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Here we demonstrate for the first time that an antibody-gold nanoparticles (AuNPs)-polymer conjugate thin-film biosensor can easily be fabricated to selectively capture Tau protein. Gold nanoparticles (AuNPs) are employed as sensing elements, thus capitalizing on their propensity to undergo assembly or disassembly in response to the adsorption or conjugation of various biomolecules on their surface, thereby forming robust interactions with the target analyte. We show that the Tau protein in its different aggregation phases can be detected, by restricting the reaction area on the solid thin polymer film and thus reducing the diffusion effects usually encountered in immunosensors. A limit of detection (LOD) of 460 pg/mL was reached, demonstrating a great potential for detecting Tau in aggregation states. This sensor based on thin polymer film could open new routes for sensing and monitoring Tau protein in biological assays and biomedical diagnosis., 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 © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

It is largely documented that neurodegenerative diseases can be effectively treated only if early diagnosed. In this context, the structural changes of some biomolecules such as Tau, seem to play a key role in neurodegeneration mechanism becoming eligible targets for an early diagnosis. Post-translational modifications are responsible to drive the Tau protein towards a transition phase from a native disorder conformation into a preaggregation state, which then straight recruits the final fibrillization process. Here, we show for the first time the detection of pre-aggregated Tau in artificial urine at femto-molar level, through the concentration effect of the pyro-electrohydrodynamic jet (p-jet) technique. An excellent linear calibration curve is demonstrated at the femto-molar level with a limit of detection (LOD) of 130 fM. Moreover, for the first time we show here the structure stability of the protein after p-jet application through a deep spectroscopic investigation. Thanks to the small volumes required and the relatively compact and cost-effective characteristics, this technique represents an innovative breakthrough in monitoring the early stage associated to neurodegeneration syndromes in different scenarios of point of care (POC) and such as for example in long-term human space exploration missions., Competing Interests: Declaration of competing interest The authors state that they are not aware of any financial or interpersonal conflicts that might have appeared to have an impact on the research presented in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Given the growing urge for plastic management and regulation in the world, recent studies have investigated the problem of plastic material identification for correct classification and disposal. Recent works have shown the potential of machine learning techniques for successful microplastics classification using Raman signals. Classification techniques from the machine learning area allow the identification of the type of microplastic from optical signals based on Raman spectroscopy. In this paper, we investigate the impact of high-frequency noise on the performance of related classification tasks. It is well-known that classification based on Raman is highly dependent on peak visibility, but it is also known that signal smoothing is a common step in the pre-processing of the measured signals. This raises a potential trade-off between high-frequency noise and peak preservation that depends on user-defined parameters. The results obtained in this work suggest that a linear discriminant analysis model cannot generalize properly in the presence of noisy signals, whereas an error-correcting output codes model is better suited to account for inherent noise. Moreover, principal components analysis (PCA) can become a must-do step for robust classification models, given its simplicity and natural smoothing capabilities. Our study on the high-frequency noise, the possible trade-off between pre-processing the high-frequency noise and the peak visibility, and the use of PCA as a noise reduction technique in addition to its dimensionality reduction functionality are the fundamental aspects of this work., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Compact and minimally invasive scanning fiber endoscopy probes with micron-level resolution have great potential in detailed tissue interrogation and early disease diagnosis, which are key applications of confocal reflectance imaging at visible wavelengths. State-of-the-art imaging probes commonly employ refractive lens triplets or gradient refractive index (GRIN) lenses as the micro-objective. However, off-axis aberration emerges as a critical factor affecting resolution, especially at the extremities of the imaging field. In response to this challenge, we propose what we believe to be a novel design integrating a metasurface with the GRIN micro-objective to address optical aberrations during beam scan. The metasurface acts as a corrector element for optical aberrations in a fiber-scanning endoscope using the same fiber for excitation and collection. Modeling such hybrid refractive-metasurface designs requires the coupling of simulation techniques across macroscale and nanoscale optics, for which we used an Ansys simulation workflow platform. Operating at a wavelength of 644 nm, this metaoptical element serves as a thin and compact aberration correction surface, ensuring uniform resolution across the entire imaging field. Experimental results from our scanning fiber endoscopy system demonstrate a notable enhancement in optical performance both on-axis and off-axis, achieving a resolution of 3 µm at the center of the imaging field. Impressively, the resolution experiences only a modest degradation by a factor of 0.13 at the edge of the field of view compared to the center.

We present a procedure for the design of multilevel metalenses and their fabrication with multiphoton-based direct laser writing. This work pushes this fast and versatile fabrication technique to its limits in terms of achievable feature size dimensions for the creation of compact high-numerical aperture metalenses on flat substrates and optical fiber tips. We demonstrate the design of metalenses with various numerical apertures up to 0.96, and optimize the fabrication process towards nanostructure shape reproducibility. We perform optical characterization of the metalenses towards spot size, focusing efficiency, and optical functionality with a fiber beam collimation design, and compare their performance with refractive and diffractive counterparts fabricated with the same technology.

Introduction: The future of human space missions relies on the ability to provide adequate food resources for astronauts and also to reduce stress due to the environment (microgravity and cosmic radiation). In this context, microgreens have been proposed for the astronaut diet because of their fast-growing time and their high levels of bioactive compounds and nutrients (vitamins, antioxidants, minerals, etc.), which are even higher than mature plants, and are usually consumed as ready-to-eat vegetables., Methods: Our study aimed to identify the best light recipe for the soilless cultivation of two cultivars of radish microgreens (Raphanus sativus, green daikon, and rioja improved) harvested eight days after sowing that could be used for space farming. The effects on plant metabolism of three different light emitting diodes (LED) light recipes (L1-20% red, 20% green, 60% blue; L2-40% red, 20% green, 40% blue; L3-60% red, 20% green, 20% blue) were tested on radish microgreens hydroponically grown. A fluorimetric-based technique was used for a real-time non-destructive screening to characterize plant methabolism. The adopted sensors allowed us to quantitatively estimate the fluorescence of flavonols, anthocyanins, and chlorophyll via specific indices verified by standardized spectrophotometric methods. To assess plant growth, morphometric parameters (fresh and dry weight, cotyledon area and weight, hypocotyl length) were analyzed., Results: We observed a statistically significant positive effect on biomass accumulation and productivity for both cultivars grown under the same light recipe (40% blue, 20% green, 40% red). We further investigated how the addition of UV and/or far-red LED lights could have a positive effect on plant metabolite accumulation (anthocyanins and flavonols)., Discussion: These results can help design plant-based bioregenerative life-support systems for long-duration human space exploration, by integrating fluorescence-based non-destructive techniques to monitor the accumulation of metabolites with nutraceutical properties in soilless cultivated microgreens., 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 © 2024 Garegnani, Sandri, Pacelli, Ferranti, Bennici, Desiderio, Nardi and Villani.)

One of the hallmarks of microgravity-induced effects in several cellular models is represented by the alteration of oxidative balance with the consequent accumulation of reactive oxygen species (ROS). It is well known that male germ cells are sensitive to oxidative stress and to changes in gravitational force, even though published data on germ cell models are scarce. We previously studied the effects of simulated microgravity (s-microgravity) on a 2D cultured TCam-2 seminoma-derived cell line, considered the only human cell line available to study in vitro mitotically active human male germ cells. In this study, we used a corresponding TCam-2 3D cell culture model that mimics cell-cell contacts in organ tissue to test the possible effects induced by s-microgravity exposure. TCam-2 cell spheroids were cultured for 24 h under unitary gravity (Ctr) or s-microgravity conditions, the latter obtained using a random positioning machine (RPM). A significant increase in intracellular ROS and mitochondria superoxide anion levels was observed after RPM exposure. In line with these results, a trend of protein and lipid oxidation increase and increased pCAMKII expression levels were observed after RPM exposure. The ultrastructural analysis via transmission electron microscopy revealed that RPM-exposed mitochondria appeared enlarged and, even if seldom, disrupted. Notably, even the expression of the main enzymes involved in the redox homeostasis appears modulated by RPM exposure in a compensatory way, with GPX1, NCF1, and CYBB being downregulated, whereas NOX4 and HMOX1 are upregulated. Interestingly, HMOX1 is involved in the heme catabolism of mitochondria cytochromes, and therefore the positive modulation of this marker can be associated with the observed mitochondria alteration. Altogether, these data demonstrate TCam-2 spheroid sensitivity to acute s-microgravity exposure and indicate the capability of these cells to trigger compensatory mechanisms that allow them to overcome the exposure to altered gravitational force.

c-MET/hepatocyte growth factor (HGF) system deregulation is a well-known feature of malignancy in several solid tumors, and for this reason this system and its pathway have been considered as potential targets for therapeutic purposes. In previous manuscripts we reported c-MET/HGF expression and the role in testicular germ cell tumors (TGCTs) derived cell lines. We demonstrated the key role of c-Src and phosphatidylinositol 3-kinase (PI3K)/AKT adaptors in the HGF-dependent malignant behavior of the embryonal carcinoma cell line NT2D1, finding that the inhibition of these onco-adaptor proteins abrogates HGF triggered responses such as proliferation, migration, and invasion. Expanding on these previous studies, herein we investigated the role of mitogen-activated protein kinase (MAPK)/extracellular signal regulated kinase (ERK) pathways in the HGF-dependent and HGF-independent NT2D1 cells biological responses. To inhibit MAPK/ERK pathways we chose a pharmacological approach, by using U0126 inhibitor, and we analyzed cell proliferation, collective migration, and chemotaxis. The administration of U0126 together with HGF reverts the HGF-dependent activation of cell proliferation but, surprisingly, does not exert the same effect on NT2D1 cell migration. In addition, we found that the use of U0126 alone significantly promotes the acquisition of NT2D1 «migrating phenotype», while collective migration of NT2D1 cells was stimulated. Notably, the inhibition of ERK activation in the absence of HGF stimulation resulted in the activation of the AKT-mediated pathway, and this let us speculate that the paradoxical effects obtained by using U0126, which are the increase of collective migration and the acquisition of partial epithelium-mesenchyme transition (pEMT), are the result of compensatory pathways activation. These data highlight how the specific response to pathway inhibitors, should be investigated in depth before setting up therapy.

Background: In the surgical scenario, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diffusion worldwide entails on the one hand the need to continue to perform surgery at least in case of emergency or oncologic surgery, in patients with or without COronaVIrus Disease 2019 (COVID-19); and on the other hand, to avoid the pandemic diffusion both between patients and medical and nursing team. The aim of this study was to report our surgical management protocol during the COVID-19 pandemic in an Italian non-referral center., Methods: Data retrieved during the outbreak for the COVID-19 pandemic, from March 8 to May 4, 2020 (study period) were analyzed and compared to data obtained during the same period in 2019 (control period)., Results: During the study period, 41 surgical procedures (24 electives, 17 emergency surgical procedures) underwent surgery in comparison to 99 procedures in the control period. Stratifying the procedures in elective and emergency surgery, and based on the indication for surgery, the only statistically significant difference was observed in the elective surgery regarding the abdominal wall surgery (0 vs. 13 procedures, P=0.0339). Statistically significant differences were not observed regarding the colorectal and the breast oncologic surgery. All stuff members were COVID-19 free., Conclusions: The present protocol proved to be safe and useful to prevent SARS-CoV-2 infection before and after surgery for both patients and stuff. The pandemic was responsible for the reduction in number of procedures performed, anyway for the oncologic surgery a statistically significant volume reduction in comparison to 2019 was not observed.

Background: Coronavirus disease 2019 (COVID-19) has caused an unprecedented change in the apparent epidemiology of acute coronary syndromes (ACS). However, the interplay between this disease, changes in pollution, climate, and aversion to activation of emergency medical services represents a challenging conundrum. We aimed at appraising the impact of COVID-19, weather, and environment features on the occurrence of ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI) in a large Italian region and metropolitan area., Methods and Results: Italy was hit early on by COVID-19, such that state of emergency was declared on January 31, 2020, and national lockdown implemented on March 9, 2020, mainly because the accrual of cases in Northern Italy. In order to appraise the independent contribution on changes in STEMI and NSTEMI daily rates of COVID-19, climate and pollution, we collected data on these clinical events from tertiary care cardiovascular centers in the Lazio region and Rome metropolitan area. Multilevel Poisson modeling was used to appraise unadjusted and adjusted effect estimates for the daily incidence of STEMI and NSTEMI cases. The sample included 1448 STEMI and 2040 NSTEMI, with a total of 2882 PCI spanning 6 months. Significant reductions in STEMI and NSTEMI were evident already in early February 2020 (all p<0.05), concomitantly with COVID-19 spread and institution of national countermeasures. Changes in STEMI and NSTEMI were inversely associated with daily COVID-19 tests, cases, and/or death (p<0.05). In addition, STEMI and NSTEMI incidences were associated with daily NO2, PM10, and O3 concentrations, as well as temperature (p<0.05). Multi-stage and multiply adjusted models highlighted that reductions in STEMI were significantly associated with COVID-19 data (p<0.001), whereas changes in NSTEMI were significantly associated with both NO2 and COVID-19 data (both p<0.001)., Conclusions: Reductions in STEMI and NSTEMI in the COVID-19 pandemic may depend on different concomitant epidemiologic and pathophysiologic mechanisms. In particular, recent changes in STEMI may depend on COVID-19 scare, leading to excess all-cause mortality, or effective reduced incidence, whereas reductions in NSTEMI may also be due to beneficial reductions in NO2 emissions in the lockdown phase., Competing Interests: Declaration of Competing Interest Prof. Biondi-Zoccai has consulted for Cardionovum, Bonn, Germany, InnovHeart, Milan, Italy, Meditrial, Rome, Italy, and Replycare, Rome, Italy., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Aims: Coronavirus disease 2019 (COVID-19) has caused an unprecedented change in the apparent epidemiology of acute coronary syndromes (ACS). However, the interplay between this disease, changes in pollution, climate, and aversion to activation of emergency medical services represents a challenging conundrum. We aimed at appraising the impact of COVID-19, weather, and environment features on the occurrence of ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI) in a large Italian region and metropolitan area., Methods and Results: Italy was hit early on by COVID-19, such that state of emergency was declared on January 31, 2020, and national lockdown implemented on March 9, 2020, mainly because the accrual of cases in Northern Italy. In order to appraise the independent contribution on changes in STEMI and NSTEMI daily rates of COVID-19, climate and pollution, we collected data on these clinical events from tertiary care cardiovascular centers in the Lazio region and Rome metropolitan area. Multilevel Poisson modeling was used to appraise unadjusted and adjusted effect estimates for the daily incidence of STEMI and NSTEMI. The sample included 1448 STEMI and 2040 NSTEMI, with a total of 2882 PCI spanning 6 months. Significant reductions in STEMI and NSTEMI were evident already in early February 2020 (all P  < 0.05), concomitantly with COVID-19 spread and institution of national countermeasures. Changes in STEMI and NSTEMI were inversely associated with daily COVID-19 tests, cases, and/or death ( P  < 0.05). In addition, STEMI and NSTEMI incidences were associated with daily NO2, PM10, and O3 concentrations, as well as temperature ( P  < 0.05). Multi-stage and multiply adjusted models highlighted that reductions in STEMI were significantly associated with COVID-19 data ( P  < 0.001), whereas changes in NSTEMI were significantly associated with both NO2 and COVID-19 data (both P  < 0.001)., Conclusion: Reductions in STEMI and NSTEMI in the COVID-19 pandemic may depend on different concomitant epidemiologic and pathophysiologic mechanisms. In particular, recent changes in STEMI may depend on COVID-19 scare, leading to excess all-cause mortality, or effective reduced incidence, whereas reductions in NSTEMI may also be due to beneficial reductions in NO2 emissions in the lockdown phase., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2020. For permissions please email: journals.permissions@oup.com.)

Background: Strong epidemiologic evidence has highlighted the role of pollution, on top of adverse climate features, as a novel cardiovascular risk factor. However, mechanistic proof that reducing pollution may be beneficial to prevent atherothrombotic events is limited. We aimed at appraising the impact of temporary traffic bans in a large metropolitan area on the risk of acute coronary syndromes., Methods: Aggregate and anonymized data from 15 tertiary cardiac care centers were obtained detailing precoronavirus disease 2019 (COVID-19) daily cases of ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI), including those treated with percutaneous coronary intervention (PCI). Data on pollutants and climate were sought for the same days. Mixed level regression was used to compare the week before vs after the traffic ban (Fortnight analysis), the 3 days before vs. after (Weekly analysis) and the Sunday before vs. after (Sunday analysis)., Results: A total of 8 days of temporary traffic bans were included, occurring between 2017 and 2020, totaling 802 STEMI and 1196 NSTEMI in the Fortnight analysis, 382 STEMI and 585 in the Weekly analysis, and 148 STEMI and 210 NSTEMI in the Sunday analysis.Fortnight and Sunday analyses did not disclose a significant impact of traffic ban on STEMI or NSTEMI (all P>0.05). Conversely, Weekly analysis showed non-significant changes for STEMI, but a significant decrease in daily NSTEMI when comparing the 3 days before the traffic ban with the ban day (P=0.043), as well as the 3 days before vs. the 3 days after the ban (P=0.025). No statistically significant effect of traffic ban was found at Fortnight, Weekly or Sunday analyses for daily mean concentrations of benzene, carbon monoxide, nitric oxide, nitrogen dioxide, ozone, sulfur dioxide, particulate matter (PM) <2.5 µm or PM <10 µm (all P>0.05). However, minimum daily concentrations showed a significant reduction of ozone during the ban in comparison to the week preceding it (P=0.034), nitric oxide during the ban in comparison to the 3 days preceding it (P=0.046), and an increase in benzene during the ban in comparison to the Sunday before (P=0.039)., Conclusions: Temporary traffic ban may favorably reduce coronary atherothrombotic events, and in particular NSTEMI, even if not globally and immediately impacting on environmental pollution. Further controlled studies are required to confirm and expand this hypothesis-generating results.

In this paper, we present the first realisation and experimentation of a new eye tracking system using an infrared (iR) laser pointer embedded into a wireless smart contact lens. We denote this contact lens prototype as the cyclops lens, in reference to the famous hero of the X-Men comics. The full eye tracker device combines the smart contact lens and its eyewear, which provides a primary source of energy and the beam detection system. We detail the assembling and encapsulation process of the main functionalities into the contact lens and present how a gaze tracking system is achieved, compared to existing conventional eye-tracking ones. Finally, we discuss future technical improvements.

Understanding molecular mechanisms responsible for bone cells unbalance in microgravity would allow the development of better countermeasures for astronauts, and eventually advancing terrestrial osteoporosis treatments. We conduct a unique investigation by using a controlled 3D in vitro cell model to mimic the bone microenvironment in microgravity aboard the SpaceX Dragon cargo ferry to the ISS. Osteoblasts (OBs), osteoclasts (OCs), and endothelial cells (ECs), seeded on Skelite discs, were cultured w/ or w/o rec-Irisin and exposed to 14 days of microgravity in the eOSTEO hardware. Gene expression analysis was assessed, and results were compared to ground controls treated within identical payloads. Our results show that the microgravity-induced downregulation of mRNA levels of genes encoding for OB key transcription factors (Atf4 -75%, P < .01; RunX2 -87%, P < .001, Osterix -95%, P < .05 vs ground) and proteins (Collagen I -84%, P < .05; Osteoprotegerin -94%, P < .05) were prevented by irisin. Despite it was not effective in preventing Trap and Cathepsin K mRNA increase, irisin induced a 2.8-fold increase of Osteoprotegerin (P < .05) that might act for reducing osteoclastogenesis in microgravity. Our results provide evidence that irisin supports OB differentiation and activity in microgravity and it might represent a countermeasure to prevent bone loss in astronauts., (© 2020 Federation of American Societies for Experimental Biology.)

Optically active (-) 589 ethyl ( S )-2-phenylbutyl thioether, (-)( S ) C -Et(PhBu)S ( I ), and its new diastereoisomeric mercury (II) chloride adduct, 1:2, (-)[( S ) S ( S ) C -Et(PhBu)S.(HgCl 2 ) 2 ] 2 , ( II ) were stereoselectively synthesized; the absorbance (UV) and circular dichroism (CD) spectra were measured and the crystal and molecular structure of complex ( II ) was determined by single-crystal X-ray diffraction. Two different Hg centres are present whose coordination environments are built by two short bonds to chloride ligands in one case, and to one chloride and one sulphur in the other one. These originate digonal units. Electroneutrality is achieved by a further chlorine, which can be considered prevalently ionic and bonded to the two Hg centres, forming square bridging systems nearly perpendicular to the digonal molecules. The coordination polyhedra can be interpreted as 2 + 4 tetragonally-compressed octahedra with the four longer contacts lying in the equatorial plane. IR spectroscopic data are consistent with the presence of one bent and one linear Cl-Hg-Cl moiety. The absolute configurations at both stereogenic centres of the formed diastereoisomeric complex ( II ) are ( S ). The ( S ) S absolute configuration at the stereogenic sulphur atom bonded to the mercury(II) atom in complex ( II ) has been related with the negative Cotton effect assigned in its circular dichroism (CD) spectrum to a charge-transfer transition at ca. 230 nm. The stereoselective oxidation of ( I ) and ( II ) with hydrogen peroxide, induced by the stereogenic carbon atom ( S ) C of the enantiopure sulphide, gave (-) 598 ethyl ( S ) C -2-phenylbutyl( S ) S -sulphoxide, (-) 598 [( S ) S ( S ) C -Et(PhBu)SO], ( III ), having 18.1% de. Oxidations carried out in the presence of a 200 molar excess of mercury(II) chloride gave (-) 598 ethyl ( S ) C -2-phenylbutyl( R ) S -sulphoxide, (-) 598 [( R ) S ( S ) C -Et(PhBu)SO], ( IV ) with 31% de, showing the cooperative influence of mercury(II) chloride on the selectivity of the oxidation reaction.

In olive, the response to environmental conditions, such as light availability, is under genetic control and requires a combination of biochemical and physiological events. We investigated the effect of irradiance in fruit development in two Italian cultivars, Leccino and Frantoio. Morphological and cyto-histological analyses, as well as water and oil content determination, were carried out in fruits exposed to a different light regime (named as light and shade fruits). Results demonstrated that the influence of light availability on fruit development depends on the cultivar. In Leccino, the fresh and the dry weight, the percentage of dry matter, the kernel and fruit diameter, the mesocarp thickness and the mesocarp cell size were higher in the light exposed fruits than in the ones grown in the shade. In Frantoio, differences between light and shade fruits were observed only at 140 DAF (Days After Flowering) and only in the kernel and fruit diameter and in the dry and fresh weight, which were higher in the light exposed fruits. Leccino, therefore, showed a greater sensitivity to the light availability. This may be related to the observed delay in the endocarp lignification as compared to the Frantoio cultivar. In each cultivar, moreover, shade and light fruits did not show differences in the timing of cell differentiation. Finally, the investigation of oil storage carried out in cyto-histological studies demonstrated that differences in oil content between fruit subjected to different light regimes correlated with the number of oil containing cells, rather than the oil content per cell. A different behaviour was observed in the two cultivars: in Leccino, the mesocarp cell size was almost twice of Frantoio, while oil drops were only 30% larger; therefore, the percentage of cell volume occupied by the oil drops was lower in Leccino than in Frantoio. The chemical analysis confirmed this observation.

Large-scale landslides at volcanic islands are one of the most dangerous geological phenomena, able to generate tsunamis whose effects can propagate far from the source. However, related deposits are scarcely preserved on-land in the geologic records, and are often difficult to be interpreted. Here we show the discovery of three unprecedented well-preserved tsunami deposits related to repeated flank collapses of the volcanic island of Stromboli (Southern Italy) occurred during the Late Middle Ages. Based on carbon datings, on stratigraphic, volcanological and archaeological evidence, we link the oldest, highest-magnitude investigated tsunami to the following rapid abandonment of the island which was inhabited at that time, contrary than previously thought. The destructive power of this event is also possibly related to a huge marine storm that devastated the ports of Naples in 1343 (200 km north of Stromboli) described by the famous writer Petrarch. The portrayed devastation can be potentially attributed to the arrival of multiple tsunami waves generated by a major landslide in Stromboli island, confirming the hypothetical hazard of these phenomena at a regional scale.

The microbiota inhabiting the soil, as well as the rhizosphere, represents a key determinant of several plant functions. Like for humans, dysbiosis of the plant-associated microbiota may be a co-causal agent in disease with still obscure eziology. In the last decades, the common reed Phragmites australis has been deeply studied for its disappearance from natural stands, but no clear causative agents have been identified and no laboratory models of such "reed die-back syndrome" (RDBS) have been developed. In this study, we try to shed light on the RDBS, by comparing the rhizosphere microbiota of five Italian P. australis populations with different degrees of decline. Results obtained showed a biogeographical meaningful pattern of rhizosphere microbiota, coupled with an impact of RDBS. Obtained data allowed to construct a two-steps predictive model which enabled the prediction of the plant health status from the microbiota taxonomic composition, independently from their geographic location. In conclusion, this study represents one of the first overviews that statistically links RDBS to alteration of rhizosphere microbiota and suggests a model for the analysis of plant-bacteria relationships in nature., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Cancer and coagulation activation are tightly related. The extent to which factors related to both these pathologic conditions concur to patient prognosis intensely animates the inherent research areas. The study herein presented aimed to the development of a tool for the assessment and stratification of risk of death and disease recurrence in early breast cancer., Methods: Between 2008 and 2010, two hundreds thirty-five (N: 235) patients diagnosed with stage I-IIA breast cancer were included. Data on patient demographics and clinic-pathologic features were collected in course of face-to-face interviews or actively retrieved from clinical charts. Plasma levels of plasminogen activator inhibitor type 1 (PAI-1), fragment 1 + 2 (F1 + 2), thrombin antithrombin complex (TAT), factor VIII (FVIII), and D-dimer (DD) were measured at breast cancer diagnosis and prior to any therapeutic procedure, including breast surgery. The risk of death was computed in terms of overall survival (OS), which was the primary outcome. For a subset of patients (N = 62), disease free survival (DFS) was also assessed as a measure of risk of disease recurrence., Results: Median follow up was 95 months (range 6-112 months). Mean age at diagnosis was 60.3 ± 13.4 years. Cancer cases were more commonly intraductal carcinomas (N: 204; 86.8%), pT1 (131; 55.7%), pN0 (141; 60%) and G2 (126; 53.6%). Elevated levels of PAI-1 (113; 48.1%) represented the most frequent coagulation abnormality, followed by higher levels of F1 + 2 (97; 41.3%), DD (63; 27.0%), TAT (34; 40%), and FVIII (29; 12.3%). In univariate models of OS, age, pT, DD, FVIII were prognostically relevant. In multivariate models of OS, age (p = 0.043), pT (p = 0.001), levels of DD (p = 0.029) and FVIII (p = 0.087) were confirmed. In the smaller subgroup of 62 patients, lymph node involvement, percent expression of estrogen receptors and levels of FVIII impacted DFS significantly., Conclusions: We developed a risk assessment tool for OS including patient- and cancer-related features along with biomarkers of coagulation activation in a cohort of early BC patients. Further studies are warranted to validate our prognostic model in the early setting and eventually extend its application to risk evaluation in the advanced setting for breast and other cancers.

Phragmites australis is a subcosmopolitan species typical of wetlands being studied in Europe for its disappearance from natural stands, a phenomenon called reed die-back syndrome (RDBS). Although it is conjectured that low genetic variability contributes to RDBS, this aspect remains neglected to this day. Using a molecular fingerprinting approach and a sequence analysis of the trnT-trnL/rbcL-psaI regions of cpDNA, this study aimed to compare the genetic structure of stable vs. RDBS-affected P. australis stands from five wetlands of central Italy. Beforehand, in order to characterize the health condition of reed populations, the occurrence of the main macromorphological descriptors for RDBS was considered on 40 reed stands. Soil samples were also collected to examine the total content of heavy metals. The current study analyzed cpDNA in 19 samples and AFLP profiles in 381 samples to investigate the genetic structure of Phragmites populations. Based on the multinomial-Dirichlet model, an analysis of candidate loci under selective pressure was also performed. The relationships among AFLP data, RDBS descriptors and chemicals were evaluated with the use of Linear Mixed Models. The analysis of the cpDNA shows the occurrence of the haplotypes M (the most widespread), and K here recorded for the first time in Italy. Three new haplotypes were also described. The DNA fingerprinting analysis has produced a total of 322 loci (98% polymorphic) and shows the medium-to-high amount of genetic diversity. The significant genetic differentiation among wetlands ( F st = 0.337) suggests either low gene flow or small effective population size. Moreover, the low amount of outlier loci (only 5; l.5% of the total), seems to indicate the scarce occurrence of selective pressure upon the reed's genome. Genetic diversity increased in relationship to the decrease in diameter and of flowering buds of the reed, two of the trends associated with the die-back. The current study rejects the hypothesis that genetic diversity massively contributed to RDBS. Moreover, significant relationships between genetic diversity and the total concentration of some heavy metals (Cr, Cu, and Zn) were highlighted, indicating possible genotoxic effects on P. australis . The current study represents a fact-finding background useful for the conservation of common reed.

Phragmites australis (Cav.) Trin. ex Steud. die-back is a widely-studied phenomenon that was first discovered in northern Europe and that, until recently, was almost unknown in the Mediterranean basin. It has been described as a complex syndrome affecting reed populations leading to their retreat and decline, with significant impacts on valuable ecosystem services. Among the factors that cause the decline, soil-living microorganisms can be crucial. The aims of this study were to analyze the diversity of oomycetes communities associated with reed stands, and to understand whether they could play a key role in the decline. Variations in the structure of oomycetes communities were studied by metabarcoding of the internal transcribed spacer (ITS) 1 region of ribosomal DNA, from the sediments of five Italian freshwater ecosystems. They were chosen to cover a large variability in terms of surface area, water depth, microclimate, and presence of documented reed retreat. From 96 samples collected from reed roots, rhizosphere, and bulk soil, we assembled 207661 ITS1 reads into 523 OTUs. We demonstrated that oomycete communities were structured by several factors, among which the most important was die-back occurrence. Our study also indicates that Pythiogeton spp. could be potentially involved in the development of die-back. The role of heavy metals in the soil was also explored, and cadmium concentration was shown to affect oomycetes distribution. This study represents a significant step forward for the characterization of microbial communities associated with reed die-back syndrome and helps to gain knowledge of the complexity of these important wet ecosystems.

Evidence on everolimus in breast cancer has placed hyperglycemia among the most common high grade adverse events. Anthropometrics and biomarkers of glucose metabolism were investigated in a observational study of 102 postmenopausal, HR + HER2- metastatic breast cancer patients treated with everolimus-exemestane in first and subsequent lines. Best overall response (BR) and clinical benefit rate (CBR) were assessed across subgroups defined upon fasting glucose (FG) and body mass index (BMI). Survival was estimated by Kaplan-Meier method and log-rank test. Survival predictors were tested in Cox models. Median follow up was 12.4 months (1.0-41.0). The overall cohort showed increasing levels of FG and decreasing BMI (p < 0.001). Lower FG fasting glucose at BR was more commonly associated with C/PR or SD compared with PD (p < 0.001). We also observed a somewhat higher BMI associated with better response (p = 0.052). More patients in the lowest FG category achieved clinical benefit compared to the highest (p < 0.001), while no relevant differences emerged for BMI. Fasting glucose at re-assessment was also predictive of PFS (p = 0.037), as confirmed in models including BMI and line of therapy (p = 0.049). Treatment discontinuation was significantly associated with changes in FG (p = 0.014). Further research is warranted to corroborate these findings and clarify the underlying mechanisms.

It is known that plant cells can contain multiple distinct vacuoles; however, the abundance of multivacuolar cells and the mechanisms underlying vacuolar differentiation and communication among different types of vacuoles remain unknown. PH1 and PH5 are tonoplast P-ATPases that form a heteromeric pump that hyper-acidifies the central vacuole (CV) of epidermal cells in petunia petals. Here, we show that the sorting of this pump and other vacuolar proteins to the CV involves transit through small vacuoles: vacuolinos. Vacuolino formation is controlled by transcription factors regulating pigment synthesis and transcription of PH1 and PH5. Trafficking of proteins from vacuolinos to the central vacuole is impaired by misexpression of vacuolar SNAREs as well as mutants for the PH1 component of the PH1-PH5 pump. The finding that PH1-PH5 and these SNAREs interact strongly suggests that structural tonoplast proteins can act as tethering factors in the recognition of different vacuolar types., (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)

Along with cadmium, lead, mercury and other heavy metals, chromium is an important environmental pollutant, mainly concentrated in areas of intense anthropogenic pressure. The effect of potassium dichromate on Lemna minor populations was tested using the growth inhibition test. Cyto-histological and physiological analyses were also conducted to aid in understanding the strategies used by plants during exposure to chromium. Treatment with potassium dichromate caused a reduction in growth rate and frond size in all treated plants and especially at the highest concentrations. At these concentrations the photosynthetic pathway was also altered as shown by the decrease of maximum quantum yield of photosystem II and the chlorophyll b content and by the chloroplast ultrastructural modifications. Starch storage was also investigated by microscopic observations. It was the highest at the high concentrations of the pollutant. The data suggested a correlation between starch storage and reduced growth; there was greater inhibition of plant growth than inhibition of photosynthesis, resulting in a surplus of carbohydrates that may be stored as starch. The investigation helps to understand the mechanism related to heavy metal tolerance of Lemna minor and supplies information about the behavior of this species widely used as a biomarker., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Testicular vasculogenesis is one of the key processes regulating male gonad morphogenesis. The knowledge of the molecular cues underlining this phenomenon is one of today's most challenging issues and could represent a major contribution toward a better understanding of the onset of testicular morphogenetic disorders. R-spondin 1 has been clearly established as a candidate for mammalian ovary determination. Conversely, very little information is available on the expression and role of R-spondin 1 during testicular morphogenesis. This study aims to clarify the distribution pattern of R-spondin 1 and other partners of its machinery during the entire period of testicular morphogenesis and to indicate the role of this system in testicular development. Our whole mount immunofluorescence results clearly demonstrate that R-spondin 1 is always detectable in the testicular coelomic partition, where testicular vasculature is organized, while Dickkopf-1 is never detectable in this area. Moreover, organ culture experiments of embryonic male UGRs demonstrated that Dickkopf-1 acted as an inhibitor of testis vasculature formation. Consistent with this observation, real-time PCR analyses demonstrated that DKK1 is able to slightly but significantly decrease the expression level of the endothelial marker Pecam1. The latter experiments allowed us to observe that DKK1 administration also perturbs the expression level of the Pdgf-b chain, which is consistent with some authors' observations relating this factor with prenatal testicular patterning and angiogenesis. Interestingly, the DKK1 induced inhibition of testicular angiogenesis was rescued by the co-administration of R-spondin 1. In addition, R-spondin 1 alone was sufficient to enhance, in culture, testicular angiogenesis.

In this paper, we present a novel rational macromodeling approach for the description of 1D blood flow in the human cardiovascular system, which is suitable for time-domain simulations. Using the analogy of the blood flow propagation problem with transmission lines and considering the hypothesis of linearized Navier-Stokes equations, a frequency-domain rational macromodel for each arterial segment has been built. The poles and the residues of each arterial segment macromodel have been calculated by means of the Vector Fitting technique. Finally, the rational macromodel of the whole cardiovascular system is obtained by properly combining the macromodels of the single arterial segments using an interconnect matrix. The rational form of the proposed cardiovascular model leads to a state-space or electrical circuit model suitable for time-domain analysis. The stability and passivity properties of the global cardiovascular model are discussed to guarantee stable time-domain simulations. The proposed macromodeling approach has been validated by pertinent numerical results. Copyright © 2015 John Wiley & Sons, Ltd., (Copyright © 2015 John Wiley & Sons, Ltd.)

Contamination of groundwater by naturally occurring arsenic has recently become a disturbing environmental problem in Viterbo area, Central Italy. Arsenic concentrations in most of the public supply networks exceed the maximum allowable limit of 10 μg/l (WHO) for drinking water. The primary purpose of this paper is to obtain a better understanding of the factors contributing to the high levels of As in water supply networks. This study focuses on (a) the determination of basic hydrochemical characteristics of groundwater, (b) the identification of the major sources and processes controlling the As contamination in public supply networks, (c) to find out possible relationships among the As and other trace elements through principal component analysis (PCA). Groundwater samples from public water supply wells and springs were collected and analysed for physico-chemical parameters and trace elements. Springs and well water samples are predominantly of the Na-HCO3, Na -Ca-HCO3 and Ca-HCO3 types and the highest arsenic concentrations were observed in Na-HCO3 type water. Eh-pH diagrams reveal that H2AsO4 (-) and HAsO4 (2-), As(V) arsenate, are the dominating As species highlighting slightly to moderately oxidizing conditions. Geochemical modeling indicates that arsenic-bearing phases were undersaturated in the groundwater, however most of the samples were saturated with respect to Fe (i.e. magnetite, hematite and goethite) and Al (diaspore and boehmite) oxide and hydroxide minerals. Concentrations of As, Li, B, Co, Sr, Mo, U and Se are highly correlated (r > 0.7) with each other, however in some groundwater samples As show also good correlations (r > 0.5) with Fe and Mn elements reflecting the relationships among the trace elements result from different geochemical processes. Evaluation of the principal component (PCA) analysis and geochemical modeling suggest that the occurrence of As and other trace element concentrations in groundwater are probably derived from (i) weathering and/or dissolution of volcanic source aquifer materials and (ii) adsorption/desorption processes on the Fe and Al oxide and hydroxide minerals.