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Environmental extremes, such as drought and flooding, are becoming increasingly common, resulting in significant crop losses. The aim of the present study was to understand the molecular response induced by drought and waterlogging conditions, and to link these responses to the physiological adaptation of plants. For this purpose, leaf RNA expression was analyzed in potted kiwifruit plants by Illumina Next Generation Sequences. Stressed plants showed an impairment of all physiological parameters (leaf-gas exchange and stem-water potential) with a more evident effect in waterlogging condition than in drought condition. However, the impact on the transcriptome in waterlogged plants was less intense than in drought stress. Drought affected several metabolic pathways, among which “plant hormone signal transduction”, “protein processing in endoplasmic reticulum”, and “mitogen-activated protein kinase signaling pathway” were the most representative in terms of number of genes involved. The genes involved in the biosynthesis of phenylpropanoids were positively influenced by both drought and waterlogging. Finally, waterlogging stimulated secondary metabolisms by upregulating the genes responsible for the biosynthesis of terpenoids and flavonoids, such as stilbenoids. The obtained results show that the two contrasting stress conditions share several common physiological responses and molecular mechanisms.

The current political, social, and economic conditions place, more than ever, the need to sustainably supply nutrients for plants, integrating low-impact, crop-adapted, variable-rate-application fertilizer solutions, at the center of attention. Fertilization plans should be based on the monitoring of soil fertility to address the proper rate of fertilizer application along with the development of techniques able to increase nutrient uptake efficiency. Monitoring and modelling analysis of the effects of agronomic management in different pedoclimatic conditions can provide several advantages, that include higher nutrient efficiency, increase in plant growth and yield, decreased fertilization costs, increased profit, reduced environmental impact. This approach should enter into a framework of precision farming methodologies for the distribution of nutrients adopted at different levels (region, farm, field, plot), to obtain the maximum efficiency of inputs.

Persimmon is a typical fruit crop of the Mediterranean region and, since it is considered a minor species, little information is available on its nutrients need. In the present experiment, it was estimated the quantity of removed and recycled nutrients by Kaki Tipo and Rojo Brillante, the two main varieties of persimmon grown in Emilia-Romagna region (Po Valley, Italy). Plants from ten mature orchards were selected and harvested; organs (leaves in summer, fruits at harvest, abscissed leaves, roots and skeleton) biomass and mineral composition were determined. The yearly uptake of macronutrients was similar for the 2 varieties, accounting for (kg ha−1): N 89-91, P 10-11, K 79-91, Ca 132-162, Mg 22-26 and S 9. While K was mostly found in fruits, Ca and Mg were mainly partitioned to leaves. Among micronutrients, Mn and Fe showed the highest values (1.1–1.3 and 1.2–2.1 kg ha−1, respectively), followed by B (370 g ha−1), while Cu and Zn showed the smallest amounts (less 100 g ha−1). Nitrogen, Ca, Mg and S were those more recycled than removed, while K showed an opposite trend; among the microelements, the annual recycled fractions of B and Mn were higher than that removed.

Critical levels (CL) of available potassium (K) in soils and leaves and maximum technical efficiency (MTE) doses are relevant information to define the best K fertilization strategies. The aim of this study was to determine reference values of K in leaves and soil, using Bayesian analysis, in order to maximize grape yield and must quality of ‘Chardonnay’ and ‘Pinot Noir’ grown in a subtropical climate. The vines were subjected to applications of 0, 20, 40, 60 and 80 kg K2O ha−1 year−1. The CL and MTE doses of K, in leaves and soils, were determined using Bayesian hierarchical models. The range of probability of the occurrence of CL in leaves was 15.8 to 18.9 g K kg−1 in ‘Chardonnay’ and 16.8 to 19.1 g K kg−1 in ‘Pinot Noir’ at flowering. Moreover, the range was 15.3 to 18.1 g K kg−1 in ‘Chardonnay’ and 16.1 to 18.2 g K kg−1 in ‘Pinot Noir’ at veraison. In the soil, the CL of available K for ‘Chardonnay’ was 27.4 mg K kg−1 and for ‘Pinot Noir’ it was 23.2 mg K kg−1. The increase of K in leaves and soil increased the TSS, while the TTA decreased in both cultivars after sufficiency rate. The MTE was estimated in ‘Pinot Noir’. The proposition of CL and/or MTE doses of K can help increase the efficiency of K fertilization in vineyards.

Abstract Organic fertilization in orchards aims at increasing soil fertility, at impacting plant productivity and environmental sustainability. This study aimed at verifying the effects of organic fertilization and fruit load on two nectarine cultivars with high and low fruit loads. The experiment was carried out in an orchard under organic management in Fratta Terme, Po valley, in northeastern Italy. Nectarine cultivars Big Top and Carene, implemented in 2017 and grafted onto GF677, were used. Three levels of compost (0, 20 and 40 t dw ha-1) were combined with two fruit loads (low and high) to set up a factorial experimental design with two factors and four randomized replicates. Compost was incorporated at 20 cm depth. The following parameters were evaluated: nitrate- and ammonium- N concentrations in soil at 20 - 40 cm depth, macro and micronutrients in leaves, tree yield, number of fruits, fruit mass and diameter, soluble solids and pulp firmness. The supply of compost enhanced nitrate-N release in soil. In both cultivars, macro- and micronutrient concentrations in leaves were not affected by organic fertilization or fruit load, except for iron, which increased as a consequence of the compost supply. Low crop load induced higher fruit size in both varieties, a fact that was observed after pit hardening. However, the organic fertilization rate did not influence tree yield, fruit mass and soluble solids.

The intensification of highly specialized viticulture has led to a dramatic decrease of soil fertility that can be restored by increasing soil organic matter using organic fertilizers. The aim of the present experiment was to evaluate the effect of different organic amendments on vine vegetative growth and nutritional status, soil N availability and microbial biomass, as well as on yield and grape quality. The experiment was carried out in 2020 and 2021, on cv. Sangiovese (Vitis vinifera L.) vines grafted on 110 Richter (V. berlandieri × V. rupestris) planted in February 2019. Plants were fertilized yearly in spring with (1) mineral fertilization (MIN), (2) municipal organic waste compost (MOW), and (3) sewage sludge compost (SS). The application of SS increased nitrate availability in both years, while the supply of organic matter (no matter the source) enhanced soil microbial biomass content. Plant nutritional status was in the optimal range for all treatments, with an increase of N in SS and K in MOW. Fruit yield in 2020 was not influenced by treatments, while in 2021 it was enhanced by MIN and MOW, which also induced a higher berry quality. Plant vegetative growth was stimulated by the application of SS. In conclusion, from these preliminary results we observed a higher N availability as a consequence of SS supply that resulted in a higher plant biomass, but reduced yield and berry quality, supporting the theory that for vineyards, N should be carefully managed to reach an equilibrium between vegetative and reproductive activity.

Soil is a non-renewable resource essential to human life [...]

Agricultural land abandonment is an emerging problem in European Union (EU), and about 11% of agricultural EU land is at high risk of abandonment in the coming 10 years. Land abandonment may have both positive and negative effects in ecosystems. Due to the potential for land abandonment to increase soil fertility, the study of vegetation succession effects on soil quality is of great importance. In this study, we investigated an abandoned vineyard where, after a period of 30 years, rows and alleys were characterized by two different forms of vegetation succession: natural recolonization by trees along the rows and by herbaceous vegetation in the alleys. No-tilled alleys covered by herbaceous vegetation of a neighboring conventionally cultivated vineyard were used as a comparison. Soil samples were chemically characterized (pH, extractable element, and available and total metals), and analyzed for the determination of carbon (C) and nitrogen (N) pools; hydrolytic and phenol oxidizing (PO) enzyme activities involved in C, N, and phosphorus (P) cycles; and the enzyme ratios. Results highlighted that natural recolonization by trees increased the organic C and N soil pools by 58% and 34%, respectively, compared to the natural recolonization by herbaceous vegetation. Moreover, natural recolonization by trees reduced β-glucosidase by 79%, urease by 100%, alkaline phosphastase by 98%, acid phosphatase specific hydrolytic activities by 50%, and catechol oxidase and laccase specific oxidative activities by 127% and 119%, respectively, compared to the renaturalization by herbaceous vegetation. In addition, the natural recolonization by trees reduced the C (βglu):C (PO) enzymes ratio by 16% compared to that of the conventional vineyard. Comparing the natural recolonization by herbaceous vegetation with that of the conventional vineyard revealed little significant difference (15% of the measured and calculated parameters); in particular, PO activities significantly decreased in the renaturalized vineyard with herbaceous vegetation by 49% (catechol oxidase) and 52% (laccase), and the C (βglu):C (PO) enzyme ratio showed a reduction (−11%) in the vineyard naturally recolonized by herbaceous vegetation compared to the conventional vineyard. This highlights that the type of vegetation succession that takes place after land abandonment may have a significant impact in terms of soil fertility and C accrual potential. These results help to focus attention on the practices used in agro-forestry that should be adopted in abandoned agro-ecosystems to increase their biodiversity, soil C stock, and soil quality, because these indicators are affected by the type of vegetative coverage.

Phosphorus (P) availability in subtropical soils does not often meet the nutritional demand of native tree species such as the ipê-roxo tree (Handroanthus heptaphyllus); therefore, it is necessary to supply P at planting. However, the impact of P on root system growth remains unknown. The aim of the current study was to investigate the effect of P application on root morphology of H. heptaphyllus plants over a 36-month period in a subtropical climate region. During the experiment, the plants subjected to fertilization with 40 kg P ha−1 were compared to untreated control. Plant roots were scanned through minirhizotron system 18 and 36 months after transplant (MAT), and generated images were used to determine total root length, mean root diameter and total root volume. Plant height and leaf P concentrations were also evaluated. Phosphorus application enhanced root and whole plant growth with a more evident effect at 36 MAT, when soil P availability decreased. The results give important information on the cultivation of H. heptaphyllus plants in soils presenting low P availability.

The aim of the present experiment was to determine if the supply of biofertilizers could differently stimulate the native microbiota, thus determining different patterns of organic material decomposition processes. The microbial composition of soil and litter was investigated by next generation sequencing using a metabarcoding approach. The chemical structure of the decomposing litterbags was investigated through the TG-DTA analysis and NIR spectroscopy. The study was conducted in an apricot orchard in Italy, and two different type of biofertilizers (AMF and Trichoderma spp.) were compared to unfertilized control over one year. Bacteria and fungi in soil, 162 days from litter deposition, evidenced differentiated clusters for control and both biofertilizers; on the other hand, only fungal composition of litterbags was modified as a consequence of Trichoderma spp. supply; no effect was observed in the bacterial community of litterbags. NIR and TG-DTA analysis evidenced a significant change over time of the chemical composition of litterbags with a faster degradation as a consequence of Trichoderma spp. supply testified by a higher degradation coefficient (1.9) than control (1.6) and AMF (1.7). The supply of biofertilizers partially modified the bacteria community of soil, while Trichoderma spp. Influenced the fungal community of the litter. Moreover, Trichoderma spp. Evidenced a faster and higher degradation of litter than AMF-biofertilizers, laying the foundation for an efficient use in orchard.

Organic materials from agro-industry processes can be used in agriculture as a way to recycle materials that still maintain a high fertilizing value. The aim of the experiment was to evaluate the value of soil applied apple juice by-product as fertilizer for pear trees. A 3-year experiment was carried out in a mature pear orchard (cv Abbé Fétel grafted onto quince MC) in the Po valley (Italy), where the following treatments were compared: 1) unfertilized control; 2) mineral N fertilization (60 kg N ha−1 year−1 split in two spring applications); 3) apple juice by-product (1.3 t ha−1 year−1, equal to 60 kg N ha−1), fully supplied at petal drop; 4) apple juice by-product, at twice the rate of the previous treatment. Apple juice by-product soil decomposition accounted for 12% in the first 6 months. At the end of the 24-month-assay, the decomposition accounted for 24% on total dry weight that makes 28% of initial C and 36% of initial N. Soil nitrate-N concentration was increased by the mineral N fertilizer, while the application of apple juice by-product increased microbial carbon. Tree growth, yield and fruit quality were not affected by treatments, while mineral N fertilization raised leaf and fruit N concentration. In conclusion, in our conditions the use of apple juice by-product did not show negative effects on tree performances and fruit quality, with some advantages related to the recycling of organic wastes in agriculture.

Soil analysis is used to estimate nutrient availability, but nutrient concentrations are not always related to yield in most fruit plants, including grapevines. Thus, additional multivariate mathematical models, such as the compositional nutrient diagnosis (CND), which takes into account leaves nutrient concentration, and yield, can contribute to estimating critical levels or sufficiency bands of elements, as well as to detect deficiency and/or excess of nutrients. The aim of the present study was to establish CND standards, and the critical level and sufficiency band of nutrients, in the grapevine Vitis vinifera L., grown in a subtropical climate region. Leaves were collected in 81 vineyards in the Campanha Gaúcha do Rio Grande do Sul region, Southern Brazil, and analyzed for macro- and micro-nutrient concentration. The yield of each vineyard was assessed. Grapevine nutritional status was calculated through the CND method. CND-r2 indices were effective in establishing the nutritional status of grapevines for macro- and micro-nutrients as sub-optimal, excessive, or balanced. The CND methodology established the critical level and sufficiency bands of nutrients more accurately than the current recommendations for grapevines. Multi-nutrient associations were more effective than the single nutrient determination in defining the threshold of a given nutrient that can reduce grapevine yield.

The aim of the present experiment was to evaluate the effectiveness of soil electrical conductivity (EC) measurement as a fast tool to assess mineral nitrogen (N) in orchards, in order to define precise N inputs that can help farmers to reduce useless fertilizer application. During one vegetative season, seven orchards of different species, supplied with mineral or organic fertilization, were monitored. Nitrate soil concentration was measured monthly by laboratory analyses, while soil EC and moisture were recorded continuously by soil probes. Nitrate and EC were positively correlated, laying the foundation for the identification of a fast and reliable index. However, while some dates showed a high Pearson correlation coefficient, no correlation was found for others. The correlation was not affected by type of fertilizer, and was higher in silty-clay-loam than in loam soils. Pooling all of the data, a significant correlation with a Pearson coefficient of 0.75 was found. The soil optimal nitrate N availability was defined by an EC in the range of 0.3 to 0.6 mS cm−1. Although these are only preliminary results, our data are promising, showing a good suitability of soil EC measurement as a means to monitor soil mineral N availability.

BACKGROUND: The emergency regarding recent immigration waves into Italy makes continued healthcare monitoring of these populations necessary. METHODS: Through a survey of hospital admissions carried out during the last five years at the S. Orsola-Malpighi General Hospital of Bologna (Italy), all causes of admission of these subjects were evaluated, together with their correlates. Subsequently, we focused on admissions due to infectious diseases. All available data regarding foreign citizens admitted as inpatients or in Day-Hospital settings of our teaching hospital from January 1, 1999, to March 31, 2004, were assessed. Diagnosis-related group (DRG) features, and single discharge diagnoses, were also evaluated, and a further assessment of infectious diseases was subsequently made. RESULTS: Within a comprehensive pool of 339,051 hospitalized patients, foreign citizen discharges numbered 7,312 (2.15%), including 2,542 males (34.8%) and 4,769 females (65.2%). Males had a mean age of 36.8±14.7 years, while females were aged 30.8±12.2 years. In the assessment of the areas of origin, 34.6% of hospitalizations were attributed to patients coming from Eastern Europe, 15.3% from Northern Africa, 7.3% (comprehensively) from Western Europe and United States, 6.9% from the Indian subcontinent, 5.9% from sub-Saharan Africa, 5.7% from Latin America, 4.1% from China, 2.5% from the Philippines, and 1.1% from the Middle East. Among women, most hospitalizations (58.8%) were due to obstetrical-gynecological procedures or diseases, including assistance with delivery (27.1%), and pregnancy complications (18.7%), followed by psycho-social disturbances (5.9%), malignancies (5.1%), gastrointestinal diseases (4.7%), and voluntary pregnancy interruption (4.4%). Among men, the most frequent causes of admissions were related to trauma (15.9%), followed by gastroenteric disorders (12%), heart-vascular diseases (8.9%), psycho-social disorders (8.4%), respiratory (7.1%), kidney (6.1%), liver (5.2%), and metabolic (4.9%) diseases, and alcohol or substance abuse (4.2%). Infectious diseases (alone or with concurrent disorders) were reported in 881 discharged individuals, representing 12.1% of the 7,312 DRGs attributed to foreign patients. The comprehensive patient population discharged from our hospital with at least one infectious disease diagnosis had lower rates of respiratory tract infections, followed by chronic viral hepatitis, HIV infection and related diseases, enterocolitis, pulmonary tuberculosis, pyelonephritis, severe skin and soft tissue infection, meningoencephalitis, and malaria, as the most frequently-reported disorders. CONCLUSIONS: Our survey, through a combined analysis of both DRGs and discharge diagnoses, allowed us to conclude that 12.1% of foreign citizens hospitalized at our General teaching Hospital of Bologna (Italy) suffered from at least one infectious disease. Respiratory tract, liver, and gastrointestinal infections, and HIV infection, were found with an appreciable frequency among discharge diagnoses, while the frequency of malaria and meningoencephalitis was lower, compared with other series. Among disorders other than infectious diseases, obstetric-gynecological conditions and post-traumatic episodes (for male patients) were the most frequent causes of hospitalization.

The hospitalizations of 1,239 patients aged 14 years or less and immigrated from extra-European Union countries in Italy were assessed in the 6-year period, from 1999 to 2004. The main demographic and clinical features were analyzed according to several variables, also distiguishing patients aged less than one year, from those aged 1-14 years. The introduction of a deed of indemnity law in 2001 profoundly changed the pattern of admissions and health care needs and exploitation during subsequent years, leading to a massive regularization of clandestine immigrants.

Patients with cystic fibrosis are not reporting particularly sever outcomes upon SARS-CoV-2 infection. Here, the authors demonstrate decreased ACE2 levels is cystic fibrosis airway epithelia associated with impaired viral entry and replication.

Spondyloarthritis are chronic inflammatory diseases affecting spine, peripheral joints and enthesis, as well as extra-articular sites (bowel, eyes, skin). Diagnosis of spondyloarthritis often is slow and requires a multidisciplinary approach. The “Early SpA Clinic” project aimed at improving the patient care and journeys, by solving some organizational issues existing in Rheumatology Clinics. The “Early SpA Clinic” involved 19 Italian Rheumatology Centers using in-depth organizational analyses to identify areas for improvement. From the results of the analyses, some organizational solutions were suggested, and their impact measured at the end of the project through specific KPI. With the implementation of the suggested organizational solutions, Centers achieved relevant results, positively impacting on all the phases of the patient journey: decrease in waiting lists (−23%) and in the time length to transit the Center (−22%), increase in the percentage of new diagnoses (+20%), in the saturation of outpatient clinic capacity (+16%), and in the patient satisfaction (+4%). Centers involved in the “Early SpA Clinic” implemented several organizational actions based on an overall assessment of their activities and on solutions that required no additional resources. Overall, the Centers achieved the “Early SpA Clinic” objectives in terms of better management of resources, personnel, spaces, equipment, in relation to the volumes of patients.

The use of copper (Cu)-based fungicides to control diseases in vineyards can cause excessive Cu accumulation in soils. Greater Cu availability is expected in acid sandy soils with low organic matter (OM), where the risk of toxicity to plants and environment contamination is high. This study aimed to study the evolution of Cu in acid, sandy soils planted with grapevines for a period of time between 2 and 32 years. Two studies were carried out in South Brazil: in the first study, soil samples, from 19 vineyards were collected and analyzed in the first 0.2 m depth-layer for the total and available Cu. In the second study, 3 soils were selected among the previous 19 according to the age of vineyard (5, 11, and 30 year-old), and their 0.60 m-depth profile was analyzed for 5 fractions of Cu (soluble, exchangeable, mineral, organic, and residual). All the soils were classified as Ultisols. The vineyards with more than 25 years under cultivation had a mean total Cu concentration of 90 mg kg−1in the 0–0.10 m layer. Approximately 80% of it was potentially available to plants. The greatest total and available Cu were found in the soil surface layers (0.2 m depth), where up to 75% of the total Cu is adsorbed in clay minerals and only 20% is complexed in the OM. [ABSTRACT FROM PUBLISHER]

The aim of this study was to evaluate the sustainability of an agro-industry sludge as a nitrogen (N) fertilizer in perennial crops by assessing its dynamics of release of: 1) N as ammonium (NH4+)- and nitrate (NO3−)-N, and 2) carbon as soil respiration. In incubation assay, application of agro-industry sludge promoted the maximum NH4+-N concentration (50 mg kg−1) 2 h after application, then it decreased with time until day 26. NO3−-N increased, reaching the maximum between day 60 and day 100, according to a second degree function. Agro-industry sludge showed a slower release of NO3−-N compared with urea. Soil basal respiration and cumulative amount of carbon dioxide were higher in sludge from day 71 on. In field, soil NO3−-N increased after fertilization treatments and was higher in Calcari Stagnic Cambisols soil. Sludge showed a potential lower environment impact in terms of mineral N release, than urea. [ABSTRACT FROM AUTHOR]

The present study compares disease characteristics, imaging modalities used, and patterns of treatment in two large cohorts of Takayasu arteritis (TAK) from Italy and India. Clinic files were retrospectively reviewed to retrieve information about initial choices of vascular imaging and immunosuppressive therapies. Unpaired t-tests compared means, and proportions were compared using Fisher’s exact test or Chi square test [Odds ratios (OR) with 95% confidence intervals (95%CI) calculated where appropriate]. The cohorts comprised 318 patients [Italy (n = 127), India (n = 191)] with similar delays to diagnosis. Ultrasound (OR Italy vs. India 9.25, 95%CI 5.02–17.07) was more frequently used in Italy and CT angiography in India (OR 0.32, 95%CI 0.20–0.51). Corticosteroid use was more prevalent and for longer duration in Italy. TAK from Italy had been more often treated with methotrexate, leflunomide or azathioprine, as opposed to tacrolimus in TAK from India (p < 0.05). Biologic or targeted synthetic disease-modifying agents were almost exclusively used in Italy. Survival on first immunosuppressive agent was longer from Italy than from India (log rank test p value 0.041). Considerable differences in the choice of initial vascular imaging modality and therapies for TAK from Italy and India could relate to prevalent socio-economic disparities. These should be considered while developing treatment recommendations for TAK.

Objectives: Infliximab (IFX) is widely used in patients with refractory Takayasu arteritis (TAK). Recently, the IFX-biosimilar CT-P13 has been introduced for the treatment of inflammatory diseases. The aim of this study was to assess the efficacy and safety of CT-P13 in patients with refractory TAK.Methods: In this prospective, open-label, single-center trial, TAK patients either already on treatment with IFX-originator (switch group) or never treated with IFX (naïve group) received CT-P13 for 52 weeks. The primary outcomes of the study were: (i) number of patients with active disease at month 6; (ii) incidence of treatment-emergent adverse events at month 12. Disease activity was assessed at month 6 and month 12 by clinical evaluation (ITAS-2020, ITAS-ESR, and ITAS-CRP scores) and imaging assessment [magnetic resonance angiography (MRA) and (18F)-FDG-PET].Results: 23 patients were recruited (21 switch, 2 naïve). At baseline, 7 patients (32%) were classified as active. At month 6, one patient voluntarily dropped out and 7 patients were still active (30%), including one patient started on a different bDMARD at month 2 due to poor disease control. Mean daily dose of prednisone equivalent was significantly lower than baseline (4.2 ± 1.9 mg vs. 4.8 ± 2.1 mg, p = 0.009). At month 12, another patient was excluded because of pregnancy desire. Five patients were classified as active (24%), including two patients started on a different bDMARD at month 2 and month 6. Mean daily dose of prednisone equivalent was significantly lower than baseline (3.3 ± 2.6, p = 0.034). No patient experienced side effects during CT-P13 infusion. Overall, one patient experienced grade 1 adverse event and 9 patients experienced grade 2 adverse events. In no case hospitalization was required. CT-P13 retention rate was 90.9% at month 6 and 90.4% at month 12.Conclusion: In this study, the use of IFX-biosimilar CT-P13 in patients with refractory TAK showed satisfying efficacy and safety profile.

Background: Aim of this study was to search for any difference in the outcome of patients with adult onset Still's disease (AOSD) treated with anakinra (ANK) in relation with the interval between disease onset and the start of anti-interleukin(IL)-1 treatment and according with the different lines of ANK treatment.Patients and Methods: One hundred and forty-one AOSD patients treated with ANK have been retrospectively assessed. Statistically significant differences (p < 0.05) were analyzed in the frequency of ANK effectiveness, primary or secondary inefficacy to ANK and rate of resolution of clinical and laboratory AOSD manifestations after 3, 6, and 12 months since ANK treatment according with different lines of treatment and different times between AOSD onset and start of ANK.Results: No significant differences were identified in the ANK effectiveness and frequency of primary or secondary inefficacy for patients starting ANK within 6 months (p = 0.19, p = 0.14, and p = 0.81, respectively) or 12 months (p = 0.37, p = 0.23, and p = 0.81, respectively) since AOSD onset compared with patients starting ANK thereafter; no significant differences were identified in ANK effectiveness and primary or secondary inefficacy according with different lines of ANK treatment (p = 0.06, p = 0.19, and p = 0.13, respectively). Patients starting ANK within 6 and 12 months since AOSD onset showed a significantly quicker decrease of erythrocyte sedimentation rate and C-reactive protein than observed among patients undergoing ANK treatment after 6 and 12 months. The number of swollen joints at the 3 month follow-up visit was significantly lower among patients undergoing ANK within 6 months since AOSD onset (p = 0.01), while no significance was identified at the 6 and 12 month assessments (p = 0.23 and p = 0.45, respectively). At the 3 and 6 month visits, the number of swollen joints was significantly higher among patients previously treated with conventional and biological disease modifying anti-rheumatic drugs (DMARDs) compared with those formerly treated only with conventional DMARDs (p < 0.017).Conclusions: Clinical and therapeutic outcomes are substantially independent of how early ANK treatment is started in AOSD patients. However, a faster ANK effectiveness in controlling systemic inflammation and resolving articular manifestations may be observed in patients benefiting from IL-1 inhibition as soon as after disease onset.

Background: Anakinra (ANA) is an effective treatment choice in patients with adult onset Still’s disease (AOSD). Variables affecting treatment survival include loss of efficacy or adverse events, but also the decision to discontinue treatment after long-term clinical remission.Objectives: Aims of this study were: (i) to assess the drug retention rate (DRR) of ANA during a long-term follow-up looking for any difference related to the line of biologic treatment, the concomitant use of conventional disease modifying anti-rheumatic drugs (cDMARDs) and the different type of AOSD (systemic versus chronic articular); (ii) to identify predictive factors of lack of efficacy, loss of efficacy, and ANA withdrawal owing to long-term remission.Methods: AOSD patients classified according with Yamaguchi criteria and treated with ANA were retrospectively enrolled in 18 Italian tertiary Centers. Demographic, laboratory, clinical and therapeutic data related to the start of ANA (baseline), the 3-month assessment and the last follow-up visit while on ANA treatment were retrospectively collected and statistically analyzed.Results: One hundred and forty-one AOSD patients (48 males, 93 females) treated with ANA for a mean period of 35.96 ± 36.05 months were enrolled. The overall DRR of ANA was 44.6 and 30.5% at the 60- and 120-month assessments, respectively, with no significant differences between: (i) biologic naïve patients and those previously treated with other biologics (log-rank p = 0.97); (ii) monotherapy and concomitant use of cDMARDs (log-rank p = 0.45); (iii) systemic and chronic articular types of AOSD (log-rank p = 0.67). No variables collected at baseline could predict primary inefficacy, while the number of swollen joints at baseline was significantly associated with secondary inefficacy (p = 0.01, OR = 1.194, C.I. 1.043–1.367). The typical AOSD skin rash was negatively related with ANA withdrawal owing to long-term remission (p = 0.03, OR = 0.224, C.I. 0.058–0.863).Conclusion: Long-term DRR of ANA has been found excellent and is not affected by different lines of biologic treatment, concomitant use of cDMARDs, or type of AOSD. The risk of losing ANA efficacy increases along with the number of swollen joints at the start of therapy, while the typical skin rash is a negative predictor of ANA withdrawal related to sustained remission.

Background: Interleukin (IL)-1 plays a crucial role in the pathogenesis of Adult onset Still’s disease (AOSD).Objectives: To evaluate the efficacy and safety of anakinra (ANA) and canakinumab (CAN) in a large group of AOSD patients.Methods: Data on clinical, serological features, and concomitant treatments were retrospectively collected at baseline and after 3, 6, and 12 months from AOSD patients (Yamaguchi criteria) referred by 18 Italian centers. Pouchot’s score was used to evaluate disease severity.Results: One hundred forty patients were treated with ANA; 4 were subsequently switched to CAN after ANA failure. The systemic pattern of AOSD was identified in 104 (74.2%) of the ANA-treated and in 3 (75%) of the CAN-treated groups; the chronic-articular type of AOSD was identified in 48 (25.8%) of the ANA-treated and in 1 (25%) of the CAN-treated groups. Methotrexate (MTX) was the most frequent disease modifying anti-rheumatic drug (DMARD) used before beginning ANA or CAN [91/140 (75.8%), 2/4 (50%), respectively]. As a second-line biologic DMARD therapy in 29/140 (20.7%) of the patients, ANA was found effective in improving all clinical and serological manifestations (p < 0.0001), and Pouchot’s score was found to be significantly reduced at all time points (p < 0.0001). No differences in treatment response were identified in the ANA-group when the patients were stratified according to age, sex, disease pattern or mono/combination therapy profile. ANA primary and secondary inefficacy at the 12-month time point was 15/140 (10.7%) and 11/140 (7.8%), respectively. Adverse events (AEs) [mainly represented by in situ (28/47, 59.5%) or diffuse (12/47, 25.5%) skin reactions and infections (7/47, 14.8%)] were the main causes for discontinuation. Pouchot’s score and clinical and serological features were significantly ameliorated at all time points (p < 0.0001) in the CAN-group, and no AEs were registered during CAN therapy. Treatment was suspended for loss of efficacy only in one case (1/4, 25%).Conclusion: This is the largest retrospective observational study evaluating the efficacy and safety of IL-1 inhibitors in AOSD patients. A good response was noted at 3 months after therapy onset in both the ANA- and CAN-groups. Skin reaction may nevertheless represent a non-negligible AE during ANA treatment.

Following publication of the original article [1], the authors reported an error in the spelling of Lorenzo Dagna’s name.

This work provides a groundwater flow and transport model of trichlorethylene and tetrachlorethylene contamination in the Cecina’s coastal aquifer. The contamination analysis, with source located in the Poggio Gagliardo area (Montescudaio, Pisa), was necessary to optimize the groundwater monitoring and remediation design. The work was carried out in two phases: • design of a conceptual model of the aquifer using GIS analysis of many stratigraphic, chemical and hydrogeological data, collected from 2004 to 2012 in six aqueduct wells; • implementation of a groundwater flow and transport numerical model using the MODFLOW 88/96 and MT3D code and the graphical user interface GroundWaterVistas 5. The conceptual model hypothesizes a multilayer aquifer in the coastal plain extended to the sandy-clay hills, recharged by rainfall and by the Cecina River. The aquifer shows important hydrodynamic features affecting both the contamination spreading, due to the presence of a perched and heavily polluted layer separate from the underlying productive aquifer, and the hydrological balance, due to a thick separation layer that limits exchanges between the river and the second groundwater aquifer. The numerical model, built using increasingly complex versions of the initial conceptual model, has been calibrated using monitoring surveys conducted by the Environmental Protection Agency of Regione Toscana (ARPAT), in order to obtain possible forecast scenarios based on the minimum and maximum flow periods, and it is currently used as a tool for decision support regarding the reclamation and/or protection of the aquifer. Future developments will regard the implementation of the multilayer transport model, based on a new survey, and the final coupling with the regional hydrological model named MOBIDIC.

BACKGROUND: Neutrophils are involved in thrombus formation. We investigated whether specific features of neutrophil activation characterize patients with acute coronary syndromes (ACS) compared to stable angina and to systemic inflammatory diseases. METHODS AND FINDINGS: The myeloperoxidase (MPO) content of circulating neutrophils was determined by flow cytometry in 330 subjects: 69 consecutive patients with acute coronary syndromes (ACS), 69 with chronic stable angina (CSA), 50 with inflammation due to either non-infectious (acute bone fracture), infectious (sepsis) or autoimmune diseases (small and large vessel systemic vasculitis, rheumatoid arthritis). Four patients have also been studied before and after sterile acute injury of the myocardium (septal alcoholization). One hundred thirty-eight healthy donors were studied in parallel. Neutrophils with normal MPO content were 96% in controls, >92% in patients undergoing septal alcoholization, 91% in CSA patients, but only 35 and 30% in unstable angina and AMI (STEMI and NSTEMI) patients, compared to 80%, 75% and 2% of patients with giant cell arteritis, acute bone fracture and severe sepsis. In addition, in 32/33 STEMI and 9/21 NSTEMI patients respectively, 20% and 12% of neutrophils had complete MPO depletion during the first 4 hours after the onset of symptoms, a feature not observed in any other group of patients. MPO depletion was associated with platelet activation, indicated by P-selectin expression, activation and transactivation of leukocyte β2-integrins and formation of platelet neutrophil and -monocyte aggregates. The injection of activated platelets in mice produced transient, P-selectin dependent, complete MPO depletion in about 50% of neutrophils. CONCLUSIONS: ACS are characterized by intense neutrophil activation, like other systemic inflammatory syndromes. In the very early phase of acute myocardial infarction only a subpopulation of neutrophils is massively activated, possibly via platelet-P selectin interactions. This paroxysmal activation could contribute to occlusive thrombosis.