In vitro and in silico antibacterial evaluation of coumarin derivatives against MDR strains of Staphylococcus aureus and Escherichia coli.

The increase in antibiotic resistance rates has attracted the interest of researchers for antibacterial compounds capable of potentiating the activity of conventional antibiotics. Coumarin derivatives have been reported to develop effective antibacterials with possible new mechanisms of action for treating infectious diseases caused by bacteria with a profile of drug resistance. In this context, the aim of the present study we have now prepared one variety of new synthetic coumarins evaluating the pharmacokinetic and chemical similarity in silico, their antimicrobial activity against Staphylococcus aureus (ATCC 25923) and Escherichia coli (ATCC 25922), and potential for the modulation of antibiotic resistance against Staphylococcus aureus (SA10) and Escherichia coli (EC06) clinical isolate bacteria by in vitro assay. The antibacterial activity and antibiotic-enhancing properties were evaluated by the broth microdilution method and pharmacokinetically characterized according to the Lipinsk rule of 5 and had their similarity analyzed in databases such as ChemBL and CAS SciFinder. The results demonstrated that only compound C13 showed significant antibacterial activity (MIC ≤256 µg/mL), and all other coumarins did not display relevant antibacterial activity (MIC ≥1024 µg/mL). However, they did modulate the antibiotics activities to norfloxacin and gentamicin, except, compound C11 to norfloxacin against Staphylococcus aureus (SA10). The in silico properties prediction and drug-likeness results demonstrated that all coumarins presented a good drug-likeness score with no violations and promising in silico pharmacokinetic profiles showing that they have the potential to be developed into an oral drug. The results indicate that the coumarin derivatives showed good in vitro antibacterial activity. These new coumarin derivatives also demonstrated the capacity to modulate antibiotic resistance with potential synergy action for current antimicrobials assayed, as antibiotic adjuvants, to reduce the emergence of antimicrobial resistance.

Effect of randomized prophylactic nitroglycerin on radial artery spasm during transradial catheterization: An analysis based on operator experience.

One limitation to transradial access (TRA) is the occurrence of spasms (RAS), for which the use of prophylactic medications is recommended. Improvement in TRA material combined with the increase in operators' expertise, might mitigate this benefit. We assess the effect of preventive nitroglycerin on RAS during TRA, evaluating the role of the operator's experience. Patients received 500 µg nitroglycerin or placebo. The operator's expertise was classified as: inexperienced (I), intermediate (M), and experienced (E). 2040 patients were included. Prophylactic use of nitroglycerin did not reduce RAS (10.8% vs. 13.4% (placebo), p = 0.07). RAS incidence was 14.5% in I, 12.5% in M, and 9.7% in E (p = 0.01). In group I, nitroglycerin reduced RAS (17.4% vs. 11.1%, p = 0.04), which was not observed in other groups. Overall, nitroglycerin does not prevent RAS, which is more common among inexperienced operators. More experienced operators could abolish preventive nitroglycerin use.

Dihydroeugenol derivatives associated with blue LED light: A different form to face multidrug resistant (MDR) bacteria.

Eugenol has already had its pharmacological properties elucidated in previous studies, including antibacterial and antifungal properties. Based on such information, this study aimed to evaluate the antibacterial and modulatory activity of coumarin compounds prepared from dihydroeugenol and to associate them with blue LED light for the same activity. For this study, five of the substances available: compound 1 (C1), 8-methoxy-2-oxo-6-propyl-2H-chromen-3-carboxylic acid, compound (C2), 3-(hydroxy(4-nitrophenyl)methyl)-8- methoxy-6-propyl-2H-chromen-2-one, compound 7 (C3), 8-hydroxy-3-(4-nitrobenzoyl)-6-propyl-2H-chromen-2-one, compound 8 (C4), 3-(4-aminobenzoyl)-8-methoxy-6-propyl-2H-chromen-2-one and Compound 9 (C5), 8-methoxy-3-(4-nitrobenzoyl)-6-propyl-2H-chromen-2-one 2-one. To determine the MIC, the broth microdilution technique was used. The products were evaluated for their potential to modulate the activity of antibiotics. Afterward, the plates were submitted to blue LED light for 20 min. When exposed to LED, C3 exhibited a decrease in MIC for SA ATCC and C5 for EC ATCC, with an average of 645.08 µg/mL for both cases. C2 and C4 exhibited synergism in a greater number of situations. However, C3 showed promising activity against S. aureus. C1 and C2 already acted better against E. coli, with the difference that C1 acted better against these bacteria when associated with LED. In general, the compounds studied here exhibited good antibacterial activity when associated with LED.

Anti-inflammatory effect, antibiotic potentiating activity against multidrug-resistant strains of Escherichia coli and Staphylococcus aureus, and evaluation of antibiotic resistance mechanisms by the ibuprofen derivative methyl 2-(-4-isobutylphenyl)propanoate.

The prevalence of multidrug-resistant (MDR) bacteria and the limited efficacy of current available antibiotics cause every year approximately 700 000 deaths per year. This study aimed to evaluate the anti-inflammatory effect and antibacterial potential of the ibuprofen derivative Methyl 2-(-4-isobutylphenyl)propanoate (MET-IBU). The molecular structure of MET-IBU was confirmed by Nuclear Magnetic Resonance (NMR) and, Attenuated Total Reflectance Fourier Transform Infrared spectroscopy (ATR-FTIR) spectroscopy. Our in vivo study using adult zebrafish model demonstrated that the ibuprofen derivative MET-IBU also possesses anti-inflammatory effect, and in vitro antibacterial activity assays showed that in the association of ampicillin, norfloxacin, and gentamicin with MET-IBU occurred reduction in the minimum inhibitory concentration (MIC) for MDR bacterial strains of Escherichia coli 06 and Staphylococcus aureus 10, indicating a potentiating in the growth inhibition of these pathogenic bacteria. Regarding the strain of Staphylococcus aureus K2068 (overexpressing mepA gene), a potentiation of ethidium bromide was found in the association with MET-IBU, indicating the action of this compound on the efflux pump mechanism present in this strains. This result corroborates the molecular docking study that indicated a high affinity of the MET-IBU with the MepA efflux pump. It was also noticed an antibiotic potentiating activity in the association MET-IBU with norfloxacin against strains of Staphylococcus aureus 1199B (overexpressing norA gene) when compared to the norfloxacin control. This enhanced antibiotic effect of MET-IBU is associated with a second resistance mechanism, which is due to the modification in the topoisomerase enzyme. These results bring attention to the ibuprofen derivative MET-IBU as possible candidate for the development of new options for the treatment of bacterial infections with protective anti-inflammatory action.

Paradigm shift in xylose isomerase usage: a novel scenario with distinct applications.

Isomerases are enzymes that induce physical changes in a molecule without affecting the original molecular formula. Among this class of enzymes, xylose isomerases (XIs) are the most studied to date, partly due to their extensive application in industrial processes to produce high-fructose corn sirups. In recent years, the need for sustainable initiatives has triggered efforts to improve the biobased economy through the use of renewable raw materials. In this context, D-xylose usage is crucial as it is the second-most abundant sugar in nature. The application of XIs in biotransforming xylose, enabling downstream metabolism in several microorganisms, is a smart strategy for ensuring a low-carbon footprint and producing several value-added biochemicals with broad industrial applications such as in the food, cosmetics, pharmaceutical, and polymer industries. Considering recent advancements that have expanded the range of applications of XIs, this review provides a comprehensive and concise overview of XIs, from their primary sources to the biochemical and structural features that influence their mechanisms of action. This comprehensive review may help address the challenges involved in XI applications in different industries and facilitate the exploitation of xylose bioprocesses.

Electrostatic interaction optimization improves catalytic rates and thermotolerance on xylanases.

Understanding the aspects that contribute to improving proteins' biochemical properties is of high relevance for protein engineering. Properties such as the catalytic rate, thermal stability, and thermal resistance are crucial for applying enzymes in the industry. Different interactions can influence those biochemical properties of an enzyme. Among them, the surface charge-charge interactions have been a target of particular attention. In this study, we employ the Tanford-Kirkwood solvent accessibility model using the Monte Carlo algorithm (TKSA-MC) to predict possible interactions that could improve stability and catalytic rate of a WT xylanase (XynAWT) and its M6 xylanase (XynAM6) mutant. The modeling prediction indicates that mutating from a lysine in position 99 to a glutamic acid (K99E) favors the native state stabilization in both xylanases. Our lab results showed that mutated xylanases had their thermotolerance and catalytic rate increased, which conferred higher processivity of delignified sugarcane bagasse. The TKSA-MC approach employed here is presented as an efficient computational-based design strategy that can be applied to improve the thermal resistance of enzymes with industrial and biotechnological applications.

Mid- to long-term clinical and echocardiographic outcomes after transcatheter aortic valve replacement with a new-generation, self-expandable system.

OBJECTIVES: The aim of the study was to evaluate mid- to late clinical and echocardiographic outcomes after transcatheter aortic valve replacement (TAVR) with Acurate neo™ (Boston Scientific, Boston, MA). BACKGROUND: TAVR is an established treatment for aortic stenosis (AS). Few data exist on mid- to long-term outcomes and durability after new-generation valves. METHODS: All consecutive patients (n = 104) who underwent Acurate neo™ implantation from 2012 to 2018 were included. Follow-up was systematically performed at 1, 6, 12, and 24 months and yearly thereafter. Outcomes were reported according to VARC-2, and structural valve deterioration (SVD) or bioprosthetic valve failure defined accordingly to new definitions. RESULTS: Mean age was 82 ± 5.4 years, 56.7% were female and the Society of Thoracic Surgeons score for mortality was 5.9 ± 4%. Patients were followed for a median of 3 years (1,092 days; IQR 1.5-4 years), and the maximum follow-up was 7 years. All-cause mortality values at 1 and 5 years were 8.5% and 40.5%, respectively. No relevant changes in mean gradient and orifice area occurred (7.9 ± 3.8 mmHg and 1.9 ± 0.3 cm2 at 1 year; 6.6 ± 2.1 mmHg and 1.8 ± 0.3 cm2 at 5 years), and there was a significant rate of paravalvular leaks resolution at 1, 2, and 3 years (p = .004; p < .001; p < .001, respectively). None of the patients had leaflet thrombosis or endocarditis. One patient developed SVD at 84 months. CONCLUSIONS: Acurate neo™ was associated with sustained echocardiographic results. Reassuring mid- to long-term outcomes was observed in this cohort of elderly patients with severe AS.

Predictive role of Selvester QRS score in patients undergoing transcatheter aortic valve replacement.

INTRODUCTION: Few data exist regarding the late clinical impact of the Selvester score prediction of myocardial fibrosis after transcatheter aortic valve replacement (TAVR). This study evaluated the predictive power of the Selvester score on survival in patients with aortic stenosis (AS) undergoing TAVR. METHODS AND RESULTS: Patients with severe AS who had preoperative electrocardiograms were included. Clinical follow-up was obtained retrospectively. The primary endpoint was all-cause mortality. Secondary endpoints were cardiovascular death and major adverse cardiac events (MACEs). Two-hundred twenty-eight patients were included (mean age, 81.5 ± 7.4 years; women, 58.3%). Deceased patients had a higher mean score (4.6 ± 3.2 vs. 1.4 ± 1.3; p < .001). At a mean follow-up of 36.2 ± 21.2 months, the Selvester score was independently associated with all-cause mortality (hazard ratio [HR], 1.65; 95% confidence interval [CI], 1.48-1.84; p < .001), cardiovascular death (HR, 1.59; 95% CI, 1.38-1.74; p < .001), and MACE (HR, 1.55; 95% CI, 1.30-1.68; p < .001). After 5 years, the mortality risk was incrementally related to the Selvester score. The involvement of the inferior wall of the left ventricle was a lower mortality risk factor (HR, 0.42; 95% CI, 0.18-0.98; p = .046). For a Selvester score of 3, the area under the curve showed 0.92, 0.94, and 0.86 (p < .001), respectively, for 1, 2, and 3 years. CONCLUSIONS: Elevated Selvester scores increase the risk of poor outcomes in patients with AS undergoing TAVR. The involvement of the anterior or lateral wall presents worse prognosis.

Evaluation of chelating and cytoprotective activity of vanillin against the toxic action of mercuric chloride as an alternative for phytoremediation.

Mercury is widely found in nature, however, in low concentrations, but anthropological activities have increased its concentration considerably. This causes various environmental hazards and human health. Many substances are capable of reversing the toxicity of mercuric chloride in the environment. The aim of the present study was to determine the chelating effect of vanillin, as well as to evaluate its capacity for cytoprotection in prokaryotic and eukaryotic plant models. Chelating activity was determined from vanillin's ability to reduce iron III ions. To evaluate cytoprotection in a unicellular prokaryotic and eukaryotic model, Escherichia coli and Candida albicans, respectively, were used. And to evaluate the cytoprotective activity in vegetables, lettuce seeds were submitted to different concentrations of mercuric chloride and its association with the sub-allelopathic concentration of vanillin (32 µg/mL). Vanillin has been found to have antioxidant activity as it can reduce iron III ions. The use of vanillin also allows for better growth and development of Lactuca sativa seed root and stem, also allowing better preservation of its biochemical structures. These results are quite important, as environmental contamination by heavy metals has increased dramatically and finding a viable alternative to grow vegetables in contaminated areas is very valid.

FTIR analysis of pyrogallol and phytotoxicity-reductive effect against mercury chloride.

Human activities, especially in industry, have contributed to soil contamination with heavy or toxic metals. The objective of this study was to determine the chelating effect and antioxidant activity of pyrogallol, as well as to evaluate its cytoprotective activity in prokaryotic and eukaryotic models, animal and plant, respectively, against toxic mercury chloride action. Antioxidant activity was determined by DPPH where pyrogallol showed considerable action, chelating even iron ions. For the microbiologic activity assays, microdilution was performed to obtain the minimal inhibitory concentration, minimum bactericidal and minimum fungicide concentration, from which the sub-inhibitory concentrations were determined. The product did not conferred cytoprotection to the tested bacteria and fungi. To evaluate plant cytoprotection, Lactuta sativa seeds were used together with the product at a sub-allelopathic concentration with different HgCl2 concentrations. In this case, the tannin conferred cytoprotection to the plant model, allowing the best growth and development of caulicles and radicles, thus preserving tissues necessary for plant survival. From the results, it is observable that pyrogallol possesses cytoprotective action in the eukaryotic plant model, this action being useful as an alternative which favors the growth of plants in contaminated areas, as the recovering of crop fields or reforestation projects.

Phytochemical characterization of the Ziziphus joazeiro Mart. metabolites by UPLC-QTOF and antifungal activity evaluation.

The aim of this study was to evaluate the antifungal and modulatory potential of the Ziziphus joazeiro bark and leaf extracts, both in isolation and in association with fluconazole, against resistant species from the Candida genus. Antifungal assays were used to determine the half maximal inhibitory concentration (IC50) of the extract in isolation and in combination with fluconazole using the broth microdilution method and spectrophotometric readings, followed by verification of the minimum fungicidal concentration by solid medium subculture. According to the cell viability curve, both extracts inhibited fungal growth in a concentration dependent manner, in addition to showing inhibitory concentrations similar to fluconazole. However, the extracts behaved in a fungistatic manner with minimum inhibitory concentration > 8.19 mg/mL and IC50 values ranging from 0.450 mg/mL to 9 mg/mL. The minimum inhibitory concentration for both extracts decreased when in combination with fluconazole, with the AEL standing out against Candida albicans URM 4387, displaying an IC50 equal to that of fluconazole (0.002 mg/mL). Nevertheless, fluconazole antagonism was observed against the tested strains. Overall, the evaluation of both extracts against Candida spp. presented inhibitory concentration values greater than fluconazole. Moreover, despite these being chemically complex crude extracts, they did demonstrate antifungal effects and properties that concur with their ethno-biological aspect.

Redox potential as a key parameter for monitoring and optimization of xylose fermentation with yeast Spathaspora passalidarum under limited-oxygen conditions.

The determination of optimum values of volumetric oxygen transfer coefficient (kLa) for Spathaspora passalidarum is an important aspect for the optimization of ethanol production from pentoses since oxygen plays a key role on yeast metabolism. By studying the fermentation of a xylose and glucose mixture, the highest ethanol volumetric productivity was achieved at a kLa of 45 h-1 (1.12 gethanol L-1 h-1), reducing the fermentation time to half when compared to other oxygen-limiting conditions that were considered optimum for other native strains, besides increasing xylose consumption rates. The high cell density fermentation showed to be a good strategy to be applied in industrial processes with S. passalidarum, enabling the complete exhaustion of a high initial substrate concentration (90 g L-1) in less than 24 h, with a final ethanol titer of 28.61 (± 0.42) g L-1. By performing a detailed investigation on oxidation-reduction potential (ORP), it was possible to conclude that the highest ethanol formation rates were registered at oxireduction potential values around - 100 mV, becoming an important parameter to be controlled when oxygen-limiting conditions are applied in industrial fermentations. The oxygen availability also affected the activity of enzyme XR and its preference for NADH or NADPH, directly affecting the activity of enzyme XDH and the redox imbalance on the xylose pathway. In addition, respirometric parameters were determined for the yeast S. passalidarum under an aerobic growth condition.

Effects of Far-Infrared Emitting Ceramic Materials on Recovery During 2-Week Preseason of Elite Futsal Players.

Nunes, RFH, Cidral-Filho, FJ, Flores, LJF, Nakamura, FY, Rodriguez, HFM, Bobinski, F, De Sousa, A, Petronilho, F, Danielski, LG, Martins, MM, Martins, DF, and Guglielmo, LGA. Effects of far-infrared emitting ceramic materials on recovery during 2-week preseason of elite futsal players. J Strength Cond Res 34(1): 235-248, 2020-We investigated the effects of far-infrared emitting ceramic materials (cFIR) during overnight sleep on neuromuscular, biochemical and perceptual markers in futsal players. Twenty athletes performed a 2-week preseason training program and during sleep wore bioceramic (BIO; n = 10) or placebo pants (PL; n = 10). Performance (countermovement jump [CMJ]; squat jump [SJ]; sprints 5, 10, and 15-m) and biochemical markers (tumor necrosis factor alpha-TNF-α, interleukin 10-IL-10, thiobarbituric acid-reactive species [TBARS], carbonyl, superoxide dismutase [SOD], catalase [CAT]) were obtained at baseline and after the 1st and 2nd week of training. Delayed-onset muscle soreness (DOMS) and training strain were monitored throughout. Changes in ΔCMJ and ΔSJ were possibly (60/36/4 [week-1]) and likely (76/22/2 [week-2]) higher in BIO. Both groups were faster in 5-m sprint in week 2 compared with baseline (p = 0.015), furthermore, BIO was likely faster in 10-m sprint (3/25/72 [week 1]). Significant group × time interaction in %ΔTNF-α were observed (p = 0.024 [week-1]; p = 0.021 [week-2]) with values possibly (53/44/3 [week 1]) and likely (80/19/1 [week 2]) higher in BIO. The %ΔIL-10 decreased across weeks compared with baseline (p = 0.019 [week-1]; p = 0.026 [week-2]), showing values likely higher in BIO (81/16/3 [week-1]; 80/17/3 [week-2]). Significant weekly increases in %ΔTBARS (p = 0.001 [week-1]; p = 0.011 [week-2]) and %ΔCarbonyl (p = 0.002 [week-1]; p < 0.001 [week-2]) were observed compared with baseline, showing likely (91/5/4 [week-1]) and possibly (68/30/2 [week-2]) higher changes in BIO. Significant weekly decreases in %ΔSOD were observed compared with baseline (p = 0.046 [week 1]; p = 0.011 [week-2]), and between week 2 and week 1 (p = 0.021), in addition to significant decreases in %ΔCAT compared with baseline (p = 0.070 [week 1]; p = 0.012 [week 2]). Training strain (p = 0.021; very -likely [0/2/98]; week 1) and DOMS was lower in BIO (likely; 7 sessions) with differences over time (p = 0.001). The results suggest that the daily use of cFIR clothing could facilitate recovery, especially on perceptual markers during the early phases of an intensive training period.

Phytotoxicity reduction of the mercury chloride effect by natural products from Eugenia jambolana Lam.: A new strategy against the toxic metal pollution.

The objective of this work was to evaluate the antioxidant, metal chelating and cytoprotective activity of the Eugenia jambolana Lam. extract, as well as of its flavonoid and tannic fractions, against the action of Mercury Chloride (HgCl2). Flavonoids were quantified and an LC-MS chromatographic analysis was performed to identify secondary metabolites. Fe2+ and Fe3+ chelation tests and antioxidant activity were carried out using the FRAP method. Microbiological tests were performed by microdilution to determine the Minimum Inhibitory Concentration (MIC). From these results the Minimum Bactericidal (MBC) and Minimum Fungicide Concentration (MFC) were evaluated. The allelopathy and cytoprotection assays were performed using eukaryotic and prokaryotic models. The results revealed the presence of phenolic acids and flavonoids in the E. jambolana extract and fractions. The sub-allelopathic concentration (64 µg/mL) was used and the results demonstrated the E. jambolana potential cytoprotective effect against mercury chloride.

Rationale and design of the Statins Evaluation in Coronary procedUres and REvascularization: The SECURE-PCI Trial.

BACKGROUND: Previous evidence suggests that acute treatment with statins reduce atherosclerotic complications, including periprocedural myocardial infarction, but currently, there are no large, adequately powered studies to define the effects of early, high-dose statins in patients with acute coronary syndrome (ACS) and planned invasive management. OBJECTIVES: The main goal of Statins Evaluation in Coronary procedUres and REvascularization (SECURE-PCI) Trial is to determine whether the early use of a loading dose of 80 mg of atorvastatin before an intended percutaneous coronary intervention followed by an additional dose of 80 mg 24 hours after the procedure will be able to reduce the rates of major cardiovascular events at 30 days in patients with an ACS. DESIGN: The SECURE-PCI study is a pragmatic, multicenter, double-blind, placebo-controlled randomized trial planned to enroll around 4,200 patients in 58 different sites in Brazil. The primary outcome is the rate of major cardiovascular events at 30 days defined as a composite of all-cause mortality, nonfatal acute myocardial infarction, nonfatal stroke, and coronary revascularization. SUMMARY: The SECURE PCI is a large randomized trial testing a strategy of early, high-dose statin in patients with ACS and will provide important information about the acute treatment of this patient population.

New roles of fluoxetine in pharmacology: Antibacterial effect and modulation of antibiotic activity.

The antimicrobial activity of psychotropic drugs, especially those of the class of mainly phenothiazines has been previously reported. Other drugs, including verapamil and trifluoperazine demonstrated to be effective against multidrug-resistant strains. Selective serotonin reuptake inhibitors (SSRIs) are antidepressant drugs that have presented significant activity against resistant bacterial resistance, but the antibacterial effect as well the antibiotic modulating properties of fluoxetine remain to be elucidated. Therefore, the present study aimed to evaluate in vitro, the antibacterial effect and the antibiotic modulating activity of fluoxetine against standard and multiresistant bacterial strains. The microorganisms used were Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli. For the antibacterial tests, 10 mg fluoxetine hydrochloride were and diluted in 1 mL of dimethyl sulfoxide (DMSO) and then diluted in sterile distilled water to a concentration of 1024 µg/mL. To determine the Minimum Inhibitory Concentrations (MICs), the drugs were diluted to concentrations ranging from 512 to 0.5 µg/mL in 96-well microdilution plates. The evaluation of the modulatory activity of fluoxetine was performed by combining this drug with the following antibiotics: Erythromycin, Gentamicin, Imipenem, Norfloxacin and Tetracycline at subinhibitory concentrations (MIC/8). Our results demonstrated that the MIC fluoxetine were 256 and 102 µg/mL against standard and resistant strains of S. aureus, respectively. The MIC of fluoxetine against both standard and resistant strains of P. aeruginosa was 161 µg/mL and against E. coli, the MIC of fluoxetine was 102 µg/mL for both standard and resistant strains, demonstrating that this drug present significant antibacterial activity. The association of fluoxetine with gentamicin and erythromycin P. aeruginosa and E. coli presented synergistic effects, demonstrating that this drug can selectively modulate the activity of antibiotics of clinical use. In conclusion, fluoxetine presented significant antibacterial effect and potential antibiotic modulating activity against multiresistant bacteria. Therefore, additional studies are needed to characterize the antimicrobial properties of this drug, as well as the clinical implications of its use in the treatment of infections by resistant microorganisms.

Serial intravascular ultrasound evaluation of the DESolve™ novolimus-eluting bioresorbable coronary scaffold system.

INTRODUCTION: Bioresorbable coronary scaffolds (BRS) have been developed to increase the late safety of coronary angioplasty by providing transitory coronary support and then being fully incorporated to the vessel wall. In the present trial, we sought to evaluate the performance and changes over time in the DESolve™ novolimus-eluting BRS using serial intravascular ultrasound (IVUS) in patients submitted to percutaneous coronary interventions. METHODS: Single-center, prospective, non-randomized study involving 17 consecutive patients submitted to implantation of the DESolve™ scaffold and serial evaluated with IVUS at different time points (post procedure, 6 and 18 months). Primary endpoint included the variation in lumen, scaffold, and vessel diameter and area along the months. RESULTS: Angiographic success was achieved in all cases. Scaffold area and volume on IVUS were significantly greater at 6 months than at baseline (6.41 ± 1.35 mm2 vs. 7.35 ± 1.53 mm2 , P < 0.002; and 101.19 ± 20.9 mm3 vs. 118.51 ± 26.6 mm3 , P = 0.001). Late lumen loss was 0.22 ± 0.30 mm at 6 months and 0.33 ± 0.44 mm at 18 months. No major adverse cardiac events occurred. At late follow-up (18 months) the scaffold was not visualized by IVUS; therefore the evaluation was restricted to lumen and vessel at that time point. CONCLUSIONS: IVUS serial evaluation of the novel DESolve BRS showed an increase in the device dimensions between baseline and 6 months, with concomitant enlargement of lumen dimensions and effective suppression of neointimal proliferation. At 18 months, no footprint of the scaffold was detected and the initial lumen enlargement was sustained.

Effect of Loading Dose of Atorvastatin Prior to Planned Percutaneous Coronary Intervention on Major Adverse Cardiovascular Events in Acute Coronary Syndrome: The SECURE-PCI Randomized Clinical Trial.

Importance: The effects of loading doses of statins on clinical outcomes in patients with acute coronary syndrome (ACS) and planned invasive management remain uncertain. Objective: To determine if periprocedural loading doses of atorvastatin decrease 30-day major adverse cardiovascular events (MACE) in patients with ACS and planned invasive management. Design, Setting, and Participants: Multicenter, double-blind, placebo-controlled, randomized clinical trial conducted at 53 sites in Brazil among 4191 patients with ACS evaluated with coronary angiography to proceed with a percutaneous coronary intervention (PCI) if anatomically feasible. Enrollment occurred between April 18, 2012, and October 6, 2017. Final follow-up for 30-day outcomes was on November 6, 2017. Interventions: Patients were randomized to receive 2 loading doses of 80 mg of atorvastatin (n = 2087) or matching placebo (n = 2104) before and 24 hours after a planned PCI. All patients received 40 mg of atorvastatin for 30 days starting 24 hours after the second dose of study medication. Main Outcomes and Measures: The primary outcome was MACE, defined as a composite of all-cause mortality, myocardial infarction, stroke, and unplanned coronary revascularization through 30 days. Results: Among the 4191 patients (mean age, 61.8 [SD, 11.5] years; 1085 women [25.9%]) enrolled, 4163 (99.3%) completed 30-day follow-up. A total of 2710 (64.7%) underwent PCI, 333 (8%) underwent coronary artery bypass graft surgery, and 1144 (27.3%) had exclusively medical management. At 30 days, 130 patients in the atorvastatin group (6.2%) and 149 in the placebo group (7.1%) had a MACE (absolute difference, 0.85% [95% CI, -0.70% to 2.41%]; hazard ratio, 0.88; 95% CI, 0.69-1.11; P = .27). No cases of hepatic failure were reported; 3 cases of rhabdomyolysis were reported in the placebo group (0.1%) and 0 in the atorvastatin group. Conclusions and Relevance: Among patients with ACS and planned invasive management with PCI, periprocedural loading doses of atorvastatin did not reduce the rate of MACE at 30 days. These findings do not support the routine use of loading doses of atorvastatin among unselected patients with ACS and intended invasive management. Trial Registration: clinicaltrials.gov Identifier: NCT01448642.

In vitro tooth reattachment techniques: A systematic review.

BACKGROUND/AIMS: Fragment reattachment is a procedure that offers advantages, such as preservation of tooth structure and maintenance of color, shape, and translucency of the original tooth. The aim of this study was to analyze the reattachment techniques used to restore anterior teeth fractured by trauma. MATERIALS AND METHODS: The PubMed, LILACS, Web of Science, Cochrane, and Scopus databases were searched in October 2016, and the search was updated in February 2017. A search of the gray literature was performed in Google Scholar and OpenGrey. Reference lists of eligible studies were evaluated to identify additional studies. Two authors assessed studies for inclusion and extracted the data. In vitro studies that evaluated permanent human teeth fractured by trauma were included. RESULTS: Twenty-one studies remained after screening. The bond strength between the fragment and the crown was evaluated in 119 experimental groups. Ten different techniques were evaluated as follows: no preparation, chamfer, bevel, anchors, overcontour, internal groove, no preparation associated with chamfer after reattachment, fragment dentin removal associated with chamfer after reattachment, bevel associated with overcontour, and groove associated with shoulder. Five different materials were used to reattach the fragment: bonding system, luting composite resin, flowable composite, microhybrid composite, and nanocomposite. CONCLUSION: Fragment reattachment using a technique with no preparation and an adhesive system associated with an intermediate composite with good mechanical properties can restore part of the resistance of the fractured tooth.

Comparison of a vascular closure device versus the radial approach to reduce access site complications in non-ST-segment elevation acute coronary syndrome patients: The angio-seal versus the radial approach in acute coronary syndrome trial.

OBJECTIVES: To compare the radial versus femoral approach using Angio-Seal for the incidence of access site complications among non-ST-segment elevation acute coronary syndrome patients undergoing invasive strategy. BACKGROUND: Arterial access is a major site of complications after invasive coronary procedures. Vascular closure devices provide more comfort to patients decreasing time to hemostasis and need for bed rest. However, the inconsistency of data proving their safety limits their routine adoption as a strategy to prevent vascular complications. METHODS: Single-center non-inferiority trial where 240 patients were randomized to radial or femoral access using Angio-Seal. The primary objective was the occurrence of complications at the arterial puncture site until 30 days after the procedure. RESULTS: There were no baseline clinical differences between groups, except for a greater prevalence of female patients in the radial group (33.3 vs. 20.0%, P = 0.020). Hemostasis was achieved in the entire radial group with the use of TR Band and in 95% of the procedures in the femoral group with Angio-Seal (P = 0.029). Except for a higher incidence of asymptomatic arterial occlusion in the radial group, there were no differences among the other analyzed outcomes. According to the noninferiority test, the use of Angio-Seal was noninferior to the radial approach, considering the margin of 15% (12.5 vs. 13.3%, difference -0.83%, 95% CI -9.31 - 7.65, P for noninferiority <0.001). CONCLUSIONS: Angio-Seal seems noninferior in the incidence of access site complications at 30 days when compared with the radial approach. © 2016 Wiley Periodicals, Inc.