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The L-PBF AlSi10Mg alloy is widely used in the production of structural parts in the transportation sector. However, the high stresses caused by the severe operating conditions require an optimal combination of mechanical and tribological properties. This paper reports on the effect of optimized T5 heat treatment (direct artificial aging: 4 h at 160 °C) and novel T6 heat treatment (rapid solution: 10 min at 510 °C, followed by artificial aging: 6 h at 160 °C) on the tribological behavior of the L-PBF AlSi10Mg alloy. Dry sliding tests (ball-on-disk) were carried out using AlSi10Mg samples as rotating disks against an Al2O3 stationary ball. The optimized T5 led to the formation of a stable protective oxide layer well adherent on the worn surface, increasing the wear resistance of the alloy. In addition, the novel T6 improved wear resistance compared to conventional T6 due to microstructural refinement induced by shorter solutionizing. The sub-surface analysis of the wear tracks highlighted the higher cohesion between the more homogeneous and finer Si particles and the α-Al matrix, as well as the improved load-bearing support compared to the coarser microstructure induced by conventional T6. Therefore, the new T6 could be the optimal solution for high-performance components.

The objectives of this review are to explore the neuronal pathways and cellular and molecular mechanisms involved in both healthy and impaired cognitive function and to discuss the role of nootropics, in particular, those with cholinergic activity, as promising interventions to preserve and/or improve cognitive performance in patients in the symptomatic pre-dementia stage, known as mild cognitive impairment (MCI).Papers were retrieved by a PubMed search, using different combinations of keywords (e.g., cognitive function AND aging AND nootropics), without limitations in terms of publication date or language.Nootropics modulate the activities of specific brain pathways involving neurotransmitters and neuromodulators that have distinct roles in the cognitive processes. The nootropic L-a-glyceryl-phosphoryl-ethanolamine (L-a GPE), by virtue of its action as a phospholipid (PL) precursor and acetylcholine (Ach) donor, targets neural stem cell aging, cholinergic depletion, oxidative stress and microglia activation, loss of entorhinal cortex neurons, and reduced hippocampal volume. Cognitive reserve levels may be linked to the resilience and adaptability of the brain to cope with age-related cognitive decline. L-a GPE may contribute to cognitive reserve preservation via its neuronal well-being promoting action.The substantial burden of age-related cognitive decline demands effective long-term and well-tolerated interventions aimed at maximizing the span of effective functioning. The use of inappropriate medication may lower cognitive reserve, thus hastening the onset of symptomatic AD, while the use of nootropics, such as L-a GPE may contribute to cognitive reserve preservation via its neuronal well-being promoting action.

Medical treatment of neuroendocrine tumours (NETs) has drawn a lot of attention due to the recent demonstration of efficacy of several drugs on progression-free survival, including somatostatin analogs, small tyrosine kinase inhibitors and mTOR inhibitors (or rapalogs). The latter are approved as therapeutic agents in advanced pancreatic NETs and have been demonstrated to be effective in different types of NETs, with variable efficacy due to the development of resistance to treatment. Early detection of patients that may benefit from rapalogs treatment is of paramount importance in order to select the better treatment and avoid ineffective and expensive treatments. Predictive markers for therapeutic response are under intensive investigation, aiming at a tailored patient management and more appropriate resource utilization. This review summarizes the available data on the tissue, circulating and imaging markers that are potentially predictive of rapalog efficacy in NETs.

Bone represents a common site of metastases for several solid tumors. However, the ability of neuroendocrine neoplasms (NENs) to localize to bone has always been considered a rare and late event. Thanks to the improvement of therapeutic options, which results in longer survival, and of imaging techniques, particularly after the introduction of positron emission tomography (PET) with gallium peptides, the diagnosis of bone metastases (BMs) in NENs is increasing. The onset of BMs can be associated with severe skeletal complications that impair the patient’s quality of life. Moreover, BMs negatively affect the prognosis of NEN patients, bringing out the lack of curative treatment options for advanced NENs. The current knowledge on BMs in gastro-entero-pancreatic (GEP) and bronchopulmonary (BP) NENs is still scant and is derived from a few retrospective studies and case reports. This review aims to perform a critical analysis of the evidence regarding the role of BMs in GEP- and BP-NENs, focusing on the molecular mechanisms underlining the development of BMs, as well as clinical presentation, diagnosis, and treatment of BMs, in an attempt to provide suggestions that can be used in clinical practice.

preliminary evaluation of different dose reduction algorithms in abdominal Computed Tomography Angiography (CTA) with standard scan protocols at 120kV vs. 80kV.prospective, randomized, crossover study. 60 consecutive patients who underwent CTA of the abdomen (Sensation 64, Siemens; Iomeprol 400 mgl/ml Bracco) for suspected or diagnosed Abdominal Aortic Aneurysm (AAA) were enrolled in the study. A standard 120kV/200mAs scan protocol was acquired in all patients (reference tube current modulated with Automatic Exposure Control). In each patient a second scan with 80kV/300mAs (Group 1; n. 20), 80kV/400mAs (Group 2; n. 20), 80kV/500mAs (Group 3; n. 20) was acquired. We used the same scan/reconstruction parameters with the same amount and kind of contrast medium. The radiation dose, the aortic attenuation values, the noise and the signal/noise ratio (S/N) were evaluated.the mean dose was 9.7±2.7mSv for 120kV (all patients), 3.6±0.8mSv in Group1 (80kV), 5.0±0.6mSv in Group 2 (80kV) and 5.9±1.2mSv in Group 3 (80kV), respectively. The aortic attenuation was 350±59HU (120kV) vs. 534±100HU (80kV), 12±3.5 (120kV) vs. 8.8±3.6 (80kV) for the whole population. Aortic attenuation and S/N were: 328±40HU (120kV) vs. 494±61HU (80kV), 11±2 (120kV) vs. 7±2 (80kV) in Group1; 353±77HU (120kV) vs. 551±117HU (80kV), 11±2.8HU (120kV) vs. 8.4±2.6 (80kV) in Group 2; 389±55HU (120kV) vs. 598±117HU (80kV), 15±5 (120kV) vs. 12±5 (80kV) in Group 3, respectively (plt;0.05).in abdominal CTA, the 80kV/400mAs scan protocol allows a radiation dose reduction of 50% without a significant reduction of S/N ratio.

The ideals of science as objectivity and consensus are - unsurprisingly - not so easy to attain in scientific practice. Science is ultimately a product of individual scientists with their own personal backgrounds and experiences, and there is no unique methodology to de-personalize and objectify knowledge. Social scientists, in particular, use a variety of tools for their investigations: They gather evidence from different sources, under different conditions and with different instruments. They are both the locus where different sources of evidence aggregate and also a direct source of evidence that comes in as intuitions and background knowledge. Acknowledging this wide variety of sources of evidence and methods in social science, different kinds of methodologies for reaching consensus have been developed. What kind of consensus is indicative of good science? What are the rules for consensus formation? And, is there a normative aspect to the formation of scientific and policy making consensus? TThe contributions of this book focus on experts: those institutional figures that act as a liaison between science and policy makers, politicians, governments, and other public domains.

AIM The aim of our controlled retrospective study was to assess the diagnostic value of sonography for detection and characterisation of changes compared to mammography and palpation. METHOD In 80 patients sonographic and clinical follow-up examinations were performed every 3 to 6 months, mammography examinations were performed every 6 to 12 months during the first 2 years after breast-preserving therapy (BPT) and irradiation. Extension, echogenicity, and configuration of lesions in sonography, and semiquantitiative description of diffuse or circumscribed changes in mammography were the basis of comparative follow-up observation. RESULTS Postoperative seromas and haematomas, initially presenting echo-free or as hypoechoic lesions, showed an increase in echogenicity within 18 months after irradiation. Fat necrosis occurred in 9.5% of patients, lymph cysts developed in 4%, granuloma in 3%, recurrence of neoplasma in 1.6%. The diffuse loss of transparency in mammography that was associated with radiation therapy, showed a peak 6-12 months after irradiation. CONCLUSION Sonography and sonographic guided puncture are mandatory tools to characterise circumscribed unclear lesions after breast-conserving therapy and irradiation in specialised centers. We recommend a 6-month interval for combined sonography, palpation, and mammography within the first 2 years after BPT and irradiation, because shorter control intervals did not result in relevant diagnostic advantages.

BACKROUND: Late effects after radiotherapy in childhood and adolescence have mainly been characterized retrospectively with small patient numbers. Therefore the German Group of Pediatric Radiation Oncology (APRO) established the " Reg Ister for the evaluation of late Side effects after radiation in Childhood and adolescence” (RiSK). After a pilot phase starting in 2001 documentation has been performed all over Germany since 2004. This analysis shows the first results of “RiSK”. PATIENTS AND METHODS: Radiation parameters including detailed organ doses as well as toxicity evaluations were collected prospectively from centers all over Germany in the study center. Standardized documentation forms were used. Documentation is planned for all children who receive radiotherapy in one of the German pediatric therapy trials. RESULTS: Until December 31st 2006, 696 documentations of radiotherapy and 526 acute as well as 836 late follow-up documentation forms have been collected. Altogether, 41 patients with late grade 3 and 16 patients with late grade 4-side effects were identified. Side effects mainly concerned joints with functional impairment (after combined radiotherapy and surgery), the bowel, skin and subcutis as well as blood parameters under continued chemotherapy. Patients with late side effects of a higher grade were mainly treated for Ewing's or soft tissue sarcomas (n=235 patients), representing 33.8% of all patients in this study. CONCLUSION: Fortunately, up to now only a few late grade 3 or 4 side effects of radiotherapy are shown for almost 700 documented patients. For further results, especially for the characterization of dose-effect-relationships, this study has to be continued with a higher patient number and a longer follow-up.

We report the results of a prospective Italian multi-center study of the effects of lanreotide, a slow-release somatostatin analog, on left ventricular morphology and function and on the prevalence of ventricular arrhythmic events in 19 patients with active, newly diagnosed, uncomplicated acromegaly. Cardiac features were evaluated with Doppler-echocardiography and 24-h Holter ECG monitoring at baseline and after 6 months of lanreotide therapy. Fifteen patients (78.9%) had left ventricular hypertrophy. Lanreotide treatment significantly decreased the left ventricular mass (127.8+/-6.9 vs 140.7+/-7.1 g/m2, p0.001) and left ventricular hypertrophy significantly disappeared in 6 of these patients. Treatment did not significantly affect systolic function, whereas it increased the Doppler-derived early-to-late mitral flow velocity, (E/A) ratio, of early-to-late trans-mitral flow velocity (1.34+/-0.1 vs 1.09+/-0.06, p=0.001). Stroke volume was slightly but not significantly increased after treatment, whereas systolic BP was significantly higher (134+/-14 vs 129+/-13 mmHg, p0.05). The 24-h mean heart rate was significantly reduced after treatment (66.5+/-11 vs 71.5+/-20 beats/min, p0.05). Supra-ventricular premature beats (50/24 h) occurred in 16.6% of patients and were unaffected by treatment. Differently, ventricular premature beats (50/24 h) occurred in 33.3% of patients before treatment vs 16.5%, after treatment. In conclusion, lanreotide reduced the left ventricular mass, and improved ventricular filling and ventricular arrhythmic profile.

Coronary artery disease (CAD) is one of the leading causes of death in developed countries. Recent literature confirmed multi detector computed tomography (MDCT) as a noninvasive imaging technique able to rule out and rule in CAD with a very high accuracy compared with Conventional Coronary Angiography (CCA). However the plaque burden and stenosis severity on MDCT is usually visually assessed with sequent inherent limitations. Recent technologies have permitted a real quantitative assessment of CAD.

Recently, a small molecule (Q94) was reported to selectively block PAR(1) /Gα(q) interaction and signalling. Here, we describe the pharmacological properties of Q94 and two analogues that share its benzimidazole scaffold (Q109, Q89). Q109 presents a modest variation from Q94 in the substituent group at the 2-position, while Q89 has quite different groups at the 1- and 2-positions.Using human microvascular endothelial cells, we examined intracellular Ca(2+) mobilization and inositol 1,4,5-trisphosphate accumulation as well as isoprenaline- or forskolin-stimulated cAMP production in response to thrombin.Q89 (10 µM) produced a leftward shift in the thrombin-mediated intracellular Ca(2+) mobilization concentration-response curve while having no effect on the E(max) . Both Q94 (10 µM) and Q109 (10 µM) reduced intracellular Ca(2+) mobilization, leading to a decrease in E(max) and an increase in EC(50) values. Experiments utilizing receptor-specific activating peptides confirmed that Q94 and Q109 were selective for PAR(1) as they did not alter the Ca(2+) response mediated by a PAR(2) activating peptide. Consistent with our Ca(2+) results, micromolar concentrations of either Q94 or Q109 significantly reduced thrombin-induced inositol 1,4,5-trisphosphate production. Neither Q94 nor Q109 diminished the inhibitory effects of thrombin on cAMP production, indicating they inhibit signalling selectively through the G(q) pathway. Our results also suggest the 1,2-disubstituted benzimidazole derivatives act as 'allosteric agonists' of PAR(1) .The Q94 and Q109 benzimidazole derivatives represent a novel scaffold for the development of new PAR(1) inhibitors and provide a starting point to develop dual signalling pathway-selective positive/negative modulators of PAR(1) .

Purpose. This study compared cardiac computed tomography (CT) and two-dimensional transthoracic echocardiography (ECC) for assessing left ventricular ejection fraction (LVEF) using real-world data from a large patient population. Materials and methods. We studied 450 patients (284 males; mean age 64 +/- 12 years; range 12-88) who underwent CT and ECC due to suspected coronary artery disease. For CT, we used multiphase short-axis reconstructions and evaluated them with a dedicated software tool that uses Simpson's rule to compute LV volumes. For ECC, computation was based on the biplane Simpson's method. Results in terms of EF were compared with the paired Student's t test, Pearson's correlation coefficient (r), and Bland-Altman analysis. Results. EF was 52%+/- 15% for CT and 55%+/- 13% for ECC. Statistically significant differences, albeit with correlation, were observed between the measurements (r=0.71; p50% and overestimated in those with EF 35%-50% and

To investigate whether transferrin receptor (CD71) expression is affected by acute HIV-1 infection, three different lymphoid cell lines (MT-4, SUPT-1, H9) were infected with HIV-1 and tested for surface CD71 expression after different incubation periods depending on cell survival after infection. We found that expression of surface CD71 was lower in cells infected with HIV-1 than in uninfected controls: the timing and extent of this down-modulation depended apparently on the different susceptibility of the cell lines to HIV-1 infection and cytopathogenicity. Citrate, a molecule capable of chelating iron, dose-dependently prevented down-modulation of surface CD71 in HIV-1 infected cells as well as viral cytopathic effects. We conclude that (i) expression of surface transferrin receptors is down-modulated by acute HIV-1 infection in T lymphoid cells, that (ii) this cell phenotypic modulation is associated with the cytopathic effects of the virus, and that (iii) these phenomena are modulated by iron chelation. These results support the view that iron metabolism may be an important area for interaction between HIV-1 and human cells.

To compare image quality of iterative reconstruction algorithm(IRIS) vs. standard filtered back projection(FBP) reconstruction in CT Coronary Angiography (CTCA).Thirty-four consecutive patients underwent CTCA for suspected or known CAD with Dual-Source CT (DSCT-Flash, Siemens). All datasets were reconstructed with 0.75/0.4 and 0.6/0.4 mm slice thickness/increment, using three standard FBP kernels (B26-B30-B46) and three comparable IRIS algorithms (I26-I30-I46). Vascular attenuation and noise were measured. CT vascular attenuation values [HU] were measured in: ascending aorta (Ao), right (RCA) and left (LCA) coronary artery, respectively. Signal-to-noise (SNR) and contrast-to-noise (CNR) ratio were calculated. A p-valuelt;0.05 was considered significant.There was no significant difference between the vascular attenuation values measured with FBP (Ao:458HU, RCA:448HU, LAD:444HU) and IRIS (Ao:456HU, RCA:446HU, LAD:442HU). Difference in noise was significant between FBP (24±SD) and IRIS (19±SD) (r=0.34;plt;0.05). Lowest noise was found for IRIS using 0.6 mm (17HU). IRIS provided a SNR and CNR significantly higher with increasing kernel sharpness. SNR was 33.3±25.1, 77.3±51.7, 37.2±36.6, 64.4±59.2, while CNR was 25.32±19.8, 58.0±36.0, 28.6±23.5, 47.6±47.3 for 0.75B, 0.75I, 0.6B and 0.6I, respectively. IRIS showed an improvement in SNR of 57% and 56% for 0.75 mm and 0.6 mm, respectively, and an improvement in CNR of 42% and 40% for 0.75 mm and 0.6 mm.In CTCA, iterative reconstructions provide a significant higher image quality compared with the conventional FBP reconstructions. (www.actabiomedica.it).

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