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Background: Breast cancer (BC) constitutes a significant public health challenge in Italy, with a considerable impact on healthcare resources and societal costs. Despite advancements in diagnostics and therapies, the economic burden of BC remains substantial, necessitating a comprehensive evaluation to inform healthcare policy and resource allocation. The aim of this study is to estimate both direct health costs and social security costs related to BC., Methods: This study utilized real-world data from the Italian Health Information System (HIS) and Local Health Unit (LHU) Umbria 2 HIS databases spanning 2010-2019. Direct health costs, encompassing hospitalizations, outpatient visits, and drug prescriptions, were assessed alongside social security costs associated with BC-related work inability. Statistical analyses and probabilistic models were employed to estimate costs and evaluate trends over time., Results: The analysis revealed an annual cost of €273 million for hospital admissions related to BC in Italy, with metastatic BC (MBC) incurring the highest average annual cost per patient (€5018). When outpatient visits and drug consumption were incorporated, the mean annual cost per patient in LHU Umbria 2 rose to €11,380 for MBC. Social security costs, predominantly comprising disability benefits (DBs), totaled €579 million annually. Overall, the study estimated the total annual economic impact of BC in Italy to exceed €1 billion, with social costs representing 50.4% of the total burden., Conclusions: This comprehensive assessment underscores the substantial economic strain imposed by BC in Italy and highlights the need for early detection and intervention strategies to mitigate costs and enhance patient outcomes. These findings offer valuable insights into the economic landscape of BC, guiding policy decisions and resource allocation efforts aimed at optimizing BC management and alleviating its societal burden., Competing Interests: Declarations. Funding: The study was funded by Daiichi sankyo. Role of the funder/sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Conflicts of interest: The authors have no relevant financial or non-financial interests to disclose. Availability of data and material: The datasets generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request. Ethics approval: Not applicable. Consent to participate: Not applicable. Consent for publication: Not applicable. Code availability: The code is available from the corresponding author upon reasonable request. Author contributions: All authors contributed to the study conception. A.M., P.S., and F.S.M. developed the study design; P.S. and M.S. conducted the statistical analysis, derived the analytical results, and wrote the first draft of the manuscript. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript., (© 2024. The Author(s).)

The fungi Botryosphaeriaceae are involved in olive declines in both the world hemispheres and in all continents where this species is cultivated. In Salento (Apulia, Italy), the Botryosphaeriaceae Neofusicoccum mediterraneum and N. stellenboschiana have been reported as the agents of a branch and twig dieback that overlaps with olive quick decline syndrome caused by Xylella fastidiosa subsp. pauca . In this study, we report the finding of Diplodia seriata , another Botryosphaeriaceae species, in Salento in Xylella fastidiosa -infected olive trees affected by symptoms of branch and twig dieback. Given that its presence was also reported in olive in the Americas and in Europe (Croatia) with different degrees of virulence, we were prompted to assess its role in the Apulian decline. We identified representative isolates based on morphological features and a multilocus phylogeny. In vitro tests showed that the optimum growth temperature of the isolates is around 25-30 °C, and that they are highly thermo-tolerant. In pathogenicity trials conducted over eleven months, D. seriata expressed a very low virulence. Nonetheless, when we imposed severe water stress before the inoculation, D. seriata significatively necrotized bark and wood in a time frame of 35 days. Moreover, the symptoms which resulted were much more severe in the trial performed in summer compared with that in autumn. In osmolyte-supplemented media with a water potential from -1 to -3 Mpa, the isolates increased or maintained their growth rate compared with non-supplemented media, and they also grew, albeit to a lesser extent, on media with a water potential as low as -7 Mpa. This suggests that olives with a low water potential, namely those subjected to drought, may offer a suitable environment for the fungus' development. The analysis of the meteorological parameters, temperatures and rainfall, in Salento in the timeframe 1989-2023, showed that this area is subjected to a progressive increase of temperature and drought during the summer. Thus, overall, D. seriata has to be considered a contributor to the manifestation of branch and twig dieback of olive in Salento. Coherently with the spiral decline concept of trees, our results suggest that heat and drought act as predisposing/inciting factors facilitating D. seriata as a contributor. The fact that several adverse factors, biotic and abiotic, are simultaneously burdening olive trees in Salento offers a cue to discuss the possible complex nature of the olive decline in Salento.

Xylella fastidiosa subsp. pauca ST53 (XFP), the causal agent of olive quick decline syndrome (OQDS), was thoroughly investigated after a 2013 outbreak in the Salento region of Southern Italy. Some trees from Ogliarola Salentina and Cellina di Nardò, susceptible cultivars in the Gallipoli area, the first XFP infection hotspot in Italy, have resprouted crowns and are starting to flower and yield fruits. Satellite imagery and Normalized Difference Vegetation Index analyses revealed a significant improvement in vegetation health and productivity from 2018 to 2022 of these trees. Lipid molecules have long been recognized as plant defense modulators, and recently, we investigated their role in XFP-positive hosts and in XFP-resistant as well as in XFP-susceptible cultivars of olive trees. Here, we present a case study regarding 36 olive trees (12 XFP-positive resprouting, 12 XFP-positive OQDS-symptomatic, and 12 XFP-negative trees) harvested in 2022 within the area where XFP struck first, killing millions of trees in a decade. These trees were analyzed for some free fatty acid, oxylipin, and plant hormones, in particular jasmonic and salicylic acid, by targeted LC-MS/MS. Multivariate analysis revealed that lipid markers of resistance (e.g., 13-HpOTrE), along with jasmonic and salicylic acid, were accumulated differently in the XFP-positive resprouting trees from both cultivars with respect to XFP-positive OQDS symptomatic and XFP-negative trees, suggesting a correlation of lipid metabolism with the resprouting, which can be an indication of the resiliency of these trees to OQDS. This is the first report concerning the resprouting of OQDS-infected olive trees in the Salento area.

In 2013, an outbreak of Xylella fastidiosa (Xf) was identified for the first time in Europe, in the extreme south of Italy (Apulia, Salento territory). The locally identified subspecies pauca turned out to be lethal for olive trees, starting an unprecedented phytosanitary emergency for one of the most iconic cultivations of the Mediterranean area. Xf pauca (Xfp) is responsible for a severe disease, the olive quick decline syndrome (OQDS), spreading epidemically and with dramatic impact on the agriculture, the landscape, the tourism and the cultural heritage of this region. The bacterium, transmitted by insects that feed on xylem sap, causes rapid wilting in olive trees due to biofilm formation, which obstructs the plant xylematic vessels. The aim of this review is to perform a thorough analysis that offers a general overview of the published work, from 2013 to December 2023, related to the Xfp outbreak in Apulia. This latter hereto has killed millions of olive trees and left a ghostly landscape with more than 8000 square kilometers of infected territory, that is 40% of the region. The majority of the research efforts made to date to combat Xfp in olive plants are listed in the present review, starting with the early attempts to identify the bacterium, the investigations to pinpoint and possibly control the vector, the assessment of specific diagnostic techniques and the pioneered therapeutic approaches. Interestingly, according to the general set criteria for the preliminary examination of the accessible scientific literature related to the Xfp outbreak on Apulian olive trees, fewer than 300 papers can be found over the last decade. Most of them essentially emphasize the importance of developing diagnostic tools that can identify the disease early, even when infected plants are still asymptomatic, in order to reduce the risk of infection for the surrounding plants. On the other hand, in the published work, the diagnostic focus (57%) overwhelmingly encompasses all other possible investigation goals such as vectors, impacts and possible treatments. Notably, between 2013 and 2023, only 6.3% of the literature reports addressing the topic of Xfp in Apulia were concerned with the application of specific treatments against the bacterium. Among them, those reporting field trials on infected plants, including simple pruning indications, were further limited (6%).

Interest has been focused in recent years on the analgesic effects exerted by adenosine and its receptors, A 1 , A 2A , A 2B , and A 3 adenosine receptor (AR) subtypes, in different in vivo models of chronic pain. In particular, it was demonstrated that selective A 3 AR agonists reduced pro-nociceptive N-type Ca 2+ channels in dorsal root ganglion (DRG) neurons isolated from rats and, by this mechanism, inhibit post inflammatory visceral hypersensitivity. In the present study, we investigate the effect of a previously reported irreversibly binding A 3 AR agonist, ICBM, on Ca 2+ currents (I Ca ) in rat DRG neurons. Present data demonstrate that ICBM, an isothiocyanate derivative designed for covalent binding to the receptor, concentration-dependently inhibits I Ca . This effect is irreversible, since it persists after drug removal, differently from the prototypical A 3 AR agonist, Cl-IB-MECA. ICBM pre-exposure inhibits the effect of a subsequent Cl-IB-MECA application. Thus, covalent A 3 AR agonists such as ICBM may represent an innovative, beneficial, and longer-lasting strategy to achieve efficacious chronic pain control versus commonly used, reversible, A 3 AR agonists. However, the possible limitations of this drug and other covalent drugs may be, for example, a characteristic adverse effect profile, suggesting that more pre-clinical studies are needed., (© 2023. The Author(s).)

Background: The epidemiological evidence on the interaction between heat and ambient air pollution on mortality is still inconsistent., Objectives: To investigate the interaction between heat and ambient air pollution on daily mortality in a large dataset of 620 cities from 36 countries., Methods: We used daily data on all-cause mortality, air temperature, particulate matter ≤ 10 μm (PM 10 ), PM ≤ 2.5 μm (PM 2.5 ), nitrogen dioxide (NO 2 ), and ozone (O 3 ) from 620 cities in 36 countries in the period 1995-2020. We restricted the analysis to the six consecutive warmest months in each city. City-specific data were analysed with over-dispersed Poisson regression models, followed by a multilevel random-effects meta-analysis. The joint association between air temperature and air pollutants was modelled with product terms between non-linear functions for air temperature and linear functions for air pollutants., Results: We analyzed 22,630,598 deaths. An increase in mean temperature from the 75 th to the 99 th percentile of city-specific distributions was associated with an average 8.9 % (95 % confidence interval: 7.1 %, 10.7 %) mortality increment, ranging between 5.3 % (3.8 %, 6.9 %) and 12.8 % (8.7 %, 17.0 %), when daily PM 10 was equal to 10 or 90 μg/m 3 , respectively. Corresponding estimates when daily O 3 concentrations were 40 or 160 μg/m 3 were 2.9 % (1.1 %, 4.7 %) and 12.5 % (6.9 %, 18.5 %), respectively. Similarly, a 10 μg/m 3 increment in PM 10 was associated with a 0.54 % (0.10 %, 0.98 %) and 1.21 % (0.69 %, 1.72 %) increase in mortality when daily air temperature was set to the 1 st and 99 th city-specific percentiles, respectively. Corresponding mortality estimate for O 3 across these temperature percentiles were 0.00 % (-0.44 %, 0.44 %) and 0.53 % (0.38 %, 0.68 %). Similar effect modification results, although slightly weaker, were found for PM 2.5 and NO 2 ., Conclusions: Suggestive evidence of effect modification between air temperature and air pollutants on mortality during the warm period was found in a global dataset of 620 cities., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Xylella fastidiosa subsp. pauca (XFP), Neofusicoccum mediterraneum , N. stellenboschiana and other fungi have been found in olive groves of Salento (Apulia, Italy) that show symptoms of severe decline. XFP is well known to be the cause of olive quick decline syndrome (OQDS). It has also been assessed that Neofusicoccum spp. causes a distinct disease syndrome, namely, branch and twig dieback (BTD). All these phytopathogens incite severe symptoms that can compromise the viability of large canopy sectors or the whole tree. However, their specific symptoms are not easily distinguished, especially during the final stages of the disease when branches are definitively desiccated. By contrast, they can be differentiated during the initial phases of the infection when some facets of the diseases are typical, especially wood discoloration, incited solely by fungi. Here, we describe the typical symptomatological features of OQDS and BTD that can be observed in the field and that have been confirmed by Koch postulate experiments. Similar symptoms, caused by some abiotic adverse conditions and even by additional biotic factors, are also described. Thus, this review aims at: (i) raising the awareness that declining olive trees in Salento do not have to be linked a priori to XFP; (ii) defining the guidelines for a correct symptomatic diagnosis to orient proper laboratory analyses, which is crucial for the application of effective control measures. The possibility that bacterium and fungi could act as a polyspecies and in conjunction with predisposing abiotic stresses is also widely discussed.

The aim of this study was to establish a link between genetic diversity and the geographic origin of Pectobacterium strains belonging to three species- P. carotovorum , P. versatile , and P. odoriferum -isolated from cabbage in Serbia by comparing their sequences with those of strains sourced from different hosts and countries in Europe, Asia, and North America. Phylogeographic relatedness was reconstructed using the Templeton, Crandall, and Sing's (TCS) haplotype network based on concatenated sequences of the housekeeping genes dnaX , icdA , mdh , and proA , while pairwise genetic distances were computed by applying the p-distance model. The obtained TCS haplotype networks indicated the existence of high intra-species genetic diversity among strains of all three species, as reflected in the 0.2-2.3%, 0.2-2.5%, and 0.1-1.7% genetic distance ranges obtained for P. carotovorum , P. versatile , and P. odoriferum , respectively. Five new haplotypes (denoted as HPc1-HPc5) were detected among cabbage strains of P. carotovorum , while one new haplotype was identified for both P. versatile (HPv1) and P. odoriferum (HPo1). None of the TCS haplotype networks provided evidence of significant correlation between geographic origin and the determined haplotypes, i.e., the infection origin. However, as haplotype network results are affected by the availability of sequencing data in public databases for the used genes and the number of analyzed strains, these findings may also be influenced by small sample size.

Here we report the medium-term effects of foliar spray and endo-therapy treatments with different doses of a Cu/Zn citric acid biocomplex (Dentamet ® ) in Xylella fastidiosa infected olive trees of Salento, Apulia region (South-east Italy). Leaf extract samples from field-treated 150 years old olive trees cvs Ogliarola salentina and Cellina di Nardò were studied by 1 H NMR-based metabolomics. The result of different applications of Dentamet ® endo-therapy after 60, 120 and 180 days in comparison with traditional foliar spray treatment and water injection as a control have been investigated. The metabolic profile analyses, performed by 1 H NMR-based metabolomic approach, indicated plant metabolites variations connected to the disease progression such as mannitol, quinic acid, and oleuropein related compounds. The best results, in terms of discrimination of the metabolic profiles with respect to water injection, were found for monthly endo-therapy treatments. Dentamet ® foliar application demonstrated more specific time related progressive effectiveness with respect to intravascular treatments. Therefore, besides a possible more effective performance of endo-therapy with respect to foliar treatments, the need of further doses/frequencies trimming to obtain long-term results was also assessed. The present field studies confirmed the indication of Dentamet ® effectiveness in metabolic variation induction, potentially linked with reducing the X. fastidiosa subspecies pauca related Olive Quick Decline Syndrome (OQDS) symptoms development.

Xylella fastidiosa subsp. pauca (Xfp), has attacked the olive trees in Southern Italy with severe impacts on the olive agro-ecosystem. To reduce both the Xfp cell concentration and the disease symptom, a bio-fertilizer restoration technique has been used. Our study applied multi-resolution satellite data to evaluate the effectiveness of such technique at both field and tree scale. For field scale, a time series of High Resolution (HR) Sentinel-2 images, acquired in the months of July and August from 2015 to 2020, was employed. First, four spectral indices from treated and untreated fields were compared. Then, their trends were correlated to meteo-events. For tree-scale, Very High Resolution (VHR) Pléiades images were selected at the closest dates of the Sentinel-2 data to investigate the response to treatments of each different cultivar. All indices from HR and VHR images were higher in treated fields than in those untreated. The analysis of VHR indices revealed that Oliarola Salentina can respond better to treatments than Leccino and Cellina cultivars. All findings were in agreement with in-field PCR results. Hence, HR data could be used to evaluate plant conditions at field level after treatments, while VHR imagery could be used to optimize treatment doses per cultivar., (© 2023. The Author(s).)

Background: Evidence on the potential interactive effects of heat and ambient air pollution on cause-specific mortality is inconclusive and limited to selected locations., Objectives: We investigated the effects of heat on cardiovascular and respiratory mortality and its modification by air pollution during summer months (six consecutive hottest months) in 482 locations across 24 countries., Methods: Location-specific daily death counts and exposure data (e.g., particulate matter with diameters ≤ 2.5 µm [PM 2.5 ]) were obtained from 2000 to 2018. We used location-specific confounder-adjusted Quasi-Poisson regression with a tensor product between air temperature and the air pollutant. We extracted heat effects at low, medium, and high levels of pollutants, defined as the 5th, 50th, and 95th percentile of the location-specific pollutant concentrations. Country-specific and overall estimates were derived using a random-effects multilevel meta-analytical model., Results: Heat was associated with increased cardiorespiratory mortality. Moreover, the heat effects were modified by elevated levels of all air pollutants in most locations, with stronger effects for respiratory than cardiovascular mortality. For example, the percent increase in respiratory mortality per increase in the 2-day average summer temperature from the 75th to the 99th percentile was 7.7% (95% Confidence Interval [CI] 7.6-7.7), 11.3% (95%CI 11.2-11.3), and 14.3% (95% CI 14.1-14.5) at low, medium, and high levels of PM 2.5 , respectively. Similarly, cardiovascular mortality increased by 1.6 (95%CI 1.5-1.6), 5.1 (95%CI 5.1-5.2), and 8.7 (95%CI 8.7-8.8) at low, medium, and high levels of O 3 , respectively., Discussion: We observed considerable modification of the heat effects on cardiovascular and respiratory mortality by elevated levels of air pollutants. Therefore, mitigation measures following the new WHO Air Quality Guidelines are crucial to enhance better health and promote sustainable development., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

For about a decade, olive groves in Apulia (Southern Italy) have been progressively destroyed by Olive Quick Decline Syndrome (OQDS), a disease caused by the bacterium Xylella fastidiosa subsp. pauca (Xfp). Recently, we described an additional wilting syndrome affecting olive trees in that area. The botryosphaeriaceous fungus Neofusicoccum mediterraneum was found associated with the diseased trees, and its high virulence toward olive trees was demonstrated. Given the common features with Branch and Twig Dieback (BTD) of olive tree, occurring in Spain and California, we suggested that the observed syndrome was BTD. During our first survey, we also found a botryosphaeriaceous species other than N. mediterraneum . In the present article, we report the morphological and molecular characterization of this fungal species which we identified as Neofusicoccum stellenboschiana . In the study, we also included for comparison additional N. stellenboschiana isolates obtained from olive trees in Latium and Tuscany region (Central Italy). The occurrence of N. stellenboschiana in olive trees is reported here for the first time in the northern hemisphere. The pathogenicity and virulence were tested in nine inoculation trials, where the Apulian N. stellenboschiana isolate was compared with the isolate from Latium and with the Apulian isolate of N. mediterraneum . Both isolates of N. stellenboschiana proved pathogenic to olive trees. They caused evident bark canker and wood discolouration when inoculated at the base of the stem of two/three-year-old trees and on one-year-old twigs. However, virulence of N. stellenboschiana was significantly lower, though still remarkable, compared with N. mediterraneum in term of necrosis progression in the bark and the wood and capacity of wilting the twigs. Virulence of N. stellenboschiana and N. mediterraneum did not substantially change when inoculations were performed in spring/summer and in autumn, suggesting that these fungal species have the potential to infect and damage olive trees in all seasons. The high thermotolerance of N. stellenboschiana was also revealed with in vitro growth and survival tests. The high virulence of these Botryosphaeriaceae species highlights their contribution in BTD aetiology and the necessity to investigate right away their diffusion and, possibly, the role of additional factors other than Xfp in the general decline of olive groves in Apulia. Hence the importance of assessing the degree of overlap of BTD/Botryosphariaceae with OQDS/Xfp is discussed.

This study focuses on interacting with insects and their ectosymbiont ( lato sensu ) microorganisms for environmentally safe plant production and protection. Some cases help compare ectosymbiont microorganisms that are insect-borne, -driven, or -spread relevant to endosymbionts' behaviour. Ectosymbiotic bacteria can interact with insects by allowing them to improve the value of their pabula. In addition, some bacteria are essential for creating ecological niches that can host the development of pests. Insect-borne plant pathogens include bacteria, viruses, and fungi. These pathogens interact with their vectors to enhance reciprocal fitness. Knowing vector-phoront interaction could considerably increase chances for outbreak management, notably when sustained by quarantine vector ectosymbiont pathogens, such as the actual Xylella fastidiosa Mediterranean invasion episode. Insect pathogenic viruses have a close evolutionary relationship with their hosts, also being highly specific and obligate parasites. Sixteen virus families have been reported to infect insects and may be involved in the biological control of specific pests, including some economic weevils. Insects and fungi are among the most widespread organisms in nature and interact with each other, establishing symbiotic relationships ranging from mutualism to antagonism. The associations can influence the extent to which interacting organisms can exert their effects on plants and the proper management practices. Sustainable pest management also relies on entomopathogenic fungi; research on these species starts from their isolation from insect carcasses, followed by identification using conventional light or electron microscopy techniques. Thanks to the development of omics sciences, it is possible to identify entomopathogenic fungi with evolutionary histories that are less-shared with the target insect and can be proposed as pest antagonists. Many interesting omics can help detect the presence of entomopathogens in different natural matrices, such as soil or plants. The same techniques will help localize ectosymbionts, localization of recesses, or specialized morphological adaptation, greatly supporting the robust interpretation of the symbiont role. The manipulation and modulation of ectosymbionts could be a more promising way to counteract pests and borne pathogens, mitigating the impact of formulates and reducing food insecurity due to the lesser impact of direct damage and diseases. The promise has a preventive intent for more manageable and broader implications for pests, comparing what we can obtain using simpler, less-specific techniques and a less comprehensive approach to Integrated Pest Management (IPM).

Lipids are central at various stages of host-pathogen interactions in determining virulence and modulating plant defense. Free fatty acids may act as substrates for oxidizing enzymes [e.g., lipoxygenases (LOXs) and dioxygenases (DOXs)] that synthesize oxylipins. Fatty acids and oxylipins function as modulators of several pathways in cell-to-cell communication; their structural similarity among plant, fungal, and bacterial taxa suggests potential in cross-kingdom communication. We provide a prospect of the known role of fatty acids and oxylipins in fungi and bacteria during plant-pathogen interactions. In the pathogens, oxylipin-mediated signaling pathways are crucial both in development and host infection. Here, we report on case studies suggesting that oxylipins derived from oleic, linoleic, and linolenic acids are crucial in modulating the pathogenic lifestyle in the host plant. Intriguingly, overlapping (fungi-plant/bacteria-plant) results suggest that different inter-kingdom pathosystems use similar lipid signals to reshape the lifestyle of the contenders and occasionally determine the outcome of the challenge., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Beccaccioli, Pucci, Salustri, Scortichini, Zaccaria, Momeni, Loreti, Reverberi and Scala.)

Background: Epidemiological literature on the health risks associated with non-optimal temperature has mostly reported average estimates across large areas or specific population groups. However, the heterogeneous distribution of drivers of vulnerability can result in local differences in health risks associated with heat and cold. We aimed to analyse the association between ambient air temperature and all-cause mortality across England and Wales and characterise small scale patterns in temperature-related mortality risks and impacts., Methods: We performed a country-wide small-area analysis using data on all-cause mortality and air temperature for 34 753 lower super output areas (LSOAs) within 348 local authority districts (LADs) across England and Wales between Jan 1, 2000, and Dec 31, 2019. We first performed a case time series analysis of LSOA-specific and age-specific mortality series matched with 1 × 1 km gridded temperature data using distributed lag non-linear models, and then a repeated-measure multivariate meta-regression to pool LAD-specific estimates using area-level climatological, socioeconomic, and topographical predictors., Findings: The final analysis included 10 716 879 deaths from all causes. The small-area assessment estimated that each year in England and Wales, there was on average 791 excess deaths (empirical 95% CI 611-957) attributable to heat and 60 573 (55 796-65 145) attributable to cold, corresponding to standardised excess mortality rates of 1·57 deaths (empirical 95% CI 1·21-1·90) per 100 000 person-years for heat and 122·34 deaths (112·90-131·52) per 100 000 person-years for cold. The risks increased with age and were highly heterogeneous geographically, with the minimum mortality temperature ranging from 14·9°C to 22·6°C. Heat-related mortality was higher in urban areas, whereas cold-related mortality showed a more nuanced geographical pattern and increased risk in areas with greater socioeconomic deprivation., Interpretation: This study provides a comprehensive assessment of excess mortality related to non-optimal outdoor temperature, with several risk indicators reported by age and multiple geographical levels. The analysis provides detailed risk maps that are useful for designing effective public health and climate policies at both local and national levels., Funding: Medical Research Council, Natural Environment Research Council, EU Horizon 2020 Programme, National Institute of Health Research., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

The World Health Assembly recognizes the growing economic and societal burden of neurological disorders, a leading cause of disability and the second cause of mortality in the world. In this context we analysed the socio-economic impact of epilepsy in Italy with a specific focus on hospitalizations and costs related to disability pensions (DPs) and ordinary disability allowances. In the case of epilepsy, between 2009 and 2015 we observed an alarming increasing trend for DPs (+26%), indicating that substantial expenses must be supported throughout the patients' lifetimes by both the social security system and the National Health Service (NHS) on top of the impact on caregivers. We also analysed the hospital expenditure on epilepsy through the information available in the Hospital Discharge Cards between 2015 and 2018. Almost all admissions (76% ordinary hospitalizations, 24% day hospitals) were acute (95%), followed by rehabilitation (4%) and long-term care (1%). The cost of acute and ordinary hospitalizations was by far the highest in 2018, the last year of analysis. This large expense due to hospitalizations could be reduced through the implementation of different organizational and management approaches. Our recommendation is that the policy maker should consider the best approach to ensure an early diagnosis for patients and provide early access to drugs and/or surgery. Finally, the adoption of new innovative treatments should improve effectiveness and, at the same time, reduce the expense of the NHS, of the social system as a whole, with a tangible improvement in patients' quality of life., Competing Interests: Conflict of interest: The authors declare no conflict of interest., (Copyright © 2022, The Authors.)

In 2013, Xylella fastidiosa (Xf) was detected for the first time in Apulia and, subsequently, recognized as the causal agent of the olive quick decline syndrome (OQDS). To contain the disease, the olive germplasm was evaluated for resistance to Xf , identifying cultivars with different susceptibility to the pathogen. Regarding this, the resistant cultivar Leccino has generally a lower bacterial titer compared with the susceptible cultivar Ogliarola salentina. Among biomolecules, lipids could have a pivotal role in the interaction of Xf with its host. In the grapevine Pierce's disease, fatty acid molecules, the diffusible signaling factors (DSFs), act as regulators of Xf lifestyle and are crucial for its virulence. Other lipid compounds derived from fatty acid oxidation, namely, oxylipins, can affect, in vitro , biofilm formation in Xf subsp. pauca (Xfp) strain De Donno, that is, the strain causing OQDS. In this study, we combined high-performance liquid chromatography-mass spectrometry-MS-based targeted lipidomics with supervised learning algorithms (random forest, support vector machine, and neural networks) to classify olive tree samples from Salento. The dataset included samples from either OQDS-positive or OQDS-negative olive trees belonging either to cultivar Ogliarola salentina or Leccino treated or not with the zinc-copper-citric acid biocomplex Dentamet ® . We built classifiers using the relative differences in lipid species able to discriminate olive tree samples, namely, (1) infected and non-infected, (2) belonging to different cultivars, and (3) treated or untreated with Dentamet ® . Lipid entities emerging as predictors of the thesis are free fatty acids (C16:1, C18:1, C18:2, C18:3); the LOX-derived oxylipins 9- and 13-HPOD/TrE; the DOX-derived oxylipin 10-HPOME; and diacylglyceride DAG36:4(18:1/18:3)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Scala, Salustri, Loreti, Pucci, Cacciotti, Tatulli, Scortichini and Reverberi.)

Xylella fastidiosa is a xylem-limited bacterium causing a range of economically important plant diseases in hundreds of crops. Over the last decade, a severe threat due to Olive Quick Decline Syndrome (OQDS), caused by Xylella fastidiosa subspecies pauca, affected the Salento olive groves (Apulia, South-East Italy). Very few phyto-therapeutics, including a Zn/Cu citric acid biocomplex foliar treatment, were evaluated to mitigate this disease. However, the traditional foliar applications result in the agro-actives reaching only partially their target. Therefore the development of novel endo-therapeutic systems was suggested. Metabolite fingerprinting is a powerful method for monitoring both, disease progression and treatment effects on the plant metabolism, allowing biomarkers detection. We performed, for the first time, short-term monitoring of metabolic pathways reprogramming for infected Ogliarola salentina and Cima di Melfi olive trees after precision intravascular biocomplex delivery using a novel injection system. Upon endo therapy, we observed specific variations in the leaf content of some metabolites. In particular, the 1 H NMR-based metabolomics approach showed, after the injection, a significant decrease of both the disease biomarker quinic acid and mannitol with simultaneous increase of polyphenols and oleuropein related compounds in the leaf's extracts. This combined metabolomics/endo-therapeutic methodology provided useful information in the comprehension of plant physiology for future applications in OQDS control., (© 2022. The Author(s).)

Olive trees are infected and damaged by Botryosphaeriaceae fungi in various countries. The botryosphaeriaceous fungus Neofusicoccum mediterraneum is highly aggressive and is a major concern for olive groves in Spain and California (USA), where it causes 'branch and twig dieback' characterized by wood discoloration, bark canker, and canopy blight. During surveys of olive groves in Apulia (southern Italy), we noticed that-in some areas-trees were heavily affected by severe branch and twig dieback. In addition, chlorosis and the appearance of red-bronze patches on the leaf preceded the wilting of the foliage, with necrotic leaves persisting on the twigs. Given the severity of the manifestation in zones also subject to olive quick decline syndrome (OQDS) caused by Xylella fastidiosa subsp. pauca , we investigated the etiology and provide indications for differentiating the symptoms from OQDS. Isolation from diseased wood samples revealed a mycete, which was morphologically and molecularly identified as N. mediterraneum. The pathogenicity tests clearly showed that this fungus is able to cause the natural symptoms. Therefore, also considering the low number of tested samples, N. mediterraneum is a potential causal agent of the observed disease. Specifically, inoculation of the twigs caused complete wilting in two to three weeks, while inoculation at the base of the stem caused severe girdling wedge-shaped cankers. The growth rate of the fungus in in vitro tests was progressively higher from 10 to 30 °C, failing to grow at higher temperatures, but keeping its viability even after prolonged exposure at 50 °C. The capacity of the isolate to produce catenulate chlamydospores, which is novel for the species, highlights the possibility of a new morphological strain within N. mediterraneum . Further investigations are ongoing to verify whether additional fungal species are involved in this symptomatology.

Background: Short-term exposure to particulate matter (PM) has been related to mortality worldwide. Most evidence comes from studies conducted in major cities, while little is known on the effects of low concentrations of PM and in less urbanized areas. We aim to investigate the relationship between PM and all-cause mortality at national level in Italy., Methods: Daily numbers of all-cause mortality were collected for all 8092 municipalities of Italy, from 2006 to 2015. A satellite-based spatiotemporal model was developed to estimate daily PM 10 (inhalable particles) and PM 2.5 (fine particles) concentrations at 1-km resolution. Multivariate Poisson regression models were fit to estimate the association between daily PM and mortality at province level, and then, results were pooled with a random-effects meta-analysis. Associations were estimated by combination of age and sex and degree of urbanization of the municipalities. Flexible functions were estimated to explore the shape of the associations at low PM concentrations., Results: We analyzed 5,884,900 deaths (40% among subjects older than 85 years, 60% occurring outside the main urban areas). National daily mean (interquartile range) PM 10 and PM 2.5 concentrations were 23 (14) μg/m 3 and 15 (11) μg/m 3 , respectively. Relative increases of mortality per 10 μg/m 3 variation in lag 0-5 (average of last six days since death) PM 10 and PM 2.5 were 1.47% (95% Confidence Intervals (CI): 1.15%, 1.79%) and 1.96% (1.33%, 2.59%), respectively. Associations were highest among elderly and women for PM 10 only, similar between rural and urbanized areas, and were present even at low concentrations, e.g., below WHO guidelines., Conclusions: Air pollution was robustly associated with peaks in daily all-cause mortality in Italy, both in large cities and in less urbanized areas of Italy. Current WHO Air Quality Guidelines (2021) for PM 10 and PM 2.5 are not sufficient to protect public health.

Background: Many regions of the world are now facing more frequent and unprecedentedly large wildfires. However, the association between wildfire-related PM 2·5 and mortality has not been well characterised. We aimed to comprehensively assess the association between short-term exposure to wildfire-related PM 2·5 and mortality across various regions of the world., Methods: For this time series study, data on daily counts of deaths for all causes, cardiovascular causes, and respiratory causes were collected from 749 cities in 43 countries and regions during 2000-16. Daily concentrations of wildfire-related PM 2·5 were estimated using the three-dimensional chemical transport model GEOS-Chem at a 0·25° × 0·25° resolution. The association between wildfire-related PM 2·5 exposure and mortality was examined using a quasi-Poisson time series model in each city considering both the current-day and lag effects, and the effect estimates were then pooled using a random-effects meta-analysis. Based on these pooled effect estimates, the population attributable fraction and relative risk (RR) of annual mortality due to acute wildfire-related PM 2·5 exposure was calculated., Findings: 65·6 million all-cause deaths, 15·1 million cardiovascular deaths, and 6·8 million respiratory deaths were included in our analyses. The pooled RRs of mortality associated with each 10 μg/m 3 increase in the 3-day moving average (lag 0-2 days) of wildfire-related PM 2·5 exposure were 1·019 (95% CI 1·016-1·022) for all-cause mortality, 1·017 (1·012-1·021) for cardiovascular mortality, and 1·019 (1·013-1·025) for respiratory mortality. Overall, 0·62% (95% CI 0·48-0·75) of all-cause deaths, 0·55% (0·43-0·67) of cardiovascular deaths, and 0·64% (0·50-0·78) of respiratory deaths were annually attributable to the acute impacts of wildfire-related PM 2·5 exposure during the study period., Interpretation: Short-term exposure to wildfire-related PM 2·5 was associated with increased risk of mortality. Urgent action is needed to reduce health risks from the increasing wildfires., Funding: Australian Research Council, Australian National Health & Medical Research Council., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Xylella fastidiosa subsp. pauca is the causal agent of "olive quick decline syndrome" in Salento (Apulia, Italy). On April 2015, we started interdisciplinary studies to provide a sustainable control strategy for this pathogen that threatens the multi-millennial olive agroecosystem of Salento. Confocal laser scanning microscopy and fluorescence quantification showed that a zinc-copper-citric acid biocomplex-Dentamet ® -reached the olive xylem tissue either after the spraying of the canopy or injection into the trunk, demonstrating its effective systemicity. The biocomplex showed in vitro bactericidal activity towards all X. fastidiosa subspecies. A mid-term evaluation of the control strategy performed in some olive groves of Salento indicated that this biocomplex significantly reduced both the symptoms and X. f. subsp. pauca cell concentration within the leaves of the local cultivars Ogliarola salentina and Cellina di Nardò. The treated trees started again to yield. A 1 H-NMR metabolomic approach revealed, upon the treatments, a consistent increase in malic acid and γ-aminobutyrate for Ogliarola salentina and Cellina di Nardò trees, respectively. A novel endotherapy technique allowed injection of Dentamet ® at low pressure directly into the vascular system of the tree and is currently under study for the promotion of resprouting in severely attacked trees. There are currently more than 700 ha of olive groves in Salento where this strategy is being applied to control X. f . subsp. pauca . These results collectively demonstrate an efficient, simple, low-cost, and environmentally sustainable strategy to control this pathogen in Salento.

Obesity is the major driver of the worldwide epidemic in type 2 diabetes (T2D). In the obese state, chronically elevated plasma free fatty acid levels contribute to peripheral insulin resistance, which can ultimately lead to the development of T2D. For this reason, drugs that are able to regulate lipolytic processes in adipocytes are predicted to have considerable therapeutic potential. Gi-coupled P2Y14 receptor (P2Y14R; endogenous agonist, UDP-glucose) is abundantly expressed in both mouse and human adipocytes. Because activated Gi-type G proteins exert an antilipolytic effect, we explored the potential physiological relevance of adipocyte P2Y14Rs in regulating lipid and glucose homeostasis. Metabolic studies indicate that the lack of adipocyte P2Y14R enhanced lipolysis only in the fasting state, decreased body weight, and improved glucose tolerance and insulin sensitivity. Mechanistic studies suggested that adipocyte P2Y14R inhibits lipolysis by reducing lipolytic enzyme activity, including ATGL and HSL. In agreement with these findings, agonist treatment of control mice with a P2Y14R agonist decreased lipolysis, an effect that was sensitive to inhibition by a P2Y14R antagonist. In conclusion, we demonstrate that adipose P2Y14Rs were critical regulators of whole-body glucose and lipid homeostasis, suggesting that P2Y14R antagonists might be beneficial for the therapy of obesity and T2D.

Xylella fastidiosa subsp. pauca, is a bacterial phytopathogen associated with the "olive quick decline syndrome" (OQDS) causing severe economic losses to olive groves in Salento area (Apulia, Italy). In a previous work, we analyzed by 1 H-NMR the metabolic pattern of naturally infected Ogliarola salentina and Cellina di Nardò susceptible cultivars untreated and treated with a zinc-copper citric acid biocomplex and we observed the treatment related variation of the disease biomarker quinic acid. In this study, we focused also on the Leccino cultivar, known to exhibit tolerance to the disease progression. The 1 H-NMR-based metabolomic approach was applied with the aim to characterize the overall metabolism of tolerant Leccino in comparison with the susceptible cultivars Ogliarola salentina and Cellina di Nardò under periodic mid-term treatment. In particular, we studied the leaf extract molecular patterns of naturally infected trees untreated and treated with the biocomplex. The metabolic Leccino profiles were analyzed for the first time and compared with those exhibited by the susceptible Cellina di Nardò and Ogliarola salentina cultivars. The study highlighted a specificity in the metabolic response of the tolerant Leccino compared to susceptible cultivars. These differences provide useful information to describe the defensive mechanisms underlying the change of metabolites as a response to the infection, and the occurrence of different levels of disease, season and treatment effects for olive cultivars.

Background: Epidemiological evidence on short-term association between ambient carbon monoxide (CO) and mortality is inconclusive and limited to single cities, regions, or countries. Generalisation of results from previous studies is hindered by potential publication bias and different modelling approaches. We therefore assessed the association between short-term exposure to ambient CO and daily mortality in a multicity, multicountry setting., Methods: We collected daily data on air pollution, meteorology, and total mortality from 337 cities in 18 countries or regions, covering various periods from 1979 to 2016. All included cities had at least 2 years of both CO and mortality data. We estimated city-specific associations using confounder-adjusted generalised additive models with a quasi-Poisson distribution, and then pooled the estimates, accounting for their statistical uncertainty, using a random-effects multilevel meta-analytical model. We also assessed the overall shape of the exposure-response curve and evaluated the possibility of a threshold below which health is not affected., Findings: Overall, a 1 mg/m 3 increase in the average CO concentration of the previous day was associated with a 0·91% (95% CI 0·32-1·50) increase in daily total mortality. The pooled exposure-response curve showed a continuously elevated mortality risk with increasing CO concentrations, suggesting no threshold. The exposure-response curve was steeper at daily CO levels lower than 1 mg/m 3 , indicating greater risk of mortality per increment in CO exposure, and persisted at daily concentrations as low as 0·6 mg/m 3 or less. The association remained similar after adjustment for ozone but was attenuated after adjustment for particulate matter or sulphur dioxide, or even reduced to null after adjustment for nitrogen dioxide., Interpretation: This international study is by far the largest epidemiological investigation on short-term CO-related mortality. We found significant associations between ambient CO and daily mortality, even at levels well below current air quality guidelines. Further studies are warranted to disentangle its independent effect from other traffic-related pollutants., Funding: EU Horizon 2020, UK Medical Research Council, and Natural Environment Research Council., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Italy was the first country outside China to experience the impact of the COVID-19 pandemic, which resulted in a significant health burden. This study presents an analysis of the excess mortality across the 107 Italian provinces, stratified by sex, age group and period of the outbreak., Methods: The analysis was performed using a two-stage interrupted time-series design using daily mortality data for the period January 2015-May 2020. In the first stage, we performed province-level quasi-Poisson regression models, with smooth functions to define a baseline risk while accounting for trends and weather conditions and to flexibly estimate the variation in excess risk during the outbreak. Estimates were pooled in the second stage using a mixed-effects multivariate meta-analysis., Results: In the period 15 February-15 May 2020, we estimated an excess of 47 490 [95% empirical confidence intervals (eCIs): 43 984 to 50 362] deaths in Italy, corresponding to an increase of 29.5% (95% eCI: 26.8 to 31.9%) from the expected mortality. The analysis indicates a strong geographical pattern, with the majority of excess deaths occurring in northern regions, where few provinces experienced increases up to 800% during the peak in late March. There were differences by sex, age and area both in the overall impact and in its temporal distribution., Conclusion: This study offers a detailed picture of excess mortality during the first months of the COVID-19 pandemic in Italy. The strong geographical and temporal patterns can be related to the implementation of lockdown policies and multiple direct and indirect pathways in mortality risk., (© The Author(s) 2020. Published by Oxford University Press on behalf of the International Epidemiological Association.)

During recent years; Xylella fastidiosa subsp. pauca (Xfp) has spread in Salento causing relevant damage to the olive groves. Measures to contain the spreading of the pathogen include the monitoring of the areas bordering the so-called "infected" zone and the tree eradication in case of positive detection. In order to provide a control strategy aimed to maintain the tree productivity in the infected areas, we further evaluated the in vitro and in planta mid-term effectiveness of a zinc-copper-citric acid biocomplex. The compound showed an in vitro bactericidal activity and inhibited the biofilm formation in representative strains of X. fastidiosa subspecies, including Xfp isolated in Apulia from olive trees. The field mid-term evaluation of the control strategy assessed by quantitative real-time PCR in 41 trees of two olive groves of the "infected" area revealed a low concentration of Xfp over the seasons upon the regular spraying of the biocomplex over 3 or 4 consecutive years. In particular, the bacterial concentration lowered in July and October with respect to March, after six consecutive treatments. The trend was not affected by the cultivar and it was similar either in the Xfp-sensitive cultivars Ogliarola salentina and Cellina di Nardò or in the Xfp-resistant Leccino. Moreover, the scoring of the number of wilted twigs over the seasons confirmed the trend. The efficacy of the treatment in the management of olive groves subjected to a high pathogen pressure is highlighted by the yielded a good oil production.

Xylella fastidiosa is a xylem-limited bacterium phylogenetically related to the xanthomonads, with an unusually large and diversified range of plant hosts. To ascertain the origin of its peculiarities, its pan-genome was scanned to identify the genes that are not coherent with its phylogenetic position within the order Xanthomonadales . The results of the analysis revealed that a large fraction of the genes of the Xylella pan-genome have no ortholog or close paralog in the order Xanthomonadales . For a significant part of the genes, the closest homologue was found in bacteria belonging to distantly related taxonomic groups, most frequently in the Betaproteobacteria . Other species, such as Xanthomonas vasicola and Xanthomonas albilineans which were investigated for comparison, did not show a similar genetic contribution from distant branches of the prokaryotic tree of life. This finding indicates that the process of acquisition of DNA from the environment is still a relevant component of Xylella fastidiosa evolution. Although the ability of Xylella fastidiosa strains to recombine among themselves is well known, the results of the pan-genome analyses stressed the additional relevance of environmental DNA in shaping their genomes, with potential consequences on their phytopathological features.

The European monitoring of excess mortality for public health action (EuroMOMO) network monitors weekly excess all-cause mortality in 27 European countries or subnational areas. During the first wave of the coronavirus disease (COVID-19) pandemic in Europe in spring 2020, several countries experienced extraordinarily high levels of excess mortality. Europe is currently seeing another upsurge in COVID-19 cases, and EuroMOMO is again witnessing a substantial excess all-cause mortality attributable to COVID-19.

An amendment to this paper has been published and can be accessed via the original article.

Background: Standardized mortality surveillance data, capable of detecting variations in total mortality at population level and not only among the infected, provide an unbiased insight into the impact of epidemics, like COVID-19 (Coronavirus disease). We analysed the temporal trend in total excess mortality and deaths among positive cases of SARS-CoV-2 by geographical area (north and centre-south), age and sex, taking into account the deficit in mortality in previous months., Methods: Data from the Italian rapid mortality surveillance system was used to quantify excess deaths during the epidemic, to estimate the mortality deficit during the previous months and to compare total excess mortality with deaths among positive cases of SARS-CoV-2. Data were stratified by geographical area (north vs centre and south), age and sex., Results: COVID-19 had a greater impact in northern Italian cities among subjects aged 75-84 and 85+ years. COVID-19 deaths accounted for half of total excess mortality in both areas, with differences by age: almost all excess deaths were from COVID-19 among adults, while among the elderly only one third of the excess was coded as COVID-19. When taking into account the mortality deficit in the pre-pandemic period, different trends were observed by area: all excess mortality during COVID-19 was explained by deficit mortality in the centre and south, while only a 16% overlap was estimated in northern cities, with quotas decreasing by age, from 67% in the 15-64 years old to 1% only among subjects 85+ years old., Conclusions: An underestimation of COVID-19 deaths is particularly evident among the elderly. When quantifying the burden in mortality related to COVID-19, it is important to consider seasonal dynamics in mortality. Surveillance data provides an impartial indicator for monitoring the following phases of the epidemic, and may help in the evaluation of mitigation measures adopted.

Since 2008, the kiwifruit industry has been devastated by a pandemic outbreak of Pseudomonas syringae pv. actinidiae (Psa), the causal agent of bacterial canker. This disease has become the most significant limiting factor in kiwifruit production. Psa colonizes different organs of the host plant, causing a specific symptomatology on each of them. In addition, the systemic invasion of the plant may quickly lead to plant death. Despite the massive risk that this disease poses to the kiwifruit industry, studies focusing on Psa ecology have been sporadic, and a comprehensive description of the disease epidemiology is still missing. Optimal environmental conditions for infection, dispersal and survival in the environment, or the mechanisms of penetration and colonization of host tissues have not been fully elucidated yet. The present work aims to provide a synthesis of the current knowledge, and a deeper understanding of the epidemiology of kiwifruit bacterial canker based on new experimental data. The pathogen may survive in the environment or overwinter in dormant tissues and be dispersed by wind or rain. Psa was observed in association with several plant structures (stomata, trichomes, lenticels) and wounds, which could represent entry points for apoplast infection. Environmental conditions also affect the bacterial colonization, with lower optimum values of temperature and humidity for epiphytic than for endophytic growth, and disease incidence requiring a combination of mild temperature and leaf wetness. By providing information on Psa ecology, these data sets may contribute to plan efficient control strategies for kiwifruit bacterial canker.

Xylella fastidiosa subsp. pauca is responsible for the "olive quick decline syndrome" (OQDS) in Salento (Apulia). The main epidemiological aspects of the syndrome are related to the pathogen spread and survival in the area, and to the biology of the insect vector. The assessment of the macro and microelements content (i.e., ionome) in soil and leaves could provide basic and useful information. Indeed, knowledge of host ionomic composition and the possibility of its modification could represent a potential tool for the management of diseases caused by X. fastidiosa . Therefore, soil and leaf ionomes of naturally infected, not infected, and zinc-copper-citric acid biocomplex treated trees of different areas of Apulia and the bordering Basilicata regions were compared. We observed that soil and leaf ionomic composition of olive farms growing in the pathogen-free areas north of the Salento Barletta-Andria-Trani BAT (Apulia) and Potenza PZ (Basilicata, Apulia bordering region) provinces is significantly different from that shown by the infected olive groves of the Salento areas (LE, BR, TA provinces). In particular, a higher content of zinc and copper both in soil and leaves was found in the studied northern areas in comparison to the southern areas. This finding could partly explain the absence of OQDS in those areas. In the infected Salento areas, the leaf ionomic profile resulted as being markedly different for the biocomplex treated compared to the untreated trees. A higher zinc content in leaves characterized treated with respect to untreated trees. On the other hand, among the not-infected trees, Xylella -resistant Leccino showed higher manganese content when compared with the higher pathogen sensitive Ogliarola salentina and Cellina di Nardò. According to these results, soil and olive leaf ionome could provide basic information for the epidemiologic study and possible control of X. f. subsp. pauca in Apulia.

Global trade and climate change are re-shaping the distribution map of pandemic pathogens. One major emerging concern is Xylella fastidiosa, a tropical bacterium recently introduced into Europe from America. In last decades, X. fastidiosa was detected in several European countries. X. fastidiosa is an insect vector-transmitted bacterial plant pathogen associated with severe diseases in a wide range of hosts. X. fastidiosa through a tight coordination of the adherent biofilm and the planktonic states, invades the host systemically. The planktonic phase is correlated to low cell density and vessel colonization. Increase in cell density triggers a quorum sensing system based on mixture of cis 2-enoic fatty acids-diffusible signalling factors (DSF) that promote stickiness and biofilm. The lipidome profile of Olea europaea L. (cv. Ogliarola salentina) samples, collected in groves located in infected zones and uninfected zones was performed. The untargeted analysis of the lipid profiles of Olive Quick Decline Syndrome (OQDS) positive (+) and negative (-) plants showed a clustering of OQDS+ plants apart from OQDS-. The targeted lipids profile of plants OQDS+ and OQDS- identified a shortlist of 10 lipids that increase their amount in OQDS+ and X. fastidiosa positive olive trees. These lipid entities, provided to X. fastidiosa subsp. pauca pure culture, impact on the dual phase, e.g. planktonic ↔ biofilm. This study provides novel insights on OQDS lipid hallmarks and on molecules that might modulate biofilm phase in X. fastidiosa subsp. pauca., Competing Interests: The authors have declared that no competing interests exist.