ObjectiveTo describe demographic and hormonal characteristics, comorbidities (diabetes mellitus and hypertension), therapeutic procedures and their effectiveness, as well as predictors of morbidity ...and mortality in a nationwide survey of Italian acromegalic patients.DesignRetrospective multicenter epidemiological study endorsed by the Italian Society of Endocrinology and performed in 24 tertiary referral Italian centers. The mean follow-up time was 120 months.ResultsA total of 1512 patients, 41% male, mean age: 45±13 years, mean GH: 31±37 μg/l, IGF1: 744±318 ng/ml, were included. Diabetes mellitus was reported in 16% of cases and hypertension in 33%. Older age and higher IGF1 levels at diagnosis were significant predictors of diabetes and hypertension. At the last follow-up, 65% of patients had a controlled disease, of whom 55% were off medical therapy. Observed deaths were 61, with a standardized mortality ratio of 1.13 95% (confidence interval (CI): 0.87–1.46). Mortality was significantly higher in the patients with persistently active disease (1.93; 95% CI: 1.34–2.70). Main causes of death were vascular diseases and malignancies with similar prevalence. A multivariate analysis showed that older age, higher GH at the last follow-up, higher IGF1 levels at diagnosis, malignancy, and radiotherapy were independent predictors of mortality.ConclusionsPretreatment IGF1 levels are important predictors of morbidity and mortality in acromegaly. The full hormonal control of the disease, nowadays reached in the majority of patients with modern management, reduces greatly the disease-related mortality.
During the last years we have carried out a renewal of the Building Management System (BMS) software of our data center with the aim of improving the data collection capability. Considering the ...complex physical distribution of the technical plants and the limits of the actual building hosting our center, a system that simply monitors and collects all the necessary information and provides alarms only in case of major failures has proven to be unsatisfactory. In 2017 we suffered a major flood due to one main water pipeline failure in the public street. After this disastrous event, clearly far beyond our control, we were however forced to reconsider completely the physical site robustness of our building in addition to the current monitoring and alarm system capabilities. It was clear that in some specific cases, alerts should be triggered hours or days before the actual main problem arises in order to allow efficient human intervention and proper escalation process. This paradigm could be easily applied to almost all the infrastructure components in our site, mainly the electric power distribution and continuity systems as well as the whole cooling devices. For this reason, in parallel to a consistent increase in the sensor widespread distribution of our BMS data collector system, a study of a predictive maintenance approach applicability to our site has been started. Predictive maintenance techniques aims at prevent unexpected infrastructure components failures or major events with the study of the whole monitoring data collection and the creation of appropriate statistical models with the help of big data analysis and machine learning techniques. An improvement in the Power Distribution Units (PDUs) monitoring in our site and the introduction of a dedicated network of water leak sensors were the first steps for increasing the data collection information at our disposal. With sufficient monitoring statistical information stored in our BMS system a preliminary and exploratory predictive data analysis proof of concept could be constructed. This could lead to the model building phase and the creation of a prototype with the aim of forecasting future infrastructure main failure events and forthcoming error conditions. The general idea is, conceivably, an approach to the predictive maintenance model where it would be possible to introduce scheduled corrective actions for the purpose of preventing potential failures in the next future and increasing the site overall reliability.
The electroluminescence (EL) of isotactic and syndiotactic poly(N-pentenyl-carbazole) (PPK), achieved by coordination polymerization, is studied in order to investigate the interrelation between the ...polymer tacticity and their physical-chemical properties. The use of these polymers in organic light-emitting diode (OLED) fabrication is also explored. Thermal and x-ray diffraction analyses of PPKs show that the isotactic stereoisomer is semicrystalline, whereas the syndiotactic one is amorphous. Optical analysis of both stereoisomers, carried out on film samples, reveals the presence of two different excimers: 'sandwich-like' and 'partially overlapping'. Nevertheless, the emission intensity ratio between 'sandwich-like' and 'partially overlapping' excimers is higher in the isotactic than in the syndiotactic stereoisomer. Using the synthesized polymers as OLED emitting layers, the influence of the polymer tacticity on the EL properties of the device is highlighted. In detail, while blue OLEDs are obtained by using the syndiotactic stereoisomer, OLEDs with a multilayer structure fabricated with the isotactic stereoisomer emit white light. The contribution of three different emissions (fluorescence, phosphorescence and electromer emissions) with comparable intensities to the detected white light is discussed.
A class of novel pyran based chromophores has been synthesized and characterized for what concerns their optical and electrochemical properties. The electronic structures were investigated in details ...by means of DFT theoretical computations. The molecular structures of the chromophores are based on a pyran core, functionalized with different electron acceptor groups, symmetrically linked to phenothiazine electron donor moieties. The dyes have different optical absorption properties, affording a set of colors ranging from orange to blue, covering most of the visible spectral region and they are characterized by high molar extinction coefficient, up to a value of 6.4·104 cm−1 M−1. The dyes were used as photosensitizers in DSSC and the photovoltaic characterization of these devices was performed under simulated solar radiation. A maximum efficiency of 2.82% has been achieved. The most promising device underwent an accelerated ageing test, performed at 85 °C for 50 days: no variation of the main electrical parameters of the DSSC was observed during the test, indicating an excellent stability for devices based on this class of photosensitizers.
Excellent time stability of DSSC based on pyran derivatives. Display omitted
•We synthesized three novel pyran based metal free photosensitizers for DSSC.•Dyes show colors ranging from orange to blue, covering the most of visible spectrum.•The electronic structure of the dyes were investigated at DFT level.•DSSC based on the reported chromophores show power conversion efficiency up to 2.8%.•Excellent device time stability determined by an accelerated aging test.
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•We synthesized four nobel metal free photosensitizers for DSSC.•Dyes are based on a pyran acceptor core symmetrically linked to carbazole donor groups.•Dyes show colors ranging from ...orange to blue, covering the most of visible spectrum.•The electronic structure of the dyes were investigated at DFT level.•DSSC based on the reported chromophores show power conversion efficiency up to 1.9%.
Four nobel metal free dyes for application as photosensitizers in DSSC have been synthesized and their chemical–physical properties characterized by UV–vis absorption spectroscopy, cyclic voltammetry and DFT theoretical computations. The dyes are based on a pyran core, functionalized with different electron acceptor groups, symmetrically linked to carbazole electron donor mojeties. The four dyes have different optical absorption properties, affording a range of colors ranging from orange to blue, covering most of the visible spectral region. All the dyes feature high molar extinction coefficient, up to a value of 1.0×105Lmol−1cm−1. The dyes were used as photosensitizers in DSSC and the photovoltaic characterization of these devices was performed under simulated solar radiation. The cell performance is higher for chromophores featuring higher LUMO energies as a consequence of a better electron injection in TiO2 oxide. A maximum power conversion efficiency of 1.9% has been achieved.
The reduction in resting metabolic rate (RMR) during weight loss exceeds that accounted for by changes in body composition by 15%, suggesting that factors other than fat-free mass (FFM) explain the ...metabolic adaptation during food restriction in obesity. Our study aimed to establish if changes in the sympathoadrenal system activity, as inferred from an integrated measure such as 24 h urinary excretion of catecholamines, may play a role in the RMR adaptation observed during dietary restriction in obese patients. Ninety-three obese female subjects consumed a low-energy diet (LED) (2930 kJ/d (700 kcal/d)) for a 3-week period. At the beginning and at the end of the study, 24 h urinary excretion of catecholamines, FFM and RMR were measured. The LED induced a significant reduction in body weight (-3·3 (SEM 0·4) KG; P < 0·01), FFM (-1·9 (sem 0·7) kg; P < 0·01) and in the fat mass (-1·2 (sem 0·5) kg; P < 0·01). Noradrenalin excretion (24 h) decreased during the LED from 264 (sem 26) during a weight-maintenance period to 171 (sem 19) nmol/24 h after consumption of the LED for 3 weeks (P < 0·001); mean 24 h adrenalin excretion did not change during the LED (22 (sem 3) during the weight-maintenance period v. 21 (sem 3) nmol/24 h after consumption of the LED for 3 weeks; NS). The LED induced a significant decrease in RMR (7300 (sem 218) v. 6831 (sem 138) kJ/24 h; P < 0·001). The only independent variable that significantly explained variations in RMR both before and after consumption of the LED for 3 weeks, was FFM (r2 0·79 and r2 0·80 respectively). Urinary noradrenalin excretion explained a further 4 % of the variability in RMR, but only before the diet, so that a role of sympathoadrenal system on RMR seems to be present in obese patients in basal conditions but not at the end of the LED.
Porcine organs are rapidly rejected after transplantation into primate recipients due to the presence of preexisting immunoglobulins that bind to terminal galactose α1,3 galactose residues ...(α-galactosyl) present on porcine glycoproteins and glycolipids. Currently available immunosuppressive reagents have been largely ineffective at controlling the synthesis of these anti-Gal antibodies. Nonantigenic hapten polymers have been shown to be effective materials for blocking humoral immune responses in various model systems. We have developed a series of α-galactosyl glycoconjugate polymers and tested their ability to block anti-Gal antibody binding in vitro and in vivo. A galactose α1,3 galactose β 1,4 GlcNAc trisaccharide free acid (TRFA) with a hexanoic acid spacer, containing five methylene groups and a carboxylic acid, was produced and coupled to a variety of polymeric backbones including dextran, branched poly(ethylene glycol) (PEG), and poly-l-lysine. The ability of monomeric TRFA and the α-galactosyl conjugates to block anti-Gal IgG and IgM binding was determined using a competition ELISA assay on defined HSA−Gal glycoconjugates and porcine microvascular endothelial cell substrates. We show that branched PEG carriers, with a TRFA sugar attached to each branch, exhibit enhanced antibody blocking ability compared to TRFA, but at higher target antigen densities these simple PEG conjugates are no more effective then an equivalent amount of TRFA in blocking anti-Gal IgM antibody interactions. In contrast, polymers of the branched PEG conjugates and linear conjugates made using dextran and poly-l-lysine were 2000 to 70000-fold more effective inhibitors of anti-Gal antibodies. In a study using nonhuman primates, a single dose infusion of polymeric PEG or dextran glycoconjugates dramatically reduced the level of circulating anti-Gal antibodies in cynomologus monkeys for at least 72 h. Glycoconjugates similar to these might be useful both to block anti-Gal interactions in vivo and to specifically control the induced anti-Gal immune response.
A Golgi preparation from Spodoptera frugiperda (IPLB-SF-21AE) cells was incubated in the presence of the mannosidase II inhibitor, swainsonine, with the oligosaccharide, M(alpha 1,3)M(alpha ...1,3)M(alpha 1,6)M(alpha 1,6) M(beta 1,4)Gn(beta 1,4)Gn (M5Gn2), the preferred substrate for the enzyme, UDP-N-acetylglucosamine:alpha-3-D-mannoside beta 1,2-N-acetylglucosaminyltransferase I (Gn-TI). This resulted in formation of the product, Gn(beta 1,2)M(alpha 1,3)M(alpha 1,3)M(alpha 1,6)M(alpha 1,6)- M(beta 1,4) Gn(beta 1,4)Gn (Gn(I)M5Gn2). A significantly increased (> 4-fold) rate of conversion of M5Gn2 to Gn(I)M5Gn2 occurred with insect cell-derived Golgi preparations that had been infected with a recombinant baculovirus for 66 h, a time at which significant amounts of complex-type oligosaccharides were assembled on a heterologous protein, human plasminogen, expressed in this system. Coupled with previous results (Davidson, D.J., Bretthauer, R.K., and Castellino, F.J. (1991) Biochemistry 30, 9811-9815) that demonstrated the occurrence of virally induced activation of a specific M6-mannosidase in IPLB-SF-21AE cells, it is clear that viral infection of lepidopteran insect cells makes available enzymes that provide and utilize the substrate, M5Gn2-protein. This is a key feature in the explanation of the previous original observations made by this laboratory, that lepidopteran insect cells are capable of assembly of complex-type oligosaccharides on glycoproteins.
Gal alpha 1,3 Gal is thought to be the major antigenic epitope present on pig tissues to which XNAs bind. Removal of antibodies directed against that structure may be critical to the success of pig ...to human xeno-transplantation. As a first step toward the development of ligands capable of removing XNAs, we have used a phage-displayed peptide library to identify a six-amino-acid peptide that binds to the lectin GS-1-B4 (which binds the carbohydrate Gal alpha 1,3 Gal). This peptide blocks the binding of GS-1-B4 to pig aortic endothelial cells. The carbohydrate Gal alpha 1,3 Gal competes with the binding of GS-1-B4 to the peptide, suggesting that they may bind the same site. Using a RBC agglutination assay, we show that this peptide inhibits the agglutination of pig RBCs by heat-inactivated human serum at concentrations similar to that of Gal alpha 1,3 Gal.
It has been shown that steroid hormones are able to influence the sympathoadrenal system activity. Therefore, we have investigated in a double blind cross-over study the effect of percutaneous ...estradiol administration (100 micrograms) on the sympathoadrenal and cardiovascular responses to mental arithmetic stress in 20 normal young males. The plasma estradiol level was 154 +/- 14 pmol/L during the estrogen session (ES) and 44 +/- 7 pmol/L during the placebo session (PL; P < 0.001). The mental stress induced a significant increase in systolic blood pressure during both the PL (F = 7.2; P < 0.001) and the ES (F = 4.8; P < 0.01); the peak obtained during PL was, however, higher than that during ES (128 +/- 2 vs. 122 +/- 3 mm Hg; P < 0.02). A significant increase in pulse rate was observed during PL (F = 4.2; P < 0.002), but not during ES (F = 2.6; P = 0.47), with the peak pulse rate being higher during mental stress in the PL than the ES (78 +/- 2 vs. 74 +/- 2 beats/min; P < 0.03). In response to the mental stress, plasma epinephrine increased significantly during PL (F = 3.2; P < 0.03), but not during ES (F = 1.1; P = 0.3). The stress-induced peak in plasma epinephrine during PL was higher than that during ES when expressed as the absolute value or the incremental peak (513 +/- 103 vs. 125 +/- 32 pmol/L; P < 0.005). The incremental peak in plasma norepinephrine obtained during PL was higher than that during ES (0.78 +/- 0.1 vs. 0.27 +/- 0.07 nmol/L; P < 0.02). Plasma free fatty acid, acetoacetate, and 3-hydroxybutyrate increased significantly from basal values during PL, but not during ES. These data show that mildly elevated levels of estradiol are able to influence the response of the adrenal medulla to mental stress in men.
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