Statistics for a football coach

This work presents a Decision Making Model riferring to the forecasts about Football World Cup in Brazil (2014). The aim of this work is to demonstrate how it is possible to approach young students to the study of Mathematics through evoking themes that are congenial to them and able to arouse their interest

Pulsed release of antidepressants from nanocomposite hydrogels

The pulsed release of three antidepressants (paroxetine, duloxetine, vortioxetine), loaded on two vinyl hydrogels bearing -amino acid residues (L-phenylalanine, L-valine) and embedded magnetic nanoparticles, was evaluated in different buffer solutions of purposely chosen pHs (2.9, 4.6, and 7.4). At low pH values the release of the drug was always small for a long period of days, and it underwent a sudden increase when a solution of pH 7.4 was maintained for a short period of hours. The releasing increase becomes much higher as greater was the residence time of the solution in contact with the hydrogel. The application of an alternating magnetic field (AMF) further increases the amount of drug released during the pH pulses. These different release variations were related to a different and reversible ability to swell of the hydrogel. The mechanism behind the process was mainly due to the different acid/base behaviour of the free carboxyl groups

Smart polyelectrolyte hydrogels: a novel platform for drug delivery

Three kinds of vinyl hydrogels with a-aminoacid residues have been considered as potential platforms for the deliver of several therapies (pain, diabetes, and mood) when loaded with appropriate drugs. The presence of ionizable groups of the L-valine, L-phenylalanine and L-histidine residues is able to modify the swelling properties of the hydrogel on the basis of its pKa values. A greater basicity constant of the functional groups improves a greater loading of the drug and a longer sustained-release pattern due to a strong polymer-drug ionic interaction. This occurs for the insulin and the paroxetine loaded on carboxylate hydrogels, and diclofenac loaded on zwitterionic hydrogels. The pH stimulation improves the swelling of the hydrogel and increases ‘on demand' the drug availability. A further remote stimulus based on alternating magnetic fields (AMF) on hydrogels containing embedded magnetic nanoparticles (CoFe2O4) allows a greater release rate of insulin and paroxetine for several pulses at physiological pH

Antibacterial Properties of Silver Nanoparticles Embedded on Polyelectrolyte Hydrogels Based on α-Amino Acid Residues

Polyelectrolyte hydrogels bearing L-phenylalanine (PHE), L-valine (AVA), and L-histidine (Hist) residues were used as scaffolds for the formation of silver nanoparticles by reduction of Ag+ ions with NaBH4. The interaction with the metal ion allowed a prompt collapse of the swollen hydrogel, due to the neutralization reaction of basic groups present on the polymer. The imidazole nitrogen of the hydrogel with Hist demonstrated greater complexing capacity with the Ag+ ion comparedtothehydrogelswithcarboxylgroups. Thesubsequentreductiontometallicsilverallowed for the restoration of the hydrogel’s degree of swelling to the starting value. Transmission electron microscopy (TEM) and spectroscopic analyses showed, respectively, a uniform distribution of the 15 nm spherical silver nanoparticles embedded on the hydrogel and peak optical properties around a wavelength of 400 nm due to the surface plasmonic effect. Unlike native hydrogels, the composite hydrogels containing silver nanoparticles showed good antibacterial activity as gram+/gram− bactericides, and higher antifungal activity against S. cerevisiae

Stimuli-responsive poly(ampholyte)s containing L-histidine residues: synthesis and protonation thermodynamics of methacrylic polymers in the free and in the cross-linked gel forms

Methacrylate-structured poly(ampholyte)s were synthesized in the homopolymer and copolymer forms starting from the N-methacryloyl-L-histidine (MHist) and the N-isopropylacrylamide (NIPAAm). They were also obtained in the cross-linked (hydrogel) form, showing a close thermodynamic behaviour as that shown by the corresponding soluble free polymer analogues. Viscometric data revealed that the minimum hydrodynamic volume of the polymer at its isoelectric point (pH 5) shifted to lower pHs as the NIPAAm content increased, and beyond a critical low MHist content the reduced viscosity decreased, even at low pHs. The phenomenon was attributed to hydrophobic forces between the isopropyl groups outweighing the repulsive electrostatic interactions of the polymer in the positively charged form. A similar behaviour was shown by the corresponding hydrogel. The latter also revealed a different phase transition phenomenon induced by external stimuli (temperature, pH, ionic strength, electric current) when compared to the acrylate-structured analogues. The polyMHist, as well as the corresponding monomer, was found for two days to be non toxic against the mouse osteoblasts (MC3T3-E1)

Angiotensin receptor/Neprilysin inhibitor effects in CRTd non-responders: From epigenetic to clinical beside

We evaluated whether Angiotensin receptor/Neprilysin inhibitors (ARNI) reduce heart failure (HF) hospitalizations and deaths in cardiac resynchronization therapy with defibrillator (CRTd) non-responders patients at 12 months of follow-up, modulating microRNAs (miRs) implied in adverse cardiac remodeling

Left bundle branch pacing and cardiac remodeling in HF patients with type 2 diabetes mellitus: epigenetic pathways and clinical outcomes

BackgroundLeft bundle branch (LBB) pacing could achieve cardiac resynchronization therapy (CRT) in patients who cannot be resynchronized via the placement of the left ventricle (LV) lead into the coronary sinus. LBB pacing could improve cardiovascular outcomes in heart failure (HF) patients with LBB block who are affected by type 2 diabetes mellitus (T2DM).Study hypothesisLBB pacing could increase the number of CRT responders and lead to the best clinical outcomes in HF patients with T2DM, inducing cardiac remodeling and improving left ventricle ejection fraction (LVEF) via microRNA (miR) modulation.MethodsIn a multicenter observational study, we enrolled 334 HF patients with LBB block and an indication to receive LBB pacing for CRT. In these patients, we evaluated the CRT responder rate, clinical outcomes, and miR expression at 1 year of follow-up.ResultsAt 1 year of follow-up, we had 223 responders (66.8%), 132 hospitalizations for HF (39.5%), 24 cardiac deaths (7.2%), and 37 all-cause deaths (11.1%), with a higher rate of HF hospitalizations (77 (69.4%) vs 55 (24.7%), p < 0.05), and cardiac deaths (13 (11.7% vs 11 (4.9%), p < 0.05) in non-responders vs responders. At the end of follow-up, we found the lowest expression of miR-26, miR-29, miR-30, miR-92, and miR-145 in LBB-pacing non-responders vs responders (p < 0.05), and a direct correlation between miR-30 (0.340, [0.833–1.915]; p 0.001), the 6-minute-walking test (6MWT; 0.168, [0.008–0.060]; p 0.011), angiotensin-receptor-neprilysin inhibitors (ARNI; 0.157, [0.183–4.877]; p 0.035), sodium-glucose-transporter-2 inhibitors (0.245, [2.242–7.283]; p 0.001), and LVEF improvements. C reactive protein (CRP) inversely correlated with LVEF improvement (−0.220, [-(0.066–0.263)]; p 0.001). ARNI (1.373, CI 95% [1.007–1.872], p 0.045), miR-30 (2.713, CI 95% [1.543–4.769], p 0.001), and 6MWT (1.288, CI 95% [1.084–1.998], p 0.001) were predictors of LBB pacing responders at 1 year of follow-up.ConclusionLBB-pacing responders evidenced miR modulation, which was linked to significant improvement of the cardiac pump. Specifically, miR-30 was linked to cardiac pump improvement and predicted responders at 1 year of follow-up in patients with T2DM

Divergence of gut permeability and mucosal immune gene expression in two gluten-associated conditions: celiac disease and gluten sensitivity

<p>Abstract</p> <p>Background</p> <p>Celiac disease (CD) is an autoimmune enteropathy triggered by the ingestion of gluten. Gluten-sensitive individuals (GS) cannot tolerate gluten and may develop gastrointestinal symptoms similar to those in CD, but the overall clinical picture is generally less severe and is not accompanied by the concurrence of tissue transglutaminase autoantibodies or autoimmune comorbidities. By studying and comparing mucosal expression of genes associated with intestinal barrier function, as well as innate and adaptive immunity in CD compared with GS, we sought to better understand the similarities and differences between these two gluten-associated disorders.</p> <p>Methods</p> <p>CD, GS and healthy, gluten-tolerant individuals were enrolled in this study. Intestinal permeability was evaluated using a lactulose and mannitol probe, and mucosal biopsy specimens were collected to study the expression of genes involved in barrier function and immunity.</p> <p>Results</p> <p>Unlike CD, GS is not associated with increased intestinal permeability. In fact, this was significantly reduced in GS compared with controls (<it>P </it>= 0.0308), paralleled by significantly increased expression of claudin (CLDN) 4 (<it>P </it>= 0.0286). Relative to controls, adaptive immunity markers interleukin (IL)-6 (<it>P </it>= 0.0124) and IL-21 (<it>P </it>= 0.0572) were expressed at higher levels in CD but not in GS, while expression of the innate immunity marker Toll-like receptor (TLR) 2 was increased in GS but not in CD (<it>P </it>= 0.0295). Finally, expression of the T-regulatory cell marker FOXP3 was significantly reduced in GS relative to controls (<it>P </it>= 0.0325) and CD patients (<it>P </it>= 0.0293).</p> <p>Conclusions</p> <p>This study shows that the two gluten-associated disorders, CD and GS, are different clinical entities, and it contributes to the characterization of GS as a condition associated with prevalent gluten-induced activation of innate, rather than adaptive, immune responses in the absence of detectable changes in mucosal barrier function.</p

Controlled Release of Antidepressant Drugs by Multiple Stimuli-Sensitive Hydrogels Based on α-Aminoacid Residues

2noTwo slightly cross-linked hydrogels bearing l-phenylalanine (Phe-Nip3) or l-valine (Ava2) residues of a copolymeric and homopolymeric vinyl structure were considered for their potential application in the psychiatric treatment of depression. Two antidepressant drugs (citalopram and trazodone) were loaded into hydrogels and their controlled release behavior monitored for several days at 25 °C in two buffer solutions of different pHs (PBS pH 7.4 and acetate pH 4.6). The different basicity constants (logKs) of the involved substance determine a different electrostatic effect between the drug ionized positively and the negatively charged hydrogel. Both the hydrogels loaded with citalopram showed a greater binding effect with respect to trazodone. In fact, for the same hydrogel, the release of citalopram in PBS (4 days) was slower than trazodone (24 h). In addition, at pH (4.6) < logK the release of the drug was much slower and durable, due to the lower capacity of ionization and swelling of the hydrogel. Additionally, the magnetic nanoparticles (CoFe2O4) embedded into the hydrogel Phe-Nip3 were an additional remote control for drug release through the stimulation of an appropriate alternating magnetic field (AMF, 20 kHz and 50 W). In these conditions, the kinetics of the drug released was substantially increased.nonemixedCasolaro, Mario; Casolaro, IlariaCasolaro, Mario; Casolaro, Ilari

Stimuli-Responsive Hydrogels Bearing α-amino acid Residues: a Potential Platform for Future Therapies

Vinyl hydrogels bearing α-aminoacid residues have been explored as platforms for the treatment of cancer, glaucoma and mood disorder therapies. Ionic/ionizable groups of the L-valine, L-phenylalanine and L-histidine residues are able to modify the swelling properties of the hydrogel on the basis of their thermodynamic characteristics. Greater basicity constants of functional groups improve a greater loading of the drug and a longer sustained-release pattern. The pH and the temperature affect the swelling of the hydrogel and increase ‘on demand’ the drug availability. A further stimulus based on alternating magnetic fields can be applied on hydrogels containing embedded magnetic nanoparticles used for site-specific controlled drug delivery. The diffusion process for the in vitro release of the drug (cisplatin, doxorubicin, pilocarpine, trazodone, citalopram and paroxetine) from the drugloaded hydrogels is mainly controlled by the drug-polymer interaction, that in the meanwhile preservs it’s bioactivity. The different interaction strength between the drug and the polymer may be a strategy to develop suitable capsules for long-term therapies