Inscriptions of Sanationes from Sanctuaries of god Asclepius. Miraculous recoveries of rheuma diseases

Inscriptions of Sanationes from Sanctuaries of god Asclepius, testifying to the gratitude of patients to the divinity, present a situation, albeit fragmentary, of main diseases which physicians thought incurable or hardly curable. Sterility, calvities, worms, paralysis, as well as clinical disorders caused by rheuma appear, along with gout/podagra, in many inscriptions too. To counter them, patients asked for the intervention of Asclepiu

Friction-Stir Welding of AA 2198 Butt Joints: Mechanical Characterization of the Process and of the Welds Through DOE Analysis

In this study, rolled plates of AA 2198 T3 aluminium alloy are friction-stir welded in butt configuration varying two fundamental process parameters: rotational and welding speeds. Two sets of empirical models based on regression analysis are developed. The first one predicts the stationary values of the in-plane and downwards forging welding forces in dependence of the process parameters under investigation. The second one predicts the mechanical strength, in particular yield and tensile strength, of the friction-stir welded joints as function of the same parameters. For the development of the empirical models, two 32 full factorial designs are used: one having the stationary values of the welding forces and the other having the yield and tensile strength as observed responses, respectively. Statistical tools such as analysis of variance, F tests, Mallows’ CP, coefficient of determination etc. are used to build and to validate the developed models. By using the desirability function approach, the optimum process parameters to simultaneously obtain maximum possible yield and tensile strength are found within the investigated range. The developed models can be effectively used to predict the stationary forces and the mechanical proprieties of the joints at 95% confidence level

Acoustic characteristics evaluation of an innovative metamaterial obtained through 3D printing technique

The reduction of interior noise level in the transportation sector is a big problem to cope with in view to increase the comfort of passengers. For this reason a great emphasis from the research community is devoted to develop new technology which are able to satisfy the mechanical requirements with concrete benefits from the acoustic point of view. Currently, it does not exist a solution for wideband range of frequency. Indeed, porous materials are characterized by outstanding dissipation in the high frequency range but they exhibit poor performance in the low and medium frequency range, where instead resonant cavities systems have the best performances but with narrow-band sound absorption. For this reason, the design and development of new materials which offers a good acoustic absorption over a wide range of frequencies is requested. In this paper, a hybrid metamaterial is designed, by coupling resonant cavities with micro-porous material and obtained through additive manufacturing technique which enables to model complex geometries that could not be feasible with classical manufacturing. Numerical and experimental studies have been conducted on the manufactured samples of PLA, with an interesting focus on the effect of each parameter which affects the absorption properties

Quantitative determination of free D-Asp, L-Asp and N-methyl-D-aspartate in mouse brain tissues by chiral separation and Multiple Reaction Monitoring tandem mass spectrometry

Several studies have suggested that free D-Asp has a crucial role in N-methyl D-Asp receptor-mediated neurotransmission playing very important functions in physiological and pathological processes. This paper describes the development of an analytical procedure for the direct and simultaneous determination of free D-Asp, L-Asp and N-methyl D-Asp in specimens of different mouse brain tissues using chiral LC-MS/MS in Multiple Reaction Monitoring scan mode. After comparing three procedures and different buffers and extraction solvents, a simple preparation procedure was selected the analytes of extraction. The method was validated by analyzing L-Asp, D-Asp and N-methyl D-Asp recovery at different spiked concentrations (50, 100 and 200 pg/μl) yielding satisfactory recoveries (75-110%), and good repeatability. Limits of detection (LOD) resulted to be 0.52 pg/μl for D-Asp, 0.46 pg/μl for L-Asp and 0.54 pg/μl for NMDA, respectively. Limits of quantification (LOQ) were 1.57 pg/μl for D-Asp, 1.41 pg/μl for L-Asp and 1.64 pg/μl for NMDA, respectively. Different concentration levels were used for constructing the calibration curves which showed good linearity. The validated method was then successfully applied to the simultaneous detection of D-Asp, L-Asp and NMDA in mouse brain tissues. The concurrent, sensitive, fast, and reproducible measurement of these metabolites in brain tissues will be useful to correlate the amount of free D-Asp with relevant neurological processes, making the LC-MS/MS MRM method well suited, not only for research work but also for clinical analyses

Darunavir-cobicistat-emtricitabine-tenofovir alafenamide: safety and efficacy of a protease inhibitor in the modern era

A fixed-dose combination consisting of darunavir (Drv), cobicistat (Cobi), emtricitabine (2',3'-dideoxy-5-fluoro-3'-thiacytidine [FTC]), and tenofovir alafenamide (Taf) has been recently approved by the European Medicines Agency for the treatment of HIV infection, and is the first ever protease-inhibitor-based single-tablet regimen. This article provides a detailed description of its pharmacokinetic, efficacy, and safety profile. The pharmacokinetics of single compounds were analyzed, with a special focus on contrasts between Drv/Cobi and Drv/ritonavir (Rtv). When comparing Cobi and Rtv, multiple interactions must be taken into account: in comparison to Rtv, Cobi is a more selective CYP3A4 inhibitor and has no clinical effect on other isoenzymes inhibited by Rtv (eg, 2C8 and 2C9). Moreover, unlike Cobi, Rtv shows in vivo induction activity on some CYP isoenzymes (eg, 1A2, 2C19, 2C8, 2C9, and 2B6), glucuronyltransferases (eg, UGT1A4), and Pgp. Drv-Cobi-FTC-Taf has recently been demonstrated to be of equal efficacy to Drv-Rtv and other protease inhibitors in both experienced (EMERALD study) and na\uefve (AMBER study) patients. Moreover, kidney and bone safety profiles have been shown to be good, as has central nervous system tolerance. Total cholesterol:low-density-lipoprotein cholesterol and total cholesterol:high-density-lipoprotein cholesterol ratios are generally high in Drv-Cobi-FTC-Taf vs Rtv-Drv-FTC + tenofovir disoproxil fumarate. An unlikely role of Drv in influencing cardiovascular risk in HIV infection has also been reported. Kidney safety profile is influenced by Cobi, with an increase in creatinine plasma concentration of 0.05-0.1 mg/dL and a parallel glomerular filtration-rate reduction of 10 mL/min within the first 4 weeks after Cobi introduction, which remains stable during treatment. Bone and central nervous system safety profiles were found to be good in randomized clinical trials of both experienced and na\uefve patients. The efficacy and safety of Drv/Cobi/FTC/Taf are comparable to other drug regimens recommended for HIV treatment

Lipid profile improvement in virologically suppressed hiv-1-infected patients switched to dolutegravir/ abacavir/lamivudine: Data from the SCOLTA project

open13noIntroduction: Metabolic disorders are common amongst HIV-infected patients. Data from real-life setting on the impact of DTG/ABC/3TC in virologically suppressed HIV-infected patients are scarce. Methods: We investigated the modification of metabolic profile including fasting glucose, lipid profile and markers of insulin resistance (IR) in experienced patients switching from a boosted protease inhibitors (bPI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen to DTG/ABC/3TC in a prospective, observational, multicenter study. Results: We enrolled 131 HIV-infected patients, of whom 91 (69.5%) males, mean age was 50.5±10.6 years. CDC stage was A in 66 (50.4%) patients, of whom 91 (69.5%) had acquired HIV through sexual contacts. The previous regimen was bPI-based in 79 patients (60.3%) and NNRTI-based in 52 (39.7%). Patients switching from NNRTI showed a significant reduction at week 24 in total cholesterol (TC) and low-density lipoprotein cholesterol (LDL). Triglycerides/high-density lipoprotein cholesterol (TG/HDL) ratio, HDL, median TG and TG/HDL ratio did not show significant modification during follow-up times. Among patients switching from a bPI, we observed a significant reduction in TC and LDL at both follow-up times and a slight increase in HDL. Triglycerides/HDL ratio, median TG and TG/HDL ratio showed a decrease over time that became significant at weeks 24 and 48. Blood glucose levels did not significantly vary during the observation period in patients switching from both bPI and NNRTI-based regimens. Conclusion: Our data suggest an improvement in lipid profile and TG/HDL ratio in pretreated HIV-1-infected patients who switched to DTG/ABC/3TC over 48 weeks, especially in those previously receiving a bPI-based regimen.openBagella P.; Squillace N.; Ricci E.; Gulminetti R.; De Socio G.V.; Taramasso L.; Pellicano G.; Menzaghi B.; Celesia B.M.; Dentone C.; Orofino G.; Bonfanti P.; Madeddu G.Bagella, P.; Squillace, N.; Ricci, Elena; Gulminetti, R.; De Socio, G. V.; Taramasso, L.; Pellicano, G.; Menzaghi, B.; Celesia, B. M.; Dentone, C.; Orofino, G.; Bonfanti, P.; Madeddu, G

Panneli aeronautici rinforzati con parti estruse saldatemediante FSW: caratterizzazionemeccanica

La Friction StirWelding (FSW) è una delle tecniche di giunzione più interessanti per l’industria aeronautica poiché,essendo un processo di saldatura allo stato solido, permette di superare tutti i problemi conosciuti collegati alletrasformazioni di fase dei processi di giunzione allo stato fuso. Tale tecnica, inoltre, permette di ridurre il peso nelleaerostrutture se comparate a quelle ottenute mediante la tecnologia del rivettamento. In questo lavoro viene presentatauna caratterizzazione meccanica di un componente ottenuto con tecnologia FSWmediante giunzioni sovrapposte (lap).Il campione simula un pannello bulkhead, ossia un pannello che separa un ambiente pressurizzato di un aeromobile(ad esempio la cabina) da ambienti non pressurizzati (ad esempio la stiva). Tali pannelli (skin) sono usualmenteirrigiditi da parti estruse rivettate sul pannello stesso (stringer). In questo caso le parti estruse, con una sezione a formadi T, sono state giuntate al pannello tramite FSWcon configurazione lap sui due lembi di appoggio. Le condizioni dicarico sono state scelte per simulare due condizioni operative reali: tensione circonferenziale (hoop stress) e trazioneperpendicolare al piano difissaggio (T-pull). I risultati permettono di apprezzare il buon comportamento atteso dalsimulatore. Una caratteristica specifica delle giunzioni in configurazione a sovrapposizione (FSWLap), ossia il difettoad uncino (hook defect), gioca un ruolo significativo nelle rotture osservate durante i test statici e nel fenomeno diinnesco delle cricche durante i test ciclici. I risultati indicano che l’attenzione dovrebbe essere focalizzata sul settaggiodei parametri di processo al fine di minimizzare il verificarsi dell’hook defect