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Abstract High sensitivity troponin T (hsTnT) is a strong predictor of adverse outcome during SARS-CoV-2 infection. However, its determinants remain partially unknown. We aimed to assess the relationship between severity of inflammatory response/coagulation abnormalities and hsTnT in Coronavirus Disease 2019 (COVID-19). We then explored the relevance of these pathways in defining mortality and complications risk and the potential effects of the treatments to attenuate such risk. In this single-center, prospective, observational study we enrolled 266 consecutive patients hospitalized for SARS-CoV-2 pneumonia. Primary endpoint was in-hospital COVID-19 mortality. hsTnT, even after adjustment for confounders, was associated with mortality. D-dimer and CRP presented stronger associations with hsTnT than PaO2. Changes of hsTnT, D-dimer and CRP were related; but only D-dimer was associated with mortality. Moreover, low molecular weight heparin showed attenuation of the mortality in the whole population, particularly in subjects with higher hsTnT. D-dimer possessed a strong relationship with hsTnT and mortality. Anticoagulation treatment showed greater benefits with regard to mortality. These findings suggest a major role of SARS-CoV-2 coagulopathy in hsTnT elevation and its related mortality in COVID-19. A better understanding of the mechanisms related to COVID-19 might pave the way to therapy tailoring in these high-risk individuals.

The erythrocyte sedimentation rate (ESR) has been used in canine medicine in several disorders, above all, to evaluate levels of inflammation. This study evaluated the ESR in canine leishmaniosis (CanL) and other inflammatory conditions. Three groups of dogs were examined: CanL affected dogs without clinical signs (INFECTED group, #25) or with clinical signs (SICK group, #43) and dogs affected by acute or acute-on-chronic conditions (OTHER DISEASE group, #65). The ESR was compared with acute phase proteins or reactants either positive or negative (leukogram, fibrinogen, iron, unsaturated iron binding capacity, ferritin, haptoglobin, and albumin) and immunological markers (gamma-globulins, IgG, and IgM). The ESR was higher in the SICK group than in the INFECTED group (median 39 vs. 11 mm/h; p < 0.0001), as well as in the OTHER DISEASE than in the INFECTED groups (median 41 vs. 11 mm/h; p < 0.0001). The ESR appeared outside the reference range for all dogs in the SICK and OTHER DISEASE groups and almost with similar values (mm/h; median 39, 95% CI 31-51 vs. 41, 95% CI 12-87; p > 0.05). The extent of changes in ESR can help to establish the severity of CanL and other inflammatory disorders. As a point-of-care test, the ESR can be used to screen dogs for unhealthy conditions, and its values correlate with the severity of any disease, including CanL.

Core-double-shell-structured nanocomposite films consisting of polyvinylidene fluoride- grafted -barium titanate (PVDF- g -BT) incorporated into a P(VDF-co-hexafluoropropylene (HFP)) copolymer matrix were produced via a solution mixing method for energy storage applications. The resulting films were thoroughly investigated via spectroscopic, thermal, and morphological analyses. Thermogravimetric data provided an enhancement of the thermal stability, while differential scanning calorimetry indicated an increase in the crystallinity of the films after the addition of PVDF- g -BT. Moreover, broadband dielectric spectroscopy revealed three dielectric processes, namely, glass-rubber relaxation (α a ), relaxation associated with the polymer crystalline phase (α c ), and slower relaxation in the nanocomposites resulting from the accumulation of charge on the interface between the PVDF- g -BT filler and the P(VDF- co -HFP) matrix. The dependence of the dielectric constant from the composition was analyzed, and we found that the highest permittivity enhancement was obtained by the highest concentration filler added to the largest concentration of P(VDF- co -HFP). Mechanical analysis revealed an improvement in Young's modulus for all nanocomposites versus pristine P(VDF- co -HFP), confirming the uniformity of the distribution of the PVDF- g -BT nanocomposite with a strong interaction with the copolymer matrix, as also evidenced via scanning electron microscopy. The suggested system is promising for use in high-energy-density storage devices as supercapacitors.

Background: Clinicians increasingly serve youths from societal/cultural backgrounds different from their own. This raises questions about how to interpret what such youths report. Rescorla et al. (2019, European Child & Adolescent Psychiatry, 28, 1107) found that much more variance in 72,493 parents' ratings of their offspring's mental health problems was accounted for by individual differences than by societal or cultural differences. Although parents' reports are essential for clinical assessment of their offspring, they reflect parents' perceptions of the offspring. Consequently, clinical assessment also requires self-reports from the offspring themselves. To test effects of individual differences, society, and culture on youths' self-ratings of their problems and strengths, we analyzed Youth Self-Report (YSR) scores for 39,849 11-17 year olds in 38 societies., Methods: Indigenous researchers obtained YSR self-ratings from population samples of youths in 38 societies representing 10 culture cluster identified in the Global Leadership and Organizational Behavioral Effectiveness study. Hierarchical linear modeling of scores on 17 problem scales and one strengths scale estimated the percent of variance accounted for by individual differences (including measurement error), society, and culture cluster. ANOVAs tested age and gender effects., Results: Averaged across the 17 problem scales, individual differences accounted for 92.5% of variance, societal differences 6.0%, and cultural differences 1.5%. For strengths, individual differences accounted for 83.4% of variance, societal differences 10.1%, and cultural differences 6.5%. Age and gender had very small effects., Conclusions: Like parents' ratings, youths' self-ratings of problems were affected much more by individual differences than societal/cultural differences. Most variance in self-rated strengths also reflected individual differences, but societal/cultural effects were larger than for problems, suggesting greater influence of social desirability. The clinical significance of individual differences in youths' self-reports should thus not be minimized by societal/cultural differences, which-while important-can be taken into account with appropriate norms, as can gender and age differences., (© 2022 Association for Child and Adolescent Mental Health.)

The increasing use of single-cell immune profiling and advanced microscopic imaging technologies has deepened our understanding of the cardiac immune system, confirming that the heart contains a broad repertoire of innate and adaptive immune cells. Leucocytes found in the healthy heart participate in essential functions to preserve cardiac homeostasis, not only by defending against pathogens but also by maintaining normal organ function. In pathophysiological conditions, cardiac inflammation is implicated in healing responses after ischaemic or non-ischaemic cardiac injury. The aim of this review is to provide a concise overview of novel methodological advancements to the non-expert readership and summarize novel findings on immune cell heterogeneity and functions in cardiac disease with a focus on myocardial infarction as a prototypic example. In addition, we will briefly discuss how biological sex modulate the cardiac immune response. Finally, we will highlight emerging concepts for novel therapeutic applications, such as targeting immunometabolism and nanomedicine., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Local dielectric spectroscopy (LDS) is a scanning probe method, based on dynamic-mode atomic force microscopy (AFM), to discriminate dielectric properties at surfaces with nanometer-scale lateral resolution. Until now a sub-10 nm resolution for LDS has not been documented, that would give access to the length scale of fundamental physical phenomena such as the cooperativity length related to structural arrest in glass formers (2-3 nm). In this work, LDS performed by a peculiar variant of intermittent-contact mode of AFM, named constant-excitation frequency modulation, was introduced and extensively explored in order to assess its best resolution capability. Dependence of resolution and contrast of dielectric imaging and spectroscopy on operation parameters like probe oscillation amplitude and free amplitude, the resulting frequency shift, and probe/surface distance-regulation feedback gain, were explored. By using thin films of a diblock copolymer of polystyrene (PS) and polymethylmethacrylate (PMMA), exhibiting phase separation on the nanometer scale, lateral resolution of at least 3 nm was demonstrated in both dielectric imaging and localized spectroscopy, by operating with optimized parameters. The interface within lamellar PS/PMMA was mapped, with a best width in the range between 1 and 3 nm. Changes of characteristic time of the secondary ( β ) relaxation process of PMMA could be tracked across the interface with PS., (© 2022 IOP Publishing Ltd.)

The most recent high-sensitivity assays for troponins I and T (hs-TnI and hs-TnT) have made it possible to detect blood concentrations up to 10 times lower than previous assays, making troponins detectable even in asymptomatic subjects without manifest cardiovascular disease. For this reason, hs-Tn, initially introduced as markers of myocardial damage in an acute setting, have also become possible markers of subclinical myocardial damage in baseline conditions. In fact, recent evidence suggests that hs-TnT and hs-TnI predict the risk of future cardiovascular events also in the context of primary prevention, and offer incremental information when added to current risk stratification models. The different association highlighted with different outcome measures, such as coronary heart disease, atherosclerotic cardiovascular disease, heart failure, and death from all causes, seems to indicate that the risk observed in asymptomatic subjects with high levels of hs-Tn is an expression of subclinical damage secondary to multiple pathophysiological mechanisms, and not only to atherothrombosis. However, the ability of hs-TnT and hs-TnI (until now used interchangeably), to provide differential predictive information, and not redundant with respect to more traditional factors, remains to be definitively clarified, both for the purpose of predicting specific outcomes and for the implementation of specific preventive strategies. To date, evidences available allow us to hypothesize their role more as markers than as risk factors., (Published on behalf of the European Society of Cardiology. © The Author(s) 2021.)

Surface displacements of a few picometers, occurring after application of an electric potential to piezoelectric materials, can be detected and mapped with nanometer-scale lateral resolution by scanning probe methods, the most notable being piezoresponse force microscopy (PFM). Yet, absolute determination of such displacements, giving access for instance to materials' piezoelectric coefficients, are hindered by both mechanical and electrostatic side-effects, requiring complex experimental and/or post-processing procedures for carrying out reliable results. The employment of quartz tuning-fork force sensors in an intermittent contact mode PFM is able to provide measurements of electrically-induced surface displacements that are not influenced by electrostatic side-effects typical of more conventional cantilever-based PFM. The method is shown to yield piezoeffect mapping on standard ferroelectric test crystals (periodically-poled lithium niobate and triglycine sulfate), as well as on a ferroelectric polymer (PVDF), with no visible influence from the applied dc electric potential., (© 2021 IOP Publishing Ltd.)

Presently several evidences support an association between acute myocardial infarction and influenza infection. The pathophysiology rationale rests on the release of inflammation cytokines, rupture of atherosclerotic plaque, and triggering of prothrombotic events leading to coronary artery occlusion. Several observational evidences support a potential role of influenza vaccine in cardiovascular prevention. It is estimated that the efficacy of influenza vaccine in preventing myocardial infarction could range between 15% and 45%. Notwithstanding the clear recommendation of numerous guidelines concerning patients with cardiovascular diseases, vaccination rates are still low in the high-risk groups. Influenza vaccine as preventive measure of cardiovascular disease still awaits support from randomized clinical trials. Nonetheless, considering the favourable cost-efficacy and safety profile of influenza vaccination, its use should be encouraged in everyday clinical practice., (Published on behalf of the European Society of Cardiology. © The Author(s) 2020.)

Renal denervation is a device-based procedure for hypertension for which safety and efficacy has been demonstrated. At present, its clinical use is still matter of debate, despite the most recent clinical trials have shown promising results with new-generation devices in various hypertensive populations. This position paper was deemed necessary by the Italian Society of Arterial Hypertension, in order to provide indications about the applications of renal denervation in the clinical setting. A state-of-the art review of the literature, focusing on safety and efficacy data, is provided. Furthermore, based on current evidence and expert consensus, clinical profiles of possible candidates for renal denervation are proposed. The selection process should take into account not only blood pressure values, global cardiovascular risk profile, but also drug adherence and tolerability and patient preferences. This position paper also defines minimum requirements for renal denervation selection centers and a flowchart for the difficult-to-treat hypertensive patient. Further studies are needed to support these preliminary indications, which are based on expert-consensus only.

As societies become increasingly diverse, mental health professionals need instruments for assessing emotional, behavioral, and social problems in terms of constructs that are supported within and across societies. Building on decades of research findings, multisample alignment confirmatory factor analyses tested an empirically based 8-syndrome model on parent ratings across 30 societies and youth self-ratings across 19 societies. The Child Behavior Checklist for Ages 6-18 and Youth Self-Report for Ages 11-18 were used to measure syndromes descriptively designated as Anxious/Depressed, Withdrawn/Depressed, Somatic Complaints, Social Problems, Thought Problems, Attention Problems, Rule-Breaking Behavior , and Aggressive Behavior . For both parent ratings ( N =  61,703) and self-ratings ( N  = 29,486), results supported aggregation of problem items into 8 first-order syndromes for all societies (configural invariance), plus the invariance of item loadings (metric invariance) across the majority of societies. Supported across many societies in both parent and self-ratings, the 8 syndromes offer a parsimonious phenotypic taxonomy with clearly operationalized assessment criteria. Mental health professionals in many societies can use the 8 syndromes to assess children and youths for clinical, training, and scientific purposes.

The adipose tissue (AT) is an endocrine organ that produces adipocytokines (adipokines), able to influence metabolic homeostasis. In the conventional classification, there are two large AT depots, characterized by different paracrine activities: the subcutaneous AT, which would mostly produce cytokines with protective properties against cardiovascular disease; and the visceral AT, responsible for the secretion of cytokines with proinflammatory, prothrombotic, and proatherogenic effects. A third component, the epicardial AT (EAT) is now receiving increasing attention due to its unique anatomical and functional proximity to the myocardium and the coronary arteries. In rodents, the EAT protects the heart from exposure to high levels of free fatty acids, and provides energy to the myocardium under high metabolic demands. The observation that atherosclerotic plaques are more prevalent in regions of coronary arteries surrounded by the EAT, while they tend to be less present in segments penetrating the myocardium (the septal branches and segments under myocardial bridges), has led to the hypothesis of a possible role of the EAT in promoting the development of atherosclerosis through endocrine and paracrine effects, in addition to the role of biomechanical forces affecting transendothelial lipid permeability into the intima. In this article, we review the clinical and molecular evidence linking the EAT and coronary artery disease through a systematic review of the literature. We, here, discuss current diagnostic techniques in evaluating the interaction between EAT and the onset of coronary artery disease and ischaemic heart disease. Finally, we review current knowledge on the underlying mechanisms by which the EAT may affect coronary atherosclerosis, and potential clinical implications of this interaction, making the EAT an attractive target for new therapeutics in cardiovascular disease., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Cystic fibrosis (CF) is a progressive genetic disease caused by mutations in the gene that produces the CF transmembrane conductance regulator (CFTR) protein. The malfunction of the CFTR protein causes a thick buildup of mucus in the lungs that clogs the airways and traps bacteria, thus leading to infections, extensive lung damage and respiratory failure. Micro-delivery systems are currently being investigated as an efficient way to cross the viscous and complex architecture of the CF mucus. In this study, we produced synthetic and natural microparticles (MPs) based on poly(dl‑lactide‑co‑glycolide) (PLGA) or gellan gum through tailored water/oil emulsion procedures. Morphological and physico-chemical characterizations were carried out on both classes of MPs showing particles having diameters within suitable ranges to reach the CF airways. In vitro biocompatibility tests were also performed on both MPs using a human lung cancer cell line (A549) demonstrating that treatment with MPs induces no cytotoxic effects. Both classes of MPs were loaded with a mucolytic agent (N‑acetyl cysteine, NAC) and their release kinetics evaluated using high performance liquid chromatography (HPLC). The analysis pointed out that the amount of NAC released from MPs resulted in a dose-dependent increment, with a rapid release kinetic to satisfy the requirement for inducing an early mucus degradation. Finally, mucolytic action of NAC-loaded MPs was evaluated in an artificial sputum model through its rheological analysis obtaining the lowest viscosity profile after the addition of drug-loaded MPs. Taken together, gained results allowed us to select suitable MPs as potential drug targeting platforms having a mucolytic action for CF treatment., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Cardiovascular diseases (CVD) including coronary artery disease (CAD) and ischemic heart disease (IHD) are the main cause of mortality in industrialized countries. Although it is well known that there is a difference in the risk of these diseases in women and men, current therapy does not consider the sexual dimorphism; i.e., differences in anatomical structures and metabolism of tissues. Here, we discuss how genetic, epigenetic, hormonal, cellular or molecular factors may explain the different CVD risk, especially in high-risk groups such as women with diabetes. We analyze whether sex may modify the effects of diabetes at risk of CAD. Finally, we discuss current diagnostic techniques in the evaluation of CAD and IHD in diabetic women.

Objective: To build on Achenbach, Rescorla, and Ivanova (2012) by (a) reporting new international findings for parent, teacher, and self-ratings on the Child Behavior Checklist, Youth Self-Report, and Teacher's Report Form; (b) testing the fit of syndrome models to new data from 17 societies, including previously underrepresented regions; (c) testing effects of society, gender, and age in 44 societies by integrating new and previous data; (d) testing cross-society correlations between mean item ratings; (e) describing the construction of multisociety norms; (f) illustrating clinical applications., Method: Confirmatory factor analyses (CFAs) of parent, teacher, and self-ratings, performed separately for each society; tests of societal, gender, and age effects on dimensional syndrome scales, DSM-oriented scales, Internalizing, Externalizing, and Total Problems scales; tests of agreement between low, medium, and high ratings of problem items across societies., Results: CFAs supported the tested syndrome models in all societies according to the primary fit index (Root Mean Square Error of Approximation [RMSEA]), but less consistently according to other indices; effect sizes were small-to-medium for societal differences in scale scores, but very small for gender, age, and interactions with society; items received similarly low, medium, or high ratings in different societies; problem scores from 44 societies fit three sets of multisociety norms., Conclusions: Statistically derived syndrome models fit parent, teacher, and self-ratings when tested individually in all 44 societies according to RMSEAs (but less consistently according to other indices). Small to medium differences in scale scores among societies supported the use of low-, medium-, and high-scoring norms in clinical assessment of individual children., (Copyright © 2012 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Aiming to develop environmentally compatible chemical syntheses, the replacement of traditional organic solvents with ionic liquids (ILs) has attracted considerable attention. ILs are special molten salts with melting points below 100 degrees C that are typically constituted of organic cations (imidazolium, pyridinium, sulfonium, phosphonium, etc.) and inorganic anions. Due to their ionic nature, they are endowed with high chemical and thermal stability, good solvent properties, and non-measurable vapor pressure. Although the recovery of unaltered ILs and recycling partly compensate their rather high cost, it is important to develop new synthetic approaches to less expensive and environmentally sustainable ILs based on renewable raw materials. In fact, most of these alternative solvents are still prepared starting from fossil feedstocks. Until now, only a limited number of ILs have been prepared from renewable sources. Surprisingly, the most available and inexpensive raw material, i.e., carbohydrates, has been hardly exploited in the synthesis of ILs. In 2003 imidazolium-based ILs were prepared from o-fructose and used as solvents in Mizoroki-Heck and Diels-Alder reactions. Later on, the first chiral ILs derived from sugars were prepared from methyl D-glucopyranoside. In the same year, a family of new chiral ILs, obtained from commercial isosorbide (dianhydro-D-glucitol), was described. A closely related approach was followed by other researchers to synthesize mono- and bis-ammonium ILs from isomannide (dianhydro-D-mannitol). Finally, a few ILs bearing a pentofuranose unit as the chiral moiety were prepared using sugar phosphates as glycosyl donors and 1-methylimidazole as the acceptor.

Laser-induced breakdown spectroscopy (LIBS) is a promising technique for in situ elemental analysis. A new mobile instrument for LIBS analysis, developed in a collaboration between Marwan Technology s.r.l. and the Applied Laser Spectroscopy Laboratory in Pisa, is presented, and some applications of it and results from it are outlined. The innovative experimental set-up, based on the use of two suitably retarded laser pulses and a standardless analysis procedure, which overcomes problems related to matrix effects, greatly improves the potential of this technique for accurate quantitative analysis.

The distribution of metallothioneins I/II in the mouse brain and their specific area distribution upon physical stress were studied. To induce physical stress, groups of mice were subjected to total darkness for different periods (2 weeks, 1 month, and 2 months). The concentration of metallothioneins, evaluated by immunohistochemistry, as well as area-specific protein expression, were found in the following quantitative order: corpus striatum, cerebellum, mesencephalon, hippocampus with fornix, parts of thalamus, and pons. All other brain areas were marginally affected, or even unaffected, in terms of immunopositive metallothionein reaction. Metallothionein I/II expression was compared with the immunopositivity of glial fibrillary acidic protein (GFAP). It is noteworthy that metallothioneins and GFAP are expressed in different types of astrocytes., (Copyright 2004 Wiley-Liss, Inc.)

Eleven Italian forensic laboratories participated in a population study based on the AB Profiler Plus loci with proficiency testing. The validated database, including 1340 individuals, is available on-line. Tests for Hardy-Weinberg equilibrium, gametic unbalance, and heterogeneity of gene frequency were generally not significant. Gene frequencies at each locus were consistent with those of two previously published Italian studies, but different from a third. Individuals of each subsample were paired, and the total number of alleles shared across the nine loci was determined in each pair. The analysis was replicated over the total sample. In addition, two samples of mother-child pairs (N=315) and full-sib pairs (N=91) were subjected to allele sharing analysis. The resulting distributions were sufficiently distinct from the sample of unrelated pairs as to be of practical usefulness.