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INTRODUCTION: This study aimed to compare the characteristics and outcomes of critically ill patients with COVID-19-associated acute kidney injury (AKI) who were treated with kidney replacement therapy (KRT) in the first and second waves of the pandemic in the megalopolis of Sao Paulo, Brazil. METHODS: A multicenter retrospective study was conducted in 10 intensive care units (ICUs). Patients aged ≥18 years, and treated with KRT due to COVID-19-associated AKI were included. We compared demographic, laboratory and clinical data, KRT parameters and patient outcomes in the first and second COVID-19 waves. RESULTS: We assessed 656 patients (327 in the first wave and 329 in the second one). Second-wave patients were admitted later (7.1±5.0 vs. 5.6±3.9 days after the onset of symptoms, p<0.001), were younger (61.4±13.7 vs. 63.8±13.6 years, p = 0.023), had a lower frequency of diabetes (37.1% vs. 47.1%, p = 0.009) and obesity (29.5% vs. 40.0%, p = 0.007), had a greater need for vasopressors (93.3% vs. 84.6%, p<0.001) and mechanical ventilation (95.7% vs. 87.8%, p<0.001), and had higher lethality (84.8% vs. 72.7%, p<0.001) than first-wave patients. KRT quality markers were independently associated with a reduction in the OR for death in both pandemic waves. CONCLUSIONS: In the Sao Paulo megalopolis, the lethality of critically ill patients with COVID-19-associated AKI treated with KRT was higher in the second wave of the pandemic, despite these patients being younger and having fewer comorbidities. Potential factors related to this poor outcome were difficulties in health care access, lack of intra-hospital resources, delay vaccination and virus variants.

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PURPOSE: To evaluate the effect of application time and viscosity of meta-phosphoric acid (MPA) and ortho-phosphoric acid (OPA) on the push-out resin-dentin bond strength (PBS) and nanoleakage (NL) at the adhesive-root dentin interface. METHODS AND MATERIALS: Ninety-six roots of premolars were endodontically prepared and randomly assigned into groups according to the (i) acid (OPA and MPA), (ii) viscosity (gel and liquid), and (iii) application time (7 and 15 seconds). Fiber posts were cemented to the roots, which were then transversally sectioned into serial slices. The slices (cervical, medium, and apical) were subjected to PBS or NL. Analysis of the dentin etching pattern was performed using scanning electron microscopy (SEM). The PBS (MPa) and NL (%) data were subjected to three-way repeated-measures analysis of variance (ANOVA) and Tukey's test (α=0.05). RESULTS: The cross-product interaction was significant for both PBS and NL (p<0.001). No significant difference in the PBS was observed with the use of OPA compared to MPA (p>0.05). Higher PBS values were observed in the groups etched for 15 seconds compared to 7 seconds, regardless of the acid, viscosity, or root third (p<0.05). Lower NL was observed for MPA etching when compared to OPA etching (p<0.05), and these values were not affected by increasing the application time or acid viscosity (p>0.05). A more pronounced etching pattern was observed with OPA than MPA regardless of the acid viscosity. CONCLUSION: The use of 40% meta-phosphoric acid promoted adequate bond strength without increasing dentin demineralization or void spaces in the hybrid layer.

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Amyloidoses are a group of disorders in which soluble proteins aggregate and deposit extracellularly in tissues as insoluble fibrils, causing organ dysfunction. Clinical management depends on the subtype of the protein deposited and the affected organs. Systemic amyloidosis may stem from anomalous proteins, such as immunoglobulin light chains or serum amyloid proteins in chronic inflammation or may arise from hereditary disorders. Hereditary amyloidosis consists of a group of rare conditions that do not respond to chemotherapy, hence the identification of the amyloid subtype is essential for diagnosis, prognosis, and treatment. The kidney is the organ most frequently involved in systemic amyloidosis. Renal amyloidosis is characterized by acellular pathologic Congo red-positive deposition of amyloid fibrils in glomeruli, vessels, and/or interstitium. This disease manifests with heavy proteinuria, nephrotic syndrome, and progression to end-stage kidney failure. In some situations, it is not possible to identify the amyloid subtype using immunodetection methods, so the diagnosis remains indeterminate. In cases where hereditary amyloidosis is suspected or cannot be excluded, genetic testing should be considered. Of note, laser microdissection/mass spectrometry is currently the gold standard for accurate diagnosis of amyloidosis, especially in inconclusive cases. This article reviews the clinical manifestations and the current diagnostic landscape of renal amyloidosis.

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This study evaluated the influence of new monomers derived from cashew nut shell liquid (CNSL) applied for dentin biomodification on resin-dentin bond strength, nanoleakage, and micropermeability to sound and artificially-created caries-affected dentin. Human dentin specimens were assigned to five groups, according to the following dentin pretreatment solutions: Absolute ethanol (control), 2 wt% grape seed extract (Vitis vinifera), 2 wt% cardol [from cashew nut shell liquid (CNSL)], 2 wt% cardol-methacrylate or 2 wt% cardanol-methacrylate applied on sound and artificial caries-affected dentin. Specimens were analyzed after 24 hour or 1 year of water storage. Microtensile bond strength (µTBS) (n=6), interface micropermeability (n=3), and silver nanoleakage (n=6) were assessed using a universal testing machine, confocal laser scanning microscope, and scanning electron microscope, respectively. In sound dentin, no difference in bond strength was observed between the groups in either storage period. In artificial caries-affected dentin, pretreatment with cardol-methacrylate resulted in statistically higher bond strength than all the other treatments in both storage periods. Cardol-methacrylate treatment resulted in less nanoleakage, along with improved interfacial integrity, compared to further treatments in artificial caries-affected dentin. Regarding micropermeability analysis, all treatments depicted deficient sealing ability when applied on artificial caries-affected dentin, with the presence of gaps in the control group. In conclusion, cardol-methacrylate is a promising plant-derived monomer to reinforce the hybrid layer, since it preserved resin-dentin bond strength and improved dentin bonding, especially to caries-affected dentin, a well-known harsh substrate for adhesion longevity.

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Amyloidoses are a group of disorders in which soluble proteins aggregate and deposit extracellularly in tissues as insoluble fibrils, causing organ dysfunction. Clinical management depends on the subtype of the protein deposited and the affected organs. Systemic amyloidosis may stem from anomalous proteins, such as immunoglobulin light chains or serum amyloid proteins in chronic inflammation or may arise from hereditary disorders. Hereditary amyloidosis consists of a group of rare conditions that do not respond to chemotherapy, hence the identification of the amyloid subtype is essential for diagnosis, prognosis, and treatment. The kidney is the organ most frequently involved in systemic amyloidosis. Renal amyloidosis is characterized by acellular pathologic Congo red-positive deposition of amyloid fibrils in glomeruli, vessels, and/or interstitium. This disease manifests with heavy proteinuria, nephrotic syndrome, and progression to end-stage kidney failure. In some situations, it is not possible to identify the amyloid subtype using immunodetection methods, so the diagnosis remains indeterminate. In cases where hereditary amyloidosis is suspected or cannot be excluded, genetic testing should be considered. Of note, laser microdissection/mass spectrometry is currently the gold standard for accurate diagnosis of amyloidosis, especially in inconclusive cases. This article reviews the clinical manifestations and the current diagnostic landscape of renal amyloidosis.

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The aim of this study was to evaluate the influence of nanofiller particles in simplified universal adhesive on the long-term microtensile bond strength and silver nitrate up-take, as well as water sorption and solubility. Commercial adhesives Ambar Universal (FGM) in nanofilled-containing version (filled) and same lot without fillers (unfilled) were donated and applied by means of etch-and-rinse strategy. Microtensile bond strength was surveyed after 24-hours or 1-year water storage. Silver nitrate uptake was assayed using scanning electron microscopy (SEM). Water sorption and solubility experiments were performed based on ISO 4049:2009. Statistical analysis was performed using two-way ANOVA and Tukey test (p<0.05). The bond strength of both the adhesives were statistically similar at 24 hours (p>0.05), but the filled group attained significant bond strength reduction after aging when compared to initial bond strength (p<0.001). Conversely, unfilled adhesive presented stable adhesion after 1-year storage (p=0.262). Silver nitrate uptake was similar for both adhesives, with little silver impregnation at the hybrid and adhesive layers. Water sorption was higher with filled adhesive compared to the unfilled one (p=0.01). Conversely, solubility was higher in unfilled in comparison to filled one (p=0.008). The presence of nanofillers in universal adhesive achieves higher water sorption and dentin bond degradation, which did not occur in the unfilled adhesive.

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OBJECTIVES: Dental resins filled with hydroxyapatite (HAp) nanoparticles have significantly revolutionized restorative dentistry offering advantages such as remineralization potential and increase of polymerization. However, these materials have limited radiopacity hindering the diagnosis of secondary caries. The present study investigated the development of a new radiopaque dental adhesive by incorporating novel pure strontium hydroxyapatite nanoparticles [Sr10(PO4)6(OH)2, SrHAp] synthesized by a simple hydrothermal method. METHODS: Strontium phosphates were prepared using co-precipitation (SrHAp0h) and hydrothermal treatment for 2 and 5h (SrHAp2h and SrHAp5h). The crystallinity, crystallite size, textural and morphology features of the nanoparticles were characterized by XRD, FT-IR, micro-Raman and TEM. Strontium hydroxyapatite (SrHAp) or calcium hydroxyapatite (HAp) nanoparticles were then incorporated (10 wt%) into an adhesive resin of a commercial three-step etch-and-rinse adhesive to evaluate the radiopacity of disk-shaped specimens, degree of conversion (DC) assessed by FT-IR and mechanical properties by three-point bending test. The unfilled adhesive was used as negative control. RESULTS: While SrHAp0h and SrHAp2h resulted a phase mixing, the pure and highly crystalline phase of strontium hydroxyapatite free of calcium was obtained with 5h hydrothermal treatment (SrHAp5h). The TEM images revealed nanorods morphology for SrHAp5h. SrHAps incorporated into adhesive showed higher radiopacity, no alteration on DC despite slightly reducing the mechanical properties. SIGNIFICANCE: Although the mechanical properties are slightly impaired, incorporation of SrHAp nanoparticles offers potential method to improve radiopacity of restorative dental resins, easing the tracking of actual remineralization effects and enabling diagnosis of recurrent caries.

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OBJECTIVE: To investigate the effects of natural collagen cross-linkers incorporation in phosphoric acid etchant on dentin biomodification, microtensile bond strength (µTBS) and nanoleakage (NL) of a two-step etch-and-rinse adhesive. METHODS: Experimental aqueous solution of 37% ortho-phosphoric acid were prepared with the addition of 2% biomodification agents: Lignin (LIG) from industrial paper production residue, Cardanol (CARD) from cashew-nut shell liquid, and Proanthocyanidin (PAC) from grape-seed extract. Negative control (NC) was acid solution without cross-linker whilst commercial control (CC) was Condac 37 gel (FGM). Dentin specimens were assayed by FTIR after 15s etching to detect collagen cross-linking. Extracted third molars were used for µTBS (n=7) and fracture mode analysis of Optibond S (Kerr), tested after 24h or 1000 thermal cycles. NL was surveyed by SEM. Statistical analysis was performed with two-way ANOVA and Tukey's test (p<0.05). RESULTS: FTIR confirmed cross-linking for all agents. µTBS of CC was the highest (46.6±6.2MPa), but reduced significantly after aging (35.7±5.2MPa) (p<0.001). LIG (30.6±3.7MPa) and CARD (28.3±1.8MPa) attained similar µTBS which were stable after aging (p>0.05). Fracture mode was predominantly adhesive. At 24h, all groups showed presence of silver uptake in hybrid layer, except CARD. After aging, CARD- and LIG-treated specimens exhibited little amount of silver penetration. CC, PAC and NC showed gaps, great nanoleakage at hybrid layer and presence of water channels in adhesive layer. SIGNIFICANCE: Altogether, ortho-phosphoric acid incorporated with LIG and CARD promotes stable resin-dentin bond strength with minor nanoleakage after aging, thereby achieving therapeutic impact without additional clinical steps.

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AIMS: The aim of this study was to find new eukaryotic sources of the l-asparaginase (l-ASNase), since the prokaryotic sources of the enzyme are well-reported as causing allergic hypersensitivity reactions in a significant number of patients. This report describes screening for l-ASNase production by filamentous fungi isolated from the Brazilian Caatinga, and the optimization of fermentation parameters to increase fungal growth and improve yield in the production of l-ASNase. METHODS AND RESULTS: Thirty-two filamentous fungi were investigated in this study. When Aspergillus terreus strain S-18 was cultured in a proline-enriched medium, intracellular l-ASNase was expressed in concurrence with reduced l-glutaminase (l-GLUase) and protease activities. Fermentation conditions were then optimized in a 5-l bioreactor system to produce a maximum volumetric yield of 108 U total of l-ASNase activity. CONCLUSIONS: The work reported here represents the first attempt to produce l-ASNase by filamentous fungi isolated from Brazil and offers a promising alternative eukaryotic source for l-ASNase production. SIGNIFICANCE AND IMPACT OF THE STUDY: In order to minimize the side effects caused by bacterial l-ASNase, the search of eukaryotic micro-organism for l-ASNase was carried out in fungi. This study demonstrates the diversity of filamentous fungi isolated from the Brazilian Caatinga Biome and the importance of knowledge of the microbial metabolism to obtain high concentrations of biotechnological products.

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OBJECTIVES: Hydroxyethyl-methacrylate (HEMA) is still widely used in simplified adhesives. Indeed, several shortcomings occur with this monomer, such as water uptake and formation of linear polymers. This study aimed to compare the effects of HEMA replacement by glycerol-dimethacrylate (GDMA) on selected physicochemical properties and bonding performance of simplified model adhesives. MATERIALS AND METHODS: Experimental simplified etch-and-rinse and self-etch adhesives were formulated containing 20 wt% HEMA or GDMA. Three-point bending test was used to obtain the elastic modulus of bar-shaped specimens, and water sorption and solubility were attained by ISO-4049 (ISO, 2009) method. Degree of conversion was surveyed by Micro-Raman spectroscopy, and microtensile bond strength was tested after 24 h or 6 months simulated pulpal pressure aging. Statistical analysis was realized with two-way ANOVA and Tukey's test (p < 0.05). RESULTS: GDMA promoted higher elastic modulus to the self-etch adhesive, and GDMA-containing etch-and-rinse adhesive achieved overall lower water sorption and solubility. The degree of conversion was statistically higher for GDMA adhesives than for HEMA etch-and-rinse one. All bond strengths dropped significantly after aging, except that of GDMA self-etch adhesive. The nanoleakage was higher and gaps were found in the interface of HEMA-containing adhesives, which were less present in GDMA equivalents. CONCLUSIONS: GDMA is a feasible hydrophilic dimethacrylate monomer to replace HEMA in simplified adhesives, thereby providing better polymerization, mechanical properties and dentin adhesion as well as lower water uptake and solubility.

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