Patients Age 40 Years and Younger With Multiple Myeloma Have the Same Prognosis as Older Patients: An Analysis of Real-World Patients' Evidence From Latin America.

PURPOSE: Multiple myeloma (MM) is a highly heterogeneous, incurable disease most frequently diagnosed in the elderly. Therefore, data on clinical characteristics and outcomes in the very young population are scarce. PATIENTS AND METHODS: We analyzed clinical characteristics, response to treatment, and survival in 103 patients with newly diagnosed MM age 40 years or younger compared with 256 patients age 41-50 years and 957 patients age 51 years or older. RESULTS: There were no statistical differences in sex, isotype, International Scoring System, renal involvement, hypercalcemia, anemia, dialysis, bony lesions, extramedullary disease, and lactate dehydrogenase (LDH). The most used regimen in young patients was cyclophosphamide, bortezomib, dexamethasone, followed by cyclophosphamide, thalidomide, dexamethasone and bortezomib, thalidomide, dexamethasone. Of the patients age 40 years or younger, only 53% received autologous stem-cell transplant (ASCT) and 71.1% received maintenance. There were no differences in overall survival (OS) in the three patient cohorts. In the multivariate analysis, only high LDH, high cytogenetic risk, and ASCT were statistically associated with survival. CONCLUSION: In conclusion, younger patients with MM in Latin America have similar clinical characteristics, responses, and OS compared with the elderly.

Mucoadhesive controlled-release formulations containing morin for the control of oral biofilms.

This study aimed to evaluate the antimicrobial and anti-biofilm activity of morin on polymicrobial biofilms and its cytotoxicity in controlled-release films and tablets based on gellan gum. Polymicrobial biofilms were formed from saliva for 48 h under an intermittent exposure regime to 1% sucrose and in contact with films or tablets of gellan gum containing 2 mg of morin each. Acidogenicity, bacterial viability, dry weight and insoluble extracellular polysaccharides from biofilms were evaluated. The cytotoxicity of morin was evaluated in oral keratinocytes. Morin released from the systems reduced the viability of all the microbial groups evaluated, as well as the dry weight and insoluble polysaccharide concentration in the matrix and promoted the control of acidogenicity when compared with the control group without the substance. Morin was cytotoxic only at the highest concentration evaluated. In conclusion, morin is an effective agent and shows antimicrobial and anti-biofilm activity against polymicrobial biofilms.

Proto-Oncogenes and Cell Cycle Gene Expression in Normal and Neoplastic Oral Epithelial Cells Stimulated With Soluble Factors From Single and Dual Biofilms of Candida albicans and Staphylococcus aureus.

This study was aimed at analyzing proto-oncogenic signaling pathway activation in normal oral keratinocytes (NOK-si) and neoplastic cell lines (SCC 25 and Detroit 562) stimulated with metabolites (soluble factors) from single and dual biofilms of Candida albicans and Staphylococcus aureus. Soluble factors (SF) from early (16-h) and mature (36-h) biofilms of C. albicans and S. aureus were collected and incubated with cell cultures, which were subsequently evaluated using gene expression via RT-qPCR, cell viability via AlamarBlueTM, and flow cytometry cell cycle analysis. In general, exposure to the SF of early and mature biofilms from C. albicans and dual species caused a major reduction in NOK-si cell viability and enhanced the sub G0 phase. This led to a decrease in gene expression. However, in this cell line, SF of S. aureus biofilms upregulated the CDKN1A gene followed by the maintenance of cell viability and a significant increase in the G2/M population. For tumor cells, SCC 25 and Detroit 562, the stimuli of SF biofilms upregulated oncogenes such as hRAS and mTOR, as well as Bcl-2 and CDKN1A. SCC 25 and Detroit 562 cells could survive even after 24 h of stimuli from both SF (early and mature). This occurred without significant changes taking place in the cell cycle progression for SCC 25, and with a significant tendency to increase the G2/M phase for Detroit 562. These results point to the fact that metabolites from prevalent clinical fungal and bacterial biofilms, C. albicans and S. aureus, can disrupt the homeostasis of normal and neoplastic oral epithelial cells. This changes proto-oncogenes' expression, specifically PI3KCA, hRAS, mTOR, BRAF, and cell cycle genes CDKN1A and Bcl-2, thus causing a disturbance in cell viability, survival, and the cell cycle profile.

Long-Term Effect of Daily Chemical Disinfection on Surface Topography and Candida Albicans Biofilm Formation on Denture Base and Reline Acrylic Resins.

PURPOSE: This study investigated the effect of long-term daily chemical disinfection on the topographic and Candida albicans biofilm formation on a denture base resin and a reline acrylic resin. MATERIAL AND METHODS: Circular samples (14 × 1.2 mm) were fabricated from a denture base (Vipi Wave) and reline acrylic resins (Tokuyama Rebase Fast II). Samples were kept in 50 ml of distilled water (48 h at 37°C). Subsequently, the samples were immersed in five different solutions: 0.5% sodium hypochlorite; 3.8% sodium perborate; 2% chlorhexidine gluconate; apple vinegar containing 4% maleic acid; and distilled water (control group). The specimen was immersed in the solutions for 8 h daily and transferred to distilled water at 37°C for more 16 h. The surface topographic and Candida albicans (ATCC 90028) biofilm formation were evaluated at baseline (before chemical disinfection) and after 1, 3 and 6 months of immersion. The surface topographic was evaluated by arithmetical roughness average (Ra) and scanning electron microscope (SEM), while the biofilm formation was evaluated by colony-forming units (CFU/ml) method and Alamar Blue assay (cell metabolism). The results were evaluated by three-way analysis of variance (ANOVAs) and post-hoc tests (α = 0.05). RESULTS: The results showed statistically significant effects from the type of acrylic resin (p = 0.029) and time (p <0.001) on the roughness of the specimen. In general, the reline resin had higher roughness than the denture base resin. In addition, the roughness of the samples after 1, 3 and 6 months of immersion in the cleaning solutions was higher than at baseline. In relation to the microbiological assays, there were no statistically significant differences (p >0.055) in the CFU/ml values of the biofilms among the different resins, periods of time and cleaning solutions. Considering the metabolism of the cells within the biofilms, the results showed that, at baseline, it was statistically significantly higher (p <0.05) than after 1, 3 and 6 months of storage. The SEM images showed that all disinfectant solutions provided surface changes of both acrylic resins (base and reline) after 1, 3 and 6 months of immersion. CONCLUSIONS: The roughness of both acrylic resins was affected by the disinfection in all cleaning agents, increasing over time, and this effect was more evident in the reline acrylic resin group. This surface change was also observed in the SEM images. While the number of cells within the biofilms was not affected by immersion in the cleaning agents, their metabolism was lower after 1, 3 and 6 months of immersion.

Properties of an acrylic resin after immersion in antiseptic soaps: Low-cost, easy-access procedure for the prevention of denture stomatitis.

Denture stomatitis triggered by Candida species requires better preventive measures. This study evaluated the physical and biological properties of a denture base acrylic resin after immersion in antiseptic soaps. Acrylic resin specimens were prepared and stored in distinct solutions for 0, 7, 14, 21, and 28 days. The solutions were as follows: DW: distilled water at 37°C (control group); DS: cycles of daily immersion in Dettol soap for 8 hours at room temperature, followed by immersion in distilled water for 16 hours at 37°C; PS: cycles of daily immersion in Protex soap, as described for the previous group; LS: cycles of daily immersion in Lifebuoy soap, as described for the DS group. The parameters evaluated at each time point were the following: biofilm formation capacity by Candida albicans and reduction of preformed fungal biofilms, cytotoxicity, surface roughness, hardness, and color change. For the fungal adhesion phase, the type of soap had a statistically significant effect (p = 0.0292), but after 24 hours, no differences were found between solutions or between storage times. Regarding the efficacy of biofilm reduction, there was a significant difference when the groups were compared to each other (p = 0.014). Dettol and Lifebuoy eliminated the preformed biofilm on the specimens. Moreover, all the soaps were classified as non-cytotoxic (on HaCaT cell line) because there was no difference in cell viability between the different groups, except after 21 days, when a decrease in cell viability occurred, regardless of the type of soap. Regarding the roughness, there was no statistically significant difference (p > 0.05) between the groups. Lifebuoy decreased resin hardness regardless of storage time (p = 0.003). After 21 and 28 days of storage, there was an increase in hardness value, regardless of the type of soap. The specimens' color, according to the National Bureau of Standards values, ranged from 0.27 to 0.58 (i.e., imperceptible or mild color changes). In general, the disinfectant soaps were not able to prevent biofilm formation, but all the soaps were effective in reducing the preformed biofilm. In addition, all soaps were non-cytotoxic and did not change surface roughness, hardness (except Lifebuoy), and color (except Lifebuoy). Therefore, immersion in two antiseptic soaps (Protex and Dettol) may be a cheap and easy procedure for preventing denture stomatitis.

Cytotoxic potential of denture base and reline acrylic resins after immersion in disinfectant solutions.

STATEMENT OF PROBLEM: The daily immersion of dentures in disinfectant solutions can cause the incorporation of toxic substances in the acrylic resins, and studies evaluating the cumulative effect of disinfectant solutions on cell culture are lacking. PURPOSE: The purpose of this in vitro study was to evaluate the cytotoxic potential of cell cultures of denture base and reline acrylic resins after immersion in disinfectant solutions. MATERIAL AND METHODS: Disk-shaped specimens (14×1.2 mm) were obtained and divided into groups (n=9) according to the disinfectant solutions (distilled water [control], 2% chlorhexidine digluconate, 3.8% sodium perborate, 0.5% sodium hypochlorite, and apple vinegar) and to the storage period (0, 1, 3, and 6 months). Solutions were changed daily. After the different storage periods, specimens were immersed in culture medium for 24 hours, and extracts were obtained. Human keratinocytes were cultivated, and the cellular metabolism was evaluated by using Alamar Blue. Data were submitted to 3-way analysis of variance and Games-Howell post hoc tests (α=.05). RESULTS: Both of the acrylic resins tested showed similar biocompatibility properties after immersion in different solutions (P=.400). Immersion in distilled water, 3.8% sodium perborate, and 0.5% sodium hypochlorite did not affect the cellular metabolism of the keratinocytes (P>.05), regardless of the immersion period and the type of acrylic resin (P>.05). Immersion in 2% chlorhexidine digluconate or apple vinegar resulted in high cytotoxicity over time, until the third month (P<.05), after which no changes were observed (P>.05). CONCLUSIONS: The type of acrylic resin (base or reline) had no significant effect on the viability of cells. Vinegar and chlorhexidine digluconate solutions increased in cytotoxic effect over time, and were strongly cytotoxic after 6 months of immersion. Sodium perborate and sodium hypochlorite were noncytotoxic in all periods of time tested.

pH-responsive poly(aspartic acid) hydrogel-coated magnetite nanoparticles for biomedical applications.

A novel multifunctional nanosystem formed by magnetite nanoparticles coated with pH-responsive poly(aspartic acid) hydrogel was developed. Magnetite nanoparticles (Fe3O4) have been intensively investigated for biomedical applications due to their magnetic properties and dimensions similar to the biostructures. Poly(aspartic acid) is a water-soluble, biodegradable and biocompatible polymer, which features makes it a potential candidate for biomedical applications. The nanoparticles surface modification was carried out by crosslinking polysuccinimide on the magnetite nanoparticles surface and hydrolyzing the succinimide units in mild alkaline medium to obtain the magnetic poly(aspartic acid) hydrogel. The surface modification in each step was confirmed by DRIFTS, TEM and zeta potential measurements. The hydrodynamic diameter of the nanosystems decreases as the pH value decreases. The nanosystems showed high colloidal stability in water and no cytotoxicity was detected, which make these nanosystems suitable for biomedical applications.