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Background Whether hyperkalaemia in CKD is chronic or transient, and whether this has different outcome implications, is not known. Methods This was an observational study of adults with CKD G3–5 from Stockholm, Sweden 2006–11. We examined individual trajectories of potassium from all measurements obtained through routine outpatient care. For each month of follow-up, we created a rolling assessment of the proportion of time in which potassium was abnormal during the previous 12 months. We defined patterns of hyperkalaemia as transient (≤50% of time during the previous year with potassium >5.0 mmol/L) and chronic (>50% of time with potassium >5.0 mmol/L), and examined whether previous hyperkalaemia pattern offers additional predictive value beyond that provided by the most recent (current) potassium value. Results We included 36 511 participants (56% women) with CKD G3–5 and median estimated glomerular filtration rate 46 mL/min/1.73 m2. Transient and chronic hyperkalaemia, respectively, were observed in 15% and 4% of patients with CKD G3a, and in 50% and 17% of patients with CKD G5. In fully adjusted models, transient (hazard ratio 1.36, 95% confidence interval 1.29–1.46) or chronic (1.16, 1.04–1.32) hyperkalaemia patterns, but not current hyperkalaemia, were associated with major adverse cardiovascular events (MACE), compared with normokalaemia. Transient hyperkalaemia (1.43, 1.35–1.52) and current potassium values, but not chronic hyperkalaemia, were associated with the risk of death. Conclusions Between 4% and 17% of patients with CKD G3–5 develop chronic hyperkalaemia. In general, hyperkalaemia predicted MACE and death; however, the lack of effect of current potassium on MACE when adjusted for the previous pattern, and the stronger effects on death than on MACE, lead us to question whether hyperkalaemia is causal in these relationships. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. 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 m2, patients with eGFR 30–59 and eGFR<30 ml/min/1.73 m2 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). 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. • Kidney dysfunction is associated to both a higher risk of atrial fibrillation and a higher risk of heart failure. • Among patients with new-onset atrial fibrillation, kidney dysfunction is a risk factor for developing heart failure. • Once heart failure has occurred, this is followed by worsened outcomes and a further deterioration in kidney function. [ABSTRACT FROM AUTHOR]

Introduction People undergoing maintenance dialysis are at high risk for fractures, but less is known about fracture incidence and associated outcomes in earlier stages of chronic kidney disease (CKD). Methods We conducted an observational analysis from the Stockholm Creatinine Measurement project, a Swedish health care utilization cohort during 2006–11. We identified all adults with confirmed CKD Stages 3–5 and no documented history of fractures and extracted information on comorbid history, ongoing medication, cardiovascular events and death. We studied incidence rates of fractures (overall and by location), with the estimated glomerular filtration rate (eGFR) as time-dependent exposure. We then studied hazard ratios [HRs and 95% confidence intervals (CIs)] for the events of death and major adverse cardiac events (MACE) using Cox regression with fracture as time-varying exposure. Results We identified 68 764 individuals with confirmed CKD (mean age 79 years, 56% women). During a median follow-up of 2.7 years, 9219 fractures occurred, of which 3105 were hip fractures. A more severe CKD stage was associated with a higher risk of fractures, particularly hip fractures: compared with CKD Stage 3a, the adjusted HR was 1.10 (95% CI 1.02–1.19), 1.32 (1.17–1.49) and 2.47 (1.94–3.15) for CKD Stage 3b, 4 and 5, respectively. Spline curves suggested a linear association with fracture risk with an eGFR <30 mL/min/1.73 m2. Compared with non-fracture periods, incident fracture was associated with a 4-fold increased mortality within 90 days [HR 4.21 (95% CI 3.95–4.49)]. The risk remained elevated beyond 90 days [HR 1.47 (95% CI 1.40–1.54)] and was stronger after hip fractures. Post-fracture MACE risk was also highest in the first 90 days [HR 4.02 (95% CI 3.73–4.33)], particularly after hip fractures, and persisted beyond 90 days [HR 1.20 (95% CI 1.10–1.30)]. Conclusion Our findings highlight the commonness of fractures and the increased risk for subsequent adverse outcomes in CKD patients. These results may inform clinical decisions regarding post-fracture clinical surveillance and fracture prevention strategies. [ABSTRACT FROM AUTHOR]

Background Little is known about the health sequelae of pneumonia in persons with chronic kidney disease (CKD). Methods We studied adults with CKD in Stockholm during 2006–11, who not previously been diagnosed with lower respiratory tract infections. We used multivariable-adjusted Cox regression with pneumonia as a time-varying exposure to estimate hazard ratios (HRs) [95% confidence intervals (CIs)] for the events of death, major adverse cardiovascular events (MACEs), acute kidney injury (AKI), CKD progression or hospitalization for urinary tract infections (UTIs)/sepsis. Cataract and knee/joint replacement served as negative control outcomes. Results We identified 71 931 adults (mean age 79 years, 59% women), of whom 8379 (12%) were diagnosed with pneumonia during follow-up; incident pneumonia was associated with 10 times higher adjusted mortality risk during the first 90 days [HR = 10.0, 95% confidence interval (CI) 9.5–10.5] and double the mortality beyond 90 days from pneumonia diagnosis (HR = 2.0; 95% CI 1.9–2.1). Incident pneumonia was similarly associated with higher adjusted risk of MACE (<90 days: HR = 12.6; 95% CI 12.0–13.3; ≥90 days: HR = 1.5; 95% CI 1.4–1.6). The adjusted risk of CKD progression and UTI/sepsis hospitalization was highest within 90 days from pneumonia but remained elevated thereafter. For AKI, the association with incident pneumonia was only seen within 90 days. Neither cataract nor knee/joint replacement was related to pneumonia. Conclusions Incident pneumonia was associated with increased risks of MACE, CKD progression, severe UTI/sepsis and death, with risks highest soon after pneumonia diagnosis but extending beyond 90 days. Our findings highlight the susceptibility for adverse outcomes of CKD patients following pneumonia diagnosis, and may inform clinical decisions regarding vaccination strategies. [ABSTRACT FROM AUTHOR]

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 m2 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 m2, −1.43 (−1.57 to −1.30) for eGFR 30–59 mL/min/1.73 m2, and −2.42 (−2.71 to −2.12) for eGFR <30 mL/min/1.73 m2). Conclusions: Incident hospitalization with cardiac diseases (i.e. HF and CHD) was significantly associated with a subsequent acceleration of eGFR decline. [ABSTRACT FROM AUTHOR]

Simple Summary: Milk is one of the most globally produced foods with a growing trend, so its environmental performance needs to be studied. This research assessed the environmental impact of cow milk according to herds' performance through climate change and photochemical ozone creation potential indicators. The quality of feeds was also addressed. Under our conditions, knowing the nutritional characteristics of diets fed to animals as an alternative to tabulated values reduces the estimated impacts of considered indicators. An estimate of the environmental impact of dairy farms in Northern Italy producing milk for hard cheese (protected designation of origin) has been obtained through a comprehensive life cycle assessment. The estimate focused on climate change (CC) and photochemical ozone creation potential (POCP) indicators, which were evaluated according to the Intergovernmental Panel on Climate Change (IPCC) guidelines and interpreted with the aid of the feeds' composition evaluated using near-infrared reflectance spectroscopy (Foss NIR-System 5000) as well as with a diet evaluation according to the NRC (National Research Council) or the CNCPS (Cornell Net Carbohydrate and Protein System) nutrient requirement modeling. Herds were classified into high-, mid-, and low-performing based on the daily milk yield per cow. A lower impact on indicators was observed as herd performance increased. The high-performing herds had a lower contribution from enteric fermentation (6.30 × 10−1 kgCO2-eq), and the more milk that they produced allowed for a differentiation of CC from land use and transformation (2.39 × 10−1 kgCO2-eq), compared to low-performing herds (3.66 × 10−1 kgCO2-eq). Compared to the IPCC approach, the CC and POCP indicator estimates were reduced when addressing the feed's quality, particularly in mid- and high-performing herds. The results could be helpful in the dairy sector as they provide an insight into how diet quality affects the environmental impact of milk. [ABSTRACT FROM AUTHOR]

Background: Concerns for hyperkalaemia limit the use of mineralocorticoid receptor antagonists (MRAs). The frequency of MRA-associated hyperkalaemia in real-world settings and the extent of subsequent MRA discontinuation are poorly quantified.Methods and Results: Observational study including all Stockholm citizens initiating MRA therapy during 2007-2010. Hyperkalaemias were identified from all potassium (K+ ) measurements in healthcare. MRA treatment lengths and dosages were obtained from complete collection of pharmacy dispensations. We assessed the 1-year incidence and clinical hyperkalaemia predictors, and quantified drug prescription changes after an episode of hyperkalaemia. Overall, 13 726 new users of MRA were included, with median age of 73 years, 53% women and median plasma K+ of 3.9 mmol/L. Within a year, 18.5% experienced at least one detected hyperkalaemia (K+  > 5.0 mmol/L), the majority within the first 3 monthsnthsnthsnthsnths of therapy. As a comparison, hyperkalaemia was detected in 6.4% of propensity-matched new beta-blocker users. Chronic kidney disease (CKD), older age, male sex, heart failure, peripheral vascular disease, diabetes and concomitant use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers and diuretics were associated with increased hyperkalaemia risk. After hyperkalaemia, 47% discontinued MRA and only 10% reduced the prescribed dose. Discontinuation rates were higher after moderate/severe (K+  > 5.5 mmol/L) and early in therapy (<3 months from initiation) hyperkalaemias. CKD participants carried the highest risk of MRA discontinuation in adjusted analyses. When MRA was discontinued, most patients (76%) were not reintroduced to therapy during the subsequent year.Conclusion: Among real-world adults initiating MRA therapy, hyperkalaemia was very common and frequently followed by therapy interruption, especially among participants with CKD. [ABSTRACT FROM AUTHOR]

We previously showed2 that stopping angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEi/ARBs), in addition to stopping MRAs, is not an uncommon reaction to hyperkalaemia, occurring in 28% of cases. We appreciated the comments by Alexandrou and Sarafidis on our study about the clinical consequences of stopping versus continuing mineralocorticoid receptor antagonist (MRA) treatment after hyperkalaemia.1 We observed that stopping MRAs, compared with continuing, was associated with a higher risk of mortality. [Extracted from the article]

The present study was conducted to assess the possible restoration of different ecological functions in a Zn-contaminated soil. Experiments were conducted in a soil microcosm contaminated with 350 mg kg of Zn and in an uncontaminated control microcosm, both incubated for 4 months. At regular intervals, potential nitrification, nitrate reductase, and β-galactosidase activity were determined. All these activities were significantly reduced just after Zn contamination in contaminated microcosms compared to the activities of the control, but then increased. In order to confirm that the restoration of ecological functions was not due to an aging phenomenon, a reinoculation protocol was also applied. A significant restoration was found for β-galactosidase activity, while for nitrate reductase activity and potential nitrification, there was a clear shift of dose-response curves but with partial overlap of the EC ranges estimation, thus indicating that different ecological functions are restored over time in Zn-contaminated soils. [ABSTRACT FROM AUTHOR]

Abstract: The indicator EPRIP (Environmental Potential Risk Indicator for Pesticide) was released in 1997 with the aim of providing farmers with advice in selecting the most suitable pesticide with the least environmental impact. EPRIP 2, the newly developed, standalone version includes several improvements in the description of driving forces, in particular plant interception, drift and runoff and new database functionalities. EPRIP 2 is based upon the Exposure Toxicity Ratio (ETR) of the predicted environmental concentration (PEC) with toxicological parameters. When several applications of different active ingredients are used within the same pest control strategy, EPRIP 2 calculates a score for each active ingredient and for the overall pest control strategy. The latter evaluation is based on the probability of the EPRIP value exceeding two fixed risk thresholds. The probability of exceeding each threshold is calculated using the risk points of every application in the strategy and taking into account the risk points for surface water, groundwater, soil and air. [Copyright &y& Elsevier]

Surface water bodies may become contaminated via spray drift following pesticide application. In this investigation, the photodegradation and sorption of chlorpyrifos was studied in four riparian macrophytes representative of Mediterranean flora (Phragmites australis, Iris pseudacorus, Equisetum pratense and Typha latifolia). The results of experiments with both the active ingredient and the formulation DURSBAN 48® EC confirm the ability of these species to interact with chemicals such as chlorpyrifos. The maximum sorption of chlorpyrifos at equilibrium was observed in Phragmites australis (22%). And, the maximum instantaneous sorption of chlorpyrifos was observed in the dried biomass of Phragmites australis (49%). The epicuticular waxes present on leaves influence photodegradation processes, resulting in a decrease in chlorpyrifos persistence depending on the nature of the extract. The half-life of chlorpyrifos residues in leaf waxes decreased from 34 to 99 minutes when irradiated. [ABSTRACT FROM AUTHOR]

An environmental risk indicator for pesticide use is presented. Environmental potential risk indicator for pesticides (EPRIP) takes into consideration the fate of pesticides in all environmental compartments. The consideration of risk covers both direct and indirect effects, and short and long-term effects.The indicator is based upon the ratio of predicted environmental concentration (PEC), which represents the estimated exposure at a local scale (field and surroundings) with short-term toxicity data. Exposure toxicity ratio (ETR) values are transformed into risk points (RP) using a scale from 1 to 5 and the final EPRIP score is obtained by multiplying the RP values calculated for each compartment: surface water, groundwater, soil and air. The EPRIP score ranges from 1 to 825 and is divided into different classes of potential environmental risk on the basis of expert judgement. To evaluate the developed method, EPRIP was applied to a test management scenario with different alternatives of herbicide treatments for maize and soya bean. Results show that the indicator is able to discriminate fairly well among the different alternatives with final EPRIP scores ranging from 3 to 196 and from 2 to 115 for maize and soya bean, respectively, suggesting the treatment with the lowest risk for the environment. In conclusion, EPRIP could be a useful tool for farmers, technical advisors and regulating authorities to provide information on the environmental effects for different pesticide treatment strategies and to facilitate the selection of the best option to reduce the risk associated with pesticide use. [Copyright &y& Elsevier]

Background Despite long-standing clinical use of sodium polystyrene sulphonate (SPS) for hyperkalaemia management in chronic kidney disease (CKD), its safety profile remains poorly investigated. Methods We undertook an observational analysis of nephrology-referred adults with incident CKD Stage 4+ in Sweden during 2006–16 and with no previous SPS use. We studied patterns of use and adverse events associated to SPS initiation during follow-up. Patterns of SPS use were defined by chronicity of treatment and by prescribed dose. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) associated with SPS initiation (time-varying exposure) for the risk of severe (intestinal ischaemia, thrombosis or ulceration/perforation) and minor (de novo dispensation of laxatives or anti-diarrheal drugs) gastrointestinal (GI) events. Results Of 19 530 SPS-naïve patients with CKD, 3690 initiated SPS during follow-up. A total of 59% took SPS chronically, with an average of three dispensations/year. The majority (85%) were prescribed lower dosages than specified on the product label. During follow-up, 202 severe and 1149 minor GI events were recorded. SPS initiation was associated with a higher incidence of severe adverse events [adjusted HR 1.25 95% CI 1.05–1.49)], particularly in those receiving per label doses [1.54 (1.09–2.17)] and mainly attributed to ulcers and perforations. SPS initiation was also associated with higher incidence of minor GI events [adjusted HR 1.11 (95% CI 1.03–1.19)], regardless of dose, and mainly accounted for by de novo dispensation of laxatives. Conclusions Initiation of SPS in patients with advanced CKD is associated with a higher risk of severe GI complications as well as the initiation of GI-related medications, particularly when prescribed at per label doses. [ABSTRACT FROM AUTHOR]

Abstract In light of the considerable pressure exerted by food production on the environment, the assessment of the environmental burdens of dietary choices has recently gained interest among the scientific community. Several studies based on life cycle thinking approach agreed that a transition from an omnivorous to either a vegan or vegetarian diets would reduce the environmental impact associated with food consumption. The majority of the studies set the system boundaries up to the retail, excluding the consumption phase and generally do not account for uncertainties. The aim of the present study was to assess how personal consumption choices and behaviour can affect the greenhouse gas emissions generated by three balanced dietary patterns (omnivorous, vegetarian and vegan), defined on the basis of nutritional recommendations for an average Italian man. It took into consideration the uncertainties associated with three elements, namely the greenhouse gas emissions due to the production of the food items, the emissions associated with cooking and the food wasted by consumers. The results of the study highlighted that, despite the higher share of greenhouse gas emissions of the supply chain stages prior to consumption (66%–74% of the total emissions), domestic behaviours have an important influence of the total greenhouse gas emissions of the diet, which can offset the lower GHG emissions due to the choice of vegetable-origin foods. In fact, 15%–21% of the total emissions are associated to the cooking phase and 11%–13% to the food waste generation. Therefore, this study remarks the importance of adopting a cradle to grave perspective when assessing the environmental burden of dietary patterns and emphasises the central role of consumers in the definition of low GHG-emitting dietary patterns. Graphical abstract Unlabelled Image Highlights • Cradle to grave approach should be preferred comparing dietary patterns. • Production of food has to be considered within consumption and food waste stages. • Omnivorous, vegetarian and vegan diets have different impact on climate. • Consumers have a central role in the definition of low GHG-emitting dietary patterns. • Further modelling efforts needed to improve the modelling of personal behaviour. [ABSTRACT FROM AUTHOR]

Background: Stromal vascular fraction cells (SVFs) hold great promise for use in regenerative medicine applications, as a result of their ability to promote the healing process through in situ differentiation and the secretion of paracrine factors. The aim of this paper was to evaluate whether and how the topical application of SVF with platelet-rich plasma (PRP) for the treatment of chronic skin ulcers modified the cutaneous perfusion of the treated areas.Methods: Perilesional laser Doppler flowmetry (LDF) and transcutaneous oximetry (tcpO2) values were recorded for a 3-month period in 15 patients with chronic skin ulcers of various etiologies, who had been previously treated with single co-administered perilesional and intralesional injections of SVF+PRP.Results: No significant differences were found between pretreatment, 1 month, and 3 month posttreatment values regarding both LDF values (basal: p = 0.10 and declivous: p = 0.0976) and declivous tcpO2 levels (p = 0.0804). The only significant difference reported was between pretreatment and 3-month posttreatment basal tcpO2 levels (p = 0.0466).Conclusions: These results may reflect improved subcapillary circulation of the treated areas at 3 months postinjection, without a significant improvement in capillary perfusion.Level of Evidence: Level IV, therapeutic study. [ABSTRACT FROM AUTHOR]

Organisms are frequently exposed to mixtures of chemical contaminants in the environment, causing a potential “cocktail effect”, or combined effect. The joint action of different molecules with similar or different modes of action could result in a potentially unlimited number of additives, synergistic or antagonistic combinations. Since the large number of contaminants makes it impossible to perform ecotoxicity tests for each potential mixture, a robust approach for prospective environmental risk assessment of chemical mixtures is needed. A number of recent publications by the European Commission and the authorities in charge prove the increasing interest that is spreading in the European community towards the topic of the assessment of chemical mixtures. The current EU regulation for Plant Protection Products authorization (Reg. 1107/2009 EC) explicitly requires the evaluation of the potential combined effects of active substances. We reviewed current methods and limitations of mixture assessment of pesticides (7 fungicides and 4 herbicides) through the analysis of the approaches adopted to investigate possible risks for different non-target organisms. The Concentration Addition (CA) approach was the most used approach to predict multiple toxicity to non-target organisms. The guidance for birds and mammals first introduced standard procedures to assess the multiple toxicity based on on CA concept. The recent aquatic EFSA guidance introduced some requirements to evaluate potential mixture toxicity, while the current guidance requirements for terrestrial organisms still lack clear indications on how to conduct the assessment. Moreover, new indications come from the draft guidance for the assessment of terrestrial plants and in-soil organisms. However, the approval and implementation of these new guidelines are still at a developmental stage. Some final considerations are drawn on the future possibilities to improve risk assessment procedures so as to identify harmful effects of pesticides mixtures on non-target organisms. [ABSTRACT FROM AUTHOR]

• Distinct phenolic and sterol signatures were related to origin and authenticity. • Cholesterol-derivatives, tyrosols and oleuropeins, were markers of terroir. • Stilbenes, lignans, phenolic acids, and flavonoids were linked to authenticity. • Supervised modelling and Artificial Neural Networks provided different markers. Extra-virgin olive oil (EVOO) is subjected to different frauds. This work aimed at integrating the untargeted phenolic and sterol signatures with supervised multivariate discriminant analysis (OPLS-DA) and Artificial Neural Networks (ANN) for tracing the authenticity (as a function of variety, origin, and the blending) of Taggiasca Ligure, a renowned Italian EVOO. Overall, 408 samples from three consecutive growing seasons were used. Despite the cultivar, season, growth altitude, and geographical origin were all contributing to phytochemical profile, OPLS-DA models allowed identifying specific markers of authenticity. Cholesterol-derivatives and phenolics (tyrosols and oleuropeins, stilbenes, lignans, phenolic acids, and flavonoids) were the best markers, based on statistics. Thereafter, ANN was used to discriminate authentic Taggiasca, and the sensitivity was 100% (32/32) thus indicating an excellent classification. Our results strengthen the concept of "terroir" for EVOO and indicate that profiling sterols and phenolics can support EVOO integrity if adequate data treatments are adopted. [ABSTRACT FROM AUTHOR]

Abstract Background Organic food is generally considered as having healthier properties as consequence of the environmental-friendly management if compared with conventional food. However, there is a lack of strong scientific evidences that organic food is significantly different from the conventional regarding nutritional properties, environmental and human health impacts. Scope and approach The main scope of the present review is to assess the differences between the organic and conventional food in terms of nutritional properties, environmental impact and consumer perception and to identify future research needed. Key findings and conclusions Nutritional properties, the "environmental friendly" concept and the consumer perception aspects were analyzed to compare organic and conventional food. In general, non-significant differences in nutrient properties and carbon food prints between organic and conventional food have been observed, even if for the both aspects significant sensitivity and uncertainty are present and specific analysis to assess them are mandatory. Consumers perceive the organic food more valued even if relatively higher prices and poorer availability of organic products compared with their conventional counterparts could limit the purchase and the quality perception. Highlights • Differences between organic and conventional food is a continue debate. • No weighty nutritional and "eco-friendly" differences between organic and conventional food were scientifically demonstrated. • Organic food is more valued by consumers. • High sensitivity and uncertainty of scientific results should be considered in the future research. [ABSTRACT FROM AUTHOR]

The article reflects on research regarding pesticides and their effect on the environment. The scholarly periodical "Journal of Environmental Science & Health" has dedicated an entire issue to academic papers that were presented at the 2006 Annual Meeting of the Mediterranean Group of Pesticide Research (MGPR) in Sardegna, Italy in September, 2006. Scientists from various countries gathered to discuss the evaluation and control of pesticides in food and the environment. The article points out details concerning the MGPR meeting to be held in Morocco in November 2007.

Thiabendazole (TBZ), is a persistent fungicide/anthelminthic and a serious environmental threat. We previously enriched a TBZ‐degrading bacterial consortium and provided first evidence for a Sphingomonas involvement in TBZ transformation. Here, using a multi‐omic approach combined with DNA‐stable isotope probing (SIP) we verified the key degrading role of Sphingomonas and identify potential microbial interactions governing consortium functioning. SIP and amplicon sequencing analysis of the heavy and light DNA fraction of cultures grown on 13C‐labelled versus 12C‐TBZ showed that 66% of the 13C‐labelled TBZ was assimilated by Sphingomonas. Metagenomic analysis retrieved 18 metagenome‐assembled genomes with the dominant belonging to Sphingomonas, Sinobacteriaceae, Bradyrhizobium, Filimonas and Hydrogenophaga. Meta‐transcriptomics/‐proteomics and non‐target mass spectrometry suggested TBZ transformation by Sphingomonas via initial cleavage by a carbazole dioxygenase (car) to thiazole‐4‐carboxamidine (terminal compound) and catechol or a cleaved benzyl ring derivative, further transformed through an ortho‐cleavage (cat) pathway. Microbial co‐occurrence and gene expression networks suggested strong interactions between Sphingomonas and a Hydrogenophaga. The latter activated its cobalamin biosynthetic pathway and Sphingomonas its cobalamin salvage pathway to satisfy its B12 auxotrophy. Our findings indicate microbial interactions aligning with the 'black queen hypothesis' where Sphingomonas (detoxifier, B12 recipient) and Hydrogenophaga (B12 producer, enjoying detoxification) act as both helpers and beneficiaries. [ABSTRACT FROM AUTHOR]

Aims: The alkaloid hordenine is one of the major allelochemicals involved in the allelopathic ability of barley (Hordeum vulgare L.), whose biosynthesis and accumulation is preferentially located in roots. Hordenine appears to have been unintentionally favored during domestication in modern and cultivated barley cultivars at the expense of another alkaloid, gramine. In this study, we assessed the content of hordenine and its two precursors, N-methyltyramine (NMT) and tyramine, in roots and root exudates of the modern spring barley cv. Solist, and particularly how they are affected due to nutrient deficiencies. Methods: We monitored the three metabolites during the early phases of barley growth i.e., up to 8 days, applying HPLC time-course and both target and untargeted metabolomic approaches. Barley plants were grown either in full nutrient solutions or in specific nutrient shortage conditions (N, S, P and Fe). Results: Results confirmed a strong decrease of the allelochemical accumulation (hordenine and the two precursors) in roots and in root exudates during both 24 h and 8 days time-course experiments. Yet, the overall tyramine content was approximately tenfold lower compared to the other two compounds. In addition, plants subjected to nitrogen (-N), sulfur (-S), phosphorus (-P) and iron (-Fe) deprivation showed nutrient-dependent accumulation of hordenine, N-methyltyramine and tyramine, as well as of other secondary metabolites. Indeed, the synthesis of hordenine and N-methyltyramine was trigged under nutrient deficiencies. Conclusions: In conclusion, this study highlighted the impact of nutrient availability on the growth-dependent accumulation patterns of all the three compounds investigated in modern barley roots. [ABSTRACT FROM AUTHOR]

Silver-induced selective pressure is becoming increasingly important due to the growing use of silver (Ag) as an antimicrobial agent in biomedical and commercial products. With demonstrated links between environmental resistomes and clinical pathogens, it is important to identify microbial profiles related to silver tolerance/resistance. We investigated the effects of ionic Ag stress on soil bacterial communities and identified resistant/persistent bacterial populations. Silver treatments of 50-400 mg Ag kg-1 soil were established in five soils. Chemical lability measurements using diffusive gradients in thin-film devices confirmed that significant (albeit decreasing) labile Ag concentrations were present throughout the 9-month incubation period. Synchrotron X-ray absorption near edge structure spectroscopy demonstrated that this decreasing lability was due to changes in the Ag speciation to less soluble forms such as Ag0 and Ag2S. Real-time PCR and Illumina MiSeq screening of 16S rRNA bacterial genes showed β-diversity changes, increasing α-diversity in response to Ag pressure, and immediate and significant reductions in 16S rRNA gene counts with varying degrees of recovery. These effects were more strongly influenced by exposure time than by Ag dose at these rates. Ag-selected dominant OTUs principally resided in known persister taxa (mainly Gram positive), including metal-tolerant bacteria and slow-growing Mycobacteria. [ABSTRACT FROM AUTHOR]

MAGNITUDE (NCT03748641) demonstrated favourable outcomes with niraparib plus abiraterone acetate plus prednisone (+AAP) versus placebo+AAP in patients with BRCA1/2 -altered metastatic castration-resistant prostate cancer (mCRPC). Imbalances in prognostic variables were reported between arms, which impacts estimation of both the clinical benefit and cost‑effectiveness of niraparib+AAP for healthcare systems. A pre-specified multivariable analysis (MVA) demonstrated improved overall survival (OS) with niraparib+AAP. Here, we used an inverse probability of treatment weighting (IPTW) model to adjust for covariate imbalances and assess time-to-event outcomes. IPTW analysis of time-to-event outcomes was conducted using data from patients with BRCA1/2 -altered mCRPC (N = 225) in MAGNITUDE. Patients received niraparib+AAP or placebo+AAP. OS, radiographic progression-free survival, time to symptomatic progression, time to initiation of cytotoxic chemotherapy and time to prostate-specific antigen progression were assessed. Weighted Kaplan-Meier curves were generated for each endpoint, and adjusted hazard ratios (HR) were obtained from a weighted Cox model. Improvements in survival outcomes were estimated for niraparib+AAP versus placebo+AAP: unadjusted median OS was 30.4 months versus 28.6 months, respectively (HR: 0.79; 95 % confidence interval [CI]: 0.55, 1.12; p = 0.183). Following IPTW, median OS increased to 34.1 months with niraparib+AAP versus a decrease to 27.4 with placebo (HR: 0.65; 95 % CI: 0.46, 0.93; p = 0.017). Similar improvements were observed for other time-to-event endpoints. IPTW adjustment provided a more precise estimate of the clinical benefit of niraparib+AAP versus placebo+AAP in patients with BRCA1/2 -altered mCRPC. Results were consistent with the pre-specified MVA, and further demonstrated the value of adjusting for baseline imbalances, particularly in smaller studies. NCT03748641 (MAGNITUDE) • Baseline characteristic imbalances can cause reduced estimated treatment efficacy. • Robustness can be shown using multiple adjustment methods for baseline imbalances. • We used novel IPTW to assess time-to-event outcomes in the phase 3 MAGNITUDE trial. • Outcomes were consistent with the pre-specified MVA, with additional value shown. • This confirmed the clinical benefit of niraparib+AAP in BRCA1/2 -altered mCRPC. [ABSTRACT FROM AUTHOR]

A Life Cycle Assessment was conducted on 55 dairy farms located in Northern Italy to investigate the effect of dairy farming performance on the environmental impact of milk production. Feeds used in diet formulation were analyzed for nutrients contents by near-infrared reflectance technique, and the real composition was used to estimate methane emissions from enteric fermentation and manure handling. The functional unit was 1 kg of fat and protein corrected milk at the farm gate. The results were expressed according to the Product Environmental Footprint (PEF) method version 2.0 for 19 impact indicators through SimaPro® software v9.0.35. Five main data categories were considered: water used on the farm, off-farm feeds, energy resources, on-farm feeds, and bedding materials. Dairy farms were ranked into high-, mid-, and low-performing herds according to the average milk yield (>32.6; 25.4–32.6; <25.4 kg milk/cow/d; respectively). Statistical analysis between groups of herds was performed using JMP (JMP® Pro 15.2.0). The environmental impacts of indicators were lower (P < 0.05) in high-performing herds compared with low-performing herds and lower (P < 0.05) for climate change, climate change-biogenic, climate change-fossil, photochemical ozone formation human health (POCP), and eutrophication terrestrial when compared with mid-performing herds. Similar values among groups were observed for acidification, ionizing radiation human health, and ozone depletion potential indicators. The off-farm and on-farm feeds categories had the highest share of value of impact indicators. The enteric fermentation and manure handling significantly contributed to greenhouse gas emissions, whereas particulate matter formation and POCP were mainly related to barn management. Results from this research could be helpful in the dairy sector through the completeness of the expected impact indicators evaluated by the PEF method. • Environmental impacts of fifty-five dairy farms in Northern Italy were assessed at farm gate. • Product Environmental Footprint guidelines were used to express results for nineteen impact indicators. • Dairy farms were ranked into high-, mid- and low-performing herd groups. • A low environmental impact characterized high-performing herds. • The off-farm and in-farm feeds data categories were most responsible for impact indicators values. [ABSTRACT FROM AUTHOR]

The European Commission has been planning limits for organic pollutants in sewage sludge for 14 years; however no legislation has been implemented. This is mainly due to lack of data on sewage sludge contamination by organic pollutants, and possible negative effects to the environment. However, waste management has become an acute problem in many countries. Management options require extensive waste characterization, since many of them may contain compounds which could be harmful to the ecosystem, such as heavy metals, organic pollutants. The present study aims to show the true European position, regarding the polycyclic aromatic hydrocarbons (PAHs) content of sewage sludge, by comparing the Italian PAHs content with European Union countries, and at assessing the suitability of sewage sludge as soil fertilizer. The FOCUS Pearl model was used to estimate the concentration of benzo [a] pyrene (B(a)Pyr), the most toxic PAH in soil, and its exposure to organisms was then evaluated. The simulated B(a)Pyr and PAHs, expressed as B(a)Pyr, concentrations in soil were much lower than the B(a)Pyr’s most conservative lowest observable effect concentration (LOEC) for soil organisms. Furthermore, the results obtained indicate that it is more appropriate to apply 5 t ha −1 sewage sludge annually than 15 t ha −1 triennially. Results suggest, the EU maximum recommended limit of 6 mg kg − 1 PAHs in sewage sludge, should be conservative enough to avoid groundwater contamination and negative effects on soil organisms. [ABSTRACT FROM AUTHOR]

Glaciers are important ecosystems, hosting bacterial communities that are adapted to cold conditions and scarcity of available nutrients. Several works focused on the composition of bacterial communities in glaciers and on the long-range atmospheric deposition of pollutants in glaciers, but it is not clear yet if ski resorts can represent a source of point pollution in near-by glaciers, and if these pollutants can influence the residing bacterial communities. To test these hypotheses, 12 samples were analyzed in Madaccio Glacier, in a 3200 m a.s.l. from two areas, one undisturbed and one close to a summer ski resort that is active since the 1930s. Chemical analyses found concentrations up to 43 ng L − 1 for PCBs and up to 168 μg L − 1 for PAHs in the contaminated area: these values are significantly higher than the ones found in undisturbed glaciers because of long-range atmospheric deposition events, and can be explained as being related to the near-by ski resort activities. Isolation of strains on rich medium plates and PCR-DGGE analyses followed by sequencing of bands allowed the identification of a bacterial community with phylogenetic patterns close to other glacier environments, with Proteobacteria and Actinobacteria the mostly abundant phyla, with Acidobacteria , Firmicutes and Cyanobacteria also represented in the culture-independent analyses. A number of isolates were identified by molecular and biochemical methods as phylogenetic related to known xenobiotic-degrading strains: glaciers subjected to chemical contamination can be important reservoirs of bacterial strains with potential applications in bioremediation. [ABSTRACT FROM AUTHOR]

Seed inoculation with beneficial microorganisms has gained importance as it has been proven to show biostimulant activity in plants, especially in terms of abiotic/biotic stress tolerance and plant growth promotion, representing a sustainable way to ensure yield stability under low input sustainable agriculture. Nevertheless, limited knowledge is available concerning the molecular and physiological processes underlying the root‐inoculant symbiosis or plant response at the root system level. Our work aimed to integrate the interrelationship between agronomic traits, rhizosphere microbial population and metabolic processes in roots, following seed treatment with either arbuscular mycorrhizal fungi (AMF) or Plant Growth‐Promoting Rhizobacteria (PGPR). To this aim, maize was grown under open field conditions with either optimal or reduced nitrogen availability. Both seed treatments increased nitrogen uptake efficiency under reduced nitrogen supply revealed some microbial community changes among treatments at root microbiome level and limited yield increases, while significant changes could be observed at metabolome level. Amino acid, lipid, flavone, lignan, and phenylpropanoid concentrations were mostly modulated. Integrative analysis of multi‐omics datasets (Multiple Co‐Inertia Analysis) highlighted a strong correlation between the metagenomics and the untargeted metabolomics datasets, suggesting a coordinate modulation of root physiological traits. [ABSTRACT FROM AUTHOR]

In this study, the volatilization of five pesticides applied to an artificial flooded paddy field was assessed using the theoretical profile shape (TPS) and the integrate horizontal flux (IHF) techniques. The dataset derived was utilized to improve the volatilization routine of the rice water quality (RICEWQ) model. The masses of pesticides ethoprophos, procymidone, metalaxyl, chlorpyrifos, and chlorpyrifos methyl volatilized from paddy water and their concentrations in paddy water were determined for a period of 6 d after application. The highest and lowest volatilization losses were observed for chlorpyrifos and metalaxyl, respectively, accounting for 3.3% and 0.03% of their initially applied amount A rapid pesticide dissipation was evident in paddy water during the study period. The RICEWQ model was used to simulate the fate of pesticides in the artificial paddy system. The Kvolat, an empiric coefficient used by the model as an input parameter, was calculated for all pesticides through model calibration. RICEWQ simulated well the fate of pesticides in paddy water. A significant regression correlation between Henry's law constant (Hk) and Kvolat of the studied compounds was established which could facilitate the parametrization of the model for describing pesticide volatilization. [ABSTRACT FROM AUTHOR]

The development of methods to extract information from landscape analysis to refine risk assessment is becoming increasingly important. This paper presents results from a pesticide surface water exposure assessment at the watershed scale, based on a combination of edge of field studies, large-scale monitoring studies, and modeling activities with GIS-based landscape analysis methodologies covering an area of approximately 3200 ha surrounding the Simeto River in Sicily (Italy). The dynamic behavior of the pesticide chlorpyrifos.-methyl was modeled in two different steps: calculation of the fraction of the application rate that is deposited beyond the field edge and simulation of the fate and persistence of the pesticide in the aquatic environment. Drift loads showed high spatial variability. Considering spray drift deposition as a fraction of the pesticide application rate, 60% of the results were ≤ 0.02 (equal to 0.04 mg/m²). Only 8.5% of the results were above 0.5. The highly variability of the landscape factors was reflected in the results. More than 60% of the predicted pesticide concentrations were less than the limit of quantification (0.05 µg/L), affecting about 75% of the total length of the river tract analyzed. Predicted pesticide concentrations were higher than 0.1 µg/L in 23% of cases, but this corresponded to an insignificant portion of the river (1.2% of the total length). These results suggest that management options such as increased no-spray zones, could provide further protection for surface water. These could be modeled to illustrate their overall impact. As an alternative, the introduction of a 20-m no-spray zone clearly reduced potential exposure, and 92% of the water body was protected. Estimated data are in agreement with data collected during a field monitoring study. [ABSTRACT FROM AUTHOR]

A potential method for cleaning water from point-source pollution by organic compounds is using biological reactors. In this study, four reactors were tested for their ability to retain and degrade pesticides. The pesticides tested were the insecticide chlorpyrifos, the fungicide metalaxyl and the herbicide imazamox. The reactors were filled with differing mixtures of vine-branch, citrus peel, urban waste and public green compost. The reactor volume was 188 l. Forced circulation of the contaminated solution was programmed to decontaminate the solution. Both retention and degradation of the compounds by the reactors was studied.Chlorpyrifos was the best retained, due to its physico-chemical characteristics, while only one substrate effectively retained metalaxyl and imazamox (citrus peel + urban waste compost). Degradation of the pesticides in the reactors was faster than published values for degradation in soil. The half-life of all pesticides in the reactors was less than 14 days, compared to literature values of 60–70 days in soil. The combined retention and fast degradation make the biofilter a feasible technique to reduce spill-related and point environmental contamination by pesticides. The technique is most effective against persistent pesticides, while for mobile pesticides, the efficiency can be improved with several passages of the contaminated solution through biofilters. [Copyright &y& Elsevier]

Current farm systems rely on the use of Plant Protection Products (PPP) to secure high productivity and control threats to the quality of the crops. However, PPP use may have considerable impacts on human health and the environment. A study protocol is presented aiming to determine the occurrence and levels of PPP residues in plants (crops), animals (livestock), humans and other non-target species (ecosystem representatives) for exposure modelling and impact assessment. To achieve this, we designed a cross-sectional study to compare conventional and organic farm systems across Europe. Environmental and biological samples were/are being/will be collected during the 2021 growing season, at 10 case study sites in Europe covering a range of climate zones and crops. An additional study site in Argentina will inform the impact of PPP use on growing soybean which is an important European protein-source in animal feed. We will study the impact of PPP mixtures using an integrated risk assessment methodology. The fate of PPP in environmental media (soil, water and air) and in the homes of farmers will be monitored. This will be complemented by biomonitoring to estimate PPP uptake by humans and farm animals (cow, goat, sheep and chicken), and by collection of samples from non-target species (earthworms, fish, aquatic and terrestrial macroinvertebrates, bats, and farm cats). We will use data on PPP residues in environmental and biological matrices to estimate exposures by modelling. These exposure estimates together with health and toxicity data will be used to predict the impact of PPP use on environment, plant, animal and human health. The outcome of this study will then be integrated with socio-economic information leading to an overall assessment used to identify transition pathways towards more sustainable plant protection and inform decision makers, practitioners and other stakeholders regarding farming practices and land use policy. [ABSTRACT FROM AUTHOR]

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 (1- 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 1- 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 1- AR antagonists ameliorates lower respiratory tract infection- associated hyperinflammation and death, as observed in COVID-19. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The occurrence of microplastics (MPs) and nanoplastics (NPs) in soils potentially induce morphological, physiological, and biochemical alterations in plants. The present study investigated the effects of MPs/NPs on lettuce (Lactuca sativa L. var. capitata) plants by focusing on (i) four different particle sizes of polyethylene micro- and nanoplastics, at (ii) four concentrations. Photosynthetic activity, morphological changes in plants, and metabolomic shifts in roots and leaves were investigated. Our findings revealed that particle size plays a pivotal role in influencing various growth traits of lettuce (biomass, color segmentation, greening index, leaf area, and photosynthetic activity), physiological parameters (including maximum quantum yield - Fv/Fm max , or quantum yield in the steady-state Fv/Fm Lss , NPQ Lss , Rfd Lss , Ft Lss , Fq Lss), and metabolomic signatures. Smaller plastic sizes demonstrated a dose-dependent impact on aboveground plant structures, resulting in an overall elicitation of biosynthetic processes. Conversely, larger plastic size had a major impact on root metabolomics, leading to a negative modulation of biosynthetic processes. Specifically, the biosynthesis of secondary metabolites, phytohormone crosstalk, and the metabolism of lipids and fatty acids were among the most affected processes. In addition, nitrogen-containing compounds accumulated following plastic treatments. Our results highlighted a tight correlation between the qPCR analysis of genes associated with the soil nitrogen cycle (such as NifH, NirK, and NosZ), available nitrogen pools in soil (including NO 3 − and NH 4), N-containing metabolites and morpho-physiological parameters of lettuce plants subjected to MPs/NPs. These findings underscore the intricate relationship between specific plastic contaminations, nitrogen dynamics, and plant performance. • Plastics particle size plays a pivotal role in influencing lettuce response. • Smaller plastic sizes showed a dose-dependent impact on aboveground plant structures. • Larger plastic size showed a major impact on root metabolome. • The specific treatment, nitrogen dynamics, and plant performance were correlated. [ABSTRACT FROM AUTHOR]

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 V. vinifera 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 [ABSTRACT FROM AUTHOR]

BACKGROUND: Tomato is one of the most important agricultural crops and it is characterized by a wide bioactive compound profile. However, little information is reported on its comprehensive polyphenol profile. In this work, 13 commercial tomato cultivars for industrial transformation were screened by ultra‐high‐pressure liquid chromatography coupled to quadrupole‐time‐of‐flight mass spectrometry (UHPLC‐QTOF‐MS) for both free and bound phenolic profiles. Thereafter, the in vitro antioxidant activity of each cultivar was assessed by ferric reducing antioxidant power (FRAP) and oxygen radical absorbance activity (ORAC) assays. Multivariate statistics, i.e. orthogonal projection to latent structures discriminant analysis (OPLS‐DA), were then used to model samples according to their distinct phenolic signatures, thus providing compounds that better discriminated between the distributions of the cultivars that were considered. RESULTS: More than 350 phenolic compounds could be identified across the samples that were considered: flavonoids (such as flavones and flavanols), hydroxycinnamic acids, lignans, and lower‐molecular‐weight phenolics were the most frequently observed classes of phenolics in tomato berries. Anthocyanins were the most abundant class among bound phenolics (being highest in the Leader F1 and Defender F1 cultivars), followed by tyrosols (mainly in Heinz cultivars). However, flavones and hydroxybenzoic acids were the most represented discriminant phenolics in the bound fraction. CONCLUSIONS: Untargeted metabolomics allowed significant differences in phenolic composition to be outlined across the tomato cultivars that were analyzed. Such differences were particularly evident regarding the free‐to‐bound phenolic ratio, hence allowing differences in the bioaccessibility of phenolics to be postulated. © 2019 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

This study aimed to assess the effectiveness of plant growth-promoting rhizobacteria (PGPR; Pseudomonas strain So_08) and arbuscular mycorrhizal fungi (AMF; Rhizoglomus irregulare BEG72 and Funneliformis mosseae BEG234) in mitigating the detrimental effects of cadmium (Cd) and zinc (Zn) stress in tomato plants. Plant biomass, root morphology, leaf relative water content, membrane stability, photosynthetic performance, chlorophyll content, and heavy metals (HMs) accumulation were determined. Furthermore, an ionomic profile was conducted to investigate whether microbial inoculants affected the uptake and allocation of macro- and micronutrients. Metabolomics with pathway analysis of both roots and leaves was performed to unravel the mechanisms underlying the differential responses to HMs stress. The findings revealed that the levels of HMs did not significantly affect plant growth parameters; however, they affected membrane stability, photosynthetic performance, nutrient allocation, and chlorophyll content. Cadmium was mainly accumulated in roots, whilst Zn exhibited accumulation in various plant organs. Our findings demonstrate the beneficial effects of PGPR and AMF in mitigating Cd and Zn stress in tomato plants. The microbial inoculations improved physiological parameters and induced differential accumulation of macro- and micronutrients, modulating nutrient uptake balance. These results provide insights into the mechanisms underlying the plant-microbe interactions and highlight the differential modulation of the biosynthetic pathways of secondary metabolites related to oxidative stress response, membrane lipids stability, and phytohormone crosstalk. [Display omitted] • Microbial biostimulants are proposed to mitigate heavy metal stress in tomato. • A tripartite interaction between tomato, microbes and heavy metals was reported. • Such interaction was found to impact mineral nutrients uptake and allocation. • Photosynthetic performance and the oxidative status were modulated. • Metabolomics unravelled unique signatures to this multifactorial response. [ABSTRACT FROM AUTHOR]

In this preliminary study, ultra-high-pressure liquid chromatography (UHPLC) coupled to quadrupole-time-of-flight mass spectrometry (QTOF) metabolomics followed by multivariate statistics was applied to discriminate nine extra-virgin olive oil (EVOO) cultivars according to their phenolic and sterolic fingerprints. The same approach was then used to discriminate EVOO samples from different geographical origins, namely six blends representative of the main growing regions in Italy (i.e., Sicily, Puglia, Umbria, Liguria, Lombardy and Tuscany). This approach allowed to putatively identify >1000 compounds, considering both polyphenols and sterols. The unsupervised hierarchical cluster analysis (HCA) and the orthogonal projections to latent structures discriminant analysis (OPLS-DA) discriminated EVOO samples according to both cultivar and geographical origin. In particular, flavonoids (i.e., anthocyanins and flavonols), hydroxycinnamic acids and cholesterol derivatives were found to be the most representative classes of compounds discriminating EVOO samples according to the two parameters (cultivar or geographical origin) selected. However, the following Venn analysis allowed to point out the discriminant markers being exclusive for cultivar or origin discrimination. In this regard, only the 9.6% of phenolics and 13.6% of sterols were in common, thus indicating that several of these discriminant compounds were exclusive of a single condition. Indeed, considering that most of the commercial EVOOs are blended, the contribution of both the cultivars used and the geographical origin must be taken into account. Unlabelled Image • Sterolic and phenolic profiles in EVOO accounted for >1000 compounds. • The chemical fingerprints of each EVOO cultivar analyzed showed differences. • Multivariate statistics discriminated EVOO according to geographical origin. • Flavonoids, hydroxycinnamics and cholesterol derivatives were the best markers. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) and aortic stenosis (AS) share many risk factors.Objectives: This study sought to evaluate whether kidney dysfunction is associated with the development of AS in the community.Methods: The study included 1,121,875 Stockholm citizens without a prior diagnosis of AS from the SCREAM (Stockholm CREAtinine Measurements) project. Estimated glomerular filtration rate (eGFR) (ml/min/1.73 m2) was calculated from serum creatinine. AS incidence during follow-up was ascertained by clinical diagnostic codes. The association between eGFR and AS incidence was estimated with multivariable Cox proportional hazards models. Sensitivity analyses included analysis of possible reverse causation bias by excluding the first 6 months to 2 years after enrollment and excluding individuals with comorbid heart failure.Results: The median age was 50 years (interquartile range [IQR]: 36 to 64 years), and 54% of participants were women. Median eGFR was 96 ml/min/1.73 m2 (IQR: 82 to 109 ml/min/1.73 m2), and 66,949 (6.0%) participants had CKD (eGFR <60 ml/min/1.73 m2). During a median follow-up of 5.1 years (IQR: 3.3 to 6.1 years), 5,858 (0.5%) individuals developed AS (incidence rate [IR] 1.13/1,000 person-years). Compared with eGFR >90 (IR 0.34/1,000 person-years), lower eGFR strata were associated with higher hazards of AS: eGFR 60 to 90 ml/min/1.73 m2; IR: 1.88; hazard ratio (HR): 1.14; 95% confidence interval (CI): 1.05 to 1.25; eGFR 45 to 59 ml/min/1.73 m2; IR: 4.61; HR: 1.17; 95% CI: 1.05 to 1.30; eGFR 30 to 44 ml/min/1.73 m2; IR: 6.62; HR: 1.22; 95% CI: 1.07 to 1.39; and eGFR 30 ml/min/1.73 m2; IR: 8.27; HR: 1.56; 95% CI: 1.29 to 1.87. Sensitivity analysis attenuated only slightly the magnitude of the association; individuals with eGFR ≤44 ml/min/1.73 m2 remained at an approximate 20% risk of AS both when excluding events within the 2 years after baseline (HR: 1.22; 95% CI: 1.06 to 1.42) and when excluding participants with heart failure (HR: 1.20; 95% CI: 1.03 to 1.39).Conclusions: CKD, even in moderate to severe stages, is associated with an increased risk of AS. [ABSTRACT FROM AUTHOR]

Abstract The stimulation of the plant response to pathogen attack by the application of resistance inducers, called elicitors, could represent an environmentally and commercially viable alternative or complement to existing pathogen control methods. In this work, the elicitor chitosan was sprayed on grape (Vitus vinifera L.) berries growing on the vine to shed light into the elicitation mechanisms underlying its application, with untreated bunches as controls. To gain a more comprehensive picture of the complex molecular processes elicited by chitosan, a proteomic approach was complemented by target and untargeted mass spectrometric analyses. The treatment altered the regulation of reactive oxygen species, with Cu/Zn superoxide dismutase and glyoxal oxidase showing up-accumulation. This might lead to an increased lignification via hypersensitive response mechanisms. Furthermore, enzymes involved in anthocyanin rather than stilbene phytoalexins accumulated in treated bunches. Stilbenes increased from 1.6 times (resveratrol) up to 3.8 times (piceid) over untreated bunches. The up accumulation of hydroperoxide lyase might lead to accumulation of oxylipins. Furthermore, the pentacyclic triterpenoids ursolate, oleanoate and betulinate increased by 1.25, 1.47 and 3.68 times in treated grape bunches (p < 0.01). Hence, the main processes underlying the response of grape fruits to chitosan treatment involved the accumulation of phenylpropanoid and triterpenoids phytoalexins, as well as the modulation of oxidative stress–related enzymes. Graphical abstract Image 1 Highlights • Chitosan treatment resulted in an elicitation of grape defense mechanisms. • The treatment altered oxidative balance in bunches. • Enzymes involved in phytoalexins synthesis were accumulated in chitosan-treated bunches. • Chitosan increased the level of terpenoids ursolate, oleanoate and betulinate. [ABSTRACT FROM AUTHOR]