Search

Abstract The XENON collaboration has published stringent limits on specific dark matter – nucleon recoil spectra from dark matter recoiling on the liquid xenon detector target. In this paper, we present an approximate likelihood for the XENON1T 1 t-year nuclear recoil search applicable to any nuclear recoil spectrum. Alongside this paper, we publish data and code to compute upper limits using the method we present. The approximate likelihood is constructed in bins of reconstructed energy, profiled along the signal expectation in each bin. This approach can be used to compute an approximate likelihood and therefore most statistical results for any nuclear recoil spectrum. Computing approximate results with this method is approximately three orders of magnitude faster than the likelihood used in the original publications of XENON1T, where limits were set for specific families of recoil spectra. Using this same method, we include toy Monte Carlo simulation-derived binwise likelihoods for the upcoming XENONnT experiment that can similarly be used to assess the sensitivity to arbitrary nuclear recoil signatures in its eventual 20 t-year exposure.

Abstract The selection of low-radioactive construction materials is of the utmost importance for rare-event searches and thus critical to the XENONnT experiment. Results of an extensive radioassay program are reported, in which material samples have been screened with gamma-ray spectroscopy, mass spectrometry, and $$^{222}$$ 222 Rn emanation measurements. Furthermore, the cleanliness procedures applied to remove or mitigate surface contamination of detector materials are described. Screening results, used as inputs for a XENONnT Monte Carlo simulation, predict a reduction of materials background ( $$\sim $$ ∼ 17%) with respect to its predecessor XENON1T. Through radon emanation measurements, the expected $$^{222}$$ 222 Rn activity concentration in XENONnT is determined to be 4.2 ( $$^{+0.5}_{-0.7}$$ - 0.7 + 0.5 ) $$\upmu $$ μ Bq/kg, a factor three lower with respect to XENON1T. This radon concentration will be further suppressed by means of the novel radon distillation system.

Abstract The selection of low-radioactive construction materials is of utmost importance for the success of low-energy rare event search experiments. Besides radioactive contaminants in the bulk, the emanation of radioactive radon atoms from material surfaces attains increasing relevance in the effort to further reduce the background of such experiments. In this work, we present the $$^{222}$$ 222 Rn emanation measurements performed for the XENON1T dark matter experiment. Together with the bulk impurity screening campaign, the results enabled us to select the radio-purest construction materials, targeting a $$^{222}$$ 222 Rn activity concentration of $$10\,\mathrm{\,}\upmu \mathrm{Bq}/\mathrm{kg}$$ 10 μ Bq / kg in $$3.2\,\mathrm{t}$$ 3.2 t of xenon. The knowledge of the distribution of the $$^{222}$$ 222 Rn sources allowed us to selectively eliminate problematic components in the course of the experiment. The predictions from the emanation measurements were compared to data of the $$^{222}$$ 222 Rn activity concentration in XENON1T. The final $$^{222}$$ 222 Rn activity concentration of $$(4.5\pm 0.1)\,\mathrm{\,}\upmu \mathrm{Bq}/\mathrm{kg}$$ ( 4.5 ± 0.1 ) μ Bq / kg in the target of XENON1T is the lowest ever achieved in a xenon dark matter experiment.

Galactic science encompasses a wide range of subjects in the study of the Milky Way and Magellanic Clouds, from young stellar objects to X-ray binaries. Mapping these populations, and exploring transient phenomena within them, are among the primary science goals of the Vera C. Rubin Observatory’s Legacy Survey of Space and Time. While early versions of the survey strategy dedicated relatively few visits to the Galactic Plane region, more recent strategies under consideration envision a higher cadence within selected regions of high scientific interest. The range of galactic science presents a challenge in evaluating which strategies deliver the highest scientific returns. Here we present metrics designed to evaluate Rubin survey strategy simulations, based on the cadence of observations they deliver within regions of interest to different topics in galactic science, using variability categories defined by timescale. We also compare the fractions of exposures obtained in each filter with those recommended for the different science goals. We find that the baseline _ v2.x simulations deliver observations of the high-priority regions at sufficiently high cadence to reliably detect variability on timescales >10 days or more. Follow-up observations may be necessary to properly characterize variability, especially transients, on shorter timescales. Combining the regions of interest for all the science cases considered, we identify those areas of the Galactic Plane and Magellanic Clouds of highest priority. We recommend that these refined survey footprints be used in future simulations to explore rolling cadence scenarios, and to optimize the sequence of observations in different bandpasses.

Abstract Xenon dual-phase time projection chambers designed to search for weakly interacting massive particles have so far shown a relative energy resolution which degrades with energy above $$\sim $$ ∼ 200 keV due to the saturation effects. This has limited their sensitivity in the search for rare events like the neutrinoless double-beta decay of $$^{136} \hbox {Xe}$$ 136Xe at its Q value, $$Q_{\beta \beta }\simeq 2.46\,\hbox {MeV}$$ Qββ≃2.46MeV . For the XENON1T dual-phase time projection chamber, we demonstrate that the relative energy resolution at $$1\,\sigma /\mu $$ 1σ/μ is as low as ($$0.80 \pm 0.02$$ 0.80±0.02 ) % in its one-ton fiducial mass, and for single-site interactions at $$Q_{\beta \beta }$$ Qββ . We also present a new signal correction method to rectify the saturation effects of the signal readout system, resulting in more accurate position reconstruction and indirectly improving the energy resolution. The very good result achieved in XENON1T opens up new windows for the xenon dual-phase dark matter detectors to simultaneously search for other rare events.

We describe the simulated data sample for the Photometric Large Synoptic Survey Telescope (LSST) Astronomical Time Series Classification Challenge (PLAsTiCC), a publicly available challenge to classify transient and variable events that will be observed by the LSST, a new facility expected to start in the early 2020s. The challenge was hosted by Kaggle, ran from 2018 September 28 to December 17, and included 1094 teams competing for prizes. Here we provide details of the 18 transient and variable source models, which were not revealed until after the challenge, and release the model libraries at https://doi.org/10.5281/zenodo.2612896. We describe the LSST Operations Simulator used to predict realistic observing conditions, and we describe the publicly available SNANA simulation code used to transform the models into observed fluxes and uncertainties in the LSST passbands (ugrizy). Although PLAsTiCC has finished, the publicly available models and simulation tools are being used within the astronomy community to further improve classification, and to study contamination in photometrically identified samples of SN Ia used to measure properties of dark energy. Our simulation framework will continue serving as a platform to improve the PLAsTiCC models, and to develop new models. [ABSTRACT FROM AUTHOR]

Globular clusters are ancient stellar populations in compact dense ellipsoids. There is no star formation and there are no core-collapse supernovae, but several lines of evidence suggest that globular clusters are rich in planets. If so, and if advanced civilizations can develop there, then the distances between these civilizations and other stars would be far smaller than typical distances between stars in the Galactic disk, facilitating interstellar communication and travel. The potent combination of long-term stability and high stellar densities provides a globular cluster opportunity. Yet the very proximity that promotes interstellar travel also brings danger, as stellar interactions can destroy planetary systems. We find, however, that large portions of many globular clusters are “sweet spots,” where habitable-zone planetary orbits are stable for long times. Globular clusters in our own and other galaxies are, therefore, among the best targets for searches for extraterrestrial intelligence (SETI). We use the Drake equation to compare the likelihood of advanced civilizations in globular clusters to that in the Galactic disk. We also consider free-floating planets, since wide-orbit planets can be ejected to travel through the cluster. Civilizations spawned in globular clusters may be able to establish self-sustaining outposts, reducing the probability that a single catastrophic event will destroy the civilization. Although individual civilizations may follow different evolutionary paths, or even be destroyed, the cluster may continue to host advanced civilizations once a small number have jumped across interstellar space. Civilizations residing in globular clusters could therefore, in a sense, be immortal. [ABSTRACT FROM AUTHOR]

Despite the care provided, some newborns, who are perfectly healthy, show functional alterations that impair a good breast attack in the first few days. This situation often leads to the early failure of lactation. We conducted a randomized single-blind controlled trial to evaluate whether four weeks of osteopathic treatment can normalize the sucking score in a group of neonates with impaired lactation ability. Forty-two healthy full-term neonates were enrolled in this study. On the basis of the sucking score and the assessment of the infant's breastfeeding skills, infants who had intrinsic breastfeeding difficulties were selected. The inclusion criteria were healthy infants born > 37 weeks, a suction score ≤ 6, and any breast milk at enrolment. At the end of the study, the sucking score was significantly greater in the osteopathic group than in the untreated group; the median sucking score in the treated group was in the normal range, while it remained lower in the untreated group. At the end of the follow-up, the percentage of exclusively breastfeeding infants in the treatment group increased by +25%. This pilot study demonstrates the efficacy of early osteopathic intervention to relieve breastfeeding difficulties in newborns in the first few weeks of life.

Tacrolimus, a calcineurin inhibitor, is an immunosuppressant used globally to prevent rejection after organ transplantation. Although it significantly improves outcomes for solid organ transplant patients, it is associated with various side effects such as nephrotoxicity and neurotoxicity. Tacrolimus-induced neurotoxicity is frequently encountered in clinical practice and can present with a variety of symptoms that may occur even at therapeutic levels. Although tacrolimus-induced neurotoxicity is well documented, there is limited literature available on pharmacologic management. Twenty-eight case reports of tacrolimus-induced neurotoxicity were identified and analyzed in addition to other literature including reviews, retrospective studies, and animal model studies. The severity of cases of tacrolimus-induced neurotoxicity reported ranged from mild symptoms that could be managed with symptomatic treatment to conditions such as posterior reversible encephalopathy syndrome and chronic inflammatory demyelinating polyradiculoneuropathy that may require more immediate intervention. This information was utilized in addition to clinical experience to compile potential management options for prevention and treatment of neurotoxic adverse events. This review is limited by the utilization of primarily retrospective studies and case reports. The available literature on the subject is largely narrative and there are no guidelines on treatment of tacrolimus-induced neurotoxicity at the time of this research. This comprehensive review may guide further studies to investigate the pathophysiology of tacrolimus-induced neurotoxicity and to define patient-specific strategies for mitigation or minimization of neurotoxicity. This is especially important given that management of tacrolimus-induced neurotoxicity can include changes to immunosuppression that can result in an increased risk of rejection., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: The COVID-19 pandemic has brought significant mental health challenges, particularly for vulnerable populations, including non-binary gender individuals. The COMET international study aimed to investigate specific risk factors for clinical depression or distress during the pandemic, also in these special populations., Methods: Chi-square tests were used for initial screening to select only those variables which would show an initial significance. Risk Ratios (RR) were calculated, and a Multiple Backward Stepwise Linear Regression Analysis (MBSLRA) was followed with those variables given significant results at screening and with the presence of distress or depression or the lack of both of them., Results: The most important risk factors for depression were female (RR = 1.59-5.49) and non-binary gender (RR = 1.56-7.41), unemployment (RR = 1.41-6.57), not working during lockdowns (RR = 1.43-5.79), bad general health (RR = 2.74-9.98), chronic somatic disorder (RR = 1.22-5.57), history of mental disorders (depression RR = 2.31-9.47; suicide attempt RR = 2.33-9.75; psychosis RR = 2.14-10.08; Bipolar disorder RR = 2.75-12.86), smoking status (RR = 1.15-5.31) and substance use (RR = 1.77-8.01). The risk factors for distress or depression that survived MBSLRA were younger age, being widowed, living alone, bad general health, being a carer, chronic somatic disorder, not working during lockdowns, being single, self-reported history of depression, bipolar disorder, self-harm, suicide attempts and of other mental disorders, smoking, alcohol, and substance use., Conclusions: Targeted preventive interventions are crucial to safeguard the mental health of vulnerable groups, emphasizing the importance of diverse samples in future research., Limitations: Online data collection may have resulted in the underrepresentation of certain population groups., Competing Interests: Declaration of competing interest None pertaining to the current paper., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: The current study aimed to investigate the rates of anxiety, clinical depression, and suicidality and their changes in health professionals during the COVID-19 outbreak., Materials and Methods: The data came from the larger COMET-G study. The study sample includes 12,792 health professionals from 40 countries (62.40% women aged 39.76 ± 11.70; 36.81% men aged 35.91 ± 11.00 and 0.78% non-binary gender aged 35.15 ± 13.03). Distress and clinical depression were identified with the use of a previously developed cut-off and algorithm, respectively., Statistical Analysis: Descriptive statistics were calculated. Chi-square tests, multiple forward stepwise linear regression analyses, and Factorial Analysis of Variance (ANOVA) tested relations among variables., Results: Clinical depression was detected in 13.16% with male doctors and 'non-binary genders' having the lowest rates (7.89 and 5.88% respectively) and 'non-binary gender' nurses and administrative staff had the highest (37.50%); distress was present in 15.19%. A significant percentage reported a deterioration in mental state, family dynamics, and everyday lifestyle. Persons with a history of mental disorders had higher rates of current depression (24.64% vs. 9.62%; p < 0.0001). Suicidal tendencies were at least doubled in terms of RASS scores. Approximately one-third of participants were accepting (at least to a moderate degree) a non-bizarre conspiracy. The highest Relative Risk (RR) to develop clinical depression was associated with a history of Bipolar disorder (RR = 4.23)., Conclusions: The current study reported findings in health care professionals similar in magnitude and quality to those reported earlier in the general population although rates of clinical depression, suicidal tendencies, and adherence to conspiracy theories were much lower. However, the general model of factors interplay seems to be the same and this could be of practical utility since many of these factors are modifiable., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: A mesothelioma cluster in Biancavilla (Sicily, Italy), drew attention to fluoro-edenite, a fibre classified by International Agency for Research on Cancer as carcinogenic to humans. Significant excesses in mortality and morbidity were observed for respiratory diseases and a significant excess of pneumoconiosis hospitalizations was reported., Objective: Aim of this study is to assess the characters of the lung damage in Biancavilla residents hospitalized with pneumoconiosis or asbestosis diagnoses., Methodology: Medical records, available radiographs and computed tomography scans were collected. The obtained imaging was reviewed by a panel of three specialists and focused on pleural and parenchymal abnormalities. Cases with an ILO-BIT or ICOERD score equal or greater than 2 were considered positive for a pneumoconiosis-like damage, cases with a score lower than 2 or insufficient quality of imaging were considered inconclusive. If no pneumoconiotic aspects were present the cases were classified as negative., Results: Out of 38 cases, diagnostic imaging for 25 cases were found. Ten cases out of 25 showed asbestosis-like features, nine subjects were considered negative. In six patients' results were inconclusive., Conclusions: Asbestosis-like features were substantiated in Biancavilla residents without known occupational exposure to asbestos. Further studies to estimate population respiratory health are required. Experimental studies on the fibrogenic potential of fluoro-edenite are needed.

Introduction: Post-traumatic stress disorder (PTSD) and complex PTSD (cPTSD) are two sibling stress-related disorders. Evidence suggests a worse clinical picture associated with cPTSD in terms of comorbidities and outcomes. However, little is known about the association between cPTSD and psychotic-like experiences (PLEs). In this study, we aim to explore differences in PLEs in a sample of 1010 late adolescents with PTSD and cPTSD symptoms., Methods: A sample of 1010 late-adolescents and young adults attending the last year of high school was selected. PLEs were assessed using the 16-items Prodromal Questionnaire (PQ-16), PTSD and cPTSD were assessed using the International Trauma Questionnaire (ITQ)., Results: 999 (501 males, 50.15% and 498 females, 49.85%) subjects had complete data on the selected variables. Of these, 91 (9.11%) and 40 (4.00%) screened positive for PTSD and cPTSD, respectively. Mean number of PLEs endorsed in subjects with PTSD, cPTSD and control groups were 7.02 (sd=2.99), 8.17 (sd=3.70) and 4.49 (sd=2.93), respectively. Mean PQ-16 distress score was 5.08 (sd=4.6) in subjects not endorsing PTSD/cPTSD, 10.11 (sd=6.17) in PTSD and 14.51 (sd=9.1) in cPTSD subjects. A linear regression analysis revealed a significant association between PTSD/cPTSD and PLEs scores (respectively, b=4.91 [3.73, 6.10] and b=10.05 [8.40, 11.70]). Such associations were reduced after adjustment for depression, anxiety and dissociation., Discussion and Conclusions: Our results find higher rates of PLEs in late adolescents screening positive for cPTSD and PTSD compared to negative subjects. Furthermore, cPTSD could be more specifically associated with distressing PLEs. These findings add to the vast literature of a worse psychopathological picture associated with cPTSD compared to PTSD, emphasizing the need for a separation between PTSD and cPTSD in terms of diagnosis and possibly treatment.

There is considerable interest in exploring effects of coronavirus disease 2019 (COVID-19) pandemic on mental health. Suicide is one of the leading causes of mortality worldwide and changes in daily life brought by the pandemic may be additional risk factors in people with pre-existing mental disorders. This rapid PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) scoping review aims to identify and analyze current evidence about the relation between COVID-19 pandemic outbreak, along with COVID-19 disease and severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection, and suicide in individuals with previously diagnosed mental disorders. First, we conducted a comprehensive review of the literature, then proceeded to discuss findings in a narrative way. Tables were constructed and articles sorted according to the studies' methodologies. 53 papers were eventually identified as eligible, among which 33 are cross-sectional studies, 9 are longitudinal studies, and 11 studies using other methodologies. Despite suffering from a mental disorder is a risk factor for suicidal behavior per se, the advent of COVID-19 pandemic may exacerbate this relation. Nevertheless, data addressing a clear correlation between suicidal behavior and the pandemic outbreak are still controversial. Longitudinal analysis using validated suicide scales and multicenter studies could provide deeper insight and knowledge about this topic., (© 2023. The Author(s).)

Background: The emotional regulation process plays a pivotal role in daily-life functioning, modulating goal-directed and adaptive behavior. Conversely, altering this cognitive function can disrupt self-regulation and bring emotional dysregulation. Emotional instability could represent a core characteristic of BPD, also modulating the BPD symptom's onset. This systematic review aims to summarize the existing literature reporting the role of emotional instability in BPD to better define the role of the impairment of the emotional processes in the onset of the cognitive and behavioral symptoms of this complex mental disorder., Methods: MEDLINE, Scopus and Web of Science were independently searched for relevant studies. Eligible studies had to be identifiable through database searching, published and accessible. This systematic review was conducted according to PRISMA guidelines. The search period was from 2012 to 14 September 2022., Results: A pool of 120 studies was identified, out of which 11 met the selection criteria and were included. Overall, the studies confirm a relationship between emotional instability and borderline personality disorder., Conclusions: The evidences retrieved seem to point out the role of the emotional impairment not only in worsening of the disorder, but could also be one of the risk factors for its onset., (© 2023. The Author(s).)

Purpose of Review: This aim of the present systematic literature review is to critically analyze problematic sexuality and sexual dysfunctions in personality disorders (PDs) and pathological personality traits., Recent Findings: An initial pool of 123 studies was found, out of which 17 met the selection criteria and were therefore included. Traumatic experiences as childhood sexual abuse and adverse childhood experiences characterize the relationship between sexual behavior and PDs. From this point of view, sexual compulsivity and sexual risk behaviors, typical of BPD and ASPD, respectively, are among the pathognomonic aspects of PDs and of pathological personality traits. A maladaptive personality functioning may manifest through a problematic sexuality and a sexual impairment. In this regard, traumatic life experiences may structure personality together with sexual functioning. Therefore, it would be useful to consider the relationship between trauma, sexuality, and personality in research and in the clinical setting., (© 2023. The Author(s).)

The protracted nature of the 2016-2017 central Italy seismic sequence, with multiple damaging earthquakes spaced over months, presented serious challenges for the duty seismologists and emergency managers as they assimilated the growing sequence to advise the local population. Uncertainty concerning where and when it was safe to occupy vulnerable structures highlighted the need for timely delivery of scientifically based understanding of the evolving hazard and risk. Seismic hazard assessment during complex sequences depends critically on up-to-date earthquake catalogues-i.e., data on locations, magnitudes, and activity of earthquakes-to characterize the ongoing seismicity and fuel earthquake forecasting models. Here we document six earthquake catalogues of this sequence that were developed using a variety of methods. The catalogues possess different levels of resolution and completeness resulting from progressive enhancements in the data availability, detection sensitivity, and hypocentral location accuracy. The catalogues range from real-time to advanced machine-learning procedures and highlight both the promises as well as the challenges of implementing advanced workflows in an operational environment., (© 2022. The Author(s).)

We report on a blinded analysis of low-energy electronic recoil data from the first science run of the XENONnT dark matter experiment. Novel subsystems and the increased 5.9 ton liquid xenon target reduced the background in the (1, 30) keV search region to (15.8±1.3)  events/(ton×year×keV), the lowest ever achieved in a dark matter detector and ∼5 times lower than in XENON1T. With an exposure of 1.16 ton-years, we observe no excess above background and set stringent new limits on solar axions, an enhanced neutrino magnetic moment, and bosonic dark matter.

Polyhydroxyalkanoates (PHAs) are a family of biopolyesters synthesized by various microorganisms. Due to their biocompatibility and biodegradation, PHAs have been proposed for biomedical applications, including tissue engineering scaffolds. Olive leaf extract (OLE) can be obtained from agri-food biowaste and is a source of polyphenols with remarkable antioxidant properties. This study aimed at incorporating OLE inside poly(hydroxybutyrate-co-hydroxyvalerate) (PHBHV) fibers via electrospinning to obtain bioactive bio-based blends that are useful in wound healing. PHBHV/OLE electrospun fibers with a size of 1.29 ± 0.34 µm were obtained. Fourier transform infrared chemical analysis showed a uniform surface distribution of hydrophilic -OH groups, confirming the presence of OLE in the electrospun fibers. The main OLE phenols were released from the fibers within 6 days. The biodegradation of the scaffolds in phosphate buffered saline was investigated, demonstrating an adequate stability in the presence of metalloproteinase 9 (MMP-9), an enzyme produced in chronic wounds. The scaffolds were preliminarily tested in vitro with HFFF2 fibroblasts and HaCaT keratinocytes, suggesting adequate cytocompatibility. PHBHV/OLE fiber meshes hold promising features for wound healing, including the treatment of ulcers, due to the long period of durability in an inflamed tissue environment and adequate cytocompatibility.

Tomatoes and their derivates represent an important source of natural biologically active components. The present study aims to investigate the protective effect of tomato peel extracts, grown in normal (RED-Ctr) or in drought stress (RED-Ds) conditions, on an experimental model of sarcopenia. The phenolic profile and total polyphenols content (TPC) of RED-Ctr and RED-Ds were determined by Ultra High-Performance Liquid Chromatography (UHPLC) analyses coupled to electrospray ionization high-resolution mass spectrometry (ESI-HR-MS). Human skeletal muscle myoblasts (HSMM) were differentiated in myotubes, and sarcopenia was induced by dexamethasone (DEXA) treatment. Differentiation and sarcopenia were evaluated by both real-time PCR and immunofluorescent techniques. Data show that myosin heavy chain 2 (MYH2), troponin T (TNNT1), and miogenin (MYOG) were expressed in differentiated myotubes. 5 μg Gallic Acid Equivalent (GAE/mL) of TPC from RED-Ds extract significantly reduced muscle atrophy induced by DEXA. Moreover, Forkhead BoxO1 (FOXO1) expression, involved in cell atrophy, was significantly decreased by RED-Ds extract. The protective effect of tomato peel extracts depended on their qualitative polyphenolic composition, resulting effectively in the in vitro model of sarcopenia.

Not only did the ongoing CoronaVIrus Disease-19 (COVID-19) pandemic cause a massive number of casualties, but also there is growing concern that the burden of its psychological aftermaths will only show up years down the road. This systematic review summarises the existing literature reporting the impact of COVID-19 on personality disorders (PDs)-related violence. MEDLINE and APA PsycINFO were independently searched for relevant studies by two authors. Eligible studies had to be identifiable through database searching, published and fully accessible. This systematic review was conducted according to Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. An initial pool of 241 studies were found, out of which 69 met the selection criteria and were, therefore, included. The majority reported a worse Mental Health Outcome (MHO) during the pandemic as related to dysfunctional personality and positive personality traits predicting a better outcome. Furthermore, increased levels of interpersonal violence (IV) and self-directed violence were reported. Further research should be conducted on the reciprocal interaction of PDs and IV during the time of pandemic. Nevertheless, the dramatic impact of restrictive measures on PDs has still to be appropriately addressed., (© 2022. The Author(s).)

The first cluster of coronavirus cases in Europe was officially detected on 21st February 2020 in Northern Italy, even if recent evidence showed sporadic first cases in Europe since the end of 2019. In this study, we have tested the presence of coronavirus in Italy and, even more importantly, we have assessed whether the virus had already spread sooner than 21st February. We use a counterfactual approach and certified daily data on the number of deaths (deaths from any cause, not only related to coronavirus) at the municipality level. Our estimates confirm that coronavirus began spreading in Northern Italy in mid-January., (© The Author(s) 2021.)

Olive leaves extract (OLE) has been extensively studied as antioxidant and antibiotic and these characteristics make it particularly interesting for use on wounds. For this reason, the aim of this study was to introduce OLE in microparticles (MP) of hyaluronic acid (MPHA-OLE) or chitosan (MPCs-OLE) to obtain a spray patch for the treatment of wounds in anatomical areas that are difficult to protect with traditional patches. The MP were characterized for particle size and ability to protect OLE from degradation, to absorb water from wound exudate, to control OLE release from MP. The MPHA and MPCs medicated or not and mixtures of the two types in different proportions were studied in vitro on fibroblasts by the scratch wound healing assay. The MP size was always less than 5 µm, and therefore, suitable for a spray patch. The MPCs-OLE could slow down the release of OLE therefore only about 60% of the polyphenols contained in it were released after 4 h. Both MPHA and MPCs could accelerate wound healing. A 50% MPHA-OLE-50% MPCs-OLE blend was the most suitable for accelerating wound healing. The MPHA-OLE-MPCs-OLE blends studied in this work were shown to have the characteristics suitable for a spray patch, thus giving a second life to the waste products of olive growers.

The mobilization of endothelial progenitor cells (EPCs) into circulation from bone marrow is well known to be present in several clinical settings, including acute coronary syndrome, heart failure, diabetes and peripheral vascular disease. The aim of this review was to explore the current literature focusing on the great opportunity that EPCs can have in terms of regenerative medicine.

Chronic leg ulcers are a common condition among adults, causing pain and social distress. Population aging has contributed to the amplification of the disease with increased cardiovascular diseases such as myocardial infarction, stroke, limb ischemia, cancers, chronic respiratory diseases, and diabetes. The aim of this study was to evaluate the influence of the Mediterranean Diet (MD) and hydration on the healing rate of the ulcers. A group of 35 patients (M/F 16/19, mean age 78 ± 10 years) with venous, arterial, or mixed ulcers was subjected to a Food Frequency Questionnaire (FFQ) and a Hydration Habits Questionnaire (HHQ). Clinical and anthropometric data were collected. A one-year follow-up was conducted. Complete ulcer healing was observed in 26% of the patients, of whom 67% had a habit of high hydration (more than 1 liter /day), regardless of adherence to the MD. In our study population, about half showed a low adherence to the MD. A moderate-high adherence to the MD showed an increase of arterial ulcer healing compared to subjects with a low adherence to the MD, however, only when associated to a consumption of more than 1 liter of water daily. In conclusion, dietary assessments could help identify patients who are likely to benefit from nutritional interventions for improving overall health and wound healing. The habit of high hydration, namely more than 1 liter daily, can influence the wound healing rate., Competing Interests: Declaration of Competing Interests None., (Copyright © 2021. Published by Elsevier Inc.)

Background: Tomato by-products contain a great variety of biologically active substances and represent a significant source of natural antioxidant supplements of the human diet. The aim of the work was to compare the antioxidant properties of a by-product from an ancient Tuscan tomato variety, Rosso di Pitigliano (RED), obtained by growing plants in normal conditions (-Ctr) or in drought stress conditions (-Ds) for their beneficial effects on vascular related dysfunction., Methods: The antioxidant activity and total polyphenol content (TPC) were measured. The identification of bioactive compounds of tomato peel was performed by HPLC. HUVEC were pre-treated with different TPC of RED-Ctr or RED-Ds, then stressed with H 2 O 2 . Cell viability, ROS production and CAT, SOD and GPx activities were evaluated. Permeation of antioxidant molecules contained in RED across excised rat intestine was also studied., Results: RED-Ds tomato peel extract possessed higher TPC than compared to RED-Ctr (361.32 ± 7.204 mg vs. 152.46 ± 1.568 mg GAE/100 g fresh weight). All extracts were non-cytotoxic. Two hour pre-treatment with 5 µg GAE/mL from RED-Ctr or RED-Ds showed protection from H 2 O 2 -induced oxidative stress and significantly reduced ROS production raising SOD and CAT activity (* p < 0.05 and ** p < 0.005 vs. H 2 O 2 , respectively). The permeation of antioxidant molecules contained in RED-Ctr or RED-Ds across excised rat intestine was high with non-significant difference between the two RED types (41.9 ± 9.6% vs. 26.6 ± 7.8%)., Conclusions: RED-Ds tomato peel extract represents a good source of bioactive molecules, which protects HUVECs from oxidative stress at low concentration.

We present the first results of the Fermilab National Accelerator Laboratory (FNAL) Muon g-2 Experiment for the positive muon magnetic anomaly a&#95;{μ}≡(g&#95;{μ}-2)/2. The anomaly is determined from the precision measurements of two angular frequencies. Intensity variation of high-energy positrons from muon decays directly encodes the difference frequency ω&#95;{a} between the spin-precession and cyclotron frequencies for polarized muons in a magnetic storage ring. The storage ring magnetic field is measured using nuclear magnetic resonance probes calibrated in terms of the equivalent proton spin precession frequency ω[over ˜]&#95;{p}^{'} in a spherical water sample at 34.7 °C. The ratio ω&#95;{a}/ω[over ˜]&#95;{p}^{'}, together with known fundamental constants, determines a&#95;{μ}(FNAL)=116 592 040(54)×10^{-11} (0.46 ppm). The result is 3.3 standard deviations greater than the standard model prediction and is in excellent agreement with the previous Brookhaven National Laboratory (BNL) E821 measurement. After combination with previous measurements of both μ^{+} and μ^{-}, the new experimental average of a&#95;{μ}(Exp)=116 592 061(41)×10^{-11} (0.35 ppm) increases the tension between experiment and theory to 4.2 standard deviations.

A novel strategy involving Olive Leaf Extract (OLE) and Cold Atmospheric Plasma (CAP) was developed as a green antimicrobial treatment. Specifically, we reported a preliminary investigation on the combined use of OLE + CAP against three pathogens, chosen to represent medical and food industries (i.e., E. coli , S. aureus and L. innocua ). The results indicated that a concentration of 100 mg/mL (total polyphenols) in OLE can exert an antimicrobial activity, but still insufficient for a total bacterial inactivation. By using plain OLE, we significantly reduced the growth of Gram positive S. aureus and L. innocua , but not Gram-negative E. coli . Instead, we demonstrated a remarkable decontamination effect of OLE + CAP in E. coli , S. aureus and L. innocua samples after 6 h. This effect was optimally maintained up to 24 h in S. aureus strain. E. coli and L. innocua grew again in 24 h. In the latter strain, OLE alone was most effective to significantly reduce bacterial growth. By further adjusting the parameters of OLE + CAP technology, e.g., OLE amount and CAP exposure, it could be possible to prolong the initial powerful decontamination over a longer time. Since OLE derives from a bio-waste and CAP is a non-thermal technology based on ionized air, we propose OLE + CAP as a potential green platform for bacterial decontamination. As a combination, OLE and CAP can lead to better antimicrobial activity than individually and may replace or complement conventional thermal procedures in food and biomedical industries.

We report on a search for nuclear recoil signals from solar ^{8}B neutrinos elastically scattering off xenon nuclei in XENON1T data, lowering the energy threshold from 2.6 to 1.6  keV. We develop a variety of novel techniques to limit the resulting increase in backgrounds near the threshold. No significant ^{8}B neutrinolike excess is found in an exposure of 0.6  t×y. For the first time, we use the nondetection of solar neutrinos to constrain the light yield from 1-2 keV nuclear recoils in liquid xenon, as well as nonstandard neutrino-quark interactions. Finally, we improve upon world-leading constraints on dark matter-nucleus interactions for dark matter masses between 3 and 11  GeV c^{-2} by as much as an order of magnitude.

The selection of low-radioactive construction materials is of utmost importance for the success of low-energy rare event search experiments. Besides radioactive contaminants in the bulk, the emanation of radioactive radon atoms from material surfaces attains increasing relevance in the effort to further reduce the background of such experiments. In this work, we present the 222 Rn emanation measurements performed for the XENON1T dark matter experiment. Together with the bulk impurity screening campaign, the results enabled us to select the radio-purest construction materials, targeting a 222 Rn activity concentration of 10 μ Bq / kg in 3.2 t of xenon. The knowledge of the distribution of the 222 Rn sources allowed us to selectively eliminate problematic components in the course of the experiment. The predictions from the emanation measurements were compared to data of the 222 Rn activity concentration in XENON1T. The final 222 Rn activity concentration of ( 4.5 ± 0.1 ) μ Bq / kg in the target of XENON1T is the lowest ever achieved in a xenon dark matter experiment., (© The Author(s) 2021.)

Estimates of the real death toll of the COVID-19 pandemic have proven to be problematic in many countries, Italy being no exception. Mortality estimates at the local level are even more uncertain as they require stringent conditions, such as granularity and accuracy of the data at hand, which are rarely met. The "official" approach adopted by public institutions to estimate the "excess mortality" during the pandemic draws on a comparison between observed all-cause mortality data for 2020 and averages of mortality figures in the past years for the same period. In this paper, we apply the recently developed machine learning control method to build a more realistic counterfactual scenario of mortality in the absence of COVID-19. We demonstrate that supervised machine learning techniques outperform the official method by substantially improving the prediction accuracy of the local mortality in "ordinary" years, especially in small- and medium-sized municipalities. We then apply the best-performing algorithms to derive estimates of local excess mortality for the period between February and September 2020. Such estimates allow us to provide insights about the demographic evolution of the first wave of the pandemic throughout the country. To help improve diagnostic and monitoring efforts, our dataset is freely available to the research community., Supplementary Information: The online version contains supplementary material available at 10.1007/s00148-021-00857-y., Competing Interests: Conflict of interestThe authors declare no competing interests., (© The Author(s) 2021.)

Purpose: To assess the reliability of CXR and to describe CXR findings and clinical and laboratory characteristics associated with positive and negative CXR., Methods: Retrospective two-center study on consecutive patients admitted to the emergency department of two north-western Italian hospitals in March 2020 with clinical suspicion of COVID-19 confirmed by RT-PCR and who underwent CXR within 24 h of the swab execution. 260 patients (61% male, 62.8 ± 15.8 year) were enrolled. CXRs were rated as positive (CXR+) or negative (CXR-), and features reported included presence and distribution of airspace opacities, pleural effusion and reduction in lung volumes. Clinical and laboratory data were collected. Statistical analysis was performed with nonparametric tests, binary logistic regression (BLR) and ROC curve analysis., Results: Sensitivity of CXR was 61.1% (95%CI 55-67%) with a typical presence of bilateral (62.3%) airspace opacification, more often with a lower zone (88.7%) and peripheral (43.4%) distribution. At univariate analysis, several factors were found to differ significantly between CXR+ and CXR-. The BLR confirmed as significant predictors only lactate dehydrogenase (LDH), C-reactive protein (CRP) and interval between the onset of symptoms and the execution of CXR. The ROC curve procedure determined that CRX+ was associated with LDH > 500 UI/L (AUC = 0.878), CRP > 30 mg/L (AUC = 0.830) and interval between the onset of symptoms and the execution of CXR > 4 days (AUC = 0.75). The presence of two out of three of the above-mentioned predictors resulted in CXR+ in 92.5% of cases, whereas their absence in 7.4%., Conclusion: CXR has a low sensitivity. LDH, CRP and interval between the onset of symptoms and the execution of CXR are major predictors for a positive CXR.

The decline of skeletal muscle mass and strength that leads to sarcopenia is a pathology that might represent an emergency healthcare issue in future years. Decreased muscle mass is also a condition that mainly affects master athletes involved in endurance physical activities. Skeletal muscles respond to exercise by reshaping the biochemical, morphological, and physiological state of myofibrils. Adaptive responses involve the activation of intracellular signaling pathways and genetic reprogramming, causing alterations in contractile properties, metabolic status, and muscle mass. One of the mechanisms leading to sarcopenia is an increase in reactive oxygen and nitrogen species levels and a reduction in enzymatic antioxidant protection. The present review shows the recent experimental models of sarcopenia that explore molecular mechanisms. Furthermore, the clinical aspect of sport sarcopenia will be highlighted, and new strategies based on nutritional supplements, which may contribute to reducing indices of oxidative stress by reinforcing natural endogenous protection, will be suggested.

Cherry fruit has a high content in flavonoids. These are important diet components protecting against oxidative stress, inflammation, and endothelial dysfunction, which are all involved in the pathogenesis of atherosclerosis, which is the major cause of cardiovascular diseases (CVD). Since the seasonal availability of fresh fruit is limited, research has been focused on cherry extract (CE), which also possesses a high nutraceutical potential. Many clinical studies have demonstrated the nutraceutical efficacy of fresh cherries, but only a few studies on CE antioxidant and anti-inflammatory activities have been carried out. Here, the results concerning the antioxidant and anti-inflammatory activities of CE are reviewed. These were obtained by an in vitro model based on Human Umbilical Vein Endothelial Cells (HUVEC). To clarify the CE mechanism of action, cells were stressed to induce inflammation and endothelial dysfunction. Considering that antioxidants' polyphenol compounds are easily degraded in the gastrointestinal tract, recent strategies to reduce the degradation and improve the bioavailability of CE are also presented and discussed. In particular, we report on results obtained with nanoparticles (NP) based on chitosan derivatives (Ch-der), which improved the mucoadhesive properties of the chitosan polymers, as well as their positive charge, to favor high cellular interaction and polyphenols intestinal absorption, compared with a non-mucoadhesive negative surface charged poly(lactic-co-glycolic) acid NP. The advantages and safety of different nanosystems loaded with natural CE or other nutraceuticals are also discussed., Competing Interests: The authors declare no conflict of interest.

Background: Recent studies have highlighted the importance of cherry and cocoa extracts consumption to protect cells from oxidative stress, paying particular attention to cocoa by-products. This study aims to investigate the protective effect of cocoa husk extract (CHE) and cherry extracts (CE) against ROS-induced oxidative stress in Human Umbilical Vein Endothelial Cells (HUVECs)., Methods: CE and CHE had antioxidant activity characterized by total polyphenols content (TPC). HUVECs were treated for 2 h and 24 h with increasing TPC concentrations of CE and CHE (5-10-25-50-100 µg Gallic Acid Equivalent (GAE)/mL) and then with H 2 O 2 for 1 h. Cell viability and ROS production were evaluated. CE and CHE polyphenols permeability on excised rat intestine were also studied., Results: CE and CHE showed a similar antioxidant activity (2.5 ± 0.01 mmol Fe 2+ /100 g FW (fresh weight) and 2.19 ± 0.09 mmol Fe 2+ /100 g FW, respectively, p > 0.05) whereas CHE had a higher TPC (7105.0 ± 96.9 mg GAE/100 g FW) than CE (402.5 ± 8.4 mg GAE/100 g), p < 0.05. The in vitro viability assay showed that both extracts were non-cytotoxic. CHE resulted in protection against ROS at lower concentrations than CE. CHE showed a 2-fold higher apparent permeability compared to CE., Conclusions: CHE represents a high-value antioxidant source, which is interesting for the food and pharmaceutical industries.

Olive leaf extract (OLE) can be obtained as biowaste and is extensively used a food supplement and an over-the-counter drug for its beneficial effects. New studies have investigated OLE concerning the role of oxidative stress in the pathogenesis of vascular disease. This in vitro study aims to evaluate if OLE extracted from the Tuscan Olea europaea protects endothelial cells against oxidative stress generated by reactive oxygen species (ROS)., Methods: OLE total polyphenols (TPs) were characterized by the Folin-Ciocalteu method. Endothelial cells were grown in conventional cultures (i.e., two-dimensional, 2D) and on a biomaterial scaffold (i.e., three-dimensional, 3D) fabricated via electrospinning. Cell viability and ROS measurement after H 2 O 2 insults were performed., Results: OLE TP content was 23.29 mg GAE/g, and oleuropein was the principal compound. The dose-dependent viability curve highlighted the absence of significant cytotoxic effects at OLE concentrations below 250 µg/mL TPs. By using OLE preconditioning at 100 µg/mL, cell viability decrease was observed, being in 3D lower than in the 2D model. OLE was protective against ROS in both models., Conclusions: OLE represents a high-value antioxidant source obtained by biowaste that is interesting for biomedical products. Using a 3D scaffold could be the best predictive model to mimic the physiological conditions of vascular tissue reaction., Competing Interests: The authors declare no conflict of interest.

All stellar-mass black holes have hitherto been identified by X-rays emitted from gas that is accreting onto the black hole from a companion star. These systems are all binaries with a black-hole mass that is less than 30 times that of the Sun 1-4 . Theory predicts, however, that X-ray-emitting systems form a minority of the total population of star-black-hole binaries 5,6 . When the black hole is not accreting gas, it can be found through radial-velocity measurements of the motion of the companion star. Here we report radial-velocity measurements taken over two years of the Galactic B-type star, LB-1. We find that the motion of the B star and an accompanying Hα emission line require the presence of a dark companion with a mass of [Formula: see text] solar masses, which can only be a black hole. The long orbital period of 78.9 days shows that this is a wide binary system. Gravitational-wave experiments have detected black holes of similar mass, but the formation of such massive ones in a high-metallicity environment would be extremely challenging within current stellar evolution theories.

This study aimed at evaluating the anti-inflammatory effect of natural cherry extract (CE), either free or encapsulated in nanoparticles (NPs) based on chitosan derivatives (Ch-der) or poly(lactic- co -glycolic acid) (PLGA), on human umbilical vein endothelial cells (HUVEC). CE from Prunus avium L. was characterized for total polyphenols, flavonoids, and anthocyanins content. CE and CE-loaded NP cytotoxicity and protective effect on lipopolysaccharide (LPS)-stressed HUVEC were tested by water-soluble tetrazolium salt (WST-1) assay. Pro- and anti-inflammatory cytokines (TNF-α, IL-6, IL-10, and PGE2) released by HUVEC were quantified by enzyme-linked immunosorbent assay (ELISA). All NP types were internalized into HUVEC after 2 h incubation and promoted the anti-inflammatory effect of free CE at the concentration of 2 µg gallic acid equivalents (GAE)/mL. CE-loaded Ch-der NPs showed the highest in vitro uptake and anti-inflammatory activity, blunting the secretion of IL-6, TNF-α, and PGE2 cytokines. Moreover, all NPs reduced the production of nitric oxide and NLRP3 inflammasome, and had a stronger anti-inflammatory effect than the major corticosteroid dexamethasone. In particular, the results demonstrate that natural CE protects endothelial cells from inflammatory stress when encapsulated in NPs based on quaternary ammonium chitosan. The CE beneficial effects were directly related with in vitro internalization of CE-loaded NPs.

Polyphenolic compounds contained in cherry extract (CE) are well known for their antioxidant and anti-inflammatory properties. Unfortunately, most of these natural compounds have low oral bioavailability, reducing their widespread use. Here, different concentrations of polyphenol-rich CE from Tuscany (Italy), encapsulated in poly(lactic- co -glycolic acid) (PLGA) nanoparticles (NPs), were compared with those encapsulated in two NP types, different from each other in terms of mucoadhesivity, obtained with chitosan derivatives (Ch-der), regarding CE gastrointestinal (GI) permeability and protective effect on oxidative stress. Different NP systems were physico-chemically characterized, and the antioxidant GI permeability was evaluated in a triple-cell co-culture model (Caco-2/HT29-MTX/Raji B), resembling the intestine. PLGA NPs efficiently entrapped CE (up to 840 µg gallic acid equivalent (GAE)/mL) without altering size (210 nm), polydispersity index (0.05), or zeta potential (-10.7 mV). Such NPs promoted permeation of encapsulated CE at a CE polyphenolic concentration of at least 2 µg GAE/mL. More mucoadhesive NPs from Ch-der, coded quaternary ammonium S-protected thiolated chitosan (QA-Ch-S-pro) NP, promoted CE GI permeation of 0.5 µg GAE/mL. At higher concentrations of Ch-der polymers, the resulting NPs containing CE were toxic toward Caco-2 and HT29-MTX cells. CE protected human umbilical vein endothelial cells (HUVECs) from oxidative stress and maintained its activity when entrapped in PLGA NPs. CE encapsulated in QA-Ch-S-pro NP protected HUVECs from oxidative stress, even more effectively than non-encapsulated CE. Furthermore, mucoadhesive NPs from Ch-der were more effective antioxidant protectors than PLGA NPs, but less cytotoxic PLGA NPs could be more useful when comparatively high therapeutic antioxidant doses are needed.

Background: Endothelial dysfunction has been associated to cardiovascular outcomes in patients with cardiovascular risk factors. Circulating endothelial progenitor cells (EPCs) play an important physiological role for their reparative potential of vascular integrity, but are numerically reduced and functionally impaired in patients with cardiovascular risks. This study assesses the effects of Extra Virgin Olive Oil (EVOO) and apple-enriched dark chocolate intake on the blood levels of EPCs. Methods : Thirty volunteers with cardiovascular risk factors, enrolled in a randomised, crossover, four-weeks trial, received a solid dark chocolate bar (40 g/day) containing 10% EVOO or 2.5% dry apples. Urine samples were analyzed for endogenous metabolites. Circulating EPCs levels, clinical data and anthropometric examinations were collected., Results: 26 volunteers (M/F:14/12, 51 ± 9 years of age) completed the study. Comparison of pre-post intervention revealed a significant increase in EPCs levels associated with EVOO-dark chocolate consumption. Most biochemical parameters were not significantly modified by both chocolates., Conclusions: This study shows that a daily consumption of a non fattening dose of dark chocolate enriched with EVOO improves blood levels of EPCs, a well known surrogate biologic marker for endothelial function., Competing Interests: The authors declare no conflict of interest

Cherries are known for their nutraceutical properties, in particular for their antioxidant ability due to their polyphenol content, which causes a reduction of cardiovascular disease (CVD) risk factors. However, once ingested these molecules are degraded in the Gastrointestinal (GI) tract before reaching the blood, which is the action site. The object of the present work is to evaluate the ability of cherry extract (CE), encapsulated in nanoparticles (NPs) based on different chitosan (Ch) derivatives, to promote a protective effect of human umbilical vein endothelial cells (HUVECs) involved in vascular dysfunction against oxidative stress. CE-loaded NPs based on quaternary ammonium chitosan (NP1) and an S-protected thiolated derivative thereof (NP2) were prepared. The mean particle size (NP1 344.9 ± 17.8, NP2 339.9 ± 68.2 nm), the polydispersity index, the encapsulation efficiency (NP1 78.4 ± 4.5, NP2 79.8 ± 0.6%), and the zeta potential (NP1 14.8 ± 0.3, NP2 15.8 ± 0.5 mV) did not appear to be significantly different. Both NP types improved the CE apparent permeation parameters with respect to the control. Conversely, CE-loaded NP2 protected HUVECs from oxidative stress and reduced reactive oxygen species (ROS) production more than CE-loaded NP1 and free CE. In addition to promoting HUVEC resistance, NP2 could be a useful tool to overcome the problem of cherry seasonality.

Objectives Aminaphtone, a naphtohydrochinone used in the treatment of capillary disorders, may affect oedema in chronic venous insufficiency. Aim of study is to investigate the effect of aminaphtone on vascular endothelial permeability in vitro and its effects on three-dimensional capillary-like structures formed by human umbilical vein endothelial cells. Method Human umbilical vein endothelial cells were treated with 50 ng/ml VEGF for 2 h and aminaphtone for 6 h. Permeability assay, VE-cadherin expression and Matrigel assay were performed. Results VEGF-induced permeability was significantly decreased by aminaphtone in a range concentration of 1-20 µg/ml. Aminaphtone restored VE-cadherin expression. Finally, 6 h pre-treatment with aminaphtone significantly preserved capillary-like structures formed by human umbilical vein endothelial cells on Matrigel up to 48 h compared to untreated cells. Conclusions Aminaphtone significantly protects endothelium permeability and stabilises endothelial cells organised in capillary-like structures, modulating VE-cadherin expression. These data might explain the clinical benefit of aminaphtone on chronic venous insufficiency.

The introduction of three-dimensional echography (3D echo) in vascular field is not recent, but it still remains a seldom-used technique because of the costs of ultrasound probe and the need of dedicated laboratories. Therefore, despite significant prognostic implications, the high diagnostic accuracy in plaque definition, and the relative ease of use, 3D echo in vascular field is a niche technique. The purpose of this review is mainly clinical and intends to demonstrate the potential strength of a 3D approach, including technical aspects, in order to present to clinicians and imagers the appealing aspects of a noninvasive and radiation-free methodology with relevant diagnostic and prognostic correlates in the assessment of carotid atherosclerosis. A comprehensive literature search (since 1990s to date) using the PubMed, MEDLINE, and Cochrane libraries databases has been conducted. Articles written in English have been assessed, including reviews, clinical trials, meta-analyses, and interventional/observational studies. Manual cross-referencing was also performed, and relevant references from selected articles were reviewed. The search was limited to studies conducted in humans. Search terms, retrieved also with PubMed Advanced search and AND/OR Boolean operators (mainly in title and abstract), included three-dimensional, echo, stroke/transient ischemic attack, predictors, carotid, imaging, and biomarkers., Competing Interests: There are no conflicts of interest.

Aortic valve stenosis (AVS) represents a cluster of different phenotypes, considering gradient and flow pattern. Circulating micro RNAs may reflect specific pathophysiological processes and could be useful biomarkers to identify disease. We assessed 80 patients (81, 76.7-84 years; 46, 57.5%females) with severe AVS. We performed bio-humoral evaluation (including circulating miRNA-1, 21, 29, 133) and 2D-echocardiography. Patients were classified according to ACC/AHA groups (D1-D3) and flow-gradient classification, considering normal/low flow, (NF/LF) and normal/high gradient, (NG/HG). Patients with reduced ejection fractionwere characterized by higher levels of miRNA1 (p = 0.003) and miRNA 133 (p = 0.03). LF condition was associated with higher levels of miRNA1 (p = 0.02) and miRNA21 (p = 0.02). Levels of miRNA21 were increased in patients with reduced Global longitudinal strain (p = 0.03). LF-HG and LF-LG showed higher levels of miRNA1 expression (p = 0.005). At one-year follow-up miRNA21 and miRNA29 levels resulted significant independent predictors of reverse remodeling and systolic function increase, respectively. Different phenotypes of AVS may express differential levels and types of miRNAs, which may retain a pathophysiological role in pro-hypertrophic and pro-fibrotic processes.

Critical limb ischemia (CLI) is the most advanced form of peripheral artery disease. It is associated with significant morbidity and mortality and high management costs. It carries a high risk of amputation and local infection. Moreover, cardiovascular complications remain a major concern. Although it is a well-known entity and new technological and therapeutic advances have been made, this condition remains poorly addressed, with significantly heterogeneous management, especially in nonexperienced centers. This review, from a third-level dedicated inpatient and outpatient cardioangiology structure, aims to provide an updated summary on the topic of CLI of its complexity, encompassing epidemiological, social, economical and, in particular, diagnostic/imaging issues, together with potential therapeutic strategies (medical, endovascular, and surgical), including the evaluation of cardiovascular risk factors, the diagnosis, and treatment together with prognostic stratification.

Endothelial progenitor cells (EPCs) contribute to ischemic tissue repair by paracrine secretion up-regulated by hypoxia. In this study we use novel nanoparticles (NPs) as carriers for a controlled release of EPC secretome (CM) to improve their angiogenic properties. The in vivo effect in ischemic hindlimb rat model was evaluated, comparing hypoxic EPC-CM-NPs with hypoxic EPC-CM alone. A proteomic characterization of hypoxic CM and the in vitro effect on endothelial cells (HUVECs) were also performed. Up to 647 protein, 17 of which with angiogenic properties, were upregulated by hypoxia. Moreover, hypoxic EPC-CM significantly promoted capillary-like structures on Matrigel. A significant increase of blood perfusion in ischemic limbs at 2 weeks with EPC-CM-loaded NPs as compared to both EPC-CM and control and a significant increase of capillary formation were observed. The use of EPC-CM-NPs significantly improved neoangiogenesis in vivo, underlining the advantages of controlled release in regenerative medicine., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Mobilization of endothelial progenitor cells (EPCs) into circulation from bone marrow in patients with acute myocardial infarction has strong scientific evidence; less is known about EPC mobilization in patients with stable coronary artery disease (CAD). The aim of this study was to investigate the association of stable ischemic heart disease with EPC levels in tissue and blood., Methods: Fifty-five consecutive patients admitted to a single treatment center for valve or coronary artery bypass grafting (CABG) surgeries were included in the study. Blood samples were collected in the morning before surgery and analyzed by flow-cytometry to determine peripheral EPC levels (EPC/ml). Tissue EPC (CD34+VEGFR2+) levels were assessed on a right atrial appendage segment., Results: Mean age was 76±5years, 48% were men, and 53% had CAD The number of CD34+ VEGFR2+ cells in the tissue of patients with CAD was significantly higher (p<0.005) and circulating EPC showed a tendency to be reduced by approximately 20% in peripheral blood of patients with CAD when compared to those without CAD., Conclusion: Patients with stable CAD had higher EPC density values (EPC/mm2) and were more likely to have lower EPC blood levels when compare with normal controls., (Copyright © 2017 Elsevier B.V. All rights reserved.)