Indium(III) complexes with lapachol: cytotoxic effects against human breast tumor cells and interactions with DNA.

Lapachol (2-hydroxy-3-(3-methylbut-2-en-1-yl)naphthalene-1,4-dione) is a 1,4-naphthoquinone-derived natural product that presents numerous bioactivities and was shown to have cytotoxic effects against several human tumor cells. Indium(III) complexes with a variety of ligands also exhibit antineoplastic activity. Indium(III) complexes [In(lap)Cl2].4H2O (1), [In(lap)2Cl(Et3N)] (2), [In(lap)3]·2H2O (3) [In(lap)(bipy)Cl2] bipy = 2,2'-bipyridine (4) and [In(lap)(phen)Cl2] phen = 1,10-phenanthroline (5) were obtained with 2-hydroxy-3-(3-methylbut-2-en-1-yl)naphthalene-1,4-dione (lapachol). Crystal structure determinations for (4) and (5) revealed that the indium(III) center is coordinated to two O atoms from lapachol, two N atoms from 1,10-phenanthroline or 2,2'-bipyridine, and two chloride anions, in a distorted octahedral geometry. Although both complexes (4) and (5) interacted with CT-DNA in vitro by an intercalative mode, only 5 exhibited cytotoxicity against MCF-7 and MDA-MB breast tumor cells. 1,10-phenanthroline and complex (5) presented cytotoxic effects against MCF-7 and MDA-MB cells, with complex (5) being threefold more active than 1,10-phenanthroline on MCF-7 cells. In addition, complex (5) significantly reduced the formation of MDA-MB-231 colonies in a clonogenicity assay. The foregoing results suggest that further studies on the cytotoxic effects and cellular targets of complex (5) are of utmost relevance.

The impact of methylene blue in colon cancer: a retrospective multicentric study.

INTRODUCTION: Discussions about the optimal lymph node (LN) count and its therapeutic consequences have persisted over time. The final LN count in colorectal tissues is affected by a variety of variables (patient, tumor, operation, pathologist, immune response). Methylene blue (MB) intra-arterial injection is a simple and inexpensive procedure that can be used to enhance lymph node count. AIM: Analyze whether there is a statistically significant difference between intra-arterial methylene blue injection and conventional dissection for the quantification of lymph nodes and determine if there is a variation in the quality of lymph node acquisition. METHODS AND RESULTS: Between 2015 and 2022, we conducted a retrospective analysis of colon cancer specimens. Data on the tumor's features, the number of lymph nodes, the number of lymph nodes that were positive, and other factors had been collected. The number of identified lymph nodes was highly significantly improved in the study group (P < 0.05). There is not a significant statistical difference between groups regarding the metastatic lymph node harvest. The group with injection of intra-arterial methylene blue shows a significantly decreased (P < 0.05) of the of cases with less than 12 lymph nodes recovered comparing with the control group. CONCLUSION: Colon cancer specimens can be easily evaluated concerning lymph nodes using the methylene blue method. Therefore, we strongly advise this approach as a standard procedure in the histological evaluation of colon cancer specimens in order to maximize the identification of lymph nodes. However, the detection of metastatic lymph nodes was unaffected significantly.

Green manure (Crotalaria juncea L.) enhances Origanum vulgare L. biomass accumulation, essential oil yield, and phytochemical properties.

Green manure (GM) may reduce the use of chemical fertilizers, been an ecologically appropriate strategy to cultivation of medicinal plants. Crotalaria juncea, is one of the most used because it adapts to different climatic and high nitrogen content. Origanum vulgare. is widely used in cooking, pharmaceutical, cosmetic industries and food products. The objectives of this study were to evaluate the GM on biomass, essential oil (EO), phenolic and antioxidant. The experiment consisted: control; 150, 300, 450, and 600 g (Sh= leaves+steam) more 200 g roots (R); 600 g aerial part; 200 g roots; and soil with 300 g cattle manure per pot. The highest dry weights were observed in the presence of GM and cattle manure (90 days). The control had an EO production 75% lower in relation to the dose of 450 g GM (Sh+R). Principal component analysis showed that GM and cattle manure positively influenced the dry weight, content, yield, and EO constituents, and total flavonoids. The GM contributed to the accumulation of the major EO compounds (trans-sabinene hydrate, thymol, terpinen-4-ol). The GM management may be beneficial for cultivating, because it can increase the production of biomass and the active components, in addition to being an inexpensive resource.

SARS-CoV-2 genomics and impact on clinical care for COVID-19.

The emergence and worldwide spread of SARS-CoV-2 during the COVID-19 pandemic necessitated the adaptation and rapid deployment of viral WGS and analysis techniques that had been previously applied on a more limited basis to other viral pathogens, such as HIV and influenza viruses. The need for WGS was driven in part by the low mutation rate of SARS-CoV-2, which necessitated measuring variation along the entire genome sequence to effectively differentiate lineages and characterize viral evolution. Several WGS approaches designed to maximize throughput and accuracy were quickly adopted by surveillance labs around the world. These broad-based SARS-CoV-2 genomic sequencing efforts revealed ongoing evolution of the virus, highlighted by the successive emergence of new viral variants throughout the course of the pandemic. These genomic insights were instrumental in characterizing the effects of viral mutations on transmissibility, immune escape and viral tropism, which in turn helped guide public health policy, the use of monoclonal antibody therapeutics and vaccine development strategies. As the use of direct-acting antivirals for the treatment of COVID-19 became more widespread, the potential for emergence of antiviral resistance has driven ongoing efforts to delineate resistance mutations and to monitor global sequence databases for their emergence. Given the critical role of viral genomics in the international effort to combat the COVID-19 pandemic, coordinated efforts should be made to expand global genomic surveillance capacity and infrastructure towards the anticipation and prevention of future pandemics.

Inhibition of α-Glycosidase by Lippia dulcis Trevir. (Verbenaceae) Preparations, Quantification of Verbascoside, and Study of Its Molecular Docking.

This study aimed to quantify verbascoside (VEB), perform molecular docking studies of VEB with the α-glucosidase (GL) of Bacillus stearothermophilus, and evaluate the inhibition of the enzyme by L. dulcis preparations. The substrate concentration and presence of reduced glutathione were evaluated for their effect on the in vitro inhibition of the GL enzyme. Assays were also performed in the presence and absence of simulated gastric fluid. The antidiabetic fractions 2 and 3 were the most inhibited GL, but their activity were significantly decreased in the presence of gastric fluid. Chromatographic analyses confirmed the predominant presence of VEB in the samples. The samples had VEB concentrations between 49.9 and 243.5 mg/g. Simulation of the molecular docking of VEB were consistent with its GL-inhibitory activity. It can conclude that the crude ethanol extract and fractions show inhibitory activity against the GL enzyme.

Impact of Colored Shade Nets on Biomass Production, Essential Oil Composition and Orientin and Isoorientin Content in Lippia gracilis Schauer.

The objective of this study was to evaluate the effect of ChromatiNet on vegetative growth, total antioxidant capacity, phenolic and essential oils (EOs) composition of Lippia gracilis. The plants were cultivated under full sunlight, black, blue and red ChromatiNet. The flavonoid content and antioxidant capacity were quantified spectrophotometrically. The C-glycosylflavone isomers (orientin and isoorientin) were isolated and identified by conventional spectroscopic techniques and measured using high-performance liquid chromatography-diode array detection. The EO was analysed by gas chromatography and gas chromatography-mass spectrometry. Environment influenced growth, total antioxidant capacity and phytochemical levels. Shoot dry weight, thymol, carvacrol and (E)-caryophyllene were favoured under red and black ChromatiNet. Root growth, EOs, caryophyllene oxide, p-cymene, flavonoids, orientin and isoorientin were favoured in sunlight. Growth and accumulation of EOs, flavonoids and photosynthetic pigments increased under blue ChromatiNet. Therefore, Lippia gracilis plants have plasticity related to the spectral quality of light and it cultivate depends of the phytochemicals of interest.

Secretome as a Tool to Treat Neurological Conditions: Are We Ready?

Due to their characteristics, mesenchymal stem cells (MSCs) are considered a potential therapy for brain tissue injury or degeneration. Nevertheless, despite the promising results observed, there has been a growing interest in the use of cell-free therapies in regenerative medicine, such as the use of stem cell secretome. This review provides an in-depth compilation of data regarding the secretome composition, protocols used for its preparation, as well as existing information on the impact of secretome administration on various brain conditions, pointing out gaps and highlighting relevant findings. Moreover, due to the ability of MSCs to respond differently depending on their microenvironment, preconditioning of MSCs has been used to modulate their composition and, consequently, their therapeutic potential. The different strategies used to modulate the MSC secretome were also reviewed. Although secretome administration was effective in improving functional impairments, regeneration, neuroprotection, and reducing inflammation in brain tissue, a high variability in secretome preparation and administration was identified, compromising the transposition of preclinical data to clinical studies. Indeed, there are no reports of the use of secretome in clinical trials. Despite the existing limitations and lack of clinical data, secretome administration is a potential tool for the treatment of various diseases that impact the CNS.

In vitro assessment of the effect of luting agents, abutment height, and fatigue on the retention of zirconia crowns luted to titanium base implant abutments.

STATEMENT OF PROBLEM: The bonding of implant-supported prostheses is determined by abutment material, convergence angle, height, surface treatment, and luting agents. However, studies evaluating the bonding of luting agents to titanium base abutments with different heights under fatigue conditions are scarce. PURPOSE: The purpose of this in vitro study was to evaluate the retention of zirconia crowns bonded with different luting agents to titanium base abutments of different heights before and after fatigue testing. MATERIAL AND METHODS: Zirconia crowns were designed, milled, and distributed into 4 experimental groups according to the luting agents (G-Multi Primer/G-Cem LinkForce [MP/GC] and Scotchbond Universal/RelyX Ultimate [SU/RU]) and titanium base abutment heights (2.5 mm and 4 mm) (n=10). Pull-out testing was performed in a universal testing machine at a crosshead speed of 1 mm/min until crown displacement. Fatigue testing was performed by an electric precision fatigue simulator (1×106 cycles; 100 N; and 15 Hz), followed by pull-out testing of fatigued specimens. Collected data were statistically evaluated by using a linear mixed model after post hoc comparisons by the least significant difference test (α=.05). RESULTS: Luting agents, abutment heights, and fatigue influenced the bonding retention of zirconia crowns to titanium base abutments. SU/RU agents promoted higher pull-out compared with MP/GC for both abutment heights before and after fatigue. Higher abutment height increased pull-out regarding lower abutment height for SU/RU materials before and after fatigue testing. Although fatigue had no significant effect on the pull-out of MP/GC, lower bond retention was observed for SU/RU after fatigue, regardless of abutment height. CONCLUSIONS: Luting agent composition and the interaction with abutment height and fatigue influenced the retention of zirconia crowns to titanium base abutments.

Development of the HIV360 international core set of outcome measures for adults living with HIV: A consensus process.

OBJECTIVES: HIV outcomes centre primarily around clinical markers with limited focus on patient-reported outcomes. With a global trend towards capturing the outcomes that matter most to patients, there is agreement that standardizing the definition of value in HIV care is key to their incorporation. This study aims to address the lack of routine, standardized data in HIV care. METHODS: An international working group (WG) of 37 experts and patients, and a steering group (SG) of 18 experts were convened from 14 countries. The project team (PT) identified outcomes by conducting a literature review, screening 1979 articles and reviewing the full texts of 547 of these articles. Semi-structured interviews and advisory groups were performed with the WG, SG and people living with HIV to add to the list of potentially relevant outcomes. The WG voted via a modified Delphi process - informed by six Zoom calls - to establish a core set of outcomes for use in clinical practice. RESULTS: From 156 identified outcomes, consensus was reached to include three patient-reported outcomes, four clinician-reported measures and one administratively reported outcome; standardized measures were included. The WG also reached agreement to measure 22 risk-adjustment variables. This outcome set can be applied to any person living with HIV aged > 18 years. CONCLUSIONS: Adoption of the HIV360 outcome set will enable healthcare providers to record, compare and integrate standardized metrics across treatment sites to drive quality improvement in HIV care.

Rehabilitation of Atrophic Maxilla With Immediate Loading of Extrasinus Zygomatic Implant.

ABSTRACT: The aim of this case series was to evaluate the long-term success rate of immediate occlusal loading of extrasinus zygomatic dental implants after a 3-year follow-up. The sample consisted of 31 patients (mean age of 64 years) with atrophic maxillae rehabilitated with 1 to 4 extrasinus zygomatic implants, placed unilaterally or bilaterally. All the patients received complete implant-supported dental prostheses with immediate loading by associating zygomatic implants with conventional implants. None of the procedures were associated with bone grafts. During the 3-year period of follow-up in the present study, all the patients attended clinical sessions and underwent radiographic exams every 6 months. In total 55 zygomatic and 69 conventional implants were placed, where 1 zygomatic and 2 conventional implants were lost, representing success rates of 98.18% and 97.20%, respectively. None of the studied patients had signs of sinusitis or changes in the maxillary sinuses. All the patients showed occlusal contact on natural antagonist teeth or implant-supported dental prostheses. Therefore, it was concluded that the use of exteriorized zygomatic implants with immediate loading represented a feasible option with high success rates for the treatment of atrophic maxilla.

Detection and Classification System for Rail Surface Defects Based on Eddy Current.

The prospect of growth of a railway system impacts both the network size and its occupation. Due to the overloaded infrastructure, it is necessary to increase reliability by adopting fast maintenance services to reach economic and security conditions. In this context, one major problem is the excessive friction caused by the wheels. This contingency may cause ruptures with severe consequences. While eddy's current approaches are adequate to detect superficial damages in metal structures, there are still open challenges concerning automatic identification of rail defects. Herein, we propose an embedded system for online detection and location of rails defects based on eddy current. Moreover, we propose a new method to interpret eddy current signals by analyzing their wavelet transforms through a convolutional neural network. With this approach, the embedded system locates and classifies different types of anomalies, enabling an optimization of the railway maintenance plan. Field tests were performed, in which the rail anomalies were grouped in three classes: squids, weld and joints. The results showed a classification efficiency of ~98%, surpassing the most commonly used methods found in the literature.

Sensors Fusion and Multidimensional Point Cloud Analysis for Electrical Power System Inspection.

Thermal inspection is a powerful tool that enables the diagnosis of several components at its early stages. One critical aspect that influences thermal inspection outputs is the infrared reflection from external sources. This situation may change the readings, demanding that an expert correctly define the camera position, which is a time consuming and expensive operation. To mitigate this problem, this work proposes an autonomous system capable of identifying infrared reflections by filtering and fusing data obtained from both stereo and thermal cameras. The process starts by acquiring readings from multiples Observation Points (OPs) where, at each OP, the system processes the 3D point cloud and thermal image by fusing them together. The result is a dense point cloud where each point has its spatial position and temperature. Considering that each point's information is acquired from multiple poses, it is possible to generate a temperature profile of each spatial point and filter undesirable readings caused by interference and other phenomena. To deploy and test this approach, a Directional Robotic System (DRS) is mounted over a traditional human-operated service vehicle. In that way, the DRS autonomously tracks and inspects any desirable equipment as the service vehicle passes them by. To demonstrate the results, this work presents the algorithm workflow, a proof of concept, and a real application result, showing improved performance in real-life conditions.

Colored shade nets induced changes in growth, anatomy and essential oil of Pogostemon cablin.

The purpose of this investigation was to determine the influence of colored shade nets on the growth, anatomy and essential oil content, yield and chemical composition of Pogostemon cablin. The plants were cultivated under full sunlight, black, blue and red nets. The harvesting was performed 5 months after planting and it was followed by the analysis of plant growth parameters, leaf anatomy, essential oil content, yield and chemical composition. The plants grown under red net have produced more leaf, shoot, total dry weight and leaf area. Plants cultivated under colored nets showed differences in morphological features. Plants maintained under red net had a higher leaf blade thickness and polar and equatorial diameter of the stomata ratio. Additionally, higher yield of essential oil in the leaves was observed under red and blue colored shade net. The essential oil of the plants grown under red net showed the highest relative percentage of patchoulol (66.84%). Therefore, it is possible using colored shade nets to manipulate P. cablin growth, as well as its essential oil production with several chemical compositions. The analyses of principal components allowed observing that pogostol has negative correlation with α-guaiene and α-bulnesene. There was difference in total dry weight and patchoulol content when the patchouli is cultured under the red colored shade nets.

Economic, human and environmental health benefits of replacing formaldehyde in the preservation of corpses.

Formaldehyde has been prominent in preserving biological tissues since the nineteenth century. Despite being admittedly harmful to health and to the environment, it is still widely used. The Morphology Department of the University of Brasília - Brazil, applied the rethink, reduce, reuse, recycle and responsibility methodology to their activities in an effort to protect the health of laboratory workers and users, save resources and reduce damage to the environment. Here we evaluate the results obtained a decade after the implementation of this proposal (2005-2015). Formaldehyde was replaced by alcohol and glycerol solutions in corpse conservation. Over five thousand dollars in public funds that would have been destined to buying preserving substances were saved annually, and over a hundred thousand liters of water that would have been contaminated and thrown into the sewage system were spared. The environment used to implement the study was improved and anatomical parts kept for study had their lifespan extended. It is noteworthy that such simple adjustments could cause pronounced changes in laboratory activities. We would avoid contaminating billions of liters of water and it would be possible to save millions if similar practices were implemented in all educational institutions having similar routines.

Four-year follow-up of a polymethyl methacrylate-based bone cement graft for optimizing esthetics in maxillary anterior implants: a case report.

Tooth loss promotes bone and gingival tissue remodeling, thus breaking the harmony between the residual ridge and natural teeth. This is critical in the anterior region of the mouth, and the integration of several dental specialties is often essential to successful rehabilitation with implants. This article describes a multidisciplinary approach to implant-supported oral rehabilitation in the maxillary anterior region, presenting a new technique for optimizing esthetics in implants. A 19-year-old woman was missing her central and lateral incisors and had 2 dental implants in the lateral incisor sites. The patient exhibited deficient thickness of the alveolar edge, loss of lip support, and absence of gingival architecture, and the implants were improperly placed. A multidisciplinary team created a correct emergence profile through a polymethyl methacrylate-based bone cement graft along with connective tissue grafts. This technique may be a useful therapeutic adjunct in dental implantology, showing good predictability and regular healing procedures.

Analysis of a local HIV-1 epidemic in portugal highlights established transmission of non-B and non-G subtypes.

The existing data support Portugal as the western European country with the highest HIV-1 subtype diversity. However, detailed phylogenetic studies of Portuguese HIV-1 epidemics are still scarce. Thus, our main goal was to analyze the phylodynamics of a local HIV-1 infection in the Portuguese region of Minho. Molecular epidemiological analysis was applied to data from 289 HIV-1-infected individuals followed at the reference hospital of the province of Minho, Portugal, at which isolated viruses had been sequenced between 2000 and 2012. Viruses of the G (29.1%) and B (27.0%) subtypes were the most frequent, followed by recombinant forms (17.6%) and the C (14.5%), F1 (7.3%), and A1 (4.2%) subtypes. Multinomial logistic regression revealed that the odds of being infected with the A1 and F1 subtypes increased over the years compared with those with B, G, or C subtypes or recombinant viruses. As expected, polyphyletic patterns suggesting multiple and old introductions of the B and G subtypes were found. However, transmission clusters of non-B and non-G viruses among native individuals were also found, with the dates of the most recent common ancestor estimated to be in the early 2000s. Our study supports that the HIV-1 subtype diversity in the Portuguese region of Minho is high and has been increasing in a manner that is apparently driven by factors other than immigration and international travel. Infections with A1 and F1 viruses in the region of Minho are becoming established and are mainly found in sexually transmitted clusters, reinforcing the need for more efficacious control measures targeting this infection route.

The Influence of Dentine on the pH of Calcium Hydroxide, Chlorhexidine Gel, and Experimental Bioactive Glass-Based Root Canal Medicament.

OBJECTIVES: To evaluate the influence of dentine on the pH of different medications in standardized simulated canals. MATERIALS AND METHODS: Forty resin blocks were divided into groups with and without dentine powder, as follows: 2% chlorhexidine gel; 2% chlorhexidine gel associated with calcium hydroxide PA; calcium hydroxide PA delivered in propylene glycol 600; and NPG delivered in distilled water. The dentine powder was obtained from the root dentine of bovine teeth and added to the medications. The simulated canals were placed in containers with 1.5 mL of deionized water and pH was monitored in multiple intervals, up to 30 days. The mean pH values were calculated and submitted to statistical analysis using paired Student's t-test and ANOVA complemented by the Tukey test (p < 0.05). RESULTS: There was no statistical difference between the groups with and without dentine powder (p > 0.05). The pH values of calcium hydroxide were significantly higher than those of NPG in the first 24 hours (p < 0.05). After 7 days, both behaved in a similar manner. CONCLUSION: The addition of dentine powder to the medications evaluated did not alter the pH of the external solution in any of the time points tested.

Early sedation and clinical outcomes of mechanically ventilated patients: a prospective multicenter cohort study.

INTRODUCTION: Sedation overuse is frequent and possibly associated with poor outcomes in the intensive care unit (ICU) patients. However, the association of early oversedation with clinical outcomes has not been thoroughly evaluated. The aim of this study was to assess the association of early sedation strategies with outcomes of critically ill adult patients under mechanical ventilation (MV). METHODS: A secondary analysis of a multicenter prospective cohort conducted in 45 Brazilian ICUs, including adult patients requiring ventilatory support and sedation in the first 48 hours of ICU admissions, was performed. Sedation depth was evaluated after 48 hours of MV. Multivariate analysis was used to identify variables associated with hospital mortality. RESULTS: A total of 322 patients were evaluated. Overall, ICU and hospital mortality rates were 30.4% and 38.8%, respectively. Deep sedation was observed in 113 patients (35.1%). Longer duration of ventilatory support was observed (7 (4 to 10) versus 5 (3 to 9) days, P = 0.041) and more tracheostomies were performed in the deep sedation group (38.9% versus 22%, P = 0.001) despite similar PaO2/FiO2 ratios and acute respiratory distress syndrome (ARDS) severity. In a multivariate analysis, age (Odds Ratio (OR) 1.02; 95% confidence interval (CI) 1.00 to 1.03), Charlson Comorbidity Index >2 (OR 2.06; 95% CI, 1.44 to 2.94), Simplified Acute Physiology Score 3 (SAPS 3) score (OR 1.02; CI 95%, 1.00 to 1.04), severe ARDS (OR 1.44; CI 95%, 1.09 to 1.91) and deep sedation (OR 2.36; CI 95%, 1.31 to 4.25) were independently associated with increased hospital mortality. CONCLUSIONS: Early deep sedation is associated with adverse outcomes and constitutes an independent predictor of hospital mortality in mechanically ventilated patients.

Simple multi-signal calibrations exploiting flow analysis systems.

Multi-signal calibrations have been recently exploited in molecular spectrochemical analysis alternatively to traditional calibration methods, improving analytical frequency and accuracy. The application of these strategies is simple and minimizes efficiently matrix effects by analyzing two calibration solutions comprising sample plus standard (S1), and sample plus blank (S2). The plot of the signals obtained with S1 and S2 at multiple settings (e.g. different wavelengths) yield a slope that can be related to the analyte concentration in the sample. Similarly, transient signals could also be related to the analyte concentration exploiting a similar strategy. Thus, in this work, two multi-signal approaches developed in flow-based systems are proposed, based on the responses at multiple wavelengths (online multi-energy calibration, OMEC), and on the dispersion profile of the samples, herein denominated multi-dispersion calibration (MDC). The calibrations were carried out with sample solutions after 2-fold dilution with a standard solution and with water. The feasibility of OMEC and MDC were demonstrated using KMnO4 solutions (without chemical reactions) under continuous and pulsed flow regimes. The applicability of this strategy was also demonstrated by the spectrophotometric determination of urea in milk and pet potty spray in a multi-pumping flow system, based on the color change of bromothymol blue after catalyzed hydrolysis by urease from jack beans (Canavalia ensiformis). MDC and OMEC were compared with external calibrations (EC) and classical standard addition. The limits of detection for urea were estimated at 13 mg L-1, 16 mg L-1, and 10 mg L-1 using MDC, MEC and EC, respectively. Recoveries from 93 to 101%, and the agreement of sample analyzes with the reference procedure demonstrated the good accuracy achieved by the proposed methods. Therefore, it was demonstrated the feasibility of MDC and OMEC for analytical purposes in a simple and efficient way with the advantages of flow-based manifolds.