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Background: Physical symptoms play an important role in late-life depression and may contribute to residual symptomatology after antidepressant treatment. In this exploratory study, we examined the role of specific bodily dimensions including movement, respiratory functions, fear of falling, cognition, and physical weakness in older people with depression.Methods: Clinically stable older patients with major depression within a Psychiatric Consultation-Liaison program for Primary Care underwent comprehensive assessment of depressive symptoms, instrumental movement analysis, dyspnea, weakness, activity limitations, cognitive function, and fear of falling. Network analysis was performed to explore the unique adjusted associations between clinical dimensions.Results: Sadness was associated with worse turning and walking ability and movement transitions from walking to sitting, as well as with worse general cognitive abilities. Sadness was also connected with dyspnea, while neurovegetative depressive burden was connected with activity limitations.Discussion: Limitations of motor and cognitive function, dyspnea, and weakness may contribute to the persistence of residual symptoms of late-life depression.

Determining the background values of chemical components in environmental matrices is a difficult task. This is particularly true in regions where the human impact due to industrial, mining, agricultural and urban activities coexists with a geological (geogenic) anomaly, which influences the concentration of certain elements in soils, waters and air. In these cases, the term geochemical baseline (GB) is preferable, since it considers the actual content of that element in the superficial environment at a given point in time, including both geogenic and anthropogenic contribution. In this study, a total of 102 top- and sub-soil (collected at 10-50 cm and 50-154 cm depth, respectively) samples and seven rocks, onto which the soils developed, were collected for the determination of GBs for selected chalcophile (As, Cu, Hg and Sb) and siderophile (Co, Cr, Ni, and V) elements in 25.6 km2 around the former mining area of Abbadia San Salvatore (Mt. Amiata, Southern Tuscany, Italy). For about one century, cinnabar (HgS) ore deposits have been exploited to produce liquid mercury from the Mt. Amiata volcanic system and its surroundings, which represents a world-class mercury district. The < 2 mm (as required by the national regulamentation) fraction of the samples was pulverized and analysed by ICP-MS (As, Hg and Sb) and ICP-AES (Co, Cr, Ni, and V) after aqua regia digestion. The compositional data analysis of multivariate compositional vectors, based on the log-ratio approach was used to assess the nature of the geochemical . According to our findings, the centred log-ratio (clr) opposed to that of raw/log transformation, enhances the spatial mapping. This also allowed to obtain better-separated variables in the robust Principal Component Analysis (rPCA). Log-ratio geographical maps evidenced that the underlying bedrock geology (parent lithologies), rather than anthropogenic causes, controls the distribution of the great majority of the elements in the top- and sub-soils. The resulting clr-PCA approach, associated with the geological features, indicates that the geochemical pattern of Hg-As is to be related to the volcanic rocks and ore-deposits, although an anthropogenic influence due to the past mining activity in the topsoils cannot be ruled out. Sb, Co, Cr, Ni, and V distribution patterns are in most cases attributed to calcareous and clay lithologies. The anomalous content of Sb found within the volcanic rocks was likely due to the presence of previously undetected old mining dump. The two data populations (volcanic and calcareus-clay lithologis) were separated into two different databases and the outliers were removed when necessary. By processing the two datasets, the US-EPA’s ProUCL software was used for calculating the GBs for the selected suite of elements. The obtained values are paramount for establishing specific guidelines and quality standards in environmental legislation and policy-making to be applied by the Municipality of Abbadia San Salvatore

The distribution of heavy metals in plants growing in soils from active and abandoned mining areas is of scientific significance as it allows one to recognize their ability to survive in a hostile environment and to provide useful indications for phytoremediation operations. In this work, soils developed in the former Hg-mining area of Abbadia San Salvatore (Tuscany, Central Italy) were analyzed for total, leached Hg, % of organic- and inorganic-related Hg. The dehydrogenase enzyme activity (DHA) was also measured with the aim to evaluate the status of the soil, being characterized by high Hg content. Eventually, the concentration of Hg in the different parts of the plants growing on these soils was analyzed. The soils showed Hg content up to 1068 mg kg− 1 and in most of them is dominated by inorganic Hg (up to 92%). The DHA concentrations were − 1day− 1, suggesting that the presence of Hg is not significantly affecting the enzymatic soil activity. This is also supported by the bioaccumulation factor (BF) that is 0 are the main forms entering the plant system, the latter derived by the GEM emitted by both the edifices hosting the roasting furnaces and the soils themselves.

Among its many functions, soil represents the active natural medium for plant growth. Different soils have various structural characteristics, that correspond to their qualitative parameters in terms of physical, chemical, and biological fertility. Because of their extremely slow formation processes, soils are also a non-renewable resource, easily subject to degradative processes. Among their mineral constituents many agrarian soils present, in addition to the fine earth, variable percentages of coarse fractions in their arable layer, which interfere with the crop growth, requiring more energy to manage cultivation operations, and damaging the machinery up to making its use impractical. In these conditions, it becomes necessary to proceed with the soil destoning, particularly for the management of Precision Farming techniques. Depending on the percentages, sizes and types of coarse fractions, the soil destoning systems concern: (i) the collection and removal of stones from the field, (ii) the on-site stones crushing, and (iii) the stone burial. In this article, we report the first evaluation of a deep burial destoning system carried out in the CREA Experimental Center of Treviglio (Italy). With the described reclamation system, a significant long-term improvement of soil quality in a 600 mm thick arable layer was achieved; avoiding the shortcomings of the destoning systems as commonly applied in agricultural lands.

The environmental impact of mining and smelting in the world-class Monte Amiata mercury (Hg) ore field has long been studied, before and after the final closure in 1982. A first summary was presented in 2015. With this contribution, we review the studies conducted in the last eight years. The most significant results include ⅰ) Hg-isotope characterization of primary ore (cinnabar), smelting waste (calcines), soil, fish and stream sediments; ⅱ) analysis of the interplay between geomorphological evolution, fluvial dynamics and Hg distribution in the Paglia River catchment, which drains the main mining areas; ⅲ) an improved quantification of the Hg loads discharged to the Mediterranean Sea; ⅳ) the use of biomonitors to reveal the dispersion of Hg; ⅴ) new detailed surveys, including innovative techniques, of Hg distribution in air; ⅵ) specific investigations to support the ongoing reclamation at Abbadia San Salvatore, the main mining and smelting center of the district, and ⅶ) the assessment of the variability of Hg distribution in air, water and soil from the reclaimed Siele mine. Despite these progresses, there are further steps to be conducted to achieve optimal management of the wide contamination evidenced in this district. It is now fully clear that the diffuse character of contamination results in unfeasible hypotheses for total remediation. Therefore, the goal is that of a sustainable coexistence between contamination and human activities. This goal may involve the following activities: a) implementation of GIS-based contamination maps as a direct operational instrument for local authorities to tune up specific limitations and regulations of human activities (e.g., fishing, instream quarrying and wildfire management); b) mitigation measures such as increasing the vegetal cover of river banks to limit erosion and runoff, and c) continuous monitoring of air, water and soil contamination, including transfer to the food chain.

The Province of Pesaro-Urbino (northern Marche, central Italy) represents one of most seismically active areas in Italy, since it is interested by the presence of two major composite seismogenic sources: i) the first one is located in the Umbria-Marche Apennines; ii) the second one is along the Adriatic coast from Cattolica to Ancona cities. This area has recently experienced an intense seismic activity, e.g., the 1781 “Cagli Earthquake” with a magnitude of 6.4 Mw, and the 1930 “Senigallia Earthquake” of 5.8 Mw. The last earthquake (5.5 Mw) occurred on November 9, 2022, with its epicenter located in the Adriatic Sea, 35 km away from the city of Pesaro. Since the geochemical knowledge of this area is limited, a large-scale sampling survey was carried out during spring and autumn 2022. A total of 87 samples were collected from different types of emergencies (i.e., cold springs, wells, mineral springs, sulfur springs and ditches) and various geological and tectonic-structural contexts. The study area is dominated by a complex sedimentary structure (e.g., limestones, clays and alluvial deposits) and by climatic and topographic conditions that may influence the chemical and isotopic composition of the investigated fluids. A detailed geochemical characterization is thus of paramount importance in order to define a geochemical background. The aim of this study was to (1) understand the possible interaction of deep-originated fluids and shallow aquifers and (2) evaluate the use of selected geochemical parameters as possible seismic tracers. The results showed the presence of five different geochemical facies: (i) calcium-bicarbonate waters with low TDS (8.8); (iv) calcium-sulfate waters; and (v) sodium-chloride waters. The water isotopic composition showed a clear meteoric origin for all the investigated samples. The composition of major dissolved gases showed two different compositional clusters: (a) N2-dominated gases with N2/Ar ratios similar to those of air and ASW (Air Saturated Water); (b) CO2- and CH4-rich gases pertaining to mineral and sulfur springs. The origin of Ca-HCO3 waters is almost exclusively related to the dissolution of carbonate minerals. On the contrary, Ca-HCO3(SO4) waters are probably originated by deep circulation pathways and interactions with the Upper Triassic Burano Formation, composed by anhydrite layers. The Ca-SO4 waters should be considered as the product of ongoing flows within Miocene gypsum formations, whilst Na-HCO3 waters as the consequence of long-lasting interactions between meteoric waters and silicate rocks (containing albite) in saturation/oversaturation conditions for carbonate-bearing minerals. Finally, the Na-Cl waters probably derive from mixing processes between meteoric and highly saline connate waters trapped into the foredeep clayey deposits. Therefore, the Ca-HCO3(SO4) and Ca-SO4 waters can be regarded as the most interesting fluids to be monitored for a geochemical network aimed at recognizing chemical and isotopic variations related to seismic activity. They are indeed showing a deeper hydrogeological pathway and appear to be less influenced by surface processes.

Aims There is still uncertainty on the management of patients with pheochromocytoma-induced CS (PICS), as only a few clinical cases have been reported. The aim of this study is to investigate the clinical presentation, management, and outcome of patients with PICS. Methods We collected retrospectively 18 patients without previously known pheochromocytoma with histologically proven PICS admitted to 8 European hospitals. Results Among the 18 patients with a mean age of 50 years, 50% were men. The main clinical features at presentation were pulmonary congestion (83%) and cyclic fluctuation of hypertension crises and hypotension (72%). On echocardiography, mean left ventricular ejection fraction (LVEF) was 25% with an atypical-Takotsubo pattern (basal/midventricular) in 50%. Laboratory exams showed increased inflammatory markers, in particular, the mean white blood count was 21.9*109/L. Inotropes/vasopressors were started in all patients and a temporary mechanical circulatory support (t-MCS) was required in 11 (61.1%) patients. All patients underwent surgical removal of the pheochromocytoma but 4 (22.2%) on t-MCS. Echocardiogram (16/17 patients) revealed a mean LVEF of 55% at discharge. Only one patient required heart transplantation (5.5%), and all patients were alive at a median follow-up of 679 days. Conclusions In patients with PICS, characteristically, an atypical Takotsubo pattern was observed in almost half of the cases. Although the use of exogenous catecholamine can be perceived as deleterious, we showed a fairly good mid-term prognosis with rapid improvement of LVEF in most, even if adrenalectomy often occurred on t-MCS.

Shape morphing materials, especially those fabricated by 4D printing, are gaining much attention due to their versatility of actuation and capability of being programmed in advance. These materials become particularly interesting for biomedical applications where implant materials could be remotely actuated, exerting a force on the surrounding tissues and cells. However, applications in this field have been restricted due to the biocompatibility of the materials and the character of the required stimuli, generally not compatible with physiological environments. Magnetic nanoparticles (MNPs) represent a great opportunity to this end; however, the actuation results in a uniform movement toward the magnet that requires anchoring of the object. Here, for the first time, the application of anisotropic Fe3O4 MNPs is described, and synthesized by a novel and easy route, that can be aligned on pre-defined patterns within objects printed by digital light processing, resulting in materials that can be actuated remotely (4D printing). These nanoparticles (178 nm x 55 nm), show good biocompatibility when directly seeded on top of human mesenchymal stem cells, despite being uptaken. Most importantly, the alignment of the MNPs can tune the movement of fabricated nanocomposite materials, resulting in complex movements of attraction or repulsion depending on the direction of the applied magnetic field. T.K., and S.C.-E. contributed equally to this work. This work was supported financially by the Province of Limburg and the Brightlands Materials Center. The authors were also grateful to the research program Innovation Fund Chemistry, which was partly financed by the Netherlands Organization for Scientific Research (NWO) under TA grant agreement 731.016.202 ("DynAM"). The authors acknowledge the Texas A&M Health Science Center College of Medicine Institute for Regenerative Medicine at Scott & White who isolated and provided the cells through a grant from NCRR of the NIH (Grant #P40RR017447).

Over the last decades, groundwater resources at global level have suffered a significant deterioration due to nitrate pollution, mainly related to the input of agricultural fertilizers, manure, sewage, and untreated urban and industrial effluents. The most impacted waters are those forming surface and shallow reservoirs, which usually play a key role in supplying waters to civil, agricultural, and industrial activities. The terminal portion of the Metauro River plain, located in central Italy along the Adriatic Sea coastline, hosts a strategic phreatic aquifer that, along with the surface water of the Metauro River, supplies water to the local population (i.e., about 60,000 people). This shallow coastal aquifer experiences a long-lasting story of nitrate contamination since the 1970s when the increase in the use of agricultural fertilizers contributed to very high levels of pollution (NO3− > 100 mg/L). This fact prompted the local authorities to carry out remediation actions that involve a pumping system to inject the NO3−-poor waters from the Metauro River course directly into the shallow aquifer. The present work was aimed at defining the contamination of nitrates in this important water resource. The main geochemical characteristics and the temporal evolution of NO3− concentrations (between 2009 and 2020), in the shallow coastal aquifer of the Metauro River plain, were analyzed by means of classical geochemical analyses and multivariate methods accounting for the compositional nature of the data, to assess the efficiency of the in-situ remediation over time.

The contribution of oxic methane production to greenhouse gas emissions from lakes is globally relevant, yet uncertainties remain about the levels up to which methanogenesis can counterbalance methanotrophy by leading to CH4 oversaturation in productive surface waters. Here, we explored the biogeochemical and microbial community variation patterns in a meromictic soda lake, in the East African Rift Valley (Kenya), showing an extraordinarily high concentration of methane in oxic waters (up to 156 µmol L−1). Vertical profiles of dissolved gases and their isotopic signature indicated a biogenic origin of CH4. A bloom of Oxyphotobacteria co-occurred with abundant hydrogenotrophic and acetoclastic methanogens, mostly found within suspended aggregates promoting the interactions between Bacteria, Cyanobacteria, and Archaea. Moreover, aggregate sedimentation appeared critical in connecting the lake compartments through biomass and organic matter transfer. Our findings provide insights into understanding how hydrogeochemical features of a meromictic soda lake, the origin of carbon sources, and the microbial community profiles, could promote methane oversaturation and production up to exceptionally high rates., Fazi et al. report on an extraordinarily high biogenic methane concentration detected in the surface water of Lake Sonachi, Kenya. Using gas chromatography and microbiome profiling, they determine that these high concentrations are associated with cyanobacterial blooms and help provide insight to methanogenesis in meromictic soda lakes.

The authors describe the point of view of the teachers for the information literacy skills of the undergraduate students. The methodology is based on the case study of the Navigate Project and in p...

Fungal promoted infections are becoming a severe health global emergency due to drug-resistant phenomena and zoonosis. This work investigated compounds bearing acyl-/selenoureido moieties and primary/secondary sulfonamide groups as novel antifungal agents acting through organism-directed selenium toxicity and inhibition of the newly emergent therapeutic target, the Carbonic Anhydrases (CAs; EC 4.2.1.1). Reported data clearly indicate that seleno-containing scaffolds with respect to the standard-of-care drugs showed appreciable antifungal activity, which was suppressed when the chalcogen was replaced with its cognate isosteric elements sulfur and oxygen. In addition, such compounds showed excellent selectivity against

Biochar, included as a soil amendment by EU Regulation 2019/1009, has been shown to increase soil organic C stock and nutrient retention. We investigated the effect of biochar incorporation alone (B) and in association with mineral (BMin), digestate (BDig) and slurry (BSlu) fertilization, compared to the respective controls without biochar (C, Min, Dig and Slu), in a silage maize–Italian ryegrass rotation, on yield, soil fertility parameters and nitrous oxide (N2O) emissions. Two types of biochar in three doses (0.2, 0.45, 0.9%) were tested in two cropping seasons. Biochar did not significantly affect maize yield; however, BDig tended to increase silage yield and the ear component compared to Dig, while BMin tended to reduce maize N uptake compared to Min. Biochar incorporation significantly increased soil organic C (+31%) and cation exchange capacity (CEC) (+13%) in all the fertilization treatments; BMin and BDig also showed an increase compared to biochar alone (B). Emission of N2O was mainly driven by fertilization, digestate exhibiting the highest emissions. Biochar addition decreased the cumulative N2O emissions consistently in all the fertilization treatments, though not significantly. The association of biochar with organic fertilizers, in particular digestate, appears promising in increasing the fertilizer efficiency and reducing N2O emissions.

To summarize the histologic findings of vasculitis, and to give some practical considerations on biopsy samples.The larger use of imaging and the discoveries of serological markers in the diagnosis of vasculitis have increased the clinical recognition of these entities. Nevertheless, biopsy remains the gold standard for diagnosis in most cases. So far, biopsies are also useful to obtain information about prognosis and to guide a more specific treatment. In recent years, less invasive diagnostic approaches have become available, lowering the risks related to the procedure and permitting a definite diagnosis in most cases. Histological examination permits a definite diagnosis of vasculitis. However, the findings may be nonspecific if not evaluated in the proper clinical setting. The interaction between clinicians and pathologists is crucial to obtain a definite diagnosis.

Antibacterial adjuvants are of great significance, since they allow one to downscale the therapeutic dose of conventional antibiotics and reduce the insurgence of antibacterial resistance. Herein, we report that O-acetylserine sulfhydrylase (OASS) inhibitors could be used as colistin adjuvants to treat infections caused by critical pathogens spreading worldwide, Escherichia coli, Salmonella enterica serovar Typhimurium, and Klebsiella pneumoniae. Starting from a hit compound endowed with a nanomolar dissociation constant, we have rationally designed and synthesized a series of derivatives to be tested against S. Typhimurium OASS isoenzymes, StOASS-A and StOASS-B. All acidic derivatives have shown good activities in the nanomolar range against both OASS isoforms in vitro. Minimal Inhibitory Concentrations (MICs) were then evaluated, as well as compounds’ toxicity. The compounds endowed with good activity in vitro and low cytotoxicity have been challenged as a potential colistin adjuvant against pathogenic bacteria in vitro and the fractional inhibitory concentration (FIC) index has been calculated to define additive or synergistic effects. Finally, the target engagement inside the S. Typhimurium cells was confirmed by using a mutant strain in which the OASS enzymes were inactivated. Our results provide a robust proof of principle supporting OASS as a potential nonessential antibacterial target to develop a new class of adjuvants.

In addition to long-term regulation of blood pressure (BP), in the kidney resides the initial trigger for hypertension development due to an altered capacity to excrete sodium and water. Betaine is one of the major organic osmolytes, and its betaine/gamma-aminobutyric acid transporter (BGT-1) expression in the renal medulla relates to interstitial tonicity and urinary osmolality and volume. This study investigated altered water and sodium balance as well as changes in antidiuretic hormone (ADH) activity in female spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rats from their 3–5 weeks of age (prehypertensive phase) to SHR’s 28–30 weeks of age (established hypertension-organ damage). Young prehypertensive SHRs showed a reduced daily urine output, an elevated urine osmolarity, and higher immunostaining of tubule BGT-1, alpha-1-Na-K ATPase in the outer medulla vs. age-matched WKY. ADH circulating levels were not different between young prehypertensive SHR and WKY, but the urine aquaporin2 (AQP2)/creatinine ratio and labeling of AQP2 in the collecting duct were increased. At 28–30 weeks, hypertensive SHR with moderate renal failure did not show any difference in urinary osmolarity, urine AQP2/creatinine ratio, tubule BGT-1, and alpha-1-Na-K ATPase as compared with WKY. These results suggest an increased sensitivity to ADH in prehypertensive female SHR. On this basis, a second series of experiments were set to study the role of ADH V1 and V2 receptors in the development of hypertension, and a group of female prehypertensive SHRs were treated from the 25th to 49th day of age with either V1 (OPC21268) or V2 (OPC 41061) receptor antagonists to evaluate the BP time course. OPC 41061-treated SHRs had a delayed development of hypertension for 5 weeks without effect in OPC 21268-treated SHRs. In prehypertensive female SHR, an increased renal ADH sensitivity is crucial for the development of hypertension by favoring a positive water balance. Early treatment with selective V2 antagonism delays future hypertension development in young SHRs.

Antibacterial adjuvants are of great significance, since they allow the therapeutic dose of conventional antibiotics to be lowered and reduce the insurgence of antibiotic resistance. Herein, we report that an O-acetylserine sulfhydrylase (OASS) inhibitor can be used as a colistin adjuvant to treat infections caused by Gram-positive and Gram-negative pathogens. A compound that binds OASS with a nM dissociation constant was tested as an adjuvant of colistin against six critical pathogens responsible for infections spreading worldwide, Escherichia coli, Salmonella enterica serovar Typhimurium, Klebisiella pneumoniae, Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, and Staphylococcus pseudintermedius. The compound showed promising synergistic or additive activities against all of them. Knockout experiments confirmed the intracellular target engagement supporting the proposed mechanism of action. Moreover, compound toxicity was evaluated by means of its hemolytic activity against sheep defibrinated blood cells, showing a good safety profile. The 3D structure of the compound in complex with OASS was determined at 1.2 Å resolution by macromolecular crystallography, providing for the first time structural insights about the nature of the interaction between the enzyme and this class of competitive inhibitors. Our results provide a robust proof of principle supporting OASS as a potential nonessential antibacterial target to develop a new class of adjuvants and the structural basis for further structure-activity relationship studies.

The aim of this trial was to investigate the effects of a blend of monoglycerides of short- and medium-chain fatty acids (SMCFA) on health status and growth of preweaned male calves from 16 to 72 days of age. The in vivo study was conducted as a complete randomised block design. Twenty Italian Holstein calves received starter administered ad libitum and 6 L of milk replacer/day (12% powder concentration) and were divided into treated (T) and control (C) groups. A preliminary in vitro antibiotic activity test of SMCFA was performed on several bacterial strains showing a minimum inhibiting concentration ranging from 0.8 to 12.5%. The group T received SMCFA (11 g/day) within the milk replacer while, to obtain isoenergetic liquid diets, the group C received additional 18 g/day of milk replacer powder. Body weight and morphological measurements of the calves were performed weekly. Health scores were checked daily. Faecal and blood samples were collected every two weeks for routine clinical investigations including serum concentration of non-esterified fatty acids and β-Hydroxybutyric acid. At the end of the trial calves were slaughtered and gastrointestinal tract (GIT) organs weighed. The group T reported a better health status and did not require Ab therapy. No differences in biometrical measurements, feed efficiency, blood parameters, and GIT measures were found between the two groups. At 44 days of age, group T showed higher β-Hydroxybutyric acid concentration compared to group C (p

The role of mitochondria in cardiac tissue is of utmost importance due to the dynamic nature of the heart and its energetic demands, necessary to assure its proper beating function. Recently, other important mitochondrial roles have been discovered, namely its contribution to intracellular calcium handling in normal and pathological myocardium. Novel investigations support the fact that during the progression toward heart failure, mitochondrial calcium machinery is compromised due to its morphological, structural and biochemical modifications resulting in facilitated arrhythmogenesis and heart failure development. The interaction between mitochondria and sarcomere directly affect cardiomyocyte excitation-contraction and is also involved in mechano-transduction through the cytoskeletal proteins that tether together the mitochondria and the sarcoplasmic reticulum. The focus of this review is to briefly elucidate the role of mitochondria as (mechano) sensors in the heart.

With the opening of the twentieth century, the beneficial river of the avant-gardes seemed to flood the entire European continent in a happy contamination of national cultures, giving life to an authentic supranational koine of artists: it was sometimes fusion of forms, styles, environments, cultures, a salutary effort to rejuvenate languages. The particular attention of the Italian Futurists to the new national realities was among the factors of particular attraction to the movement for South Slavs whose representative was Josip (Sibe) Miličić, who called for cultural and political renewal of his country. His direct encounter with Marinetti and Boccioni seems to leave its mark on his poetry both structurally and thematically: in the collection from 1914, Miličić reveals a new sensibility and a new rhythm: in one of his war lyrics, the futurist suggestions materialize in his first onomatopoeic attempt, suitable to undermine the lyricism of the verse by intensifying the link between the phonic aspect and the meaning. Despite their common interventionism, the Great War found the Croat and the Italian Futurists on opposite political positions concerning the Dalmatian islands and the Italian expansionism on the Adriatic. The poet’s war experience lead him to a “mature” phase starting in the twenties with his first article-manifesto. At this time he was able to reprocess his own critical identity: affirming his deeply anti-materialist and anti-industrial spiritualism, his standpoints by then had become very distant from Marinetti’s insights.

Antibacterial adjuvants are of great significance, since they allow one to downscale the therapeutic dose of conventional antibiotics and reduce the insurgence of antibacterial resistance. Herein, we report that

Dissolved and suspended toxic elements in water discharged from abandoned and active mining areas pose several critical issues, since they represent a threat to the environment. In this work, we investigated the water, suspended particulates, and stream sediments of a 2.1 km long creek (Fosso della Chiusa) that is fed by waters draining the galleries of the abandoned Hg mining area of Abbadia San Salvatore (Mt. Amiata, Tuscany, central Italy). The geochemical results show evidence that the studied matrices are characterized by relatively high concentrations of Hg and As, whereas those of Sb are generally close to or below the instrumental detection limit. Independent of the matrices, the concentration of As decreases from the emergence point to the confluence with the Pagliola creek. In contrast, Hg concentrations display more complex behavior, as water and sediment are mainly characterized by concentrations that significantly increase along the water course. According to the geoaccumulation index (Igeo), sediments belong to Class 6 (extremely contaminated) for Hg. The Igeo of As varies from Class 6, close to the emergence, to Class 2 (moderately contaminated), dropping to Class 0 (uncontaminated) at the confluence with the Pagliola creek. Finally, the total mass load of Hg and As entering the Pagliola creek was computed to be 1.3 and 0.5 kg/year, respectively, when a mean flow rate of 40 L/s was considered. The calculated loads are relatively low, but, when the Fosso della Chiusa drainage basin is taken into account, the specific load is comparable to, or even higher than, those of other mining areas.

Funder: British Heart Foundation Cambridge Centre of Excellence, Funder: The National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre and NIHR Rare Disease Translational Research Collaboration, Funder: NHS Health Education England, Funder: NIHR Cambridge Biomedical Research Centre, Funder: Isaac Newton fellowship, Funder: NIHR Leicester Biomedical Research Centre and the John and Lucille Van Geest Foundation, BACKGROUND: This work is aimed at improving the understanding of cardiometabolic syndrome pathophysiology and its relationship with thrombosis by generating a multi-omic disease signature. METHODS/RESULTS: We combined classic plasma biochemistry and plasma biomarkers with the transcriptional and epigenetic characterisation of cell types involved in thrombosis, obtained from two extreme phenotype groups (morbidly obese and lipodystrophy) and lean individuals to identify the molecular mechanisms at play, highlighting patterns of abnormal activation in innate immune phagocytic cells. Our analyses showed that extreme phenotype groups could be distinguished from lean individuals, and from each other, across all data layers. The characterisation of the same obese group, 6 months after bariatric surgery, revealed the loss of the abnormal activation of innate immune cells previously observed. However, rather than reverting to the gene expression landscape of lean individuals, this occurred via the establishment of novel gene expression landscapes. NETosis and its control mechanisms emerge amongst the pathways that show an improvement after surgical intervention. CONCLUSIONS: We showed that the morbidly obese and lipodystrophy groups, despite some differences, shared a common cardiometabolic syndrome signature. We also showed that this could be used to discriminate, amongst the normal population, those individuals with a higher likelihood of presenting with the disease, even when not displaying the classic features.

In amyotrophic lateral sclerosis (ALS), motor neurons become hyperexcitable and spontaneously discharge electrical impulses causing fasciculations. These can be detected by two noninvasive methods: high-density surface electromyography (HDSEMG) and muscle ultrasonography (MUS). We combined these methods simultaneously to explore the electromechanical properties of fasciculations, seeking a novel biomarker of disease.Twelve ALS patients and thirteen healthy participants each provided up to 24 minutes of recordings from the right biceps brachii (BB) and gastrocnemius medialis (GM). Two automated algorithms (Surface Potential Quantification Engine and a Gaussian mixture model) were applied to HDSEMG and MUS data to identify correlated electromechanical fasciculation events.We identified 4,197 correlated electromechanical fasciculation events. HDSEMG reliably detected electromechanical events up to 30 mm below the skin surface with an inverse correlation between amplitude and depth in ALS muscles. Compared to Healthy-GM muscles (mean = 79.8 ms), electromechanical latency was prolonged in ALS-GM (mean = 108.8 ms; p = 0.0458) and ALS-BB (mean = 112.0 ms; p = 0.0128) muscles. Electromechanical latency did not correlate with disease duration, symptom burden, sum muscle power score or fasciculation frequency.Prolonged fasciculation electromechanical latency indicates impairment of the excitation-contraction coupling mechanism, warranting further exploration as a potential novel biomarker of disease in ALS.This study points to an electromechanical defect within the muscles of ALS patients.

Although terrestrial hydrothermal systems are considered among the most fascinating environments, how their unique and extreme conditions can affect microorganisms selection and the role in biogeochemical cycles has not yet been well elucidated. A combined geochemical and microbiological exploration in waters and sediments from 10 sampling points along a sharp temperature gradient (15–90°C) within an extremely acidic hydrothermal system (Pisciarelli Spring, Campi Flegrei area, southern Italy) displayed how hydrothermal fluids influence the microbial dynamics. This area was characterized by high levels of reduced gaseous species (e.g. H2S, H2, CH4, CO) and very low pH values (

Additional file 1: Fig. S1. Overview of experimental design. A. Parameters used to define lean individuals amongst blood donors and controls. B. Overview of the analysis set-up to determine the effects of bariatric surgery. To minimise batch effects, 20 additional blood donors ("Controls") were recruited and were not previously present in the original BluePrint cohort. We applied a set of filters (METHODS) to identify low risk individuals within the 20 Controls, designed hereafter as "Lean-Control". C. Overview of multi-omics integration. In brief, data from 202 individuals identified as blood donors ("BD") in the present study, were collected from BluePrint consortium. It included, for monocytes and neutrophils, H3K27ac ChIP-seq, RNA-seq and 450K methylation arrays. Additionally, we obtained anthropometric measurements (BW, BMI) and generated plasma biochemistry assays, plasma metabolomics, plasma lipidomics on samples collected from the same individuals at the same time. Case groups were composed of obese individuals referred for bariatric surgery and lipodystrophy patients. Data for these groups were generated in this study. We applied a set of filters (METHODS) to identify low risk individuals within the 202 blood donors, designed hereafter as "Lean-BD".

Additional file 6. Extended methods describing biochemical profiling.

Additional file 4: Fig. S4. Related to Figure 3���Multi-omic signatures of extreme phenotype groups and their use in prediction. A. Plots showing individuals ranked by their predicted probability of belonging to the obese group. As in Figure 3C, but for the Methylation (monocytes), RNA-Seq (monocytes), Metabolites, and ChIP-Seq (monocytes) data layers. B. Multi-omic model trained using lipodystrophy patients often predicts obese individuals to belong to the lipodystrophy group. As in Figure 3C (final plot), but training the multi-layer model using the Lipodystrophy and Lean-BD groups (rather than the Obese and Lean-BD groups). Using this model, Obese individuals were often predicted as belonging to the Lipodystrophy group.

Wider pea (Pisum sativum L.) cultivation has great interest for European agriculture, owing to its favorable environmental impact and provision of high-protein feedstuff. This work aimed to investigate the extent of genotype × environment interaction (GEI), genetically based trade-offs and polygenic control for crude protein content and grain yield of pea targeted to Italian environments, and to assess the efficiency of genomic selection (GS) as an alternative to phenotypic selection (PS) to increase protein yield per unit area. Some 306 genotypes belonging to three connected recombinant inbred line (RIL) populations derived from paired crosses between elite cultivars were genotyped through genotyping-by-sequencing and phenotyped for grain yield and protein content on a dry matter basis in three autumn-sown environments of northern or central Italy. Line variation for mean protein content ranged from 21.7 to 26.6%. Purely genetic effects, compared with GEI effects, were over two-fold larger for protein content, and over 2-fold smaller for grain and protein yield per unit area. Grain yield and protein content exhibited no inverse genetic correlation. A genome-wide association study revealed a definite polygenic control not only for grain yield but also for protein content, with small amounts of trait variation accounted for by individual loci. On average, the GS predictive ability for individual RIL populations based on the rrBLUP model (which was selected out of four tested models) using by turns two environments for selection and one for validation was moderately high for protein content (0.53) and moderate for grain yield (0.40) and protein yield (0.41). These values were about halved for inter-environment, inter-population predictions using one RIL population for model construction to predict data of the other populations. The comparison between GS and PS for protein yield based on predicted gains per unit time and similar evaluation costs indicated an advantage of GS for model construction including the target RIL population and, in case of multi-year PS, even for model training based on data of a non-target population. In conclusion, protein content is less challenging than grain yield for phenotypic or genome-enabled improvement, and GS is promising for the simultaneous improvement of both traits.

By means of single-crystal X-ray diffraction we have revealed the breaking of centrosymmetry when lowering the temperature under T$_s$ = 200 K concomitantly with the setting of a commensurate superstructure in the small A-site quadruple perovskite YMn$_3$Mn$_4$O$_{12}$. This results is in agreement with all data already reported for this compounds and solve the previous inconsistency about the Yttrium position. The superstructure is characterized by the appearing of satellite reflections in the single crystal pattern, consistent with an I-centered pseudo-orthorhombic commensurate supercell with $a \approx \sqrt{a_F} = 10.4352(7)$ \AA, $b \approx 2b_F = 14.6049(9)$ \AA, $c \approx \sqrt{c_F} = 10.6961(7)$ \AA and $\beta = 90.110(3)^\circ$, where F stands for the "fundamental" high-temperature cell ($a_F \approx c_F \approx 7.45$ \AA, $b_F \approx 7.34$ \AA, and $\beta \approx 90^\circ$). The space-group was unequivocally found to be Ia, which is non polar, thus allowing for a non-zero polarization in the material. We then have investigated in detail the pyrocurrent, transport, dielectric and the DC and AC magnetic properties of polycrystalline sample of YMn$_3$Mn$_4$O$_{12}$ over a wide temperature range. These measurements clearly highlight several critical temperatures in the material and correlation between the different orders: i) the centrosymmetry is broken at high temperature (T$_S$ = 200K), ii) then the long-range magnetic order of B-sites occurs at T$_{N,B}$ = 108 K and at this same temperature the compound enters in an insulating dielectric state. iii) Finally, a remnant polarization is stabilized concomitantly with a magnetic anomaly at T* = 70 K. We propose that YMn$_3$Mn$_4$O$_{12}$ is a peculiar magnetic ferroelectric in which the polar state is driven by short-range magnetic order.

Additional file 5: Fig. S5. Related to Figure 3���A common pattern of associations between the prioritised lipid species and known CMS risk factors. The pattern of association between the prioritised lipids and known CMS risk factors in the NASH cohort (NASH cohort; left) agrees with the results from the present study (BD cohort; right).

Additional file 2: Fig. S2. Related to Figure 1���WGCNA analysis with BD individuals metabolite values and cluster functional annotation. A. Heatmap of BD individuals eigen-metabolites adjacencies in the consensus eigen-metabolites network. Each row and column correspond to one eigen metabolite (labelled by consensus module colour). The heatmap is colour-coded by adjacency, yellow indicating high adjacency (positive correlation) and blue low adjacency (negative correlation) as shown by the colour legend. B. Beeswarm plot using average eigen metabolites per cluster. Colours indicate cohorts.

Additional file 3: Fig. S3. Related to Figure 2���Summary plots of different feature numbers in all comparisons. Barplots showing the number of features significantly different for each comparison in H3K27ac distribution (ChIP-Seq), gene expression (RNA-Seq) and DNA methylation (RRBS). Each bar is colour coded to represent the different cell types.

The study proposes a process analytical technology (PAT) approach for the control of milk coagulation through near infrared spectroscopy (NIRS), computing multivariate statistical process control (MSPC) charts, based on principal component analysis (PCA). Reconstituted skimmed milk and commercial pasteurized skimmed milk were mixed at two different ratios (60:40 and 40:60). Each mix ratio was prepared in six replicates and used for coagulation trials, monitored by fundamental rheology, as a reference method, and NIRS by inserting a probe directly in the coagulation vat and collecting spectra at two different acquisition times, i.e., 60 s or 10 s. Furthermore, three failure coagulation trials were performed, deliberately changing temperature or rennet and CaCl2 concentration. The comparison with fundamental rheology results confirmed the effectiveness of NIRS to monitor milk renneting. The reduced spectral acquisition time (10 s) showed data highly correlated (r > 0.99) to those acquired with longer acquisition time. The developed decision trees, based on PC1 scores and T2 MSPC charts, confirmed the suitability of the proposed approach for the prediction of coagulation times and for the detection of possible failures. In conclusion, the work provides a robust but simple PAT approach to assist cheesemakers in monitoring the coagulation step in real-time.

Wetlands are hotspots of CH4 emissions to the atmosphere, mainly sustained by microbial decomposition of organic matter in anoxic sediments. Several knowledge gaps exist on how environmental drivers shape CH4 emissions from these ecosystems, posing challenges in upscaling efforts to estimate global emissions from waterbodies. In this work, CH4 and CO2 diffusive fluxes, along with chemical and isotopic composition of dissolved ionic and gaseous species, were determined from two wetlands of Tuscany (Italy): (i) Porta Lake, a small wetland largely invaded by Phragmites australis reeds experiencing reed die-back syndrome, and (ii) Massaciuccoli Lake, a wide marsh area including open-water basins and channels affected by seawater intrusion and eutrophication. Both wetlands were recognized as net sources of CH4 to the atmosphere. Our data show that the magnitude of CH4 diffusive emission was controlled by CH4 production and consumption rates, being mostly governed by (i) water temperature and availability of labile carbon substrates and (ii) water column depth, wind exposure and dissolved O2 contents, respectively. This evidence suggests that the highest CH4 diffusive fluxes were sustained by reed beds, providing a large availability of organic matter supporting acetoclastic methanogenesis, with relevant implications for global carbon budget and future climate models.

Aims Takotsubo Syndrome (TS) occurs as an acute coronary syndrome (ACS) characterized by severe left ventricular (LV) dysfunction that typically recovers spontaneously within days or weeks and in the absence of obstructive coronary artery disease. Although during the acute phase it is well documented that an exaggerated sympathetic tone plays a central role in the development of TS, whether an impaired sympatho-vagal balance may persist long after the acute phase, despite the recovery of left ventricular function, is still an open issue. Interestingly, recent evidences suggest that an impairment in central autonomic network not only persist long after the acute event but also may be pre-existent before the acute onset of TS. The Aim of the study was to investigate whether an impairment of the autonomic function is still present long after a TS event. Methods and results We evaluated 67 patients (91% female, mean age 66 ± 8 years) divided into three groups: 24 with a history of TS (1 year after acute event), 21 subjects with a previous history of acute coronary syndrome (ACS) and complete LV ejection fraction recovery (1 year after acute event) and 22 age- and gender-matched healthy subjects. All patients underwent a non-invasive beat-to-beat arterial blood pressure and heart rate recording (short term: 5 min), after at least 3 days of β-blockers wash-out, to obtain heart rate variability (HRV) and spontaneous baroreflex sensitivity (sBRS) data. An overall autonomic dysfunction was found in both TS and ACS groups compared to controls. In particular, a lower heart rate variability, expressed as lower SDNN, has been found in TS and ACS groups compared to controls (31 ± 12 vs. 25 ± 11 vs. 41 ± 22; P = 0.006—Figure A) as a consequence of blunted vagal tone, expressed as lower RMSSD (20 ± 12 vs. 19 ± 11 vs. 40 ± 37; P = 0.007—Figure B) and higher sympathetic tone, expressed as higher LF/HF ratio (P = 0.007 Figure C) which was found to be higher in TS even when compared to ACS (TS: 3.5 ± 2.5 vs. ACS: 2.1 ± 1.7; P = 0.011). Moreover, fractal analysis of HRV showed higher complexity of heart rate regulation, expressed as higher fractal dimension (DFA 1.48 ± 0.06 vs. 1.53 ± 0.05 vs. 1.40 ± 0.10; P Conclusions An autonomic dysfunction, characterized by a hyper-sympathetic tone, reduced baroreflex sensitivity and increased peripheral adrenergic control of blood pressure, persists in TS patients long after the acute phase.

Aims Arterial hypertension (AHT) represents the leading cause of heart failure (HF). A complex cardiovascular (CV) continuum of events leads to the progression from AHT to left ventricular hypertrophy (LVH), the hallmark of hypertensive heart (HH), towards heart failure with preserved ejection fraction (HFpEF) or reduced ejection fraction (HFrEF). Cardiopulmonary exercise testing (CPET) represents an important tool to evaluate HF patients (both with HFpEF and HFrEF) allowing quantification of functional capacity and mechanisms of dyspnoea as well as providing prognostic markers. To investigate CPET responses in AHT patients at various stages of disease progression from AHT to LVH and HF with preserved and reduced ejection fraction. Methods and results From a CPET registry of 1.397 consecutive subjects, 92 patients were selected (matched according to age, gender, BMI, CV risk factors, beta-blockers) and divided into four groups: 23 AHT patients without LVH, 23 HH patients, 23 HFpEF patients and 23 HFrEF. HFrEF were defined according to LV-EF values while HFpEF were defined according to the presence of NYHA Class ≥2 and HFA-PEFF Score. Mean age was 65 ± 10 years, mean BMI was 28.5 ± 5, male gender was prevalent 83% and 33% had diabetes. Both HFpEF and HFrEF showed lower cardiorespiratory fitness (peak VO2; P Conclusions Despite the intrinsic differences in ejection fraction, both HFpEF and HFrEF shares similar cardiopulmonary mechanisms and cardiovascular responses to exercise. CPET may represent a useful tool in order to identify and stratify hypertensive heart patients with HFpEF with high diagnostic accuracy.

Aims Arterial hypertension (AHT) represents the leading cause of cardiovascular disease (CVD) and premature death worldwide. Essential AHT accounts for 95% of all cases of hypertension; although the aetiology of essential AHT is still largely unknown, a pivotal role of autonomic nervous system has been proposed and demonstrated. Both excessive sympathetic tone and vagal withdrawal, that define autonomic dysfunction, has been associated with essential AHT. The aim of our study was to investigate the relationship between blood pressure and autonomic function in essential hypertension; this was done comparing 24 h heart rate variability and 24 h blood pressure data, simultaneously collected, in a population of essential AHT subjects. Methods A prospective registry of 179 consecutive not selected essential AHT patients were considered in the present study. All patients underwent cardiac evaluation at the Primary and Secondary Cardiovascular Prevention Unit of the Don Gnocchi Foundation of Parma. All subjects underwent 24 h ECG monitoring, and 24 h Ambulatory Blood Pressure Monitoring, during the same day. Twenty-four hours Heart Rate variability analysis included: Time-domain, frequency-domain and non-linear domain. Results Mean age was 60 0a11.7 years, male gender was prevalent (68.4%). Among the population 26 (14.7%) subjects had diabetes; the prevalence of family history of CVD was 61.7% and 66.5% had dyslipidaemia; body mass index mean values were 27.6 7.4.3. In the whole population, the prevalence of uncontrolled AHT was 80.5%, divided into: 53.1% systo-diastolic, 17.9% isolated systolic, and 9.5% isolated diastolic. The prevalence of untreated AHT (recent diagnosis) was 40.2%, while treated AHT was 59.8% and only 19.6% had controlled blood pressure values (AHT at target). 12.3% of patients were treated with Beta Blockers. A significant correlations between diastolic blood pressure (DBP) values (24 h and day-time), LF/HF ratio (24 h) (r = 0.200; P = 007) and DFA alfa1 (24 h) (r = 0.325; P = 0.000), two know markers of sympathetic tone, were found. A higher sympathetic tone, expressed as high LF/HF, was found in isolated diastolic AHT compared to other types of AHT and the lowest sympathetic tone was found in isolated systolic AHT. Considering non-linear (complexity) analysis, DFA alfa1 (24 h) showed a significant correlation with DBP values that remained independent even after multiple adjustment for BMI, age, gender and Beta Blockers (β = 0.218; P = 0.011). Moreover, the lack of DBP control was associated with high sympathetic tone (LF/HF 3.8 112.3 vs 5.5 .33.3; P Conclusion Diastolic blood pressure and uncontrolled diastolic AHT, rather than systolic AHT, are associated with a hyper-sympathetic tone rather than with blunted vagal tone. The lack of heart rate dipping during night-time in AHT is associated with blunted vagal activation rather than a persistent night-time hyper-adrenergic tone.

Azelaic Acid (AzA) is a 9-carbon atom dicarboxylic acid, with numerous pharmacological uses in dermatology. Its effectiveness in papulopustular rosacea and acne vulgaris, among other dermatological disorders such as keratinization and hyper-pigmentation, is thought to be related to its anti-inflammatory and antimicrobial properties. It is a by-product of Pityrosporum fungal mycelia metabolism but also it is found in different cereals such as barley, wheat, and rye. Diverse topical formulations of AzA exist in commerce, and it is mainly produced via chemical synthesis. In this study we describe the extraction of AzA from whole grains and whole-grain flour (Triticum durum Desf.) through green methods. Seventeen different extracts were prepared and analyzed for their AzA content by HPLC-MS methods and then screened for their antioxidant activity using spectrophotometric assays (ABTS, DPPH, and Folin–Ciocalteu). Minimum-inhibitory-concentration (MIC) assays against several bacterial and fungal pathogens were performed, to validate their antimicrobial activity. The obtained results indicate that whole grain extracts provide a wider spectrum of activity than the flour matrix; in particular, the Naviglio® extract showed higher AzA content, while the hydroalcoholic ultrasound-assisted extract provided better antimicrobial and antioxidant activity. The data analysis was performed using principal component analysis (PCA), as an unsupervised-pattern-recognition technique, to extract useful analytical and biological information.