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

Mechanical behaviour and phase transition mechanisms of a shape memory alloy by means of a novel analytical model

The aim of the present paper is to examine both the fatigue behaviour and the phase transition mechanisms of an equiatomic pseudo-elastic NiTi Shape Memory Alloy through cyclic tests (up to 100 loading cycles). More precisely, miniaturised dog-bone specimens are tested by using a customised testing machine and the contents of both austenite and martensite phase are experimentally measured by means of X-Ray diffraction (XRD) analyses. On the basis of such experimental results in terms of martensite content, an analytical model is here formulated to correlate the stress-strain relationship to the phase transition mechanisms. Finally, a validation of the present model by means of experimental data pertaining the stress-strain relationship is performed

High-MgO lavas associated to CFB as indicators of plume-related thermochemical effects: the case of ultra-titaniferous picrite-basalt from the Northern Ethiopian-Yemeni plateau

A comprehensive petrological and geochemical dataset is reported in order to define the thermo-compositional characteristics of Ti (Fe)-enriched picrite-basalt lavas (HT2, TiO2 3-7 wt%), erupted close to the axial zone of the inferred Afar mantle plume, at the centre of the originally continuous Ethiopian-Yemeni CFB plateau (ca. 30Ma) which is zonally arranged with progressively lower Ti basalts (HT1, TiO2 2-4 wt%; LT, TiO2 1-3 wt%) toward the periphery. Integrated petrogenetic modelling based on major and trace element analyses of bulk rocks, minerals and melt inclusions in olivines, as well as Sr-Nd-Pb-He-O isotope compositional variations enables us to make several conclusions. 1) The phase equilibria constraints indicate that HT2 primary picrites were generated at ca. 1570°C mantle potential temperatures (Tp) in the pressure range 4-5 GPa whereas the HT1 and LT primary melts formed at shallower level (< 2 to 3 GPa, Tp 1530 °C for HT1 and 1430°C for LT). Thus the Afar plume head was a thermally and compositionally zoned melting region with maximum excess temperatures of 300-350°C with respect to the ambient mantle. 2) The HT2 primary melts upwelled nearly adiabatically to the base of the continental crust (ca. 1 GPa) where fractionation of olivine, followed by clinopyroxene, led to variably differentiated picritic and basaltic magmas. 3) Trace element modelling requires that the primary HT2 melts were generated - either by fractional or batch melting (F 9-10%) - from a mixed garnet peridotite source (85%) with 15% eclogite (derived from transitional MORB protoliths included in Panafrican terranes) that has to be considered a specific Ti-Fe and incompatible element enriched component entrained by the Afar plume. 4) The LT, HT1 and HT2 lavas have 143Nd/144Nd = 0.5131-0.5128, whereas Sr-Pb isotopes are positively correlated with TiO2, varying from 87 Sr/86Sr 0.7032 and 206Pb/204Pb 18.2 in LT basalts to 87Sr/86Sr 0.7044 and 206Pb/204Pb 19.4 in HT2 picrite-basalts. High 3He/4He (15-20 RA) ratios are exclusively observed in HT2 lavas, confirming earlier evidence that these magmas require a component of deep mantle in addition to eclogite, while the LT basalts may more effectively reflect the signature of the pre-existing mantle domains. The comparison between high-MgO (13-22%) lavas from several Phanerozoic CFB provinces (Karoo, Paranà-Etendeka, Emeishan, Siberia, Deccan, North Atlantic Province) shows that they share extremely high mantle potential temperatures (Tp 1550-1700°C) supporting the view that hot mantle plumes are favoured candidates for triggering many LIPs. However, the high incompatible element and isotopic variability of these high-MgO lavas (and associated CFB) suggest that plume thermal anomalies are not necessarily accompanied by significant and specific chemical effects, which depend on the nature of mantle materials recycled during the plume rise, as well as by the extent of related mantle enrichments (if any) on the pre-existing lithospheric section

Rapporto sul mercato del lavoro della provincia Bologna : anno 2009

Il Rapporto esamina l’andamento del mercato del lavoro della provincia di Bologna nel corso dell’anno 2009, segnalando le debolezze registrate e approfondendo le caratteristiche sistemiche. La analisi è svolta integrando le numerose fonti statistiche disponibili che descrivono i differenti aspetti dell’economia provinciale con l’elaborazione dei dati di fonte provinciale tratti dal database del Sistema Informativo del Lavoro dell’Emilia-Romagna (SILER) e dei Servizi dei Centri per l’Impiego (CIP). The Report examines the labor market dynamics of the Province of Bologna during 2009, highlighting weaknesses and deepening the structural features of the labor system. The study is developed by integrating information drawn by the many available statistical sources which describe different aspects of provincial economy with the elaboration of the proprietary data extracted by the databases SILER (Labour informative system of Emilia-Romagna) and CIP (Centres for the Employment)

Evidence of a low-temperature dynamical transition in concentrated microgels

A low-temperature dynamical transition has been reported in several proteins. We provide the first observation of a `protein-like' dynamical transition in nonbiological aqueous environments. To this aim we exploit the popular colloidal system of poly-N-isopropylacrylamide (PNIPAM) microgels, extending their investigation to unprecedentedly high concentrations. Owing to the heterogeneous architecture of the microgels, water crystallization is avoided in concentrated samples, allowing us to monitor atomic dynamics at low temperatures. By elastic incoherent neutron scattering and molecular dynamics simulations, we find that a dynamical transition occurs at a temperature $T_d\sim250$~K, independently from PNIPAM mass fraction. However, the transition is smeared out on approaching dry conditions. The quantitative agreement between experiments and simulations provides evidence that the transition occurs simultaneously for PNIPAM and water dynamics. The similarity of these results with hydrated protein powders suggests that the dynamical transition is a generic feature in complex macromolecular systems, independently from their biological function

Estratégia Empresarial : Formato de la Estratégia

La estrategia empresarial es uno de los campos de estudio que mayor interés ha despertado en el mundo académico y de los negocios. Articula las potencialidades de la empresa, mediante la acción coordinada y complementaria de sus componentes. En el presente trabajo se analiza los aspectos relevantes que intervienen en la formación de la estrategia para fortalecer la posición de una empresa, mediante este análisis se pretende entender que aspectos son considerados al momento de plantear una estrategia que contribuya al logro de los objetivos organizacionales. La formación de la estrategia denominada como planeación estratégica, se enfoca desde un principio en el desarrollo de la misión visión, estas implican resolver una serie de “cómos”: cómo hacer crecer el negocio, satisfacer a los clientes, ser mejores que los rivales y responder ante las condiciones cambiantes del mercado. En la formación de la estrategia se encuentra la escuela de pensamiento la cual está compuesta por diferentes escuelas propuestas por Henry Mintzberg, esta brinda aportaciones teóricas que muestran el papel central del medio ambiente externo a las organizaciones en el diseño de la estrategia principal. La formación de la estrategia toma en cuenta las decisiones de estrategia funcional, la estrategia funcional ampara las necesidades y propósitos del área funcional en relación con el cumplimiento de sus metas y objetivos. La estrategia corporativa define los negocios a los cuales la compañía se dedica, las oportunidades y amenazas que surgirán en el entorno y los objetivos de crecimiento que será preciso alcanzar. También maneja líneas de productos en base a factores: factores de crecimiento de mercado y participación del mercado. La metodología utilizada en la presente investigación, es la investigación documental, esta metodología genera un conocimiento valido y confiable para otras investigaciones que podrían llevarse a cabo dentro del área de administración estratégica

Anti-inflammatory and antioxidant properties of HDLs are impaired in type 2 diabetes.

ObjectiveIn mice, 4F, an apolipoprotein A-I mimetic peptide that restores HDL function, prevents diabetes-induced atherosclerosis. We sought to determine whether HDL function is impaired in type 2 diabetic (T2D) patients and whether 4F treatment improves HDL function in T2D patient plasma in vitro.Research design and methodsHDL anti-inflammatory function was determined in 93 T2D patients and 31 control subjects as the ability of test HDLs to inhibit LDL-induced monocyte chemotactic activity in human aortic endothelial cell monolayers. The HDL antioxidant properties were measured using a cell-free assay that uses dichlorofluorescein diacetate. Oxidized fatty acids in HDLs were measured by liquid chromatography-tandem mass spectrometry. In subgroups of patients and control subjects, the HDL inflammatory index was repeated after incubation with L-4F.ResultsThe HDL inflammatory index was 1.42 ± 0.29 in T2D patients and 0.70 ± 0.19 in control subjects (P < 0.001). The cell-free assay was impaired in T2D patients compared with control subjects (2.03 ± 1.35 vs. 1.60 ± 0.80, P < 0.05), and also HDL intrinsic oxidation (cell-free assay without LDL) was higher in T2D patients (1,708 ± 739 vs. 1,233 ± 601 relative fluorescence units, P < 0.001). All measured oxidized fatty acids were significantly higher in the HDLs of T2D patients. There was a significant correlation between the cell-free assay values and the content of oxidized fatty acids in HDL fractions. L-4F treatment restored the HDL inflammatory index in diabetic plasma samples (from 1.26 ± 0.17 to 0.71 ± 0.11, P < 0.001) and marginally affected it in healthy subjects (from 0.81 ± 0.16 to 0.66 ± 0.10, P < 0.05).ConclusionsIn patients with T2D, the content of oxidized fatty acids is increased and the anti-inflammatory and antioxidant activities of HDLs are impaired

EFFECTS OF OXIDISED LDL ON NITRIC OXIDE AND ENDOTHELIN-1 PRODUCTION IN HUMAN MICROVASCULAR ENDOTHELIUM: ROLE OF THROMBOXANE A2 RECEPTOR

LDL particles modulate the release of NO and endothelin-1 by the endothelium. To what extent these effects depend on LDL concentration and degree of oxidation and eventually what is the role of tromboxane A2 receptor is unknown. HMEC-1 were exposed for 24-h to a) 3 concentrations (50, 100 and 200 ?g/ml) of either native, low- or medium-oxidised LDL, b) 8-epi-PGF2? (F2?IP, 10-11, 10-10, 10-9, and 10-8 M) either alone or with TXA2 receptor blocker SQ 29.548 (10-6 M), c) native, low- and medium-oxidised LDL either alone or with SQ 29.548 (10-6 M). In all experiments intracellular eNOS, and NO2/NO3, endothelin-1 and interleukin-6 concentration in the medium were measured. Both native and oxidised LDL induced a NO2/NO3 accumulation with dose and degree of oxidation acting synergistically; eNOS was stimulated only by oxidised LDL. F2?IP, NO2/NO3 and eNOS with SQ 29.548 completely preventing these effects but only partially the effect of LDL. IL-6 was also synergistically stimulated by LDL dose and degree of oxidation but not by direct exposure to F2?IP nor was affected by SQ 29.548. Both native and oxidised LDL stimulated endothelin-1 production independently of dose or degree of oxidation. F2?IP had a modest stimulatory effect while the effect of SQ 29.548 was evident only with oxidised LDL. In HMEC-1 LDL dose and degree of oxidation synergistically stimulate NO and IL-6 production and the effect on NO is largely mediated through the TXA2 receptor. LDL simultaneously facilitate endothelin-1 production independently of the dose and degree of oxidation

Bidirectional hebbian plasticity induced by low-frequency stimulationin basal dendrites of rat barrel cortex layer 5 pyramidal neurons

According to Hebb’s original hypothesis (Hebb,1949), synapses are reinforced when presynaptic activity triggers postsynaptic firing, resulting in long-term potentiation (LTP) of synaptic efficacy. Long-term depression (LTD) is a use-dependent decrease in synaptic strength that is thought to be due to synaptic in put causing a weak postsynaptic effect. Although the mechanisms that mediate long-term synaptic plasticity have been investigated for at least three decades not all question have as yet been answered. Therefore, we aimed at determining the mechanisms that generate LTP or LTD with the simplest possible protocol Low-frequency stimulation of basal dendrite inputs in Layer 5 pyramidal neurons of the rat barrel cortex induces LTP. This stimulation triggered an EPSP, an action potential (AP) burst, and a Ca2+ spike. The same stimulation induced LTD following manipulations that reduced the Ca2+ spike and Ca2+ signal or the AP burst. Low-frequency whisker deflections induced similar bidirectional plasticity of action potential evoked responses in anesthetized rats. These results suggest that both in vitro and in vivo similar mechanisms regulate the balance between LTP and LTD. This simple induction form of bidirectional hebbian plasticity could be present in the natural conditions to regulate the detection, flow, and storage of sensorimotor informationWork supported by “Ministerio de Ciencia y Tecnología y Ministerio de Ciencia e Innovación” grants (BFU2005-07486, BFU2008-03488, SAF2009-10339, BFU2011-23522, BFU2012-36107, BFU2013-43668-P and BFU2016-80802-P) and a “Comunidad Autónoma de Madrid” (GR/SAL/0877/2004) grant. Dr .D. Fernández de Sevilla was a post doctoral fellow at the “Instituto Cajal,” funded by GR/SAL/0877/2004 and a “Ministerio de Ciencia and Tecnología” grant (BFU2005-07486).He was subsequently supported by a Ramón y Cajal Contract and is now a Professor at the “Departamento de Anatomía, Histología y Neurociencia, Facultad de Medicina, Universidad Autónoma de Madrid.” Dr. Andrea Diez was a doctoral fellow funded by the BFU2011-23522 grant and is now a post doctoral fellow funded by “Ministerio de Ciencia e Innovación” grant (BFU2013- 43741-P) at the “Departamento de Anatomía, Histología y Neurociencia, Facultad de Medicina, Universidad Autónoma de Madrid.” N. Barros-Zulaica was a doctoral fellow funded by the BFU2012-36107 gran