Diabetic kidney disease. new clinical and therapeutic issues. Joint position statement of the Italian Diabetes Society and the Italian Society of Nephrology on "the natural history of diabetic kidney disease and treatment of hyperglycemia in patients with type 2 diabetes and impaired renal function"

Recent epidemiological studies have disclosed heterogeneity in diabetic kidney disease (DKD). In addition to the classical albuminuric phenotype, two new phenotypes have emerged, i.e., “nonalbuminuric renal impairment” and “progressive renal decline”, suggesting that DKD progression toward end-stage kidney disease in diabetic patients may occur through two distinct pathways heralded by a progressive increase in albuminuria and decline in renal function independent of albuminuria, respectively. Besides the natural history of DKD, also the management of hyperglycemia in patients with type 2 diabetes and reduced renal function has profoundly changed in the last two decades. New anti-hyperglycemic drugs have become available for treatment of these individuals and the lowest estimated glomerular filtration rate safety thresholds for some of the old agents have been reconsidered. This joint document of the Italian Diabetes Society (SID) and the Italian Society of Nephrology (SIN) reviews the natural history of DKD in the light of the recent epidemiological literature and provides updated recommendations on anti-hyperglycemic treatment with non-insulin agents in DKD patients

bioactive nanocomposites for dental application obtained by reactive suspension method

AbstractHydroxyapatite (HA) filled poly(methyl methacrylate)/poly(hydroxyethyl methacrylate) (PMMA/PHEMA) blends were prepared by reactive suspension method: HA was synthesized by co-precipitation process directly within a HEMA solution and the so-obtained suspension was polymerized in the presence of PMMA. HA particles were obtained in form of nanorods with a length of 50–200 nm and a diameter of 10–30 nm. A significant increase in glass transition temperature was observed in the nanocomposites with respect to the unfilled polymer blends. Dynamic-mechanical thermal analysis showed a significant increase in the storage modulus in the nanocomposites measured in the rubbery region. This increase was unpredicted by Mooney's predictive equation and was attributed to the presence of cross-linking points due to the in situ generated HA particles. An increase in the elastic modulus was also observed at room temperature in compression and three-point bending tests. The presence of HA in the polymer blends resulte..

Minorenni vittime di omicidio a Milano (Italia): 1993-2017

This study aims to examine the phenomenon of homicide with victims under 18 years-old in a wide and multiethnic metropolitanarea in the north of Italy. We’re dealing with a type of crime that generates a widespread alarm and a common concern.The data analysis, approached with a multidisciplinary strategy, presented in this paper is based on forensic reports of the Instituteof Legal Medicine of the University of Milan, to provide a detailed framework of the homicides of minors that took place inthe territorial jurisdiction of Milan and Monza Prosecutor’s Office between 1993 and 2017. Quantitative and qualitative analysiswere conducted regarding victims’ socio-demographic characteristics (gender, age, nationality), weapons used, places and modalityof body discovery, murderers, motives of the killing and type of relationship between offenders and victims. Purpose of thispaper is to compare the present set of data with the ones provided by the international literature, as well as make some criminologicalobservations on this matter with a view to preventing the phenomenon. To this end, some representative case studieshave been added, their characteristics and also the relationships between offender and victim have been discussed.Questo studio esamina il fenomeno dell'omicidio con vittime di età inferiore ai 18 anni in una vasta e multietnica area metropolitanadel nord Italia, un tipo di crimine che genera allarme e preoccupazione. L'analisi dei dati, affrontata con una metodologia multidisciplinare,è basata sui verbali autoptici dell'Istituto di Medicina Legale dell'Università di Milano, al fine di fornire un quadro dettagliatodegli omicidi con vittima minorenne che si sono verificati nella giurisdizione territoriale della Procura di Milano e Monzatra il 1993 e il 2017. Sono state condotte analisi quantitative e qualitative sulle vittime, quali le caratteristiche socio-demografiche(genere, età, nazionalità), le armi utilizzate, i luoghi e le modalità di rinvenimento del corpo, le caratteristiche dell’omicida, i motividell'uccisione e il tipo di relazione tra criminale e vittima. Scopo di questo studio è confrontare l'attuale insieme di dati con quelliforniti dalla letteratura internazionale, nonché porre alcune considerazioni di carattere preventivo. A tal fine, sono stati presentatianche alcuni casi studio rappresentativi, discutendone le caratteristiche peculiari e le relazioni tra l'autore del reato e la vittima

Plasma levels of PRO-C3, a type III collagen synthesis marker, are associated with arterial stiffness and increased risk of cardiovascular death

Background and aims: The N-terminal propeptide of type III collagen (PRO-C3) assay measures a pro-peptide released during type III collagen synthesis, an important feature of arterial stiffening and atherogenesis. There is a clinical need for improved non-invasive, cheap and easily accessible methods for evaluating individuals at risk of cardiovascular disease (CVD). In this study, we investigate the potential of using circulating levels of PRO-C3 to mark the degree of vascular stenosis and risk of cardiovascular events. Methods: Baseline plasma levels of PRO-C3 were measured by ELISA in subjects belonging to the SUrrogate markers for Micro- and Macro-vascular hard endpoints for Innovative diabetes Tools (SUMMIT) cohort (N = 1354). Associations between PRO-C3 levels with vascular characteristics, namely stiffness and stenosis, and risk of future cardiovascular events were explored. Subjects were followed up after a median of 35 months (interquartile range 34–36 months), with recorded outcomes cardiovascular death and all-cause mortality. Results: We found a correlation between PRO-C3 levels and pulse wave velocity (rho 0.13, p = 0.000009), a measurement of arterial stiffness. Higher PRO-C3 levels were also associated with elevated blood pressure (rho 0.07, p = 0.014), as well as risk of cardiovascular mortality over a three-year follow-up period (OR 1.56, confidence interval 1.008–2.43, p = 0.046). Conclusions: Elevated circulating PRO-C3 levels are associated with arterial stiffness and future cardiovascular death, in the SUMMIT cohort, suggesting a potential value of PRO-C3 as a novel marker for declining vascular health.</p

The cosmic web of dwarf galaxies in a warm versus cold dark matter universe: mock galaxies in CDM and WDM simulations

Using cosmological simulations, we show that the cosmic web of dwarf galaxies in a warm dark matter (WDM) universe, wherein low mass halo formation is heavily suppressed, is nearly indistinguishable to that of a cold dark matter (CDM) universe whose low mass halos are not seen because galaxy formation is suppressed below some threshold mass. Low mass warm dark matter halos are suppressed nearly equally in all environments. For example, WDM voids in the galaxy distribution are neither larger nor emptier than CDM voids, once normalized to the same total galaxy number density and assuming galaxy luminosity scales with halo mass. It is thus a challenge to find hints about the dark matter particle in the cosmic web of galaxies. However, if the scatter between dwarf galaxy luminosity and halo properties is large, low mass CDM halos would sometimes host bright galaxies thereby populating voids that would be empty in WDM. Future surveys that will capture the small scale clustering in the local volume could thus help determine whether the CDM problem of the over-abundance of small halos with respect to the number density of observed dwarf galaxies has a cosmological solution or an astrophysical solution

The Novel Collagen Matrikine, Endotrophin, is Associated with Mortality and Cardiovascular Events in Patients with Atherosclerosis

Background: Rupture of atherosclerotic plaques is the major cause of acute cardiovascular events. The biomarker PRO-C6 measuring Endotrophin, a matrikine of collagen type VI, may provide valuable information detecting subjects in need of intensified strategies for secondary prevention. Objective: In this study, we evaluate endotrophin in human atherosclerotic plaques and circulating levels of PRO-C6 in patients with atherosclerosis, to determine the predictive potential of the biomarker. Methods: Sections from the stenotic human carotid plaques were stained with the PRO-C6 antibody. PRO-C6 was measured in serum of patients enrolled in the Carotid Plaque Imagining Project (CPIP) (discovery cohort, n = 577) and the innovative medicines initiative surrogate markers for micro- and macrovascular hard end-points for innovative diabetes tools (IMI-SUMMIT, validation cohort, n = 1,378). Median follow-up was 43 months. Kaplan–Meier curves and log-rank tests were performed in the discovery cohort. Cox proportional hazard regression analysis (HR with 95% CI) was used in the discovery cohort and binary logistic regression (OR with 95% CI) in the validation cohort. Results: PRO-C6 was localized in the core and shoulder of the atherosclerotic plaque. In the discovery cohort, PRO-C6 independently predicted future cardiovascular events (HR 1.089 [95% CI 1.019 −1.164], p = 0.01), cardiovascular death (HR 1.118 [95% CI 1.008 −1.241], p = 0.04) and all-cause death (HR 1.087 [95% CI 1.008 −1.172], p = 0.03). In the validation cohort, PRO-C6 predicted future cardiovascular events (OR 1.063 [95% CI 1.011 −1.117], p = 0.017). Conclusion: PRO-C6 is present in the atherosclerotic plaque and associated with future cardiovascular events, cardiovascular death and all-cause mortality in two large prospective cohorts

PPARgamma in dendritic cells and T cells drives pathogenic type-2 effector responses in lung inflammation

Type-2 immune responses are well-established drivers of chronic inflammatory diseases, such as asthma, and represent a large burden on public health systems. The transcription factor PPARγ is known to promote M2-macrophage and alveolar macrophage development. Here, we report that PPARγ plays a key role in both T cells and dendritic cells (DCs) for development of type-2 immune responses. It is predominantly expressed in mouse Th2 cells in vitro and in vivo as well as human Th2 cells from allergic patients. Using conditional knockouts, we show that PPARγ signaling in T cells, although largely dispensable for IL-4 induction, is critical for IL-33–driven Th2 effector function in type-2 allergic airway responses. Furthermore, we demonstrate that IL-4 and IL-33 promote up-regulation of PPARγ in lung-resident CD11b+ DCs, which enhances migration to draining lymph nodes and Th2 priming capacity. Thus, we uncover a surprising proinflammatory role for PPARγ and establish it as a novel, important mediator of DC–T cell interactions in type-2 immunity

Probing deformed commutators with macroscopic harmonic oscillators

A minimal observable length is a common feature of theories that aim to merge quantum physics and gravity. Quantum mechanically, this concept is associated to a nonzero minimal uncertainty in position measurements, which is encoded in deformed commutation relations. In spite of increasing theoretical interest, the subject suffers from the complete lack of dedicated experiments and bounds to the deformation parameters are roughly extrapolated from indirect measurements. As recently proposed, low-energy mechanical oscillators could allow to reveal the effect of a modified commutator. Here we analyze the free evolution of high quality factor micro- and nano-oscillators, spanning a wide range of masses around the Planck mass $m_{\mathrm{P}}$ (${\approx 22\,\mu\mathrm{g}}$), and compare it with a model of deformed dynamics. Previous limits to the parameters quantifying the commutator deformation are substantially lowered.Comment: 11 pages, 3 figures, reference adde

Effect of aneuploidy on cellular adaptation to hyper-osmotic and ionic stress

Aneuploidy, the condition of having an impaired karyotype is a distinctive characteristic of cancer cells and has been proposed to promote cancer evolution by conferring drug resistance and aggressive phenotypes. At a cellular level, aneuploidy, by massively changing the transcriptome and the proteome, has a profound impact on cellular phenotype. Specifically, aneuploidy has negative effect on cellular fitness in normal growth conditions in which euploid cells are already optimized to live. However, when the growth conditions are unfavorable, different aneuploid strains showed improved growth in different environmental or genetic perturbations. Adaptive mechanisms were linked to upregulation of specific genes on the aneuploid chromosome, suggesting that cells with different karyotypes have different phenotypes and fitness potential. At the same time, aneuploidy has been shown to promote further chromosome and genetic instability that could lead to the generation of a genomically heterogeneous aneuploid populations. I therefore hypothesize that aneuploidy might increase cellular evolvability via two mechanisms: first aneuploidy increases genetic and karyotypic instability and therefore generates population of cells carrying different phenotypes. Second, each different karyotype is associated with a different set of phenotypes. Therefore, these two mechanisms combined increase phenotypic variation which ultimately leads to higher adaptive potential. The aim of my project, performed using the yeast S. cerevisiae, is to test if evolvability of euploid and aneuploid cellular populations correlates with their level of genomic instability, when cells are challenged with an environmental perturbation. For this purpose, a collection of isogenic euploid and aneuploid yeast strains containing simple and complex karyotypes has been evolved in different conditions through serial passages, and evolution has been assessed as deviation from initial ratio in competition experiments between strains of same ploidy tagged with two fluorophores.Doctor of Philosoph