Platelet-activating factor and protease-activated receptor 2 cooperate to promote neutrophil recruitment and lung inflammation through nuclear factor-kappa B transactivation.

Although it is well established that platelet-activated receptor (PAF) and protease-activated receptor 2 (PAR2) play a pivotal role in the pathophysiology of lung and airway inflammatory diseases, a role for a PAR2-PAFR cooperation in lung inflammation has not been investigated. Here, we investigated the role of PAR2 in PAF-induced lung inflammation and neutrophil recruitment in lungs of BALB/c mice. Mice were pretreated with the PAR2 antagonist ENMD1068, PAF receptor (PAFR) antagonist WEB2086, or aprotinin prior to intranasal instillation of carbamyl-PAF (C-PAF) or the PAR2 agonist peptide SLIGRL-NH2 (PAR2-AP). Leukocyte infiltration in bronchoalveolar lavage fluid (BALF), C-X-C motif ligand 1 (CXCL)1 and CXCL2 chemokines, myeloperoxidase (MPO), and N-acetyl-glycosaminidase (NAG) levels in BALF, or lung inflammation were evaluated. Intracellular calcium signaling, PAFR/PAR2 physical interaction, and the expression of PAR2 and nuclear factor-kappa B (NF-КB, p65) transcription factor were investigated in RAW 264.7 cells stimulated with C-PAF in the presence or absence of ENMD1068. C-PAF- or PAR2-AP-induced neutrophil recruitment into lungs was inhibited in mice pretreated with ENMD1068 and aprotinin or WEB2086, respectively. PAR2 blockade impaired C-PAF-induced neutrophil rolling and adhesion, lung inflammation, and production of MPO, NAG, CXCL1, and CXCL2 production in lungs of mice. PAFR activation reduced PAR2 expression and physical interaction of PAR2 and PAFR; co-activation is required for PAFR/PAR2 physical interaction. PAR2 blockade impaired C-PAF-induced calcium signal and NF-κB p65 translocation in RAW 264.7 murine macrophages. This study provides the first evidence for a cooperation between PAFR and PAR2 mediating neutrophil recruitment, lung inflammation, and macrophage activation.

From species descriptions to diversity patterns: the validation of taxonomic data as a keystone for ant diversity studies reproducibility and accuracy.

Research findings in natural sciences need to be comparable and reproducible to effectively improve our understanding of ecological and behavioural patterns. In this sense, knowledge frontiers in biodiversity studies are directly tied to taxonomic research, especially in species-rich tropical regions. Here we analysed the taxonomic information available in 470 studies on Brazilian ant diversity published in the last 50 years. We aimed to quantify the proportion of studies that provide enough data to validate taxonomic identification, explore the frequency of studies that properly acknowledge their taxonomic background, and investigate the primary resources for ant identification in Brazil. We found that most studies on Brazilian ant diversity (73.6%) explicitly stated the methods used to identify their specimens. However, the proportion of papers that provide complete data for the repository institutions and vouchered specimens is vanishingly small (5.8%). Additionally, only 40.0% of the studies consistently presented taxon authorities and years of description, rarely referencing taxonomic publications correctly. In turn, the number of specialists and institutions consulted for ant identification in Brazil has increased in the last years, along with the number of studies that explicitly provide their taxonomic procedures for ant identification. Our findings highlight a shift between generations regarding the recognition of taxonomy as fundamental science, deepening our understanding of biodiversity.

Testing the context dependence of ant nutrient preference across habitat strata and trophic levels in Neotropical biomes.

Animals are integrated into the wider ecosystem via their foraging and behavior. The compensation hypothesis predicts that animals target their foraging efforts (i) toward nutrients that are scarce in the environment and (ii) toward nutrients that are not present in the usual diet of species, which varies across trophic levels. Understanding how foraging for resources varies locally, such as across habitat strata, and trophic levels will help to elucidate the links between the local environment and communities to the ecological functions that animals mediate. We examined whether the relative resource use of ants varies consistently along a habitat strata gradient and across trophic levels across Neotropical biomes. We placed 4500 baited tubes, each containing one of five liquid resources (sugar, amino acid, lipid, sodium, and distilled water) in one of three habitat strata (subterranean, epigaeic, and arboreal) across 60 transects in Amazon, Atlantic Forest, Caatinga, Cerrado, Pampa, and Pantanal biomes. We assessed the relative resource use of all ants across the habitat strata and among two different trophic groups across biomes. The relative preference for sugar increased from subterranean to arboreal strata in all biomes, while the relative preference for lipids decreased at this gradient in five biomes. We also found that in general sugar-consuming ants foraged more for sugar and less for lipids than predatory ants across biomes. Conversely, we found no consistency across biomes in nutrient preference of amino acid and sodium across habitat strata or trophic levels. Overall, our results indicate sugar limitation in the arboreal stratum and lipid limitation on the ground across biomes and that the trophic level of ants strongly determines their foraging efforts-possibly because ants try to fix their dietary nutrient imbalances. Hence, our findings suggest strong local niche partitioning of sugar and lipid use across habitat strata and trophic levels and that other large spatial scale processes influence the local amino acid and sodium dynamics.

Os animais se integram nos ecossistemas pelos seus esforços e comportamento de forrageio. A hipótese da compensação prevê que os animais direcionam seus esforços de forrageio para (i) nutrientes que são escassos no ambiente e (ii) para nutrientes que não estão presentes em sua dieta, que variam entre os níveis tróficos. Assim, entender como a busca de recursos varia localmente entre os estratos de habitat e entre níveis tróficos, ajudará a entender as conexões entre o ambiente e suas comunidades com as funções ecológicas mediadas pelos animais. Avaliamos se o uso relativo de recursos das formigas varia consistentemente em um gradiente de estratos de habitat e em diferentes níveis tróficos nos biomas Neotropicais. Disponibilizamos um total de 4.500 tubos contendo um de cinco recursos líquidos (açúcar, aminoácido, lipídio, sódio e água destilada) em três estratos de habitat (subterrâneo, epigéico e arbóreo) em 60 transectos distribuídos nos biomas Amazônia, Mata Atlântica, Caatinga, Cerrado, Pampa e Pantanal. Avaliamos o uso relativo de recursos de todas as formigas ao longo dos estratos de habitat e entre dois grupos tróficos diferentes nos biomas. A preferência relativa por açúcar aumentou do estrato subterrâneo para o arbóreo em todos os biomas, enquanto a preferência relativa por lipídios diminuiu neste gradiente em cinco biomas. Também descobrimos que, em geral, as formigas consumidoras de açúcar procuram mais açúcar e menos lipídios do que as formigas predadoras nos biomas. Por outro lado, não encontramos consistência entre biomas na preferência nutricional de aminoácidos e sódio nos estratos de habitat ou níveis tróficos. No geral, nossos resultados indicam limitação de açúcar no estrato arbóreo e limitação de lipídios no solo em todos os biomas e que o nível trófico das formigas determina fortemente seus esforços de forrageamento - possivelmente porque as formigas tentam corrigir seus desequilíbrios de nutrientes na dieta. Portanto, nossas descobertas sugerem forte partição de nicho local de uso de açúcar e lipídios em estratos de habitat e níveis tróficos e que outros processos de grande escala espacial influenciam a dinâmica local de aminoácidos e sódio.

Study of the compression behavior of functionally graded lattice for customized cranial remodeling orthosis.

Deformational plagiocephaly is a head deformity that occurs in newborns, treated in severe cases with helmets named cranial remodeling orthoses (CRO). Current CROs can fail to adapt to head growth, causing excessive pressure sores and other complications, and may lead to poor clinical results. In this work, we experimentally and numerically study the compressive behavior of a functionally graded lattice that may be used in future work as a potential inner lining for a CRO with a customized density distribution. This work is divided into five stages. First, we describe the design of all lattices involved in the study. Second, we measure the mechanical properties of the bulk material used in the manufacturing of the lattices. Third, we study the effect of unit cell size variation, testing three homogenous body-centered cubic (BCC) lattices, and creating a numerical model for the prediction of the compressive behavior of various lattices with different unit cell sizes. Fourth, we study the effects of truss diameter variation, designing and testing three homogenous lattices with different truss diameters. Finally, we design a BCC lattice with a truss diameter gradient and analyze compressive deformations in numerical and experimental compression studies. The numerical simulations of the compression of the homogenous and graded lattices agree with the experimental measurements, both in unit cell variation and in truss diameter variation. In the graded lattice, the compression displacements observed in each region are proportional to their density and agree with the numerical simulation. Truss diameter variation was found to have a wider range of compressive responses than unit cell size variation without major changes in the overall geometry of the lattice and found more suitable for the intended application. The studies showed the potential of the functionally graded lattice for use in the CRO.

ATLANTIC ANTS: a data set of ants in Atlantic Forests of South America.

Ants, an ecologically successful and numerically dominant group of animals, play key ecological roles as soil engineers, predators, nutrient recyclers, and regulators of plant growth and reproduction in most terrestrial ecosystems. Further, ants are widely used as bioindicators of the ecological impact of land use. We gathered information of ant species in the Atlantic Forest of South America. The ATLANTIC ANTS data set, which is part of the ATLANTIC SERIES data papers, is a compilation of ant records from collections (18,713 records), unpublished data (29,651 records), and published sources (106,910 records; 1,059 references), including papers, theses, dissertations, and book chapters published from 1886 to 2020. In total, the data set contains 153,818 ant records from 7,636 study locations in the Atlantic Forest, representing 10 subfamilies, 99 genera, 1,114 ant species identified with updated taxonomic certainty, and 2,235 morphospecies codes. Our data set reflects the heterogeneity in ant records, which include ants sampled at the beginning of the taxonomic history of myrmecology (the 19th and 20th centuries) and more recent ant surveys designed to address specific questions in ecology and biology. The data set can be used by researchers to develop strategies to deal with different macroecological and region-wide questions, focusing on assemblages, species occurrences, and distribution patterns. Furthermore, the data can be used to assess the consequences of changes in land use in the Atlantic Forest on different ecological processes. No copyright restrictions apply to the use of this data set, but we request that authors cite this data paper when using these data in publications or teaching events.

Temperature and productivity distinctly affect the species richness of ectothermic and endothermic multitrophic guilds along a tropical elevational gradient.

The diversity of endotherms and ectotherms may be differently affected by ambient temperature and net primary productivity (NPP). Additionally, little is known about how these drivers affect the diversity of guilds of different trophic levels. We assessed the relative role of temperature and NPP in multitrophic guilds of ectothermic (arthropods: ants, ground beetles, spiders, and harvestmen) and endothermic (large mammals) animals along a tropical elevational gradient. We sampled arthropods at eight elevation belts and large mammals at 14 elevation belts in Atlantic rainforest (ranging from 600 to 2450 m.a.s.l.) of Itatiaia National Park, Southeast Brazil. Overall arthropod species richness was more associated with temperature than overall large-mammal species richness, while the latter was more associated with NPP. When separated into trophic guilds, we found that the species richness associated with NPP increased across arthropod trophic levels from herbivores to predators. Conversely, although NPP influenced large-mammal herbivore species richness, its effects did not seem to accumulate across large-mammal trophic levels since the species richness of large-mammal omnivores was more associated with temperature and none of the variables we studied influenced large-mammal predators. We suggest that thermal physiological differences between ectotherms and endotherms are responsible for the way in which arthropods and large mammals interact with or are constrained by the environment. Furthermore, the inconsistency regarding the role of temperature and NPP on species richness across multitrophic guilds of ectotherms and endotherms could indicate that thermal physiological differences might also interfere with energy use and flux in the food web.

Alkaloid and acetogenin-rich fraction from Annona crassiflora fruit peel inhibits proliferation and migration of human liver cancer HepG2 cells.

Plant species from Annonaceae are commonly used in traditional medicine to treat various cancer types. This study aimed to investigate the antiproliferative potential of an alkaloid and acetogenin-rich fraction from the fruit peel of Annona crassiflora in HepG2 cells. A liquid-liquid fractionation was carried out on the ethanol extract of A. crassiflora fruit peel in order to obtain an alkaloid and acetogenin-rich fraction (AF-Ac). Cytotoxicity, proliferation and migration were evaluated in the HepG2 cells, as well as the proliferating cell nuclear antigen (PCNA), vinculin and epidermal growth factor receptor (EGFR) expression. In addition, intracellular Ca2+ was determined using Fluo4-AM and fluorescence microscopy. First, 9 aporphine alkaloids and 4 acetogenins that had not yet been identified in the fruit peel of A. crassiflora were found in AF-Ac. The treatment with 50 µg/mL AF-Ac reduced HepG2 cell viability, proliferation and migration (p < 0.001), which is in accordance with the reduced expression of PCNA and EGFR levels (p < 0.05). Furthermore, AF-Ac increased intracellular Ca2+ in the HepG2 cells, mobilizing intracellular calcium stores, which might be involved in the anti-migration and anti-proliferation capacities of AF-Ac. Our results support the growth-inhibitory potential of AF-Ac on HepG2 cells and suggest that this effect is triggered, at least in part, by PCNA and EGFR modulation and mobilization of intracellular Ca2+. This study showed biological activities not yet described for A. crassiflora fruit peel, which provide new possibilities for further in vivo studies to assess the antitumoral potential of A. crassiflora, especially its fruit peel.

Diaspore Removal by Ants Does Not Reflect the Same Patterns of Ant Assemblages in Mining and Rehabilitation Areas.

Mining is responsible for drastic ecosystem changes and rehabilitation is used to promote the return of functions after these impacts. In this scenario, we investigated the responses of ant assemblages and diaspore removal by ants to the transformations caused by mining and rehabilitation predicting that (a) the increase in plant density (a proxy for mining intensity) led to an increase in ant richness, percentage of diaspores removed, and changes in species composition that in turn are correlated with changes in environmental variables; (b) the increase in vegetation structure (a proxy for rehabilitation ages) led to an increase in ant richness, percentage of diaspores removed, and changes in species composition that in turn are correlated with changes in environmental variables. Additionally, we also verified which functional groups were primarily responsible for diaspore removal. We sampled arboreal and epigeic ants, diaspore removal by ants, and environmental variables. We found that ant richness and diaspore removal in mining intensity gradient are positively correlated to plant density. Although vegetation structure is positively correlated with ant richness, we found no changes in diaspore removal in rehabilitation gradient. Epigeic omnivore and epigeic generalist predator ants were the most responsible for diaspore removal. Then, we observed that mining decreases ant richness, altering ant assemblages and their functions, and rehabilitation with exotic plants is ineffective to promote the colonization by the main diaspore-removing ants.

Temperature and productivity distinctly affect the species richness of ectothermic and endothermic multitrophic guilds along a tropical elevational gradient

The diversity of endotherms and ectotherms may be differently affected by ambient temperature and net primary productivity (NPP). Additionally, little is known about how these drivers affect the diversity of guilds of different trophic levels. We assessed the relative role of temperature and NPP in multitrophic guilds of ectothermic (arthropods: ants, ground beetles, spiders, and harvestmen) and endothermic (large mammals) animals along a tropical elevational gradient. We sampled arthropods at eight elevation belts and large mammals at 14 elevation belts in Atlantic rainforest (ranging from 600 to 2450 m.a.s.l.) of Itatiaia National Park, Southeast Brazil. Overall arthropod species richness was more associated with temperature than overall large-mammal species richness, while the latter was more associated with NPP. When separated into trophic guilds, we found that the species richness associated with NPP increased across arthropod trophic levels from herbivores to predators. Conversely, although NPP influenced large-mammal herbivore species richness, its effects did not seem to accumulate across large-mammal trophic levels since the species richness of large-mammal omnivores was more associated with temperature and none of the variables we studied influenced large-mammal predators. We suggest that thermal physiological differences between ectotherms and endotherms are responsible for the way in which arthropods and large mammals interact with or are constrained by the environment. Furthermore, the inconsistency regarding the role of temperature and NPP on species richness across multitrophic guilds of ectotherms and endotherms could indicate that thermal physiological differences might also interfere with energy use and flux in the food web.

Early use of nitazoxanide in mild Covid-19 disease: randomized, placebo-controlled trial

The antiparasitic drug nitazoxanide is widely available and exerts broad-spectrum antiviral activity in vitro. However, there is no evidence of its impact on SARS-CoV-2 infection. In a multicenter, randomized, double-blind, placebo-controlled trial, adult patients who presented up to 3 days after onset of Covid-19 symptoms (dry cough, fever, and/or fatigue) were enrolled. After confirmation of SARS-CoV2 infection by RT-PCR on nasopharyngeal swab, patients were randomized 1:1 to receive either nitazoxanide (500 mg) or placebo, TID, for 5 days. The primary outcome was complete resolution of symptoms. Secondary outcomes were viral load, general laboratory tests, serum biomarkers of inflammation, and hospitalization rate. Adverse events were also assessed. From June 8 to August 20, 2020, 1,575 patients were screened. Of these, 392 (198 placebo, 194 nitazoxanide) were analyzed. Median time from symptom onset to first dose of study drug was 5 (4-5) days. At the 5-day study visit, symptom resolution did not differ between the nitazoxanide and placebo arms. However, at the 1-week follow-up, 78% in the nitazoxanide arm and 57% in the placebo arm reported complete resolution of symptoms (p=0.048). Swabs collected were negative for SARS-CoV-2 in 29.9% of patients in the nitazoxanide arm versus 18.2% in the placebo arm (p=0.009). Viral load was also reduced after nitazoxanide compared to placebo (p=0.006). No serious adverse events were observed. In patients with mild Covid-19, symptom resolution did not differ between the nitazoxanide and placebo groups after 5 days of therapy. However, early nitazoxanide therapy was safe and reduced viral load significantly. Take home messageThis was the first study to evaluate the effect of early nitazoxanide therapy in mild Covid-19. Nitazoxanide did not accelerate symptom resolution after 5 days of therapy; however, reduced viral load significantly with no serious adverse events.

Pediatric multiple sclerosis: from clinical basis to imaging spectrum and differential diagnosis.

Pediatric multiple sclerosis (MS) deserves special attention because of its impact on cognitive function and development. Although knowledge regarding pediatric MS has rapidly increased, understanding the peculiarities of this population remains crucial for disease management. There is limited expertise about the efficacy and safety of current disease-modifying agents. Although pathophysiology is not entirely understood, some risk factors and immunological features have been described and are discussed herein. While the revised International Pediatric MS Study Group diagnostic criteria have improved the accuracy of diagnosis, the recently revised McDonald criteria also offer some new insights into the pediatric population. It is fundamental that radiologists have strong knowledge about the vast spectrum of demyelinating disorders that can occur in childhood to ensure appropriate diagnosis and provide early treatment.

Ambipolar Resistive Switching in an Ultrathin Surface-Supported Metal-Organic Framework Vertical Heterojunction.

Memristors (MRs) are considered promising devices with the enormous potential to replace complementary metal-oxide-semiconductor (CMOS) technology, which approaches the scale limit. Efforts to fabricate MRs-based hybrid materials may result in suitable operating parameters coupled to high mechanical flexibility and low cost. Metal-organic frameworks (MOFs) arise as a favorable candidate to cover such demands. The step-by-step growth of MOFs structures on functionalized surfaces, called surface-supported metal-organic frameworks (SURMOFs), opens the possibility for designing new applications in strategic fields such as electronics, optoelectronics, and energy harvesting. However, considering the MRs architecture, the typical high porosity of these hybrid materials may lead to short-circuited devices easily. In this sense, here, it is reported for the first time the integration of SURMOF films in rolled-up scalable-functional devices. A freestanding metallic nanomembrane provides a robust and self-adjusted top mechanical contact on the SURMOF layer. The electrical characterization reveals an ambipolar resistive switching mediated by the humidity level with low-power consumption. The electronic properties are investigated with density functional theory (DFT) calculations. Furthermore, the device concept is versatile, compatible with the current parallelism demands of integration, and transcends the challenge in contacting SURMOF films for scalable-functional devices.

Technical Note: Assessment of electromagnetic tracking systems in a surgical environment using ultrasonography and ureteroscopy instruments for percutaneous renal access.

PURPOSE: Electromagnetic tracking systems (EMTSs) have been proposed to assist the percutaneous renal access (PRA) during minimally invasive interventions to the renal system. However, the influence of other surgical instruments widely used during PRA (like ureteroscopy and ultrasound equipment) in the EMTS performance is not completely known. This work performs this assessment for two EMTSs [Aurora® Planar Field Generator (PFG); Aurora® Tabletop Field Generator (TTFG)]. METHODS: An assessment platform, composed by a scaffold with specific supports to attach the surgical instruments and a plate phantom with multiple levels to precisely translate or rotate the surgical instruments, was developed. The median accuracy and precision in terms of position and orientation were estimated for the PFG and TTFG in a surgical environment using this platform. Then, the influence of different surgical instruments (alone or together), namely analogic flexible ureterorenoscope (AUR), digital flexible ureterorenoscope (DUR), two-dimensional (2D) ultrasound (US) probe, and four-dimensional (4D) mechanical US probe, was assessed for both EMTSs by coupling the instruments to 5-DOF and 6-DOF sensors. RESULTS: Overall, the median positional and orientation accuracies in the surgical environment were 0.85 mm and 0.42° for PFG, and 0.72 mm and 0.39° for TTFG, while precisions were 0.10 mm and 0.03° for PFG, and 0.20 mm and 0.12° for TTFG, respectively. No significant differences were found for accuracy between EMTSs. However, PFG showed a tendency for higher precision than TTFG. AUR, DUR, and 2D US probe did not influence the accuracy and precision of both EMTSs. In opposition, the 4D probe distorted the signal near the attached sensor, making readings unreliable. CONCLUSIONS: Ureteroscopy- and ultrasonography-assisted PRA based on EMTS guidance are feasible with the tested AUR or DUR together with the 2D probe. More studies must be performed to evaluate the probes and ureterorenoscopes' influence before their use in PRA based on EMTS guidance.

Surface-based registration between CT and US for image-guided percutaneous renal access - A feasibility study.

PURPOSE: As a crucial step in accessing the kidney in several minimally invasive interventions, percutaneous renal access (PRA) practicality and safety may be improved through the fusion of computed tomography (CT) and ultrasound (US) data. This work aims to assess the potential of a surface-based registration technique and establish an optimal US acquisition protocol to fuse two-dimensional (2D) US and CT data for image-guided PRA. METHODS: Ten porcine kidney phantoms with fiducial markers were imaged using CT and three-dimensional (3D) US. Both images were manually segmented and aligned. In a virtual environment, 2D contours were extracted by slicing the 3D US kidney surfaces and using usual PRA US-guided views, while the 3D CT kidney surfaces were transformed to simulate positional variability. Surface-based registration was performed using two methods of the iterative closest point algorithm (point-to-point, ICP1; and point-to-plane, ICP2), while four acquisition variants were studied: (a) use of single-plane (transverse, SPT ; or longitudinal, SPL ) vs bi-plane views (BP); (b) use of different kidney's coverage ranges acquired by a probe's sweep; (c) influence of sweep movements; and (d) influence of the spacing between consecutive slices acquired for a specific coverage range. RESULTS: BP view showed the best performance (TRE = 2.26 mm) when ICP2 method, a wide kidney coverage range (20°, with slices spaced by 5°), and a large sweep along the central longitudinal view were used, showing a statistically similar performance (P = 0.097) to a full 3D US surface registration (TRE = 2.28 mm). CONCLUSIONS: An optimal 2D US acquisition protocol was evaluated. Surface-based registration, using multiple slices and specific sweep movements and views, is here suggested as a valid strategy for intraoperative image fusion using CT and US data, having the potential to be applied to other image modalities and/or interventions.

A Novel Tetrasubstituted Imidazole as a Prototype for the Development of Anti-inflammatory Drugs.

Although inflammation is a biological phenomenon that exists to protect the host against infections and/or related problems, its unceasing activation results in the aggravation of several medical conditions. Imidazoles, whether natural or synthetic, are molecules related to a broad spectrum of biological effects, including anti-inflammatory properties. In this study, we screened eight novel small molecules of the imidazole class synthesized by our research group for their in vitro anti-inflammatory activity. The effect of the selected molecules was confirmed in an in vivo inflammatory model. We also analyzed whether the effects were caused by inhibition of nuclear factor kappa B (NF-κB) transcription factor transmigration. Of the eight imidazoles tested, methyl 1-allyl-2-(4-fluorophenyl)-5-phenyl-1H-imidazole-4-acetate (8) inhibited nitric oxide metabolites and pro-inflammatory cytokine (TNF-α, IL-6, and IL-1ß) secretion in J774 macrophages stimulated with LPS. It also attenuated leukocyte migration and exudate formation in the pleural cavity of mice challenged with carrageenan. Furthermore, imidazole 8 reverted the oxidative stress pattern triggered by carrageenan in the pleural cavity by diminishing myeloperoxidase, superoxide dismutase, catalase, and glutathione S-transferase activities and reducing the production of nitric oxide metabolites and thiobarbituric acid-reactive substances. Finally, these effects can be attributed, at least in part, to the ability of this compound to prevent NF-κB transmigration. In this context, our results demonstrate that imidazole 8 has promising potential as a prototype for the development of a new anti-inflammatory drug to treat inflammatory conditions in which NF-κB and oxidative stress play a prominent role. Graphical Abstract ᅟ.

Isolated Compounds from Natural Products with Potential Antidiabetic Activity - A Systematic Review.

BACKGROUND: Worldwide, Type 2 diabetes has become a growing health problem. While many research articles in the field of ethnopharmacology have focused on the antidiabetic properties of medicinal plant species, insufficient evidence remains regarding their therapeutic use. Studies using both in vitro and in vivo models are necessary to evaluate various medicinal plants species, used in folk medicine, by using scientific criteria. METHODS: This review focuses on isolated compounds from medicinal plant species that have reported antidiabetic activity in diabetes models. Searches using MEDLINE/PUBMED and SCOPUS databases were conducted to find articles in English on compounds isolated from plant species that have been tested using in vivo and/or in vitro diabetes models and published between 01/01/2005 and 12/31/2015. RESULTS: The majority of studies involved in vitro assays that used the analysis of enzymes and receptors to investigate the antidiabetic mechanisms of active compounds at the molecular level. Compounds that have been reported to have important anti-diabetic activity with defined mechanisms were identified, including quercetin, oleanolic acid, kaempferol, ursolic acid, rutin, ß-sitosterol, and mangiferin. CONCLUSION: This review contributes to the field of ethnopharmacology and should impact the design of new strategies in the search of novel compounds for the treatment of diabetic conditions.

A new methodology for assessment of pectus excavatum correction after bar removal in Nuss procedure: Preliminary study.

PURPOSE: The objective is to present a new methodology to assess quantitatively the impact of bar removal on the anterior chest wall, among patients with pectus excavatum who have undergone the Nuss procedure, and present a preliminary study using this methodology. METHODS: We propose to acquire, for each patient, the surface of the anterior chest wall using a three-dimensional laser scanner at subsequent time points (short term: before and after surgery; long term: follow-up visit, 6months, and 12months after surgery). After surfaces postprocessing, the changes are assessed by overlapping and measuring the distances between surfaces. In this preliminary study, three time points were acquired and two assessments were performed: before vs after bar removal (early) and before vs 2-8weeks after bar removal (interim). In 21 patients, the signed distances and volumes between surfaces were computed and the data analysis was performed. RESULTS: This methodology revealed useful for monitoring changes in the anterior chest wall. On average, the mean, maximum, and volume variations, in the early assessment, were -0.1±0.1cm, -0.6±0.2cm, and 47.8±22.2cm3, respectively; and, in the interim assessment, were -0.5±0.2cm, -1.3±0.4cm, and 122.1±47.3cm3, respectively (p<0.05). Data analysis revealed that the time the bar was in situ was inversely and significantly correlated with postretraction and was a relevant predictor of its decrease following surgery (p<0.05). Additionally, gender and age suggested influencing the outcome. CONCLUSIONS: This methodology is novel, objective and safe, helping on follow-up of pectus excavatum patients. Moreover, the preliminary study suggests that the time the bar was in situ may be the main determinant of the anterior chest wall retraction following bar removal. Further studies should continue to corroborate and reinforce the preliminary findings, by increasing the sample size and performing long-term assessments. LEVELS OF EVIDENCE: III.

ESI-MS2 and Anti-inflammatory Studies of Cyclopropanic Triterpenes. UPLC-ESI-MS and MS2 Search of Related Metabolites from Donella ubanguiensis.

INTRODUCTION: Triterpenes are one of the largest secondary metabolites groups spread in the plant kingdom with various skeletons. These metabolites have showed various bioactivities including anti-inflammatory activity. OBJECTIVE: The study aims to explore the mass spectrometry fragmentation of donellanic acids A-C (DA A-C), three compounds identified from Donella ubanguiensis; in addition, the fragmentation behaviour of these metabolites will serve as a fingerprint to search and characterise triterpenes congeners in fruits, bark and wood crude extracts of D. ubanguiensis. This work was prompted by the anti-inflammatory activity on leukocyte migration, exudate concentrations and myeloperoxidase activity obtained for DA A-B. METHODOLOGY: The bioactivity was performed on mouse model of pleurisy induced by carrageenan and the parameters were analysed by veterinarian automated cell counter and colorimetric assays. While the tandem mass analyses of DA A-C were carried out by a direct infusion ESI-QTOF-MS/MS, the extracts were studied by UPLC-ESI-QTOF-MS and UPLC-ESI-QTOF-MS/MS. RESULTS: DA A displayed interesting anti-inflammatory activity by inhibiting leukocyte migration, exudate concentrations and myeloperoxidase activity (p < 0.05) while DA B was weakly active (p > 0.05). Moreover, the diagnostic of the MS2 behaviour of DA A-C in conjunction with the chromatograms and the obtained MS2 data of the crude extract led to the characterisation of three cyclopropane triterpenes (T1-T3) and six saponins (T4-T9) from the fruits, the bark, and the wood extracts. CONCLUSIONS: Donella species deserve more investigation since metabolites related to the anti-inflammatory compound (DA A) could be identified. Copyright © 2016 John Wiley & Sons, Ltd.

Air Pollution and Deaths among Elderly Residents of São Paulo, Brazil: An Analysis of Mortality Displacement.

BACKGROUND: Evaluation of short-term mortality displacement is essential to accurately estimate the impact of short-term air pollution exposure on public health. OBJECTIVES: We quantified mortality displacement by estimating single-day lag effects and cumulative effects of air pollutants on mortality using distributed lag models. METHODS: We performed a daily time series of nonaccidental and cause-specific mortality among elderly residents of São Paulo, Brazil, between 2000 and 2011. Effects of particulate matter smaller than 10 µm (PM10), nitrogen dioxide (NO2) and carbon monoxide (CO) were estimated in Poisson generalized additive models. Single-day lag effects of air pollutant exposure were estimated for 0-, 1- and 2-day lags. Distributed lag models with lags of 0-10, 0-20 and 0-30 days were used to assess mortality displacement and potential cumulative exposure effects. RESULTS: PM10, NO2 and CO were significantly associated with nonaccidental and cause-specific deaths in both single-day lag and cumulative lag models. Cumulative effect estimates for 0-10 days were larger than estimates for single-day lags. Cumulative effect estimates for 0-30 days were essentially zero for nonaccidental and circulatory deaths but remained elevated for respiratory and cancer deaths. CONCLUSIONS: We found evidence of mortality displacement within 30 days for nonaccidental and circulatory deaths in elderly residents of São Paulo. We did not find evidence of mortality displacement within 30 days for respiratory or cancer deaths. Citation: Costa AF, Hoek G, Brunekreef B, Ponce de Leon AC. 2017. Air pollution and deaths among elderly residents of São Paulo, Brazil: an analysis of mortality displacement. Environ Health Perspect 125:349-354; http://dx.doi.org/10.1289/EHP98.

Temperature Modulates the Secretome of the Phytopathogenic Fungus Lasiodiplodia theobromae.

Environmental alterations modulate host-microorganism interactions. Little is known about how climate changes can trigger pathogenic features on symbiont or mutualistic microorganisms. Current climate models predict increased environmental temperatures. The exposing of phytopathogens to these changing conditions can have particularly relevant consequences for economically important species and for humans. The impact on pathogen/host interaction and the shift on their biogeographical range can induce different levels of virulence in new hosts, allowing massive losses in agricultural and health fields. Lasiodiplodia theobromae is a phytopathogenic fungus responsible for a number of diseases in various plants. It has also been described as an opportunist pathogen in humans, causing infections with different levels of severity. L. theobromae has a high capacity of adaptation to different environments, such as woody plants, moist argillaceous soils, or even humans, being able to grow and infect hosts in a wide range of temperatures (9-39°C). Nonetheless, the effect of an increase of temperature, as predicted in climate change models, on L. theobromae is unknown. Here we explore the effect of temperature on two strains of L. theobromae - an environmental strain, CAA019, and a clinical strain, CBS339.90. We show that both strains are cytotoxic to mammalian cells but while the environmental strain is cytotoxic mainly at 25°C, the clinical strain is cytotoxic mainly at 30 and 37°C. Extracellular gelatinolytic, xylanolytic, amylolytic, and cellulolytic activities at 25 and 37°C were characterized by zymography and the secretome of both strains grown at 25, 30, and 37°C were characterized by electrophoresis and by Orbitrap LC-MS/MS. More than 75% of the proteins were identified, mostly enzymes (glycosyl hydrolases and proteases). The strains showed different protein profiles, which were affected by growth temperature. Also, strain specific proteins were identified, such as a putative f5/8 type c domain protein - known for being involved in pathogenesis - by strain CAA019 and a putative tripeptidyl-peptidase 1 protein, by strain CBS339.90. We showed that temperature modulates the secretome of L. theobromae. This modulation may be associated with host-specificity requirements. We show that the study of abiotic factors, such as temperature, is crucial to understand host/pathogen interactions and its impact on disease.