Quality Control Optimization for Minimizing Security Risks Associated with Mesenchymal Stromal Cell-Based Product Development.

Mesenchymal stromal cells (MSCs) have been considered a therapeutic strategy in regenerative medicine because of their regenerative and immunomodulatory properties. The translation of MSC-based products has some challenges, such as regulatory and scientific issues. Quality control should be standardized and optimized to guarantee the reproducibility, safety, and efficacy of MSC-based products to be administered to patients. The aim of this study was to develop MSC-based products for use in clinical practice. Quality control assays include cell characterization, cell viability, immunogenicity, and cell differentiation; safety tests such as procoagulant tissue factor (TF), microbiological, mycoplasma, endotoxin, genomic stability, and tumorigenicity tests; and potency tests. The results confirm that the cells express MSC markers; an average cell viability of 96.9%; a low expression of HLA-DR and costimulatory molecules; differentiation potential; a high expression of TF/CD142; an absence of pathogenic microorganisms; negative endotoxins; an absence of chromosomal abnormalities; an absence of genotoxicity and tumorigenicity; and T-lymphocyte proliferation inhibition potential. This study shows the relevance of standardizing the manufacturing process and quality controls to reduce variability due to the heterogeneity between donors. The results might also be useful for the implementation and optimization of new analytical techniques and automated methods to improve safety, which are the major concerns related to MSC-based therapy.

Cyclic Fatigue Resistance of Blue Heat-Treated Instruments at Different Temperatures.

The main aim is to evaluate the cyclic fatigue resistance of blue heat-treated instruments with different kinematics. Twenty-four endodontic instruments of the same brand were used for each of three experimental groups: VB (Vortex Blue 40/0.04), RB (RECIPROC Blue 40/0.06), and XB (X1 Blue 40/0.06). The instruments were randomly distributed and subjected to temperatures of 20°C and 37°C. The fatigue test was performed using a stainless steel device. Data were analysed using the Shapiro-Wilk test, Student's t-test, the F test, and Tukey's and Tamhane tests at significance level P=0.05. The instruments' cyclic fatigue resistance at both temperatures differed significantly for each instrument type (P < 0.001). The RB instruments displayed greater cyclic fatigue resistance at the tested temperatures compared with the VB and XB instruments (P < 0.001). Reciprocating kinematics positively influenced cyclic fatigue resistance. Blue heat-treated instruments showed decreased cyclic fatigue resistance as the temperature increased (P < 0.001).

Influence of Temperature on the Cyclic Fatigue Resistance of Reciproc Blue Instruments.

AIM: To evaluate the cyclic fatigue resistance of Reciproc blue (RB) 40/0.06 instruments tested at room temperature (20° ± 0.5°C) and at body temperature (37° ± 0.5°C) in a simulated stainless steel canal. MATERIALS AND METHODS: Twenty-four new RB 40/0.06 instruments were randomly divided into two groups (n = 12) according to the temperature used. Dynamic fatigue testing was performed using an artificial stainless steel canal with a 60° curvature angle and a 5-mm radius of curvature. The temperature was controlled throughout the experiment with an underwater thermometer and a thermostat. The data were analyzed descriptively using the IBM SPSS 23.0 program, considering p < 0.05. RESULTS: The time to fracture of the RB instruments differed significantly between the two temperatures (1083.82 seconds at 20°C and 403.80 seconds at 37°C). No significant differences were found in fragment size. CONCLUSION: An increase in temperature reduces the cyclic fatigue resistance of RB 40/0.06 instruments. The results of the study suggest that an intracanal cooling system can be favorable to the fracture resistance of the tested instruments. CLINICAL SIGNIFICANCE: A cooling system of the root canal system is important in endodontic as it favors the cyclic fatigue resistance of Ni-Ti instruments.

Genotoxic, metabolic, and biological responses of Chironomus sancticaroli Strixino & Strixino, 1981 (Diptera: Chironomidae) after exposure to BBP.

Benzyl butyl phthalate (BBP), which is widely used in industrial production, reaches the aquatic environment, mainly owing to improper disposal of plastic products. In the water, it remains adsorbed to sedimentary particles causing toxic effects in aquatic invertebrates such as Chironomidae, which are important in maintaining ecosystem dynamics and are an important link in the food chain. However, the effects of BBP on Chironomidae are still poorly known. Thus, the toxic effects of BBP on Chironomus sancticaroli at acute (48 h), subchronic (8 d), and chronic (25 d) exposures of concentrations between 0.1 and 2000 µg·L-1 were determined. Genotoxicity effects, changes in the oxidative stress pathway, and development and emergence of organisms were evaluated. Biochemical markers showed a reduction in cholinesterase (ChE) activity, indicating a neurotoxic effect on acute exposure (1-1000 µg·L-1). The antioxidant pathway, glutathione S-transferase (GST) activity showed reduction on acute (0.1; 1-2000 µg·L-1) and subchronic (1-2000 µg·L-1) exposures and reduction in superoxide dismutase (SOD) activity at all evaluated concentrations, suggesting oxidative stress. In contrast, lipid peroxidation was not observed. DNA damage occurred on acute (10 µg·L-1) and subchronic (10-2000 µg·L-1) exposures, indicating genotoxic effects. At concentrations above 10 µg·L-1, no emergence of adults occurred, while lower concentrations (0.1 and 1 µg·L-1) showed a reduction in the number of adults, mainly males. The observed effects indicate that BBP is genotoxic and causes biochemical alterations presenting high toxicity at the population level.

Influence of Temperature on the Cyclic Fatigue of Nickel-Titanium Instruments with Different Heat Treatments on Severely Curved Canals.

AIM: This study aims to investigate the influence of temperatures of 20 °C and 37 °C on the resistance to cyclic fatigue of NiTi instruments with different heat treatments, as tested in severely curved simulated canals. MATERIALS AND METHODS: Seventy-two instruments were distributed according to the temperature used (20 °C and 37 °C): XP-endo Shaper (30/0.01), ProDesign Logic (30/0.05), and iRaCe (30/0.04). The instruments were rotated freely until the occurrence of fracture inside an artificial severely curved stainless steel canal, which had a 90° angle of curvature and a curvature radius of 5 mm. Kolmogorov-Smirnov, Wilcoxon, ANOVA, and Kruskal-Wallis tests were performed. A p value of <0.05 was considered statistically significant. RESULTS: XP-endo Shaper instruments presented higher NCF values and time to failure compared with ProDesign Logic and iRaCe instruments at 20 °C and 37 °C (p < 0.001). CONCLUSION: Within the limitations of this study, the results show that the body temperature (37 °C) significantly lowers the resistance to cyclic fatigue of all instruments compared with 20 °C. CLINICAL SIGNIFICANCE: Body temperature is an important factor in the results of cyclic fatigue tests.

Biological, biochemical and genotoxic effects of Sb in the midge Chironomus sancticaroli Strixino and Strixino, 1981 (Diptera: Chironomidae).

In aquatic systems, antimony (Sb) is found in the water column and associated with sediment particles being bioavailable to organisms. Consequently, toxic effects have been detected in benthic invertebrates, but the toxicity after Sb exposure in Chironomidae have not been investigated. Were investigated DNA damage, activities of cholinesterase (ChE), alpha and beta esterase (EST-α, EST-ß), glutathione S-transferase (GST), catalase (CAT), and superoxide dismutase (SOD) and lipid peroxidation after acute (48 h) and subchronic exposure (8 d). We also investigated the effects of subchronic (8 d) on development of larvae and chronic (25 d) Sb exposure on emergence and size of adults of Chironomus sancticaroli. Were analyze Sb nominal concentrations ranged from 0.5 to 800 µg.L-1. Genotoxic effects occurred at higher concentrations upon acute (50, 800 µg.L-1) and subchronic exposure (50 µg.L-1). Acute exposure increased ChE, EST-α, EST-ß, and GST activities. Subchronic Sb exposure increased EST-α activity at 0.2 µg.L-1 and GST activity at 5 µg.L-1. CAT activity increased at all concentrations while increasing lipid peroxidation levels were observed (1 µg.L-1, 5 µg.L-1 and 50 µg.L-1), indicating oxidative stress. All concentrations of Sb delayed larval development and decreased the number of emerging adults. At high concentrations (50, 500, 800 µg.L-1), the emerging adults were smaller. In conclusion, these varying genotoxic, biochemical and biological effects of Sb make a notable impact on the reproduction and population dynamics of C. sancticaroli.

Antibacterial Activity of Rosmarinus officinalis, Zingiber officinale, Citrus aurantium bergamia, and Copaifera officinalis Alone and in Combination with Calcium Hydroxide against Enterococcus faecalis.

This study aimed to evaluate the efficacy of different concentrations of essential oils combined with calcium hydroxide against Enterococcus faecalis. Thirteen experimental groups were formed: NC (negative control); PC (positive control); GC (growth control); SC (sterilization control); RO (Rosmarinus officinalis); ROH (calcium hydroxide + RO); ZO (Zingiber officinale); ZOH (calcium hydroxide + ZO); AB (Citrus aurantium bergamia); ABH (calcium hydroxide + AB); CO (Copaifera officinalis); COH (calcium hydroxide + CO); DWH (calcium hydroxide and distilled water). After reconstitution of the E. faecalis strain, microdilution testing was performed to define the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). The data were tabulated in an Excel spreadsheet, and the MIC and MBC were calculated in accordance with the Bacteriological Analytical Handbook. MICs in the range of 0 to 100 mg/ml were only observed in the ROH group. The RO, ROH, AB, ZO, and ZOH presented absolute data for MBC. Bacterial growth was detected in the DWH group at all concentrations tested. The combination of the essential oils tested here with calcium hydroxide appears promising as an intracanal medication in endodontic treatment because of its effectiveness against Enterococcus faecalis. Essential oils are important in endodontic therapy since calcium hydroxide, the gold standard intracanal medication, is not effective against E. faecalis.

Validity evidence of the Zulliger-SC Test to children's assessment / Evidências de validade do Zulliger-SC para avaliação de crianças / Evidencias de validez del Test Zulliger-SC para evaluación de niños

Due to the demand for instruments to assess aspects of the personality of children, we aimed find evidence for the validity of the Zulliger test in the Comprehensive System (ZSC). 173 children participated in this study of Fortaleza-CE with ages between 6 years and 11 years and 6 months, 48.5% were from public schools and 53.1% female. The children were divided into three age groups, 6 and 7 years, 8 and 9 years and 10 and 11 years. The instruments used were the Zulliger test and the test of Raven's Coloured Progressive Matrices - Special Scale. We made the analysis of descriptive statistics and compared the variables of Zulliger test through the One Way ANOVA test. The significant variables were FQu (p<0.005) and R, ma, D, Xu%, Na, Ls, Fd, (T), GHR and (2) (p<0.05), which contributed with validity evidences of ZSC with children. (AU)

Devido à demanda de instrumentos que avaliem aspectos da personalidade de crianças, objetivou-se buscar evidências de validade para o teste de Zulliger pelo Sistema Compreensivo (ZSC). Participaram dessa pesquisa 173 crianças de Fortaleza-CE com a idade entre 6 e 11 anos e 6 meses, sendo 48,5% de escolas públicas e 53,1% do sexo feminino. As crianças foram divididas em três faixas etárias, a saber, 6 e 7 anos, 8 e 9 anos e 10 e 11 anos. Os instrumentos utilizados foram o teste ZSC e o teste das Matrizes Progressivas Coloridas de Raven ­ Escala Especial. Foram feitas as análises de estatística descritiva e a comparação das variáveis do teste ZSC por meio do teste One Way ANOVA. As variáveis significativas foram FQu (p < 0,005) e R, ma, D, Xu%, Na, Ls, Fd, (T), GHR e (2) (p < 0,05), dados que contribuíram com evidências de validade do ZSC com crianças. (AU)

Debido a la demanda de instrumentos para evaluar aspectos de la personalidad de los niños, el objetivo de este estudio fue encontrar evidencias de vlidez del test Zulliger por el Sistema Comprensivo (ZSC). Participaron de esta investigación 173 niños de Fortaleza-CE con edades entre 6 y 11 años y 6 meses, siendo 48,5% de escuelas públicas y 53,1% de sexo femenino. Los niños fueron divididos en tres grupos por edad, a saber, 6 y 7, 8 y 9, 10 y 11 años. Los instrumentos utilizados fueron el test ZSC y el test de las Matrices Progresivas Coloridas de Raven - Escala Especial. Se hicieron análisis de estadística descriptiva y comparación de las variables del test ZSC por medio del test One Way ANOVA. Las variables significativas fueron FQu (p<0,005) y R, ma, D, Xu%, Na, Ls, Fd, (T), GHR y (2) (p<0,05), datos que contribuyeron con evidencias de validez del ZSC con los niños. (AU)