion) up to 9.7 mg equivalents/kg during the pancreatic step. As proposed in the literature, the increase in hydroxytyrosol might be the result of the combined effect of lipase(s) activity and acidic conditions. Taken together, the present findings corroborate the suitability of untargeted metabolomics coupled to in vitro digestion methods to investigate the bioaccessibility of phenolic compounds. In this regard, a significant impact of in vitro gastrointestinal digestion on polyphenolic profiles has been detected, thus suggesting the need to account for actual bioaccessibility values rather than just considering the amounts in the raw commodity.
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http://dx.doi.org/10.3390/antiox9040302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7222208PMC
April 2020

Glucagon-like peptide-1 receptor agonists and the risk of cardiovascular events in diabetes patients surviving an acute myocardial infarction.

Eur Heart J Cardiovasc Pharmacother 2021 Mar;7(2):104-111

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Nobels väg 12A, 171 77 Stockholm, Sweden.

Aims: Trial evidence indicates that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may reduce the risk of cardiovascular (CV) events in patients with diabetes and myocardial infarction (MI). We aimed to expand this observation to routine care settings.

Methods And Results: Prospective observational study including all patients with diabetes surviving an MI and registered in the nationwide SWEDEHEART registry during 2010-17. Multivariable Cox regression analyses were used to estimate the association between GLP-1 RAs use and the study outcome, which was a composite of stroke, heart failure, Re-infarction, or CV death. Covariates included demographics, comorbidities, presentation at admission, and use of secondary CV prevention therapies. In total, 17 868 patients with diabetes were discharged alive after a first event of MI. Their median age was 71 years, 36% were women and their median estimated glomerular filtration rate was 75 mL/min/1.73m2. Of those, 365 (2%) were using GLP-1 RAs. During median 3 years of follow-up, 7005 patients experienced the primary composite outcome. Compared with standard of diabetes care, use of GLP-1 RAs was associated with a lower event risk [adjusted hazard ratio (HR) 0.72; 95% confidence interval (CI): 0.56-0.92], mainly attributed to a lower rate of re-infarction and stroke. Results were similar after propensity score matching or when compared with users of sulfonylurea. There was no suggestion of heterogeneity across subgroups of age, sex, chronic kidney disease, and STEMI.

Conclusion: GLP-1 RAs use, compared with standard of diabetes care, was associated with lower risk for major CV events in healthcare-managed survivors of an MI.
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http://dx.doi.org/10.1093/ehjcvp/pvaa004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957901PMC
March 2021

Pigmented sorghum polyphenols as potential inhibitors of starch digestibility: An in vitro study combining starch digestion and untargeted metabolomics.

Food Chem 2020 May 23;312:126077. Epub 2019 Dec 23.

Department for Sustainable Food Process, Università Cattolica del Sacro Cuore, Via Emilia Parmense 84, 29122 Piacenza, Italy.

Polyphenols from five pigmented sorghum (PS) flours were in vitro evaluated as possible modulators of starch digestibility. White sorghum (WS) flour was used as control. Untargeted metabolomics depicted the phenolic composition of raw and cooked flours (obtained through heating at 100 °C for 30 min in water) highlighting differences in flavonoids and phenolic acids. Raw PS flours were characterized by greater tannin and kafirin contents when compared to WS, and, after cooking, PS flours had greater resistant starch (from 4.2 to 21.4 g /100 g dry matter), and lower starch hydrolysis index (HI) with respect to cooked WS. Multivariate statistics showed that flavonoids characterizing PS were the most discriminant compounds during the in vitro digestion. In addition, kafirin and total tannins content (on raw ingredients) along with the anthocyanin profiles (on cooked samples) were negative correlated with HI. Therefore, PS flours might be good candidates for the formulation of functional foods.
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http://dx.doi.org/10.1016/j.foodchem.2019.126077DOI Listing
May 2020

Identification of phenolic markers for saffron authenticity and origin: An untargeted metabolomics approach.

Food Res Int 2019 12 26;126:108584. Epub 2019 Jul 26.

Department for sustainable food process, Università Cattolica del Sacro Cuore, Via Emilia Parmense 84, 29122 Piacenza, Italy.

Saffron is a high-quality and expensive spice being widely subjected to adulteration. An UHPLC-ESI/QTOF-MS metabolomic-based approach was therefore used to investigate the discrimination potential between adulterated (added with different percentage of other parts of the flower) and authentic saffron, as well as to trace its geographical origin. Both unsupervised (hierarchical clustering) and supervised OPLS-DA multivariate statistics allowed discriminating authentic saffron from styles added of other floral components, as well as PDO (Protected Designation of Origin) vs non PDO saffron samples according to their chemical fingerprints. The proposed markers were then validated through ROC curves. Anthocyanins and glycosidic flavonols were the best markers of the styles' adulteration. However, other flavonoids (mainly free flavonols and flavones), together with protocatechuic aldehyde and isomeric forms of hydroxybenzoic acid, were also validated as markers for the discrimination of PDO vs non PDO saffron samples. This work outlines the potential of untargeted metabolomics based on UHPLC-ESI/QTOF mass spectrometry for saffron authenticity and traceability.
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http://dx.doi.org/10.1016/j.foodres.2019.108584DOI Listing
December 2019

Efficacy and safety of edoxaban compared with warfarin according to the burden of diseases in patients with atrial fibrillation: insights from the ENGAGE AF-TIMI 48 trial.

Eur Heart J Cardiovasc Pharmacother 2020 07;6(3):167-175

TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Hale Building, Room 7022, 60 Fenwood Road, Boston, MA 02115, USA.

Aims: Non-vitamin K antagonist oral anticoagulants represent a new option for prevention of embolic events in patients with atrial fibrillation (AF). However, little is known about the impact of non-cardiac comorbidities on the efficacy and safety profile of these drugs.

Methods And Results: In a post hoc analysis of the ENGAGE AF-TIMI 48 trial, we analysed 21 105 patients with AF followed for an average of 2.8 years and randomized to either a higher-dose edoxaban regimen (HDER), a lower-dose edoxaban regimen, or warfarin. We used the updated Charlson Comorbidity Index (CCI) to stratify the patients according to the burden of concomitant disease (CCI = 0, 1, 2, 3, and ≥4). The treatment groups were then compared for safety, efficacy, and net clinical outcomes across CCI categories. There were 32.0%, 7.3%, 42.1%, 12.7%, and 6.0% of patients with CCI scores of 0, 1, 2, 3, and ≥4, respectively. A CCI score ≥4 was associated with significantly higher rates of thromboembolic events, bleeding, and death compared to CCI = 0 (P < 0.05 for each). The annualized rates of the primary net clinical outcome (stroke/systemic embolism, major bleeding, or death) for CCI = 0, 1, 2, 3, or ≥4 were 5.9%, 8.7%, 6.6%, 10.3%, and 13.6% (Ptrend < 0.001). There were no significant interactions between treatment with HDER vs. warfarin and efficacy, safety, and net outcomes across the CCI groups (P-interaction > 0.10 for each).

Conclusion: Although increasing CCI scores are associated with worse outcomes, the efficacy, safety, and net clinical outcomes of edoxaban vs. warfarin were independent of the degree of comorbidity present.
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http://dx.doi.org/10.1093/ehjcvp/pvz061DOI Listing
July 2020

Untargeted metabolomics with multivariate analysis to discriminate hazelnut (Corylus avellana L.) cultivars and their geographical origin.

J Sci Food Agric 2020 Jan 19;100(2):500-508. Epub 2019 Nov 19.

Department for Sustainable Food Process, Università Cattolica del Sacro Cuore, Piacenza, Italy.

Background: In the present study a metabolomics-based approach was used to discriminate among different hazelnut cultivars and to trace their geographical origins. Ultra-high-pressure liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry (UHPLC-ESI/QTOF-MS) was used to profile phenolic and sterolic compounds.

Results: Compounds were identified against an in-house database using accurate monoisotopic mass and isotopic patterns. The screening approach was designed to discern 15 hazelnut cultivars and to discriminate among the geographical origins of six cultivars from the four main growing regions (Chile, Georgia, Italy, and Turkey). This approach allowed more than 1000 polyphenols and sterols to be annotated. The metabolomics data were elaborated with both unsupervised (hierarchical clustering) and supervised (orthogonal projections to latent structures discriminant analysis, OPLS-DA) statistics. These multivariate statistical tools allowed hazelnut samples to be discriminated, considering both 'cultivar type' and 'geographical origin'. Flavonoids (anthocyanins, flavanols and flavonols - VIP scores 1.34-1.49), phenolic acids (mainly hydroxycinnamics - VIP scores 1.35-1.55) together with cholesterol, ergosterol, and stigmasterol derivatives (VIP scores 1.34-1.49) were the best markers to discriminate samples according to geographical origin.

Conclusions: This work illustrates the potential of untargeted profiling of phenolics and sterols based on UHPLC-ESI/QTOF mass spectrometry to discriminate hazelnut and support authenticity and origin. © 2019 Society of Chemical Industry.
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http://dx.doi.org/10.1002/jsfa.9998DOI Listing
January 2020

Association of Acute Increases in Plasma Creatinine after Renin-Angiotensin Blockade with Subsequent Outcomes.

Clin J Am Soc Nephrol 2019 09 8;14(9):1336-1345. Epub 2019 Aug 8.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden.

Background And Objectives: Data from observational and interventional studies provide discordant results regarding the relationship between creatinine increase after renin-angiotensin system inhibition (RASi) and adverse outcomes. We compared health outcomes among patients with different categories of increase in creatinine upon initiation of RASi in a large population-based cohort.

Design, Setting, Participants, & Measurements: We performed a retrospective analysis of the Stockholm CREAtinine Measurements database, which contains complete information on diagnoses, medication dispensation claims, and laboratory test results for all Stockholm citizens accessing health care. Included were 31,951 adults initiating RASi during 2007-2011 with available pre- and postinitiation creatinine monitoring. Multivariable Cox regression was used to compare mortality, cardiovascular and ESKD events among individuals with different ranges of creatinine increases within 2 months after starting treatment.

Results: In a median follow-up of 3.5 years, acute increases in creatinine were associated with mortality (3202 events) in a graded manner: compared with creatinine increases <10%, a 10%-19% increase showed an adjusted hazard ratio (HR) of 1.15 (95% confidence interval [95% CI], 1.05 to 1.27); HR 1.22 (95% CI, 1.07 to 1.40) for 20%-29%; HR 1.55 (95% CI, 1.36 to 1.77) for ≥30%. Similar graded associations were present for heart failure (2275 events, <0.001) and ESKD (52 events; <0.001), and, less consistently, myocardial infarction (842 events, 0.25). Results were robust across subgroups, among continuing users, when patients with decreases in creatinine were excluded from the reference group, and after accounting for death as a competing risk.

Conclusions: Among real-world monitored adults, increases in creatinine (>10%) after initiation of RASi are associated with worse health outcomes. These results do not address the issue of discontinuation of RASi when plasma creatinine increases but do suggest that patients with increases in creatinine have higher subsequent risk of cardiovascular and kidney outcomes.
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http://dx.doi.org/10.2215/CJN.03060319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6730502PMC
September 2019
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