Publications by authors named "Silva"

87,892 Publications

Metabolism-driven post-translational modifications of H3K9 in early bovine embryos.

Reproduction 2021 Aug 4;162(3):181-191. Epub 2021 Aug 4.

Laboratory of Embryonic Metabolism and Epigenetics, Center of Natural Sciences and Humanities, Universidade Federal do ABC, Santo André, São Paulo, Brazil.

Metabolic and molecular profiles were reported as different for bovine embryos with distinct kinetics during the first cleavages. In this study, we used this same developmental model (fast vs slow) to determine if the relationship between metabolism and developmental kinetics affects the levels of acetylation or tri-methylation at histone H3 lysine 9 (H3K9ac and H3K9me3, respectively). Fast and slow developing embryos presented different levels of H3K9ac and H3K9me3 from the earliest stages of development (40 and 96 hpi) and up to the blastocyst stage. For H3K9me3, both groups of embryos presented a wave of demethylation and de novo methylation, although it was more pronounced in fast than slow embryos, resulting in blastocysts with higher levels of this mark. The H3K9ac reprogramming profile was distinct between kinetics groups. While slow embryos presented a wave of deacetylation, followed by an increase in this mark at the blastocyst stage, fast embryos reduced this mark throughout all the developmental stages studied. H3K9me3 differences corresponded to writer and eraser transcript levels, while H3K9ac patterns were explained by metabolism-related gene expression. To verify if metabolic differences could alter levels of H3K9ac, embryos were cultured with sodium-iodoacetate (IA) or dichloroacetate (DCA) to disrupt the glycolytic pathway or increase acetyl-CoA production, respectively. IA reduced H3K9ac while DCA increased H3K9ac in blastocysts. Concluding, H3K9me3 and H3K9ac patterns differ between embryos with different kinetics, the second one explained by metabolic pathways involved in acetyl-CoA production. So far, this is the first study demonstrating a relationship between metabolic differences and histone post-translational modifications in bovine embryos.
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http://dx.doi.org/10.1530/REP-21-0134DOI Listing
August 2021

Effective recovery of ytterbium through biosorption using crosslinked sericin-alginate beads: A complete continuous packed-bed column study.

J Hazard Mater 2021 Jul 26;421:126742. Epub 2021 Jul 26.

School of Chemical Engineering, University of Campinas, Albert Einstein Avenue, 13083-852 Campinas, Brazil.

The recovery of rare-earth from secondary sources is essential for cleaner production. The development of natural biocomposites is promising for this purpose. Sericin is a waste protein from silk manufacturing. The highly polar groups on the surface of sericin facilitate blending and crosslinking with other polymers to produce biocomposites with improved properties. In this work, we investigate ytterbium recovery onto a natural biocomposite based on sericin/alginate/poly(vinyl alcohol) (SAPVA) in packed-bed column, aiming to establish a profitable application for sericin. Effects of flow rate and ytterbium inlet concentration showed that the highest exhaustion biosorption capacity (128.39 mg/g) and lowest mass transfer zone (4.13 cm) were reached under the operating conditions of 0.03 L/h and 87.95 mg/L. Four reusability cycles were performed under the optimum operating conditions using 0.3 mol/L HNO. Ytterbium recovery was highly successful; desorption efficiency was higher than 97% and a final ytterbium-rich concentrate (3870 mg/L) was 44 times higher than input concentration. Regenerated beads characterization showed that the cation exchange mechanism plays a major function in continuous biosorption of ytterbium. SAPVA beads also showed higher biosorption/desorption performance for ytterbium than other competing ions. These results suggest the application of SAPVA may be an alternative for large-scale ytterbium recovery.
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http://dx.doi.org/10.1016/j.jhazmat.2021.126742DOI Listing
July 2021

Determination of quinclorac by adsorptive stripping voltammetry in rice samples without sample pretreatment.

J Environ Sci Health B 2021 Aug 4:1-10. Epub 2021 Aug 4.

Applied Electroanalytical Group, Department of Chemistry, Federal University of Viçosa, Viçosa, Brazil.

A novel voltammetric method with practically no sample pretreatment was developed for determination of Quinclorac (QNC) in rice samples by using a working Carbon Paste Electrode (CPE) modified with ionic liquid, with deposition potential (E) of -1.43 V for 30 s in NaOH 0.01 mol L. The systematic influence of cations and anions of imidazole ionic liquids on the composition of CPE has evaluated. The best electrode composition was 65% (w/w) of graphite powder, 30% (w/w) of mineral oil and 5.0% (w/w) of CminBF ionic liquid (1-butyl-3-methylimidazolium tetrafluoroborate). The matrices analyzed were deionized water and extracts of upland rice: white, brown, peel and seed. The limits of quantification ranged between 0.954 mg kg and 3.61 mg kg. The recovery percentages of QNC in rice samples ranged between 90% and 121%. The simplicity and good analytical frequency enable the proposed method to be used to obtain preliminary information on the presence of QNC, prior to the implementation of more detailed, costly and elaborate quantitative analyses. The technique can be applied in the study and evaluation of sorption mechanisms, metabolization of the herbicide in plants and its persistence and degradation in the environment.
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http://dx.doi.org/10.1080/03601234.2021.1959181DOI Listing
August 2021

A Conceptual Model and Taxonomy for Collaborative Augmented Reality.

IEEE Trans Vis Comput Graph 2021 Aug 4;PP. Epub 2021 Aug 4.

To support the nuances of collaborative work, many researchers have been exploring the field of Augmented Reality (AR),aiming to assist in co-located or remote scenarios. Solutions using AR allow taking advantage from seamless integration of virtualobjects and real-world objects, thus providing collaborators with a shared understanding or common ground environment. However,most of the research efforts, so far, have been devoted to experiment with technology and mature methods to support its design anddevelopment. Therefore, it is now time to understand were do we stand and how well can we address collaborative work with AR, tobetter characterize and evaluate the collaboration process. In this paper, we perform an analysis of the different dimensions that shouldbe taken into account when analysing the contributions of AR to the collaborative work effort. Then, we bring these dimensions forwardinto a conceptual framework and propose an extended human-centered taxonomy for the categorization of the main features of Collaborative AR. Our goal is to foster harmonization of perspectives for the field, which may help create a common ground forsystematization and discussion. We hope to influence and improve how research in this field is reported by providing a structured list ofthe defining characteristics. Finally, some examples of the use of the taxonomy are presented to show how it can serve to gatherinformation for characterizing AR-supported collaborative work, and illustrate its potential as the grounds to elicit further.
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http://dx.doi.org/10.1109/TVCG.2021.3101545DOI Listing
August 2021

Enhanced Interplay between Host-Guest and Spin-Crossover Properties through the Introduction of an N Heteroatom in 2D Hofmann Clathrates.

Inorg Chem 2021 Aug 4. Epub 2021 Aug 4.

Instituto de Ciencia Molecular and Departamento de Química Inorgánica, Universidad de Valencia, Catedrático Beltrán Martínez 2, Paterna, València E-46980, Spain.

Controlled modulation of the spin-crossover (SCO) behavior through the sorption-desorption of invited molecules is an extensively exploited topic because of its potential applications in molecular sensing. For this purpose, understanding the mechanisms by which the spin-switching properties are altered by guest molecules is of paramount importance. Here, we show an experimental approach revealing a direct probe of how the interplay between SCO and host-guest chemistry is noticeably activated by chemically tuning the host structure. Thus, the axial ligand 4-phenylpyridine (4-PhPy) in the 2D Hofmann clathrates {Fe(4-PhPy)[M(CN)]} (; M = Pt, Pd) is replaced by 2,4-bipyridine (2,4-Bipy), resulting in the isomorphous compounds {Fe(2,4-Bipy)[M(CN)]} (; M = Pt, Pd), which basically differ from the former in that they have a noncoordinated N heteroatom in the ancillary aromatic substituent, i.e., 2-pyridyl instead of phenyl. Our chemical, magnetic, calorimetric, and structural characterizations demonstrate that this subtle chemical composition change provokes outstanding modifications not only in the capability to adsorb small guests as water or methanol but also in the extent to which these guests affect the SCO characteristics.
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http://dx.doi.org/10.1021/acs.inorgchem.1c01925DOI Listing
August 2021

S-adenosylmethionine induces mitochondrial dysfunction, permeability transition pore opening and redox imbalance in subcellular preparations of rat liver.

J Bioenerg Biomembr 2021 Aug 4. Epub 2021 Aug 4.

Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.

S-adenosylmethionine (AdoMet) predominantly accumulates in tissues and biological fluids of patients affected by liver dysmethylating diseases, particularly glycine N-methyltransferase, S-adenosylhomocysteine hydrolase and adenosine kinase deficiencies, as well as in some hepatic mtDNA depletion syndromes, whose pathogenesis of liver dysfunction is still poorly established. Therefore, in the present work, we investigated the effects of S-adenosylmethionine (AdoMet) on mitochondrial functions and redox homeostasis in rat liver. AdoMet decreased mitochondrial membrane potential and Ca retention capacity, and these effects were fully prevented by cyclosporin A and ADP, indicating mitochondrial permeability transition (mPT) induction. It was also verified that the thiol-alkylating agent NEM prevented AdoMet-induced ΔΨm dissipation, implying a role for thiol oxidation in the mPT pore opening. AdoMet also increased ROS production and provoked protein and lipid oxidation. Furthermore, AdoMet reduced GSH levels and the activities of aconitase and α-ketoglutarate dehydrogenase. Free radical scavengers attenuated AdoMet effects on lipid peroxidation and GSH levels, supporting a role of ROS in these effects. It is therefore presumed that disturbance of mitochondrial functions associated with mPT and redox unbalance may represent relevant pathomechanisms of liver damage provoked by AdoMet in disorders in which this metabolite accumulates.
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http://dx.doi.org/10.1007/s10863-021-09914-3DOI Listing
August 2021

Cirrhosis regression after SVR with indirect methods of fibrosis analysis: How far is it real?

Clin Exp Med 2021 Aug 4. Epub 2021 Aug 4.

Department of Clinical Medicine, Botucatu Medical School, São Paulo State University (UNESP), Av. Prof. Mário Rubens Guimarães Montenegro, s/n - UNESP, Botucatu, São Paulo, Brazil.

Hepatitis C virus has infected over 71 million people worldwide, and it is the main cause of cirrhosis in the western world. Currently, the treatment involves direct-acting antiviral agents (DAAs) and its main goal is to achieve sustained virologic response (SVR). The aim of this study was to evaluate the impact of SVR using DAAs in the improvement of liver fibrosis using scores evaluation by indirect method, liver function, and inflammation indirect biomarkers. Patients with cirrhosis with SVR after treatment (n = 104) were evaluated using liver function scores, indirect fibrosis methods, alpha-fetoprotein, and ferritin at t-base and t-SVR. Statistically significant positive results in all parameters were observed: 54 patients were classified as 5 in the CP score in t-base, and 77 in t-SVR; a significant decrease was observed in MELD score, alpha-fetoprotein, ferritin, APRI, FIB-4 and liver stiffness in liver elastography. We did not observe difference in the liver function scores between regressors and non-regressors of liver stiffness, as well as in indirect inflammation biomarkers. The measurements of fibrosis using the indirect methods have significantly decreased in patients with cirrhosis treated who achieved SVR associated with decreased indirect inflammation biomarkers and improved liver function scores.
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http://dx.doi.org/10.1007/s10238-021-00749-1DOI Listing
August 2021

Large sphenoid mucocele presenting with cranial neuropathies in a 10-year-old boy: case report and literature review.

Childs Nerv Syst 2021 Aug 4. Epub 2021 Aug 4.

University of Miami, Miller School of Medicine, Miami, FL, USA.

Introduction: Mucoceles in the sphenoid sinus are rare, making up 1-3% of all paranasal sinus mucoceles. Sphenoid sinus mucoceles among pediatric patients are uncommon and have a range of presentations due to their proximity to other structures, in rare cases causing oculomotor and visual disturbances through expansion and mass effect.

Case Report: We present a case of a large expansile sphenoid sinus mucocele causing cranial nerve III and VI palsies in a 10-year-old boy. Endoscopic resection of the mucocele was performed for diagnosis and decompression, leading to immediate relief of the patient's symptoms and improvement in cranial nerve function. Post-operative imaging showed complete resolution of the mucocele.

Conclusion: Our case report and review of the current literature emphasizes that prompt diagnosis and intervention can lead to a good clinical outcome and prevention of permanent cranial neuropathy.
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http://dx.doi.org/10.1007/s00381-021-05314-5DOI Listing
August 2021

Larval excretion/secretion of dipters of Lucilia cuprina species induces death in promastigote and amastigote forms of Leishmania amazonensis.

Pathog Dis 2021 Aug 4. Epub 2021 Aug 4.

Laboratory of Immunoparasitology of Neglected Diseases and Cancer, Department of Pathological Sciences, Center for Biological Sciences State University of Londrina, PR, Brazil.

Leishmaniasis is a neglected tropical disease that affects millions of people around the world. Larval excretion/secretion (ES) of the larvae of flies of the Calliphoridae family has microbicidal activity against Gram-positive and Gram-negative bacteria, in addition to some species of Leishmania. Our study aimed at assessing the in vitro efficacy of Lucilia cuprina larval ES against the promastigote and amastigote forms of Leishmania amazonensis, elucidating possible microbicidal mechanisms and routes of death involved. Larval ES was able to inhibit the viability of L. amazonensis at all concentrations, induce morphological and ultrastructural changes in the parasite, retraction of the cell body, roughness of the cytoplasmic membrane, leakage of intracellular content, ROS production increase, induction of membrane depolarization, and mitochondrial swelling, the formation of cytoplasmic lipid droplets and phosphatidylserine exposure, thus indicating the possibility of apoptosis-like death. To verify the efficacy of larval ES on amastigote forms, we performed a phagocytic assay, measurement of total ROS, and NO. Treatment using larval ES reduced the percentage of infection and the number of amastigotes per macrophage of lineage J774A.1 at all concentrations, increasing the production of ROS and TNF-α, thus indicating possible pro-inflammatory immunomodulation and oxidative damage. Therefore, treatment using larval ES is effective at inducing the death of promastigotes and amastigotes of L. amazonensis even at low concentrations.
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http://dx.doi.org/10.1093/femspd/ftab040DOI Listing
August 2021

Conformations of voltage-sensing domain III differentially define NaV channel closed- and open-state inactivation.

J Gen Physiol 2021 Sep 4;153(9). Epub 2021 Aug 4.

Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO.

Voltage-gated Na+ (NaV) channels underlie the initiation and propagation of action potentials (APs). Rapid inactivation after NaV channel opening, known as open-state inactivation, plays a critical role in limiting the AP duration. However, NaV channel inactivation can also occur before opening, namely closed-state inactivation, to tune the cellular excitability. The voltage-sensing domain (VSD) within repeat IV (VSD-IV) of the pseudotetrameric NaV channel α-subunit is known to be a critical regulator of NaV channel inactivation. Yet, the two processes of open- and closed-state inactivation predominate at different voltage ranges and feature distinct kinetics. How inactivation occurs over these different ranges to give rise to the complexity of NaV channel dynamics is unclear. Past functional studies and recent cryo-electron microscopy structures, however, reveal significant inactivation regulation from other NaV channel components. In this Hypothesis paper, we propose that the VSD of NaV repeat III (VSD-III), together with VSD-IV, orchestrates the inactivation-state occupancy of NaV channels by modulating the affinity of the intracellular binding site of the IFMT motif on the III-IV linker. We review and outline substantial evidence that VSD-III activates in two distinct steps, with the intermediate and fully activated conformation regulating closed- and open-state inactivation state occupancy by altering the formation and affinity of the IFMT crevice. A role of VSD-III in determining inactivation-state occupancy and recovery from inactivation suggests a regulatory mechanism for the state-dependent block by small-molecule anti-arrhythmic and anesthetic therapies.
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http://dx.doi.org/10.1085/jgp.202112891DOI Listing
September 2021

[Mental health and organizational quality of primary healthcare services in Brazil].

Cad Saude Publica 2021 28;37(7):e00267720. Epub 2021 Jul 28.

Faculdade de Medicina, Universidade Estadual Paulista, Botucatu, Brasil.

The study aimed to assess the quality of care for persons with mental health distress in primary healthcare services in Brazil and the association with organizational structure variables. This evaluative study used data from the Brazilian National Program to Improve Acess and Quality in Primary Care (PMAQ-AB), collected in 2018. The study excluded teams that reported not performing this type of care. The sum of the 13 selected mental health indicators produced a score that was classified in three groups of quality: G1 (0 to 5 points - lower quality), G2 (6 to 9 points - medium quality), and G3 (10 to 13 points - higher quality), and the results were associated with nine organizational context variables favoring the teams' permanence in the respective quality groups. The study evaluated 36,384 teams, located in 5,026 municipalities (counties). The score ranged from 1 to 13 points (G1 = 9.7%; G2 = 25.1%; G3 = 65.2%). Having an environment favorable to dispensing medicines and privacy during patient consultations; existence of a medical specialist, psychologist, and pharmacist; inter-consultation with the Expanded Family Health Care Centers (NASF) and Centers for Psychosocial Care (CAPS); and weekly or biweekly team meetings, were more frequent in the teams with higher quality (p < 0.001). In conclusion, structural conditions related to infrastructure and availability of healthcare workers, as well as inter-consultation and spaces for reflection to discuss the (re)organization of work processes in care for patients with mental health distress are factors that influence the quality of care, requiring attention, especially given recent political setbacks.
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http://dx.doi.org/10.1590/0102-311X00267720DOI Listing
July 2021

Epidemiological characteristics and temporal trends of new leprosy cases in Brazil: 2006 to 2017.

Cad Saude Publica 2021 28;37(7):e00130020. Epub 2021 Jul 28.

Instituto de Saúde Coletiva, Universidade Federal da Bahia, Salvador, Brasil.

Our study aims to describe trends in new case detection rate (NCDR) of leprosy in Brazil from 2006 to 2017 overall and in subgroups, and to analyze the evolution of clinical and treatment characteristics of patients, with emphasis on cases diagnosed with grade 2 physical disabilities. We conducted a descriptive study to analyze new cases of leprosy registered in the Brazilian Information System for Notificable Diseases (SINAN), from 2006-2017. We calculated the leprosy NCDR per 100,000 inhabitants (overall and for individuals aged < 15 and ≥ 15 years) by sex, age, race/ethnicity, urban/rural areas, and Brazilian regions, and estimated the trends using the Mann-Kendall non-parametric test. We analyzed the distributions of cases according to relevant clinical characteristics over time. In Brazil, there was a sharp decrease in the overall NCDR from 23.4/100,000 in 2006 to 10.3/100,000 in 2017; among children < 15 years, from 6.94 to 3.20/100,000. The decline was consistent in all Brazilian regions and race/ethnicity categories. By 2017, 70.2% of the cases were multibacillary, 30.5% had grade 1 (G1D) or 2 (G2D) physical disabilities at diagnosis and 42.8% were not evaluated at treatment completion/discharge; cases with G2D at diagnosis were mostly detected in urban areas (80%) and 5% of cases died during the treatment (leprosy or other causes). Although the frequency of leprosy NCDR decreased in Brazil from 2006 to 2017 across all evaluated population groups, the large number of cases with multibacillary leprosy, physical disabilities or without adequate evaluation, and among children suggest the need to reinforce timely diagnosis and treatment to control leprosy in Brazil.
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http://dx.doi.org/10.1590/0102-311X00130020DOI Listing
July 2021

Effects of clown activities on patients eligible for palliative care in primary health care.

Rev Bras Enferm 2021 28;74(5):e20200431. Epub 2021 Jul 28.

Universidade Federal de Mato Grosso do Sul. Três Lagoas, Mato Grosso do Sul, Brazil.

Objective: Evaluate the effects of clown activities on quality of life, depression, stress, anxiety, aid, and social support in patients eligible for palliative care (PC) attended in Primary Health Care (PHC).

Method: A quasi-experimental study, with pre-intervention and post-intervention evaluation, carried out with 16 patients eligible for early PC in PHC in a Midwestern city. Patients received 24 visits with home-based clown activities.

Results: The interventions evidenced improved quality of life and social support, with significant results for the Social Activities dimension (p = 0.023). Increased scores for Anxiety (p = 0.007) and Depression (p = 0.023) were also observed.

Conclusion: Clown activities can bring positive results for the quality of life and social support of patients eligible for PC at home. They should be encouraged to interact with family knowledge and enhance humanized care, integral and centered on human relationships in PHC.
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http://dx.doi.org/10.1590/0034-7167-2020-0431DOI Listing
July 2021

Effect of increasing doses of chitosan to grazing beef steers on the relative population and transcript abundance of and cellulolytic and amylolytic bacterias.

Anim Biotechnol 2021 Aug 4:1-7. Epub 2021 Aug 4.

Institute for Agrarian and Regional Development, Federal University of the South and Southeast of Pará, Marabá, Brazil.

This paper aims to investigate the influence of increasing chitosan doses on the relative proportion and abundance of cellulotytic, amylolytic bacteria, and transcripts for grazing cattle. Five rumen cannulated crossbread steers [3.6 months and 300 ± 25 kg body LW (live weight), mean ± standard deviation] were used in a 5 × 5 latin square design, randomly assigned to treatment sequence containing chitosan added to 0, 400, 800, 1200, or 1600 mg/kg concentrate. There was the effect of chitosan on the population of , , and . The lowest population of these bacteria of 576.60 mg/kg DM (dry matter), 1010.40 mg/kg DM, and 634.80 mg/kg DM were noted when chitosan was added at levels of 3.87, 4.16, and 3.52. Except for , which was not affected by increasing chitosan doses, supplementation of this additive in the concentrate quadratically increased the relative abundance of and Supplemental 740 mg CHI/kg concentrate for grazing steers receiving concentrate at 150 grams/100 kg LW is recommended to promote minimal effect on the relative population and abundance of cellulolytics and amylomatics and to restrict growth.
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http://dx.doi.org/10.1080/10495398.2021.1954936DOI Listing
August 2021

An adverse outcome pathway for lung surfactant function inhibition leading to decreased lung function.

Curr Res Toxicol 2021 27;2:225-236. Epub 2021 May 27.

National Research Centre for the Working Environment, Copenhagen, Denmark.

Inhaled substances, such as consumer products, chemicals at the workplace, and nanoparticles, can affect the lung function in several ways. In this paper, we explore the adverse outcome pathway (AOP) that starts when inhaled substances that reach the alveoli inhibit the function of the lung surfactant, and leads to decreased lung function. Lung surfactant covers the inner surface of the alveoli, and regulates the surface tension at the air-liquid interface during breathing. The inhibition of the lung surfactant function leads to alveolar collapse because of the resulting high surface tension at the end of expiration. The collapsed alveoli can be re-opened by inspiration, but this re-opening causes shear stress on cells covering the alveoli. This can damage the alveolar-capillary membrane integrity, allowing blood components to enter the alveolar airspace. Blood components, such as albumin, can interact with the lung surfactant and further inhibit its function. The collapse of the alveoli is responsible for a decrease in the surface area available for blood oxygenation, and it reduces the volume of air that can be inhaled and exhaled. These different key events lead to decreased lung function, characterized by clinical signs of respiratory toxicity and reduced blood oxygenation. Here we present the weight of evidence that supports the AOP, and we give an overview of the methods available and to measure each key event of the pathway, and how this AOP can potentially be used in screening for inhalation toxicity.
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http://dx.doi.org/10.1016/j.crtox.2021.05.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8320609PMC
May 2021

prediction of clinical signs of respiratory toxicity in rats following inhalation exposure.

Curr Res Toxicol 2021 21;2:204-209. Epub 2021 May 21.

National Research Centre for the Working Environment, Copenhagen, Denmark.

To date there are no OECD validated alternative approaches to study toxicity following inhalation exposure to airborne chemicals. The available OECD test guidelines for acute inhalation toxicity aim to estimate a value of the lethal air concentration of the test chemical leading to the death of 50% of the exposed animals (LC), to satisfy hazard classification and labelling requirements. This paper explores the view that alternative approaches must compare to outcomes of existing guideline methods to become accepted and implemented in a regulatory context. This case study describes the initiatives taken to validate the lung surfactant bioassay, an cell-free method, and discusses the challenges faced. While the lung surfactant bioassay could not predict the GHS classification for acute inhalation toxicity of 26 chemicals, the assay successfully predicted the clinical signs of respiratory toxicity observed during or shortly after exposure as reported in registration dossiers. The lung surfactant bioassay is a promising alternative approach to assess the potential of chemicals to cause changes to respiration remaining after exposure (indicating decreased lung function), and can be combined with other test methods in an integrated approach to testing and assessment of inhaled substances.
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http://dx.doi.org/10.1016/j.crtox.2021.05.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8320621PMC
May 2021

Short- and long-term effects on reproductive parameters of female Wistar rats after exposure to rosuvastatin starting in pre-puberty.

Curr Res Toxicol 2020 Jun 27;1:149-160. Epub 2020 Nov 27.

Department of Structural and Functional Biology, São Paulo State University (Unesp), Institute of Biosciences, Botucatu, SP, Brazil.

Statins are a class of drugs that act lowering lipid levels by inhibiting cholesterol biosynthesis. Additionally, statins can act by "pleiotropic effects", related to the inhibition of synthesis of the other mevalonate pathway products. Rosuvastatin is a third-generation statin and has shown better results in reducing cholesterol concentrations when compared to other statins. Recent studies suggest that rosuvastatin may act as an endocrine disruptor that potentially damages the hormonal axis and, consequently reproductive development and function of male rats. However, the effects of rosuvastatin exposure on rat female reproductive parameters remain unknown. In this study female rats were exposed to rosuvastatin at the doses of 0 (control), 3, or 10 mg/Kg.bw/day from pre-puberty to adulthood. No alterations in the female reproductive parameters were observed at a dose of 3 mg/Kg.bw. However, females exposed to 10 mg/Kg.bw exhibited shorter estrous cycles, altered copulatory behavior, decreased serum prolactin level, and alterations in the liver, pituitary and placental weights, parameters to some extent influenced by the reproductive hormonal axis signaling pathway. On the other hand, pubertal onset, reproductive hormone levels, fertility, and histological parameters of the ovary, uterus, and placenta were unaltered by exposure to both doses of this statin. Thus, rosuvastatin exposure, at the higher dose, altered the reproductive function of female rats, probably due to the pleiotropic effects of this statin. Additional studies on the effects of this statin on female reproductive function and development are encouraged to better characterize its mode of action.
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http://dx.doi.org/10.1016/j.crtox.2020.11.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8320644PMC
June 2020

Antigen Delivery to DEC205 Dendritic Cells Induces Immunological Memory and Protective Therapeutic Effects against HPV-Associated Tumors at Different Anatomical Sites.

Int J Biol Sci 2021 13;17(11):2944-2956. Epub 2021 Jul 13.

Vaccine Development Laboratory, Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.

The generation of successful anticancer vaccines relies on the ability to induce efficient and long-lasting immune responses to tumor antigens. In this scenario, dendritic cells (DCs) are essential cellular components in the generation of antitumor immune responses. Thus, delivery of tumor antigens to specific DC populations represents a promising approach to enhance the efficiency of antitumor immunotherapies. In the present study, we employed antibody-antigen conjugates targeting a specific DC C-type lectin receptor. For that purpose, we genetically fused the anti-DEC205 monoclonal antibody to the type 16 human papillomavirus (HPV-16) E7 oncoprotein to create a therapeutic vaccine to treat HPV-associated tumors in syngeneic mouse tumor models. The therapeutic efficacy of the αDEC205-E7 mAb was investigated in three distinct anatomical tumor models (subcutaneous, lingual and intravaginal). The immunization regimen comprised two doses of the αDEC205-E7 mAb coadministered with a DC maturation stimulus (Polyinosinic:polycytidylic acid, poly (I:C)) as an adjuvant. The combined immunotherapy produced robust antitumor effects on both the subcutaneous and orthotopic tumor models, stimulating rapid tumor regression and long-term survival. These outcomes were related to the activation of tumor antigen-specific CD8 T cells in both systemic compartments and lymphoid tissues. The αDEC205-E7 antibody plus poly (I:C) administration induced long-lasting immunity and controlled tumor relapses. Our results highlight that the delivery of HPV tumor antigens to DCs, particularly via the DEC205 surface receptor, is a promising therapeutic approach, providing new opportunities for the development of alternative immunotherapies for patients with HPV-associated tumors at different anatomical sites.
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http://dx.doi.org/10.7150/ijbs.57038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8326119PMC
July 2021

Correction to: Prevalence, indications and demographic characteristics of Botulinum neurotoxin use in a tertiary oculoplastic centre.

Eye (Lond) 2021 Aug 3. Epub 2021 Aug 3.

Department of Ophthalmology, University Hospitals of Leicester, Leicester Royal Infirmary, Leicester, UK.

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http://dx.doi.org/10.1038/s41433-021-01712-wDOI Listing
August 2021

Genome-wide approaches for the identification of markers and genes associated with sugarcane yellow leaf virus resistance.

Sci Rep 2021 Aug 3;11(1):15730. Epub 2021 Aug 3.

Centre of Molecular Biology and Genetic Engineering (CBMEG), University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.

Sugarcane yellow leaf (SCYL), caused by the sugarcane yellow leaf virus (SCYLV) is a major disease affecting sugarcane, a leading sugar and energy crop. Despite damages caused by SCYLV, the genetic base of resistance to this virus remains largely unknown. Several methodologies have arisen to identify molecular markers associated with SCYLV resistance, which are crucial for marker-assisted selection and understanding response mechanisms to this virus. We investigated the genetic base of SCYLV resistance using dominant and codominant markers and genotypes of interest for sugarcane breeding. A sugarcane panel inoculated with SCYLV was analyzed for SCYL symptoms, and viral titer was estimated by RT-qPCR. This panel was genotyped with 662 dominant markers and 70,888 SNPs and indels with allele proportion information. We used polyploid-adapted genome-wide association analyses and machine-learning algorithms coupled with feature selection methods to establish marker-trait associations. While each approach identified unique marker sets associated with phenotypes, convergences were observed between them and demonstrated their complementarity. Lastly, we annotated these markers, identifying genes encoding emblematic participants in virus resistance mechanisms and previously unreported candidates involved in viral responses. Our approach could accelerate sugarcane breeding targeting SCYLV resistance and facilitate studies on biological processes leading to this trait.
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http://dx.doi.org/10.1038/s41598-021-95116-1DOI Listing
August 2021

Driving regeneration, instead of healing, in adult mammals: the decisive role of resident macrophages through efferocytosis.

NPJ Regen Med 2021 Aug 3;6(1):41. Epub 2021 Aug 3.

STROMALab, Université de Toulouse, CNRS ERL5311, EFS, ENVT, Inserm U1031, UPS, Toulouse, France.

Tissue repair after lesion usually leads to scar healing and thus loss of function in adult mammals. In contrast, other adult vertebrates such as amphibians have the ability to regenerate and restore tissue homeostasis after lesion. Understanding the control of the repair outcome is thus a concerning challenge for regenerative medicine. We recently developed a model of induced tissue regeneration in adult mice allowing the comparison of the early steps of regenerative and scar healing processes. By using studies of gain and loss of function, specific cell depletion approaches, and hematopoietic chimeras we demonstrate here that tissue regeneration in adult mammals depends on an early and transient peak of granulocyte producing reactive oxygen species and an efficient efferocytosis specifically by tissue-resident macrophages. These findings highlight key and early cellular pathways able to drive tissue repair towards regeneration in adult mammals.
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http://dx.doi.org/10.1038/s41536-021-00151-1DOI Listing
August 2021

Chronic Antidiabetic Actions of Leptin: Evidence from Parabiosis Studies for a CNS-Derived Circulating Antidiabetic Factor.

Diabetes 2021 Aug 3. Epub 2021 Aug 3.

Department of Physiology and Biophysics, Mississippi Center for Obesity Research, Cardiovascular-Renal Research Center, University of Mississippi Medical Center, Jackson, MS.

We used parabiosis to determine whether the central nervous system (CNS)-mediated antidiabetic effects of leptin are mediated by release of a brain-derived circulating factor(s). Parabiosis was surgically induced at 4 weeks of age and an intracerebroventricular (ICV) cannula was placed in the lateral cerebral ventricles at 12 weeks of age for ICV infusion of leptin or saline vehicle. Ten days after surgery, food intake, body weight and blood glucose were measured for 5 consecutive days and insulin-deficiency diabetes was induced in all rats by a single streptozotocin (STZ) injection (40 mg/kg). Five days after STZ injection, leptin or vehicle was infused ICV for 7 days, followed by 5-day recovery period. STZ increased blood glucose and food intake. Chronic ICV leptin infusion restored normoglycemia in leptin-infused rats while reducing blood glucose by ∼27% in conjoined vehicle-infused rats. This glucose reduction was caused mainly by decreased hepatic gluconeogenesis. Chronic ICV leptin infusion also reduced net cumulative food intake and increased GLUT4 expression in skeletal muscle in leptin/vehicle compared to vehicle/vehicle conjoined rats. These results indicate that leptin's CNS-mediated antidiabetic effects are mediated, in part, by release into the systemic circulation of a leptin-stimulated factor(s) that enhances glucose utilization and reduces liver gluconeogenesis.
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http://dx.doi.org/10.2337/db21-0126DOI Listing
August 2021

Green photocatalytic remediation of Fenthion using composites with natural red clay and non-toxic metal oxides with visible light irradiation.

Environ Technol 2021 Aug 3:1-25. Epub 2021 Aug 3.

Instituto de Química, Universidade Federal da Bahia, Campus de Ondina, Salvador 40170-290, Bahia, Brazil.

In the present work, composites with non-toxic metal oxides, such as TiO and ZnO, and a natural red clay () reach in hematite were used in the photocatalytic degradation of Fenthion. The composite TiO/Taua (0.5:1 wt. ratio) and pure TiO were prepared by sol-gel method while ZnO/Taua (0.5:1 wt. ratio) and pure ZnO were prepared by Pechini method. The materials were characterized by XRD, SEM, EDX, and DRS. The anatase phase was formed in both pure TiO and TiO/Taua, while the hexagonal phase was formed in pure ZnO and ZnO/Taua. The bandgap energies for the two composites were narrowed compared to the respective pure oxides as consequence of the hematite (α-FeO, E = 2.1 eV) in the red clay, reaching 2.1 eV for TiO/Taua and 2.0 eV for ZnO/Taua, while the bandgap energies for pure TiO and ZnO were 3.2 eV and 3.0 eV, respectively. Fenthion was not degraded in the dark, but the concentration droped 20% after 180 minutes under visible light irradiation without photocatalyst and 60% after 210 minutes in the presence of the pure red clay. Both TiO/Taua and ZnO/Taua composites were also photocatalytic active to degrade Fenthion (λ > 420 nm), with degradation of 78% (in 180 minutes) and 85% (in 210 minutes) respectively. In the optimized conditions (pH 2, 100 mg L of HO and 30 mg L of Fenthion), the ZnO/Taua composite was the most efficient, reaching 89% degradation in up to 30 minutes, with Fenthion sulfoxide as the degradation product.
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http://dx.doi.org/10.1080/09593330.2021.1964611DOI Listing
August 2021

Efficient tyrosinase nano-inhibitor based on carbon dots behaving as a gathering of hydrophobic cores and key chemical group.

Colloids Surf B Biointerfaces 2021 Jul 28;207:112006. Epub 2021 Jul 28.

Departamento de Química Fundamental, CCEN, Universidade Federal de Pernambuco, Recife 50670-901, PE, Brazil. Electronic address:

Small organic molecules have been extensively applied to achieve enzymatic inhibition. Although numerous efforts have been made to deliver efficient inhibitors, small inhibitors applications are hindered by many drawbacks. Moreover, reporters comprising nanoparticle inhibitory activity against enzymes are very scarce in the literature. In this scenario, carbon nanodots (CDs) emerge as promising candidates for efficient enzyme inhibition due to their unique properties. Here, CDs specific molecular characteristics (core composition and chemical surface groups) have been investigated to produce a more potent enzyme inhibition. Mushroom tyrosinase (mTyr) has been adopted as an enzymatic prototype. The CDs revealed a high affinity to mTyr (Ka ≈ 10 M), mainly through hydrophobic forces and followed by slight mTyr structural alteration. CDs competitively inhibit mTyr, with low inhibition constant (K = 517.7 ± 17.0 nM), which is up 70 fold smaller then the commercial inhibitor (kojic acid) and the starch nanoparticles previously reported. The results expose that the CDs act as a hydrophobic agglomerate with carboxyl groups on its surface, mimicking characteristics found on small molecule inhibitors (but with superior performance). All these results highlight the CD excellent potential as an efficient low toxic Tyr inhibitor, opening the prospect of using these nanoparticles in the cosmetic and food industries.
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http://dx.doi.org/10.1016/j.colsurfb.2021.112006DOI Listing
July 2021

IgG Antibody response to the Sputnik V vaccine: previous SARS-CoV-2 seropositive individuals might need just one vaccine dose.

Int J Infect Dis 2021 Jul 31. Epub 2021 Jul 31.

Servicio Autónomo Instituto de Biomedicina, Universidad Central de Venezuela, Caracas, Venezuela.; Universidad de Las Américas (UDLA), Quito, Ecuador. Electronic address:

Introduction: . Serology tests play an important role in assessing the immune system's response to a previous SARS-CoV-2 infection or to vaccination. In Venezuela, before and after receiving the Sputnik V vaccine, we evaluated the IgG antibody response against the nucleocapsid protein (NP) and the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 in a cohort of 86 individuals.

Methods: . Antibody responses against NP and RBD were determined with an ELISA just before, 3 weeks after the first and 6 weeks after the second dose of the vaccine.

Results: Before vaccination, 59 individuals were seronegative and the other 27 were seropositive for SARS-CoV-2 antigens NP and/or RBD. Of the seronegative cohort, 42% did not develop a measurable IgG immune response against RBD after the first vaccine dose but all (100%) had a strong IgG response after two vaccine doses. All seropositive individuals developed a strong IgG antibody response against RBD after the first vaccine dose, with antibody levels approximately 40% higher than the seronegative individuals who had received two doses. Moreover, the previously seropositive subjects showed no significant increase in IgG antibody response against RBD after the second vaccine dose.

Conclusions: We demonstrated that two dose of the Sputnik V vaccine triggers antibody response in all individuals of this study. The second vaccine dose of Sputnik V has no impact on the IgG response for who were seropositive for SARS-CoV-2 antigens prior to vaccination.
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http://dx.doi.org/10.1016/j.ijid.2021.07.070DOI Listing
July 2021

Acute intermittent hypoxia evokes ventilatory long-term facilitation and active expiration in unanesthetized rats.

Respir Physiol Neurobiol 2021 Jul 31:103768. Epub 2021 Jul 31.

Department of Physiology and Pathology, School of Dentistry of Araraquara, São Paulo State University (UNESP), Araraquara, Brazil. Electronic address:

Acute intermittent hypoxia (AIH) modifies the functioning of the respiratory network, causing respiratory motor facilitation in anesthetized animals and a compensatory increase in pulmonary ventilation in freely behaving animals. However, it is still unclear whether the ventilatory facilitation induced by AIH in unanesthetized animals is associated with changes in the respiratory pattern. We found that Holtzman male rats (80-150 g) exposed to AIH (10 × 6% O for 30-40 s every 5 min, n = 9) exhibited a prolonged (30 min) increase in baseline minute ventilation (P < 0.05) compared to control animals (n = 13), combined with the occurrence of late expiratory peak flow events, suggesting the presence of active expiration. The increase in ventilation after AIH was also accompanied by reductions in arterial CO and body temperature (n = 5-6, P < 0.05). The systemic treatment with ketanserin (a 5-HT receptor antagonist) before AIH prevented the changes in ventilation and active expiration (n = 11) but potentiated the hypothermic response (n = 5, P < 0.05) when compared to appropriate control rats (n = 13). Our findings indicate that the ventilatory long-term facilitation elicited by AIH exposure in unanesthetized rats is linked to the generation of active expiration by mechanisms that may depend on the activation of serotonin receptors. In contrast, the decrease in body temperature induced by AIH may not require 5-HT receptor activation.
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http://dx.doi.org/10.1016/j.resp.2021.103768DOI Listing
July 2021

Functional and concurrent training do not impair immune function and improve functional fitness in postmenopausal women: A randomized controlled trial.

Exp Gerontol 2021 Jul 31:111504. Epub 2021 Jul 31.

Department of Physical Education, Post Graduate Program in Physical Education and Post Graduate Program in Physiology Sciences, Center of Biological and Health Sciences, Federal University of Sergipe, São Cristóvão, Brazil.

Purpose: To evaluate the effects of functional and concurrent training on immune function and functional fitness in postmenopausal women.

Materials And Methods: A randomized controlled trial was performed on 108 women aged 60 or older who were randomly assigned among the groups: control group (CG: n = 40; 63.88 ± 3.64 years); functional training (FT: n = 32; 63.88 ± 3.79 years); and concurrent training (CT: n = 36; 64.83 ± 4.00 years). Immune function was measured by the expression of the T-lymphocyte function-related surface markers (CD28 and CD57). Functional fitness was assessed using physical tests similar to daily activities, i.e., five times sit to stand, timed up and go, and gallon-jug shelf-transfer.

Results: Regarding immune function, there was only a time effect, without between-group differences. Specifically, FT and CT show a reduction and increase in CD4+ and CD8+ T cells, respectively, without impairment in the subpopulations analyzed, while CG showed a reduction in naive T cells (CD8+CD28+). For functional fitness tests, there was a time × group interaction effect for all tests, the FT and CT were superior to the CG, with FT showing differences after the fourth week, while the CT showed this effect after the eighth week of intervention.

Conclusion: FT and CT do not impair immune function and similarly improve functional fitness in postmenopausal women.

Clinical Trials Registry: RBR-2d56bt.
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http://dx.doi.org/10.1016/j.exger.2021.111504DOI Listing
July 2021

Does Platelet-Rich Fibrin Prevent Hemorrhagic Complications After Dental Extractions in Patients Using Oral Anticoagulant Therapy?

J Oral Maxillofac Surg 2021 Jul 8. Epub 2021 Jul 8.

Professor, Division of Oral Radiology, Federal University of Ceará, Postgraduate Program in Dentistry, Fortaleza, Ceará, Brazil.

Purpose: The number of anticoagulated patients requiring dental extractions and other minor dentoalveolar surgical procedures has increased significantly. The purpose of this study was to determine whether the use of platelet-rich fibrin (PRF) prevents hemorrhagic complications after dental extractions in patients being treated with oral anticoagulants.

Methods: A 2-phase PROSPERO-registered systematic review of published within-subject controlled trials (CRD42020186678) was conducted in accordance with the PRISMA statement. Searches were conducted through Medline via PubMed, Web of Science, LILACS, Central Cochrane, Scopus, DOSS, and Google Scholar, until May 2020. The predictor variable was the study group (PRF vs use/non-use of other hemostatic agents). The main outcome of interest was the risk of bleeding after tooth extraction and the covariates were postoperative complications. Data analysis included synthesis of results, risk of bias (RoB) evaluation, meta-analysis (random effects; I²-based heterogeneity; 95% confidence), and certainty of evidence assessment.

Results: From a total of 216 articles, 3 articles (low-moderate RoB) were included for evaluation in this systematic review and meta-analysis. A total of 130 patients were involved. The outcomes of the meta-analysis showed that the use of PRF in extraction wounds did not reduce the risk of bleeding after extraction in anticoagulated patients (P= .330; I² = 99%). Furthermore, the use of PRF did not improve pain scores (P = .470; I² = 96%) or the risk of postoperative alveolitis (P = .4300; I² = 38%) in anticoagulated patients. The certainty of the evidence ranged from moderate to low.

Conclusions: The findings of this systematic review and meta-analysis suggest that PRF does not prevent hemorrhagic complications after tooth extraction in patients using oral anticoagulant therapy.
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http://dx.doi.org/10.1016/j.joms.2021.07.003DOI Listing
July 2021

EAACI guideline: Anaphylaxis (2021 update).

Allergy 2021 Aug 3. Epub 2021 Aug 3.

NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton; Clinical and Experimental Sciences and Human Development in Health, Faculty of Medicine, University of Southampton, Southampton; and The David Hide Asthma and Allergy Research Centre, St Mary's Hospital, Isle of Wight, UK.

Anaphylaxis is a clinical emergency which all healthcare professionals need to be able to recognise and manage. The European Academy of Allergy and Clinical Immunology Anaphylaxis multidisciplinary Task Force has updated the 2014 guideline. The guideline was developed using the AGREE II framework and the GRADE approach. The evidence was systematically reviewed and recommendations were created by weighing up benefits and harms. The guideline was peer-reviewed by external experts and reviewed in a public consultation. The use of clinical criteria to identify anaphylaxis is suggested with blood sampling for the later measurement of tryptase. The prompt use of intramuscular adrenaline as first line management is recommended with the availability of adrenaline autoinjectors to patients in the community. Pharmacokinetic data should be provided for adrenaline autoinjector devices. Structured, comprehensive training for people at risk of anaphylaxis is recommended. Simulation training and visual prompts for healthcare professionals are suggested to improve the management of anaphylaxis. It is suggested that school policies reflect anaphylaxis guidelines. The evidence for the management of anaphylaxis remains mostly at a very low level. There is an urgent need to prioritise clinical trials with the potential to improve the management of patients at risk of anaphylaxis.
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http://dx.doi.org/10.1111/all.15032DOI Listing
August 2021
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