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Music resonates differently in every single person according to human culture and characteristics. Individual differences such as personality traits may play a key role in modulating the emotional response to music and yet relatively little is known about the underlying structure of Italian musical preferences. On these bases, the current research presents a replication of the structure of the MUSIC Model and examines its relationships with personality traits. A sample of 2,104 participants completed an online survey. The current study is divided into three parts: 1) an exploratory factor analysis study, 2) a confirmatory factor analysis study to verify the emerged structure, and 3) a structural equation modeling for the investigation of the relationships between music and personality. Findings confirmed a latent five-factor structure that was labeled as follows: 1) Mellow: classical, gospel, opera, and religious; 2) Unpretentious: alternative, bluegrass, and new age; 3) Sophisticated: jazz, blues, soul R&B; 4) Intense: heavy metal, punk, and rock; and 5) Contemporary: dance electronica, world (international), pop, reggae, and rap hip-hop. Overall, findings suggested musical preferences are subject to some personality traits. These results could be considered a promising starting point to generate new theories to use music in therapeutic contexts for preventing well-being.

Peanut (Arachis hypogaeaL.) is susceptible to leaf spot diseases caused by the fungi Nothopassalora personataand Passalora arachidicola, which can decrease yield substantially. Chlorothalonil is one of the most widely used fungicides to control these diseases but was recently banned in the European Union due to toxicity to amphibians and fish. Dodine is an alternative fungicide with a similar range of activity. However, information about its impact on the peanut physiology is lacking. The objectives of this study were to assess the effect of dodine on leaf photosynthesis, yield, and pod quality of peanut and evaluate the potential of dodine as a replacement of chlorothalonil in the control of leaf spot diseases. A 3‐year field experiment was conducted using Georgia‐06G. Treatments consisted of chlorothalonil at 0.86 kg a.i. ha−1(high rate), chlorothalonil at 0.43 kg a.i. ha−1(low rate), dodine at 0.68 kg a.i. ha−1(high rate), and dodine at 0.34 kg a.i. ha−1(low rate). Photosynthetic efficiency was altered by fungicide in only a few instances, and a clear trend was not observed. The high rate of dodine resulted in the least defoliation caused by leaf spot of all fungicide treatments. Pod maturity, yield, and grading parameters were not affected by fungicide. Overall, dodine did not impact negatively the photosynthetic activity, pod quality, and yield of peanut. Moreover, this chemistry was efficient in controlling leaf spot diseases under heavy disease pressure; therefore, dodine is a potential replacement of chlorothalonil in the control of leaf spot diseases in peanut. Leaf photosynthetic efficiency was generally not impacted by chlorothalonil or dodine application.Pod maturity profile, pod yield, and grading parameters did not differ among the fungicide treatments.The selection between chlorothalonil or dodine did not impact the quality and value of peanut pods.High rate of dodine resulted in the lowest defoliation caused by leaf spot diseases of all fungicide treatments.Dodine is a potential alternative to chlorothalonil in the control of leaf spot diseases in peanut.

The process in which locally confined epithelial malignancies progressively evolve into invasive cancers is often promoted by unjamming, a phase transition from a solid-like to a liquid-like state, which occurs in various tissues. Whether this tissue-level mechanical transition impacts phenotypes during carcinoma progression remains unclear. Here we report that the large fluctuations in cell density that accompany unjamming result in repeated mechanical deformations of cells and nuclei. This triggers a cellular mechano-protective mechanism involving an increase in nuclear size and rigidity, heterochromatin redistribution and remodelling of the perinuclear actin architecture into actin rings. The chronic strains and stresses associated with unjamming together with the reduction of Lamin B1 levels eventually result in DNA damage and nuclear envelope ruptures, with the release of cytosolic DNA that activates a cGAS–STING (cyclic GMP-AMP synthase–signalling adaptor stimulator of interferon genes)-dependent cytosolic DNA response gene program. This mechanically driven transcriptional rewiring ultimately alters the cell state, with the emergence of malignant traits, including epithelial-to-mesenchymal plasticity phenotypes and chemoresistance in invasive breast carcinoma.

Despite much progress in improving graft outcome during cardiac transplantation, chronic allograft vasculopathy (CAV) remains an impediment to long-term graft survival. MicroRNAs (miRNAs) emerged as regulators of the immune response. Here, we aimed to examine the miRNA network involved in CAV. miRNA profiling of heart samples obtained from a murine model of CAV and from cardiac-transplanted patients with CAV demonstrated that miR-21 was most significantly expressed and was primarily localized to macrophages. Interestingly, macrophage depletion with clodronate did not significantly prolong allograft survival in mice, while conditional deletion of miR-21 in macrophages or the use of a specific miR-21 antagomir resulted in indefinite cardiac allograft survival and abrogated CAV. The immunophenotype, secretome, ability to phagocytose, migration, and antigen presentation of macrophages were unaffected by miR-21 targeting, while macrophage metabolism was reprogrammed, with a shift toward oxidative phosphorylation in naïve macrophages and with an inhibition of glycolysis in pro-inflammatory macrophages. The aforementioned effects resulted in an increase in M2-like macrophages, which could be reverted by the addition of L-arginine. RNA-seq analysis confirmed alterations in arginase-associated pathways associated with miR-21 antagonism. In conclusion, miR-21 is overexpressed in murine and human CAV, and its targeting delays CAV onset by reprogramming macrophages metabolism.

Despite much progress in improving graft outcome during cardiac transplantation, chronic allograft vasculopathy (CAV) remains an impediment to long‐term graft survival. MicroRNAs (miRNAs) emerged as regulators of the immune response. Here, we aimed to examine the miRNA network involved in CAV. miRNA profiling of heart samples obtained from a murine model of CAV and from cardiac‐transplanted patients with CAV demonstrated that miR‐21 was most significantly expressed and was primarily localized to macrophages. Interestingly, macrophage depletion with clodronate did not significantly prolong allograft survival in mice, while conditional deletion of miR‐21 in macrophages or the use of a specific miR‐21 antagomir resulted in indefinite cardiac allograft survival and abrogated CAV. The immunophenotype, secretome, ability to phagocytose, migration, and antigen presentation of macrophages were unaffected by miR‐21 targeting, while macrophage metabolism was reprogrammed, with a shift toward oxidative phosphorylation in naïve macrophages and with an inhibition of glycolysis in pro‐inflammatory macrophages. The aforementioned effects resulted in an increase in M2‐like macrophages, which could be reverted by the addition of L‐arginine. RNA‐seq analysis confirmed alterations in arginase‐associated pathways associated with miR‐21 antagonism. In conclusion, miR‐21 is overexpressed in murine and human CAV, and its targeting delays CAV onset by reprogramming macrophages metabolism. The authors show that, after heart transplantation, microRNA‐21 is overexpressed in chronic allograft vasculopathy (CAV), that pharmacological and genetic modulation of microRNA‐21 mitigated CAV, and that microRNA‐21 antagonism abrogated CAV by reprogramming macrophage metabolism.

This study aimed to describe the preliminary results of a modified sympathicotomy for cardiac sympathetic denervation (CSD), which may reduce the predictive risk and intraoperative surgical time of the procedure.

The majority of the currently used and developed anti-infectives are poorly water-soluble molecules. The poor solubility might lead to limited bioavailability and pharmacological action of the drug. Novel pharmaceutical materials have thus been designed to solve those problems and improve drug delivery. In this study, we propose a facile method to produce sub-microcarriers (sMCs) by electrostatic gelation of anionic ß-Cyclodextrin (aß-CD) and chitosan. The average hydrodynamic size ranged from 400-900 nm by carefully adjusting polymer concentrations and N/C ratio. The distinct host-guest reaction of Cyclodextrin derivative is considered as a good approach to enhance solubility, and prevent drug recrystallization, and thus was used to develop sMC to improve the controlled release profile of a poorly soluble and clinically relevant anti-infective Ciprofloxacin. The optimal molar ratio of Ciprofloxacin to aß-CD was found to be 1:1, which helps maximize encapsulation efficiency (~90%) and loading capacity (~9%) of Ciprofloxacin loaded sMCs. Furthermore, to recommend the future application of the developed sMCs, the dependence of cell uptake on sMCs size (500, 700, and 900 nm) was investigated in vitro on dTHP-1 by both flow cytometry, and confocal microscopy. The results demonstrate that, regardless of their size, an only comparatively small fraction of the sMCs was taken up by the macrophage-like cells, while most of the carriers were merely adsorbed to the cell surface after 2 h incubation. After continuing the incubation to reach 24 h, the majority of the sMCs was found intracellularly. However, the sMCs had been designed to release sufficient amount of drug within 24 h, the subsequent phagocytosis of the carrier may be considered as an efficient pathway for its safe degradation and elimination. In summary, the developed sMC is a suitable system with promising perspectives recommended for pulmonary extracellular infection therapeutic.

Mechanisms mediating the cardiovascular and renal protection exerted by SGLT2 inhibitors are still partially unknown. We investigated whether dapagliflozin modulates systemic and renal vascular function and structure, and induces epigenetic modifications.

Amphiphilic polymer-based drug delivery systems hold potential in enhancing pharmacokinetics and therapeutic efficacy due to their ability to simultaneously codeliver different drugs in a controlled manner. We propose here a facile method for synthesizing a new amphiphilic polymer, farnesylated glycol chitosan (FGC), which self-assembles into nanoparticles upon being dispersed in aqueous media. The characteristics of FGC nanoparticles, in particular the size, could be tuned in a range from 200 to 500 nm by modulating the degree of farnesylation and the pH and polymer concentration during particle preparation. Carrier capacity, release kinetics, and surface modification of the established system were investigated using different model compounds. The colloids were biocompatible and stable at biologically relevant pH values. The interactions between the carriers and human mucus were examined by multiple particle tracking, which revealed that ∼80% of the particles remain immobilized within the mucus matrix. These results postulate FGC as a versatile drug delivery platform.

Endothelial dysfunction and arterial stiffness are early vascular alterations, linked to oxidative stress and inflammation, with prognostic significance in essential hypertensive patients. P2X7receptors (P2X7R), responding to extracellular ATP, are encoded by a highly polymorphic gene and modulate inflammatory responses and cell growth, potentially playing a role in the control of vascular tone. This study evaluated the effects of P2X7R gene polymorphisms (single nucleotide polymorphisms, SNPs) on a detailed vascular hypertensive phenotype.

Persistent inflammation and oxidative stress influence the progression of diabetic nephropathy. Metalloproteinases (MMPs) participate in extracellular matrix remodeling. Statins show favorable anti-inflammatory effects in chronic kidney disease. We evaluated the effect of rosuvastatin on inflammatory and pro-fibrotic responses due to exposure to different glucose or free fatty acid (FFA) concentrations.

Adiposity contributes to the insulin resistance and endothelial dysfunction of the hypertensive state; the inflammatory network and the metalloprotease (MMP)/tissue inhibitor of metalloprotease (TIMP) system modulate vascular structure and function.

Clinical manifestations of thrombotic microangiopathies (TMA) are secondary to platelet aggregation and thrombotic occlusion of the microvasculature of the affected organs. Abnormalities in von Willebrand factor (vWF) in these patients were considered instrumental in promoting the process leading to microvascular thrombosis. We evaluated the capacity of plasma in these patients to induce adhesion of normal platelets and thrombus formation under conditions of controlled fluid shear stress. We also studied vWF multimeric distribution to establish whether abnormalities of this glycoprotein correlate with platelet adhesion and thrombus formation. Plasma from patients in the acute phase and remission showed the same capacity to induce platelet adhesion and thrombus formation at a low level of shear rate (600 sec-1) as plasma from control subjects. At a high shear rate (1,500 sec-1), platelet adhesion and thrombus dimensions were significantly increased (P< 0.05) by plasma from patients with TMA compared with controls. The capacity to enhance thrombus formation at high shear stress was present during the acute phase and disease remission and did not correlate with the presence of unusually large vWF multimers. Increased thrombus formation with patient plasma is completely normalized by blocking the interaction of vWF with the platelet receptors, glycoprotein (GP)Ib and GPIIb-IIIa, suggesting that the phenomenon is completely mediated by vWF. Our results suggest the possibility of an intrinsically altered vWF molecule in these patients that is probably more effective than normal vWF in mediating platelet adhesion and thrombus formation.

We isolated three XenopuscDNA clones, Xcalp1, Xcalp2and Xcalp3, which encode different forms of calpastatin mRNA. Compared to the canonical form of mammalian calpastatin, the predicted Xcalp3protein contained a very long N-terminal domain L and an additional inhibitory domain. The other two deduced calpastatin proteins were truncated forms, both lacking domain L and containing four (Xcalp2) and two (Xcalp1) inhibitory domains, respectively. The presence of Xcalp1, Xcalp2and Xcalp3transcripts was detected by in situ hybridization in the notochord from the embryonic stage 20 to stage 36, afterwards the expression was only present in the growing tailbud. As shown by RT-PCR, the three calpastatin mRNAs were also expressed in the adult brain.

We investigated here the changes in von Willebrand factor (vWF) multimers in recurrent, sporadic and familial forms of hemolytic uremic syndrome (HUS)/thrombotic thrombocytopenic purpura (TTP) to see whether they are actually proteolyzed in vivo in these patients. Molecular determinants of fragments in vWF were also characterized to identify possible sites of cleavage of the subunit. Unusually large vWF multimers were found in blood of 8 of 10 patients with recurrent HUS/TTP, both in the acute phase and in remission, but never in familial and sporadic cases. Instead, all of the groups showed evidence of enhanced fragmentation of vWF multimers during the acute phase. Increased fragmentation was also shown by decrease in native 225-kD vWF subunit. In recurrent and sporadic HUS/TTP, enhanced fragmentation normalized at remission, but the abnormality persisted in familial HUS/TTP patients. The latter findings suggest that patients with familial HUS/TTP may have a congenital abnormality in vWF processing. Analysis with specific monoclonal antibodies showed the presence of the normal vWF fragments with apparent molecular mass of 189, 176, and 140 kD in all patients; however, in 6 recurrent and in 5 familial cases, novel fragments that differed in size from normal ones were found. The size of these abnormal fragments differed from one patient to another and none of them was ever found in normal plasma. These results documented, for the first time in HUS/TTP, an abnormal cleavage of the vWF subunit that might account for the increased fragmentation observed in these patients.

No relevant conflicts of interest to declare.

Somatic mutations of calreticulin (CALR) have been described in approximately 30-40% of JAK2 and MPL unmutated Essential Thrombocythemia and Primary Myelofibrosis patients. CALR is an endoplasmic reticulum (ER) chaperone responsible for proper protein folding and calcium retention. Recent data demonstrated that the TPO receptor (MPL) is essential for the development of CALR mutant-driven Myeloproliferative Neoplasms (MPNs). However, the precise mechanism of action of CALR mutants haven't been fully unraveled. In order to assess whether and how CALR mutations could affect the physiological CALR protein functions in the ER and thus contributing through other mechanisms to the development of MPNs, we decided to study the role of mutated CALR in K562 cells, devoid of MPL expression. To this end, K562 cells stably expressing either wt CALRor the two most common CALR mutated variants CALRdel52 and CALRins5 were generated via retroviral mediated gene transfer.

Philadelphia negative chronic myeloproliferative neoplasms (MPNs) are acquired clonal disorders of hematopoietic stem cell. Among MPNs, Primary Myelofibrosis (PMF) carries the worst prognosis with severe clinical hallmarks, including bone marrow failure, extramedullary hematopoiesis and splenomegaly. MNPs are intimately associated with high level of pro-inflammatory cytokines (i.e., transforming growth factor-β1, TGF-β1) and excess generation of Reactive Oxygen Species (ROS) that are, at least in part, responsible for disease progression. Recently, extensive studies have provided unequivocal evidences that differentially expressed microRNAs (miRNAs) may play a role in MNP's pathogenesis. The miRNA expression profile performed on CD34+ hematopoietic stem/progenitor cells (HSPCs) obtained from PMF patients (R. Norfo et al., Blood, 2014), allowed us to identify miR-382-5p as up-regulated miRNA. Overexpression experiments using miRNA mimic in normal CD34+ cells have demonstrated its central role in granulocyte fate decision (R. Zini et al., Stem Cell and Dev, 2016).

Vannucchi: Novartis: Consultancy, Research Funding, Speakers Bureau; Baxalta: Speakers Bureau; Shire: Speakers Bureau.

Vannucchi: Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

Primary Myelofibrosis (PMF) is a Philadelphia-negative myeloproliferative neoplasm characterized by the presence of hyperplastic/dysplastic megakaryocytes and the development of myelofibrosis and osteosclerosis. This disruption of the bone marrow (BM) structure results from a deregulated release of growth factors by malignant hematopoietic cells, particularly monocytes and megakaryocytes, that activate BM stromal cells (Desterke-C, Mediators Inflamm, 2015). Therefore, it remains of primary importance to identify novel therapeutic strategies to restore BM microenvironment homeostasis in PMF patients.

Primary Myelofibrosis (PMF) belongs to the Philadelphia negative Myeloproliferative Neoplasms (MPNs) and is characterized by hematopoietic stem-cell derived clonal myeloproliferation, involving especially megakaryocyte (MK) lineage, bone marrow fibrosis and extramedullary hematopoiesis. Recent studies have suggested that alterations in miRNAs expression could play a critical role in MPN's pathogenesis. In order to shed some light on this issue, we have previously performed the integrative analysis (IA) of gene and miRNA expression profiles of PMF CD34+ hematopoietic stem/progenitor cells (HSPCs) isolated from 42 PMF patients compared with 31 healthy donors (R. Norfo et al., Blood, 2014). IA identified miR-494-3p as one of the most upregulated miRNAs in PMF CD34+ cells associated to the highest number of downregulated predicted targets (eighty-six, Fig. 1).