Optimal Controller Identification for multivariable non-minimum phase systems.

This work deals with data-driven control for non-minimum phase (NMP) systems, where the goal is to design a controller for a plant whose model is unknown by using a batch of input-output data collected from it. The approach is based on the Model Reference paradigm, where a transfer function matrix - the reference model - is used to specify the desired closed-loop performance. The NMP systems issue in Model Reference approaches is a well-known problem in control literature and it is no different in data-driven methods. This work explains how to adapt the formulation of the Optimal Controller Identification (OCI) method to cope with this class of systems. Considering a convenient parametrization of the reference model and a flexible performance criterion, it is possible to identify the NMP transmission zeros of the plant along with the optimal controller parameters, as it will be shown. Both diagonal and block-triangular reference model structures are treated in detail. Simulation examples show the effectiveness of the proposed approach.

Mechanical and Optical Characterization of Single-shade Resin Composites Used in Posterior Teeth.

OBJECTIVES: This study aimed to evaluate the optical and mechanical performance of two single-shade resin-based composites (RBCs) compared to those of a conventional RBC for restoring posterior teeth. METHODS: Two single-shade RBCs, Omnichroma (Tukoyama) and Vittra Unique APS (FGM), and a conventional RBC, Filtek Z350XT shade A2 (3M Oral Care), were evaluated in this study. The optical shade-matching performance was measured using a spectrophotometer. The light emitted by VALO Grand (Ultradent) and transmitted through the 2.0-mm RBC specimens was evaluated using beam profiling. Knoop hardness (KH, N/mm2), degree of conversion (DC, %) at the top and bottom, flexural strength (FS, MPa), elastic modulus (E, GPa), postgel shrinkage (Shr, %), and shrinkage stress (MPa) were evaluated. Scanning electron microscopy (SEM) was used to characterize the filler. Data for FS, E, and Shr were analyzed by one-way analysis of variance (ANOVA) and KH and DC by repeated one-way ANOVA measurement followed by Tukey test (α=0.05). The modified von Mises stress values, light transmission, and SEM images were analyzed qualitatively. RESULTS: All single-shade RBCs exhibited higher chromatic adaptation than the Filtek Z350XT (p<0.001). Omnichroma exhibited less color difference than Vittra Unique APS, irrespective of the shade. The light transmitted through Omnichroma and Vittra Unique APS increased during polymerization. KH and DC values were significantly reduced from the top to the bottom of the specimens for all RBCs (p<0.001); however, the ratio values were always higher than 80%. In general, all RBCs demonstrated similar mechanical properties. All RBCs exhibited a similar FS (p=0.083) and Shr value (p=0.144). Filtek Z350XT exhibited significantly higher E (p<0.001) than both single-shade RBCs. All RBCs exhibited similar shrinkage stress during restoration and similar residual stress during occlusal loading. CONCLUSIONS: Single-shade Omnichroma and Vittra Unique APS increased light transmission during light-activation, demonstrating better chromatic adaptation than conventional Filtek Z350XT. In general, Omnichroma and Vittra Unique APS exhibited similar mechanical properties and shrinkage stress distributions as Filtek Z350XT during light-activation and occlusal loading.

Analysis of Calcium and Phosphate Ion Extraction From Dental Enamel by Bleaching Gels Using Ion Chromatography, Micro-CT, and SEM.

OBJECTIVES: To evaluate the volume and depth of enamel loss promoted by 37.5% and 7.5% hydrogen peroxide (HP) gels, and quantify the loss of calcium (Ca) and phosphate (P) ions by using ion chromatography (IC) analysis after bleaching. METHODS: Sixty bovine enamel specimens were randomly divided into three groups: Control - no bleaching gel; HP37.5%, application of HP 37.5% for 45 minutes for 14 days; and HP7.5%, application of HP 7.5% for 3 applications of 8 minutes. The surface analysis (n=5) was performed using a scanning electron microscope (SEM) and dispersive energy system (EDS) to calcium and phosphorus dosage. The micro-CT was used for the enamel loss analysis (n=5). IC was used to analyze extracted Ca and P (n=10). Data were analyzed by one-way ANOVA and two-way repeated measures ANOVA, followed by Tukey and Dunnett's tests (α=0.05). RESULTS: Significantly higher volume and depth of enamel loss were found for bleached groups compared with the control group. HP7.5% had significantly higher enamel change than HP37.5%. SEM showed higher enamel porosity for HP37.5% and HP7.5% compared to control. The IC demonstrated a significant increase of Ca incorporated into the gel, however, only HP7.5% had a higher P presence than the control group. The HP7.5% showed higher Ca and P ion exchange than HP37.5% (p<0.001). CONCLUSION: HP37.5% and HP7.5%, caused enamel mineral changes compared with the control group. The IC method was demonstrated to be an effective methodology for detecting enamel mineral loss by the bleaching gel.

Research Note: Antimicrobial resistance profile of Enterococcus spp. isolated from the eggshell of laying hens submitted to pharmacological treatment.

The occurrence of antimicrobial resistance in microorganisms isolated from eggshells, especially Enterococcus, might serve as a parameter to assess the selection of bacteria due to the use of drugs in the diet of laying hens. In order to evaluate the frequency and the antimicrobial resistance profile of Enterococcus spp. isolated from the eggshells, 225 Hy-line laying hens were submitted to a 25-d long trial. The treatments were the following: hens fed ration without antimicrobials (control) and groups that received oxytetracycline (10 mg kg-1), doxycycline (20 mg kg-1), lincomycin (50 mg kg-1), and enrofloxacin (10 mg kg-1) in the ration for 5 d. Six replications were analyzed per treatment, composed of a pool of 5 eggs each. They were collected before treatment and on days 3, 6, 15, and 25, totaling 150 samples. Eggshells were submitted to counts of Enterococcus spp., which were identified by proteomic analyses. Antimicrobial resistance was determined by the disk-diffusion test. It was observed that 97.3% (n = 146) of the samples were contaminated with Enterococcus spp. There were no differences (P > 0.05) in the bacterial counts between treatments on the same day of evaluation. E. faecalis and E. faecium were the most frequent on the eggshells of all treatments. Multiresistance to the four classes of antimicrobials was also verified in the isolated bacteria. A total of 83% of the Enterococcus isolates showed resistance to neomycin, which was not administered to the hens, demonstrating an environmental problem. Thus, feeding laying hens with diets added with antimicrobials induces drug resistance in Enterococcus spp., isolated form the eggshells.

Spiramyin-loaded PLGA implants for the treatment of ocular toxoplasmosis: development, characterization, biocompatibility, and anti-toxoplasma activity.

Ocular toxoplasmosis is the major cause of infectious posterior uveitis worldwide, inducing visual field defect and/or blindness. Despite the severity of this disease, an effective treatment is still lacking. In this study, spiramycin-loaded PLGA implants were developed aiming at the treatment of ocular toxoplasmosis. Implants were manufactured by a hot-molding technique, characterized by Fourier Transform Infrared Spectroscopy, X-Ray Diffraction, Differential Scanning Calorimetry, Scanning Electron Microscopy; evaluated in terms of ocular biocompatibility by immunofluorescence, flow cytometry, cell migration, Hen's egg test-chorioallantoic membrane (HET-CAM) irritation test; and investigated in terms of in vitro efficacy against Toxoplasma gondii . Characterization techniques indicated that spiramycin was dispersed into the polymeric chains and both substances preserved their physical structures in implants. The HET-CAM test indicated that implants did not induce hemorrhage or coagulation, being non-irritant to the CAM. ARPE-19 cells showed viability by MTT assay, and normality in cell cycle kinetics and morphology, without stimulating cell death by apoptosis. Finally, they were highly effective against intracellular parasites without inducing human retinal pigment epithelial cell death. In conclusion, spiramycin-loaded PLGA implants represent a promising therapeutic alternative for the local treatment of ocular toxoplasmosis.

A laboratory evaluation of cell viability, radiopacity and tooth discoloration induced by regenerative endodontic materials.

AIM: To analyse the cytotoxicity, colour change and radiopacity of MTA Flow (MTA), UltraCal XS (UC) and Bio-C Temp (BT). METHODOLOGY: Human dental pulp cells (hDPCs) stimulated with lipopolysaccharide (LPS) were placed in contact with several dilutions of culture media previously exposed to the experimental materials and tested for cell viability using MTT. Bovine teeth were prepared to simulate an open apex and to mimic extensive crown fracture. The roots were filled with a mixture of agar and blood, and the materials placed over this mixture. The control group consisted of teeth filled only with agar and blood. Colour assessment analyses were performed before and immediately after material insertion and repeated at 30, 45 and 60 days using a spectrophotometer. The total colour change (ΔEab , ΔE00 and whiteness index (WI)) was calculated based on the CIELAB colour space. Digital radiographs were acquired for radiopacity analysis. Cell viability was analysed by one-way anova, whilst differences in colour parameters (ΔEab , ΔE00 and WI) were assessed by two-way repeated measures anova (α = 0.05). Tukey's test was used to compare the experimental groups, and Dunnett's test was used to compare the experimental groups with the control group. RESULTS: MTA, UC and BT had similar cell viability to that of the control group (DMEM) (P > 0.05), except for the BT group at the 1 : 1 and 1 : 2 dilutions, which had significantly lower viability (P < 0.001). All materials were associated with discoloration values greater than what is considered to be the acceptable threshold, and BT resulted in less or similar tooth colour change than MTA and UC, respectively. Decreasing radiopacity over time was observed only in the MTA group (P = 0.007). Lower values of radiopacity were found in the BT group compared with the UC and MTA groups (P < 0.001). CONCLUSIONS: The new bioceramic material (BT) had acceptable cell viability, similar to that of MTA and UC at the highest dilutions, and BT resulted in less tooth colour change than MTA and UC. Despite its lower radiopacity, BT was identified radiographically.

Intra-articular leflunomide-loaded poly(ε-caprolactone) implants to treat synovitis in rheumatoid arthritis.

Rheumatoid arthritis is an autoimmune pathology that manifests as chronic inflammatory arthropathy and synovitis. Treatment of rheumatoid arthritis is based on the administration of different types of drugs, including leflunomide, an antirheumatic drug. However, the long-term systemic use of leflunomide may be associated with adverse effects. Local therapy could be an efficient strategy to treat synovitis triggered by rheumatoid arthritis without inducing adverse effects. In this study, leflunomide-loaded poly(ε-caprolactone) implants (leflunomide PCL implants) were evaluated as local drug delivery systems capable of attenuating inflammation and angiogenesis, which represent events of synovitis. Leflunomide PCL implants were designed by hot molding technique; and they were characterized by FTIR and DSC. These analytical techniques demonstrated the chemical integrity and dispersion of drug into the polymeric chains. Then, a spectrophometric method was developed and validated to quantify the leflunomide incorporated into the PCL implants and released from them. Linearity was obtained by ordinary least squares regression method to estimate the linear regression equation. Residues were evaluated considering normality, independence and homoscedasticity. Precision was lower than 5 %, and accuracy ranged from 98 to 104.5 %. Quantitation limit was 2.0 µg mL-1. PCL implants provided controlled and sustained release of leflunomide for 30 consecutive days after inserting these systems in the subcutaneous tissue of mice. The main mechanisms of drug delivery were solubilization and diffusion from polymer. Then, a non-biocompatible sponge was inserted into the subcutaneous tissue of mice to function as a frame to develop the inflammatory and angiogenic processes. Leflunomide PCL implants were inserted in direct contact with the sponge. At 4, 7 and 10 days after-sponge implantation, the key components of inflammatory angiogenesis were measured to verify the regression of these events induced by drug. Leflunomide controlled released from polymeric implants downregulated the neutrophil and monocyte/macrophage infiltration due to the reduced expression of myeloperoxidase (MPO) and N-acetyl-ß-d-glucosaminidase (NAG), respectively. As the influx of these pro-inflammatory cells was modulated by leflunomide, the production of nitric oxide (NO), a pro-inflammatory substance, reached low concentrations in the sponge. As a consequence of the modulation of inflammation at the pathological site, the angiogenic process was downregulated, since the hemoglobin levels in the sponge were drastically reduced. The accumulation of leflunomide in the pathological site did not induce nephrotoxicity or hepatototoxicity, as confirmed by histological analyses. Finally, intra-articular leflunomide PCL implants represent a potential therapeutic alternative to treat locally the synovitis triggered by rheumatoid arthritis without inducing systemic adverse effects.

Effect of Simulated Pulpal Microcirculation on Temperature When Light Curing Bulk Fill Composites.

OBJECTIVES: To evaluate the effect of light curing bulk fill resin composite restorations on the increase in the temperature of the pulp chamber both with and without a simulated pulpal fluid flow. METHODS AND MATERIALS: Forty extracted human molars received a flat occlusal cavity, leaving approximately 2 mm of dentin over the pulp. The teeth were restored using a self-etch adhesive system (Clearfil SE Bond, Kuraray) and two different bulk fill resin composites: a flowable (SDR, Dentsply) and a regular paste (AURA, SDI) bulk fill. The adhesive was light cured for 20 seconds, SDR was light cured for 20 seconds, and AURA was light cured for 40 seconds using the Bluephase G2 (Ivoclar Vivadent) or the VALO Cordless (Ultradent) in the standard output power mode. The degree of conversion (DC) at the top and bottom of the bulk fill resin composite was assessed using Fourier-Transform Infra Red spectroscopy. The temperature in the pulp chamber when light curing the adhesive system and resin composite was measured using a J-type thermocouple both with and without the presence of a simulated microcirculation of 1.0-1.4 mL/min. Data were analyzed using Student t-tests and two-way and three-way analyses of variance (α=0.05 significance level). RESULTS: The irradiance delivered by the light-curing units (LCUs) was greatest close to the top sensor of the MARC resin calibrator (BlueLight Analytics) and lowest after passing through the 4.0 mm of resin composite plus 2.0 mm of dentin. In general, the Bluephase G2 delivered a higher irradiance than did the VALO Cordless. The resin composite, LCU, and region all influenced the degree of cure. The simulated pulpal microcirculation significantly reduced the temperature increase. The greatest temperature rise occurred when the adhesive system was light cured. The Bluephase G2 produced a rise of 6°C, and the VALO Cordless produced a lower temperature change (4°C) when light curing the adhesive system for 20 seconds without pulpal microcirculation. Light curing SDR produced the greatest exothermic reaction. CONCLUSIONS: Using simulated pulpal microcirculation resulted in lower temperature increases. The flowable composite (SDR) allowed more light transmission and had a higher degree of conversion than did the regular paste (AURA). The greatest temperature rise occurred when light curing the adhesive system alone.

Desenvolvimento de escore preditor de sucesso imediato e tardio pós valvoplastia mitral percutânea em pacientes portadores de estenose mitral / Development of early and late success predictor score after percutaneous mitral valvuloplasty in patients with mitral stenosis

INTRODUÇÃO: Os dados de resultados a longo prazo após valvoplastia mitral percutânea (VMP) em pacientes portadores de estenose mitral ainda são escassos e os sistemas de pontuação atuais têm limitações. Propomos um novo escore capaz de predizer sucesso imediato e tardio em pacientes elegíveis para o tratamento de estenose mitral por VMP, baseando-se nas análises de características ecocardiográficas, fatores clínicos e hemodinâmicos relevantes. MÉTODOS: Análise retrospectiva de 1582 pacientes com estenose mitral grave que foram submetidos à VMP no período de agosto de 1987 a junho de 2011 em um único centro. O período de seguimento dos pacientes apresentou mediana de 8,3 anos, com um seguimento máximo de até 23 anos. O desfecho combinado foi composto de morte cardiovascular, nova VMP ou cirurgia para plastia/troca valvar mitral. Dois modelos estatísticos foram construídos para prever a sobrevivência imediata e de longo prazo livre de eventos. RESULTADOS: A média de idade dos pacientes foi de 36,8±12,9 anos e houve prevalência do sexo feminino (86,4%). A maioria dos pacientes no momento da VMP apresentavam classe funcional New York Heart Associaton (NYHA) III (57,7%) e escore de Wilkins entre 9-11 (49,1%). Na análise multivariada para predição de sucesso imediato tiveram significância estatística a idade, tamanho de átrio esquerdo, gradiente transvalvar mitral médio e pontuação pelo escore de Wilkins. Para predição de sucesso tardio tiveram significância estatística idade, classe funcional, tamanho de átrio esquerdo e pontuação pelo escore de Wilkins. CONCLUSÃO: Na ampla população estudada tornou-se evidente que não somente o escore de Wilkins parece ter relevância na predição de sucesso imediato e tardio para os pacientes com estenose mitral reumática submetidos a VMP. Além de parâmetros ecocardiográficos, os parâmetros clínicos e hemodinâmicos também parecem contribuir de forma importante no sucesso imediato do procedimento, bem como no tempo livre de intervenções e mortalidade a longo prazo. (AU)

Association between biomechanical alterations and migratory ability of semaphorin-3A-treated thymocytes.

BACKGROUND: Class 3 semaphorins are soluble proteins involved in cell adhesion and migration. Semaphorin-3A (Sema3A) was initially shown to be involved in neuronal guidance, and it has also been reported to be associated with immune disorders. Both Sema3A and its receptors are expressed by most immune cells, including monocytes, macrophages, and lymphocytes, and these proteins regulate cell function. Here, we studied the correlation between Sema3A-induced changes in biophysical parameters of thymocytes, and the subsequent repercussions on cell function. METHODS: Thymocytes from mice were treated in vitro with Sema3A for 30min. Scanning electron microscopy was performed to assess cell morphology. Atomic force microscopy was performed to further evaluate cell morphology, membrane roughness, and elasticity. Flow cytometry and/or fluorescence microscopy were performed to assess the F-actin cytoskeleton and ROCK2. Cell adhesion to a bovine serum albumin substrate and transwell migration assays were used to assess cell migration. RESULTS: Sema3A induced filopodia formation in thymocytes, increased membrane stiffness and roughness, and caused a cortical distribution of the cytoskeleton without changes in F-actin levels. Sema3A-treated thymocytes showed reduced substrate adhesion and migratory ability, without changes in cell viability. In addition, Sema3A was able to down-regulate ROCK2. CONCLUSIONS: Sema3A promotes cytoskeletal rearrangement, leading to membrane modifications, including increased stiffness and roughness. This effect in turn affects the adhesion and migration of thymocytes, possibly due to a reduction in ROCK2 expression. GENERAL SIGNIFICANCE: Sema3A treatment impairs thymocyte migration due to biomechanical alterations in cell membranes.