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Ultrasound elastography provides diagnostic information based on tissue elasticity. There is a lack of specific studies on the application of elastography in canine intestinal assessment. Therefore, we reviewed comparative medicine studies and those referring to the literature listed in the databases. Static and dynamic elastography techniques are widely applied in human intestinal diseases, especially Chron's disease, but few studies have investigated the application of these modalities in canine enteropathies. This case raises questions about the use of new diagnostic imaging techniques in veterinary gastroenterology and highlights the need for further research. Hence, this study aimed to review the literature on the physical principles of elastography and its clinical application in the intestinal evaluation of dogs., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Oliveira, et al.)

Valproic acid (VA) is a widely used drug for the treatment of diseases affecting the central nervous system. Due to its epigenetic modulatory potential, it has been studied for possible therapeutic application in anticancer therapies. However, the VA exhibits different side effects in its application. Thus, synthetic coordination complexes with valproate can generate promising candidates for new active drugs with reduced toxicity. In this sense, we investigated the genotoxic and mutagenic potential of the sodium valproate and of the mixed ternary mononuclear Mg complex based on VA with 1,10-phenanthroline (Phen) ligand - [Mg (Valp) 2 Phen], in Saccharomyces cerevisiae and V79 cells. The MTT and clonal survival assays in V79 cells indicated that the Mg complex has higher cytotoxicity than sodium valproate. A similar cytotoxicity profile is observed in yeast. This fact is possibly due to the intercalation capacity of [Mg(Valp) 2 Phen], inducing DNA strand breaks, as observed in the comet assay and micronucleus test. In this sense, members of the NER, HR, NHEJ and TLS repair pathways are required for the repair of DNA lesions induced by [Mg(Valp) 2 Phen]. Interestingly, BER proteins apparently increase the cytotoxic potential of the drug. Furthermore, the [Mg(Valp) 2 Phen] showed higher cytotoxicity in V79 cells and yeast when compared to sodium valproate indicating applicability as a cytotoxic agent., (© 2024 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society). Published by John Wiley & Sons Ltd.)

Dinizia Excelsa is an Amazonian tree with a wide range of applications as a raw material in the industry. The objective of this study was to extract, characterize, and evaluate the biological activities of xylan extracted from Dinizia excelsa wood. The xylan was obtained in five stages, including delignification, precipitation, purification, and freeze-drying. The physicochemical analysis of xylan included the determination of monosaccharides, elemental composition, FTIR analysis, 2D nuclear magnetic resonance spectroscopy, and the determination of molecular weight. Xylan had an extraction yield of 28.44% and an elemental composition of 35.03% carbon, 5.65% hydrogen, and 59.32% oxygen. FTIR analysis revealed similarities between Dinizia excelsa xylan and commercial xylan. 2D NMR analysis confirmed the presence of characteristic xylan groups. Furthermore, xylan has a low molecular weight. In vitro cytotoxicity tests demonstrated low toxicity, indicating its potential for biological applications. Immunomodulatory activity assays revealed that xylan stimulated cell proliferation and the production of anti-inflammatory cytokines. The anticoagulant activity of xylan was low compared to heparin. The antioxidant activity of xylan was weaker compared to ascorbic acid and butylated hydroxytoluene (BHT). These results indicate that xylan from Dinizia excelsa has potential for several biomedical applications due to its immunomodulatory and anticoagulant properties.

Enteropathies are prevalent in dog internal medicine, and their diagnosis involves a lengthy process. One of the tests requested is for biomarkers, which are important as they can provide data on intestinal functionality, intensity of inflammation, and response to treatment, and can help determine the prognosis. This study aimed to conduct a literature review on the main serum and fecal intestinal biomarkers in dogs and proposed to refine the correlations between these indicators and enteropathies. It was observed that the main biomarkers used in the intestinal evaluation of dogs were alpha 1-proteinase inhibitory factor, immunoglobulin A, methylmalonic acid, serum folate, serum cobalamin, C-reactive protein, fecal and serum calprotectin, and dysbiosis index. However, we suggest that more research be carried out to clarify the relationship between enteropathies and intestinal biomarkers. We noticed a lack of studies on specific intestinal markers and indicator variables in healthy dogs and those with various enteropathies; moreover, no data are available on the association of these laboratory parameters., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Iago Martins Oliveira et al.)

Overexposure to blue light due to the excessive use of electronic devices has been implicated in premature skin aging and eye damage, among other injuries to health. This study aimed to synthesize two azo derivatives of the 2-(amino-2'-hydroxyphenyl) benzoxazole and explore their potential as UV and blue light filters, proposing a new spectral profile. The synthesis of the heterocyclic compounds involved condensation reactions and diazotation. The derivatives 2-(benzoxazol-2-yl)-5-[(2-hydroxynaphthyl)diazenyl]phenol and 2-(benzoxazol-2-yl)-4-[(2-hydroxynaphthyl)diazenyl]phenol were synthesized with a yield greater than 70%. Solubility was evaluated in seven different solvents. The maximum absorption wavelengths (λ max ) were determined using UV-Vis scanning spectrophotometry in the range of 200-600 nm. Photostability was assessed using a solar simulator and the Sun protection factor (SPF) was determined using in vitro methodology. Cytotoxicity was evaluated using the MTT assay in V79 cells. These compounds were able to absorb UVA, UVB, and blue light, with λ max ranging from 300 to 500 nm and demonstrated photostability after 3 h of exposure to solar simulator with an SPF higher than 45. The compounds exhibited solubility in all lipophilic solvents tested. Regarding cytotoxicity, IC50 values were comparable to other filters. These findings indicate that both compounds hold promise as potential organic filters., (© 2024 John Wiley & Sons Ltd.)

Glyphosate, the world's most widely used herbicide, has a low toxicity rating despite substantial evidence of adverse health effects. Furthermore, glyphosate-based formulations (GBFs) contain several other chemicals, some of which are known to be harmful. Additionally, chronic, and acute exposure to GBFs among rural workers may lead to health impairments, such as neurodegenerative diseases and cancer. P53 is known as a tumor suppressor protein, acting as a key regulator of the cellular response to stress and DNA damage. Therefore, mutations in the TP53 gene, which encodes p53, are common genetic alterations found in various types of cancer. Therefore, this study aimed to evaluate the cytotoxicity and genotoxicity of GBF in two glioblastoma cell lines: U87MG (TP53-proficient) and U251MG (TP53-mutant). Additionally, the study aimed to identify the main proteins involved in the response to GBF exposure using Systems Biology in a network containing p53 and another network without p53. The MTT assay was used to study the toxicity of GBF in the cell lines, the clonogenic assay was used to investigate cell survival, and the Comet Assay was used for genotoxicity evaluation. For data analysis, bioinformatics tools such as String 12.0 and Stitch 5.0 were applied, serving as a basis for designing binary networks in the Cytoscape 3.10.1 program. From the in vitro test analyses, it was observed a decrease in cell viability at doses starting from 10 ppm. Comet Assay at concentrations of 10 ppm and 30 ppm for the U251MG and U87MG cell lines, respectively observed DNA damage. The network generated with systems biology showed that the presence of p53 is important for the regulation of biological processes involved in genetic stability and neurotoxicity, processes that did not appear in the TP53-mutant network., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Fernanda Rabaioli da Silva reports equipment, drugs, or supplies was provided by Conselho Nacional de Desenvolvimento Científico e Tecnológico - CNPq (Brazil). If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Studies have demonstrated the susceptibility of companion animals to natural infection with SARS-CoV-2. Using quantitative reverse transcription polymerase chain reaction and sequencing analyses, this study investigated SARS-CoV-2 RNA excretion in pets in households with infected owners. Oropharyngeal and rectal swabs were collected from dogs and cats in Parana, Southern Brazil, between October 2020 and April 2021. Viral RNA was detected in 25% of cats and 0.98% of dog oropharyngeal swabs; however, systemic, respiratory, and gastrointestinal signs were absent. Complete viral genomes belonged to the Gamma lineage. Phylogenetic analyses indicated that pet samples were probably derived from human-positive cases in Parana. Viral excretion in the oropharynx was more frequent in cats than in dogs. Mutations in the S protein characteristic of Gamma strains were present in all sequenced SARS-CoV-2 strains. The receptor-binding domain of these Brazilian strains did not show any additional mutations not reported in the Gamma strains. Mutations in NSP6, NSP12, and N proteins previously mapped to strains that infect deer or minks were detected. This study highlights the importance of actively monitoring the SARS-CoV-2 strains that infect pets with continued viral exposure. Monitoring genetic changes is crucial because new variants adapted to animals may pose human health risks.

This study aimed to analyze the incidence of work-related musculoskeletal disorders (WMSD) in Brazil from 2007 to 2019, examining the spatial, temporal, and spatiotemporal patterns of their occurrence. An ecological time series study was conducted using spatial analysis techniques. WMSD morbidity data from 2007 to 2019 were collected from the Brazilian Information System for Notificable Diseases of the Brazilian Health Informatics Department. Incidence rates were standardized and smoothed using the local empirical Bayes' theorem. Time trends were analyzed by segmented linear regression. Spatial analysis was performed using Moran's univariate global (I) and local (LISA) indexes. The spatiotemporal scan statistic was used to identify high-risk spatiotemporal clusters for WMSD. A total of 93,387 cases of WMSD were recorded in Brazil. Temporal trends showed an increase in all regions except the Northeast, which remained stable. The incidence of WMSD showed a spatial dependence, with spatial and space-time clusters identified, especially in the Southeast region, overlapping the largest economic-industrial center of the country. The spatiotemporal clustering observed in one region suggests the highest level of industrial and economic development. Our findings highlight the need to implement intersectoral surveillance policies, inspect working conditions, and invest in the prevention and promotion of workers' health.

A heterogenized Mn(III) porphyrin-based catalyst was prepared for dye degradation. The new Mn(III) complex of 5,15-bis(4-aminophenyl)-10,20-diphenylporphyrin was immobilized, via covalent bond, in chloropropyl silica gel, generating the material (Sil-Cl@MnP) with a loading of 23 μmol manganese porphyrin (MnP) per gram of Sil-Cl. This material was used as a catalyst in degradation reactions of model dyes, a cationic dye [methylene blue (MB)] and an anionic dye (reactive red 120, RR120), using PhI(OAc) 2 and H 2 O 2 as oxidants. The oxidation reactions were carried out after the dye reached adsorption/desorption equilibrium with the catalytic material, with a much higher percentage of adsorption being observed for the cationic MB dye (20%) than for the anionic RR120 dye (3%), which may be associated with electrostatic attraction or repulsion effects, respectively, with the negatively charged surface of the silica (zeta potential measurement for Sil-Cl@MnP, ζ = -19.2 mV). In general, there was a higher degradation percentage for MB than for RR120, probably because the size and charge of RR120 would hinder its approach to the MnP active species on the silica surface. With respect to the oxidant, the PhI(OAc) 2 -based systems showed a higher degradation percentage than those of H 2 O 2 . It was observed that the increase in the oxidant concentration promoted a significant increase in the degradation of MB, with a degradation of approximately 65%. The efficiency of the catalyst was also evaluated after successive additions of the oxidant every 2 h, and it can be seen that the catalyst had no loss of efficiency, with a degradation percentage greater than 80% being observed after 8 h of reaction. The phytotoxicity of the products formed in the system was evaluated in a 1:23.5:188 molar ratio Sil-Cl@MnP: MB:PhI(OAc) 2 was used. In these studies, phytotoxicity was found for the germination of lettuce seeds when the original solution was used without dilution; however, when diluted (10% V/V), the results were close to the positive and negative controls. Thus, the material obtained proved to be a potential candidate for application in the degradation reactions of environmental pollutants., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

COVID-19 has affected more than half a billion people worldwide, with more than 6.3 million deaths, but the pathophysiological mechanisms involved in lethal cases and the host determinants that determine the different clinical outcomes are still unclear. In this study, we assessed lung autopsies of 47 COVID-19 patients and examined the inflammatory profiles, viral loads, and inflammasome activation. Additionally, we correlated these factors with the patient's clinical and histopathological conditions. Robust inflammasome activation was detected in the lungs of lethal cases of SARS-CoV-2. Experiments conducted on transgenic mice expressing hACE2 and infected with SARS-CoV-2 showed that Nlrp3-/- mice were protected from disease development and lethality compared to Nlrp3+/+ littermate mice, supporting the involvement of this inflammasome in disease exacerbation. An analysis of gene expression allowed for the classification of COVID-19 patients into two different clusters. Cluster 1 died with higher viral loads and exhibited a reduced inflammatory profile than Cluster 2. Illness time, mechanical ventilation time, pulmonary fibrosis, respiratory functions, histopathological status, thrombosis, viral loads, and inflammasome activation significantly differed between the two clusters. Our data demonstrated two distinct profiles in lethal cases of COVID-19, thus indicating that the balance of viral replication and inflammasome-mediated pulmonary inflammation led to different clinical outcomes. We provide important information to understand clinical variations in severe COVID-19, a process that is critical for decisions between immune-mediated or antiviral-mediated therapies for the treatment of critical cases of COVID-19., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 de Sá et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Orthopedic procedures are associated with severe postoperative pain. In TPLO, the block commonly used is the sciatic nerve block associated with the femoral nerve block. In orthopedic surgeries in human medicine, the iPACK block associated with the adductor canal block has been used as alternatives that do not affect the strength of the quadriceps femoris muscle. The objective of this study was to evaluate the trans and postoperative analgesic effect of the association of iPACK block and adductor canal block, as well as to evaluate the patient's motor recovery after surgery. Four patients were selected, without distinction of breed and gender, weighing more than 22lb, referred to TPLO. All patients underwent the combination of iPACK block and adductor canal block with 0.5% bupivacaine. The intraoperative evaluation was carried out by measuring mean arterial pressure, heart rate and respiratory rate, and all patients were stable during the procedure. The postoperative evaluation was carried out based on the assessment of pain using the modified Glasgow scale, in which all patients scored less than 05/24, and assessment of ambulation through videos using the adapted Muzzi scale, presenting ambulation between grade 1 and 2. No patient required intraoperative or postoperative analgesic rescue., Competing Interests: Conflict of interests: DSR, IMO, LRRS, YSKS and GNSC – No conflict of interest

Objective: To review the pathological diagnosis of possible cases and/or hidden cases of malignant mesothelioma (MM) between 2000 and 2012 using the Hospital-Based Cancer Registry database in the state of São Paulo, Brazil., Methods: Possible cases were retrieved by assessing the database. Inclusion criteria were being older than 30 years of age and having ICD-O-3 topography and morphology codes related to MM. A board of expert pathologists reviewed the pathology reports and requested paraffin blocks in cases that demanded revision. After staining with calretinin, D2-40, WT-1 (as positive MM markers) and Ber-EP4 and MOC31 (as negative MM markers), cases were divided and studied independently by a pair of pathologists to confirm or discard the diagnosis of MM., Results: Our sample comprised 482 cases from 25 hospitals, and 130 needed further histological revision. We received 73 paraffin blocks with adequate material. After board analysis, there were 9 cases with a definitive diagnosis of MM, improving the diagnostic rate in 12%. Two cases of previously diagnosed MM were discarded by review., Conclusions: Our results confirm that part of MM underdiagnosis and underreporting in Brazil is due to incomplete or mistaken pathological diagnosis.

Objective: To analyze the temporal trend of human papillomavirus (HPV) vaccination coverage among the female population aged 10 to 14 years, living in the state of Goiás, Brazil, between 2014 and 2022., Methods: This was an ecological time series study using data from the Brazilian National Health System Information Technology Department (Departamento de Informática do Sistema Único de Saúde - DATASUS); the annual vaccination coverage rate was calculated based on the number of second doses administered; the trend of the rates was analyzed using the Prais-Winsten model., Results: A total of 407,217 second doses of the quadrivalent HPV vaccine were administered to the female population aged 10-14 years, with annual vaccination coverage rates ranging from 12.3% (2019) to 30.0% (2015), and an annual percentage change (APC) of 0.7% (95%CI 0.9; 0.2; p-value = 0.030)., Conclusion: In Góias state, the quadrivalent HPV vaccine coverage rate was below the national target (80%), showing a stationary trend in the time series.

The presence of biofilms in drinking water distribution systems (DWDS) is responsible for water quality deterioration and a possible source of public health risks. Different factors impact the biological stability of drinking water (DW) in the distribution networks, such as the presence and concentration of nutrients, water temperature, pipe material composition, hydrodynamic conditions, and levels of disinfectant residual. This review aimed to evaluate the current state of knowledge on strategies for DW biofilm disinfection through a qualitative and quantitative analysis of the literature published over the last decade. A systematic review method was performed on the 562 journal articles identified through database searching on Web of Science and Scopus, with 85 studies selected for detailed analysis. A variety of disinfectants were identified for DW biofilm control such as chlorine, chloramine, UV irradiation, hydrogen peroxide, chlorine dioxide, ozone, and others at a lower frequency, namely, electrolyzed water, bacteriophages, silver ions, and nanoparticles. The disinfectants can impact the microbial communities within biofilms, reduce the number of culturable cells and biofilm biomass, as well as interfere with the biofilm matrix components. The maintenance of an effective residual concentration in the water guarantees long-term prevention of biofilm formation and improves the inactivation of detached biofilm-associated opportunistic pathogens. Additionally, strategies based on multi-barrier processes by optimization of primary and secondary disinfection combined with other water treatment methods improve the control of opportunistic pathogens, reduce the chlorine-tolerance of biofilm-embedded cells, as well as decrease the corrosion rate in metal-based pipelines. Most of the studies used benchtop laboratory devices for biofilm research. Even though these devices mimic the conditions found in real DWDS, future investigations on strategies for DW biofilm control should include the validity of the promising strategies against biofilms formed in real DW networks., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The contamination of indoor areas is a global health problem that can cause the dispersion of infectious diseases. In that sense, it is urgent to find new strategies applying a lower concentration of the traditional chemicals used for cleaning and disinfection. Ultraviolet radiation (UV), in particular far-UV-C (200-225 nm), has emerged as a successful, powerful, easy-to-apply, and inexpensive approach for bacterial eradication that still requires scientific assessment. This study investigated new strategies for disinfection based on far-UV-C (222 nm) combined with chlorine and mechanical cleaning, providing an innovative solution using low doses. The bactericidal activity of far-UV-C (222 nm) was tested at an intensity of irradiation from 78.4 μW/cm 2 to 597.7 μW/cm 2 (for 1 min) against Escherichia coli and Staphylococcus epidermidis adhered on polystyrene microtiter plates. It was further tested in combination with mechanical cleaning (ultrasounds for 1 min) and free chlorine (0.1, 0.5, and 1 mg/L for 5 min). The triple combination consisting of mechanical cleaning + free chlorine (0.5 mg/L) + far-UV-C (54 mJ/cm 2 ) was tested against cells adhered to materials found in hospital settings and other public spaces: polyvinyl chloride (PVC), stainless steel (SS), and polyetheretherketone (PEEK). Disinfection with far-UV-C (54 mJ/cm 2 ) and free chlorine at 0.5 mg/L for 5 min allowed a total reduction of culturable E. coli cells and a logarithmic reduction of 2.98 ± 0.03 for S. epidermidis. The triple combination of far-UV-C, free chlorine, and mechanical cleaning resulted in a total reduction of culturable cells for both adhered bacteria. Bacterial adhesion to PVC, SS, and PEEK occurred at distinct extents and influenced the bactericidal activity of the triple combination, with logarithmic reductions of up to three. The overall results highlight that, based on culturability assessment, far-UV-C (54 mJ/cm 2 ) with chlorine (0.5 mg/L; 5 min) and mechanical cleaning (1 min) as an efficient disinfection strategy using mild conditions. The combination of culturability and viability assessment of disinfection is recommended to detect regrowth events and increase the effectiveness in microbial growth control., Competing Interests: Declaration of competing interest The authors declare that they have no competing financial interests or conflicts of interest in the writing of this article., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

This study evaluated different herbage allowances from mid to late pregnancy on pre- and postpartum physiological responses, milk production, and the performance of Nellore cows and the preweaning growth of their female offspring. Sixty multiparous Nellore cows were blocked by their body weight (BW; 425 ± 36 kg) and body condition score (BCS; 3.67 ± 0.23, scale 1-5) and randomly allocated to twelve pastures. Treatments consisted of two different herbage allowances (HA) during pregnancy: low HA (LHA; 2.80 kg DM/kg of BW) and high HA (HHA; 7.60 kg DM/kg of BW). Both treatment groups were fed 1 g/kg BW of a protein supplement. After calving, all cow-calf pairs were combined in a single group. The effects of maternal treatment × day of the study were detected for herbage mass and allowance, the stocking rate and forage crude protein, and for cow BW, BCS, and carcass measures ( p < 0.01). Milk yield corrected to 4% fat, while the levels of fat total solids and cow plasma IGF-1 and urea were different ( p ≤ 0.04) between treatments. HHA offspring was heavier ( p ≤ 0.05) at 120 days and at weaning. A high herbage allowance can be implemented from mid-gestation until calving to increase cow prepartum performance, post-partum milk yield and composition, and positively modulate female offspring preweaning growth.

Background: Cholinesterase is a biomarker for poisonings by anticholinesterase agents, but its reference values are scarce, and possible interaction with collars containing parasiticides has not been studied., Objectives: We aimed to evaluate the serum cholinesterase activity of healthy dogs without a history of contact with anticholinesterase agents and healthy animals exposed to commercial collars containing organophosphate., Methods: Ninety-nine dogs were used and included healthy animals without recent exposure to anticholinesterase agents and healthy animals previously exposed to diazinon collars. Serum quantification of the enzyme butyrylcholinesterase (BuchE) through spectrophotometry was conducted on all samples. In experiment 1, BuchE activity was quantified at time 0 and 7 days after, a time when the samples were kept at -18°C. In experiment 2, sampling times were 0, 7, 14, 21, 28, and 56 days., Results: Time 0 values were 4622.38 ± 1311.53 U/L. After 7 days, a significant decay was observed, with a mean of 3934.45 ± 1430.45 U/L. Spearman's test was performed, finding a weak correlation between ALT, creatinine, total plasma proteins, age, weight, red blood cells, platelets, leukocytes, and BuchE activities. In experiment 2, the mean at time 0 was 4753 ± 454.8 U/L. With exposure to the collar, there was a decay of up to 93% after 14 days., Conclusions: Normality values of serum BuchE in healthy dogs without a history of exposure to anticholinesterase agents were 4360.8-4883.96 U/L. Freezing serum caused a decrease in BuchE activity. Exposure to commercial collars containing diazinon also reduced BuchE activity without clinical signs, indicating that previously exposed animals should be evaluated carefully., (© 2023 American Society for Veterinary Clinical Pathology.)

Hypothyroidism and thyrotoxicosis are associated with male reproductive disorders, but little is known about the influence of the thyroid hormone milieu on seminal vesicle (SV) function and metabolism. In this sense, we investigated the effects of hypothyroidism and thyrotoxicosis induced in adulthood Wistar male rats on SV function and identified new thyroid hormone targets on male reproduction regulation using novel proteomic approaches. Hypothyroidism reduces SV size and seminal fluid volume, which are directly associated with low testosterone and estradiol levels, while thyrotoxicosis increases Esr2 and Dio1 expression in the SV. We found 116 differentially expressed proteins. Hypothyroidism reduces the expression of molecular protein markers related to sperm viability, capacitation and fertilization, protection against oxidative stress and energetic metabolism in SV, while it increases the expression of proteins related to tissue damage. In conclusion, thyroid dysfunction in the adult phase impairs several morphological, molecular and functional characteristics of SV., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The expansion and intensification of livestock production is predicted to promote the emergence of pathogens. As pathogens sometimes jump between species, this can affect the health of humans as well as livestock. Here, we investigate how livestock microbiota can act as a source of these emerging pathogens through analysis of Streptococcus suis , a ubiquitous component of the respiratory microbiota of pigs that is also a major cause of disease on pig farms and an important zoonotic pathogen. Combining molecular dating, phylogeography, and comparative genomic analyses of a large collection of isolates, we find that several pathogenic lineages of S. suis emerged in the 19th and 20th centuries, during an early period of growth in pig farming. These lineages have since spread between countries and continents, mirroring trade in live pigs. They are distinguished by the presence of three genomic islands with putative roles in metabolism and cell adhesion, and an ongoing reduction in genome size, which may reflect their recent shift to a more pathogenic ecology. Reconstructions of the evolutionary histories of these islands reveal constraints on pathogen emergence that could inform control strategies, with pathogenic lineages consistently emerging from one subpopulation of S. suis and acquiring genes through horizontal transfer from other pathogenic lineages. These results shed light on the capacity of the microbiota to rapidly evolve to exploit changes in their host population and suggest that the impact of changes in farming on the pathogenicity and zoonotic potential of S. suis is yet to be fully realized.

Ras guanine nucleotide exchange factor member 1b (RasGEF1b) of the RasGEF/CDC25 domain-containing family is preferentially expressed by macrophages. However, information is lacking about its role in macrophage function. In this study, we generated mice with ubiquitous deletion of Rasgef1b and used RNA-seq-based transcriptomics to compare the global gene expression in wild-type and knock-out primary bone-marrow-derived macrophages under basal conditions and after lipopolysaccharide (LPS) treatment. Transcriptional filtering identified several genes with significantly different transcript levels between wild-type and knock-out macrophages. In total, 49 and 37 differentially expressed genes were identified at baseline and in LPS-activated macrophages, respectively. Distinct biological processes were significantly linked to down-regulated genes at the basal condition only, and largely included chemotaxis, response to cytokines, and positive regulation of GTPase activity. Importantly, validation by RT-qPCR revealed that the expression of genes identified as down-regulated after LPS stimulation was also decreased in the knock-out cells under basal conditions. We used a luciferase-based reporter assay to showcase the capability of RasGEF1b in activating the Serpinb2 promoter. Notably, knockdown of RasGEF1b in RAW264.7 macrophages resulted in impaired transcriptional activation of the Serpinb2 promoter, both in constitutive and LPS-stimulated conditions. This study provides a small collection of genes that shows relative expression changes effected by the absence of RasGEF1b in macrophages. Thus, we present the first evidence that RasGEF1b mediates the regulation of both steady-state and signal-dependent expression of genes and propose that this GEF plays a role in the maintenance of the basal transcriptional level in macrophages., (© 2023. The Author(s).)

The potential of pentapotassium bis(peroxymonosulphate) bis(sulphate) (OXONE) to control biofilms in drinking water distribution systems (DWDS) was evaluated and compared to chlorine disinfection. Mature biofilms of drinking water (DW)-isolated Stenotrophomonas maltophilia were formed using a simulated DWDS with a rotating cylinder reactor (RCR). After 30 min of exposure, OXONE at 10 × minimum bactericidal concentration (MBC) caused a significant 4 log reduction of biofilm culturability in comparison to the unexposed biofilms and a decrease in the number of non-damaged cells below the detection limit (4.8 log cells/cm 2 ). The effects of free chlorine were restricted to approximately 1 log reduction in both biofilm culturability and non-damaged cells. OXONE in synthetic tap water (STW) at 25 ºC was more stable over 40 days than free chlorine in the same conditions. OXONE solution exhibited a disinfectant decrease of about 10% of the initial concentration during the first 9 days, and after this time the values remained stable. Whereas possible reaction of chlorine with inorganic and organic substances in STW contributed to free chlorine depletion of approximately 48% of the initial concentration. Electron paramagnetic resonance (EPR) spectroscopy studies confirmed the presence of singlet oxygen and other free radicals during S. maltophilia disinfection with OXONE. Overall, OXONE constitutes a relevant alternative to conventional DW disinfection for effective biofilm control in DWDS., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Callingcard Vine (Entada polystachya (L.) DC. var. polystachya - Fabaceae) is a common plant in coastal thickets from western Mexico through Central America to Colombia and Brazil, especially in Amazon biome. It has been popularly used as a urinary burning reliever and diuretic. However, the plant chemical constituents are poorly understood and Entada spp. genotoxic potential have not been previously investigated. In the present study we determined the chemical composition of the aqueous E. polystachya crude seed extract (EPCSE) and evaluated the cytotoxic, genotoxic and mutagenic properties of EPCSE in Salmonella typhimurium and Chinese hamster fibroblast (V79) cells. Cytotoxic activity was also evaluated in tumor cell lines (HT29, MCF7 and U87) and non-malignant cells (MRC5). The chemical analysis by High Resolution Mass Spectrometry (HRMS) of EPCSE indicated the presence of saponin and chalcone. The results of the MTT and clonal survival assays suggest that EPCSE is cytotoxic to V79 cells. Survival analysis showed higher IC 50 in non-tumor compared with tumor cell lines. EPCSE showed induction of DNA strand breaks as revealed by the alkaline comet assay and micronucleus test. Using the modified comet assay, it was possible to detect the induction of oxidative DNA base damage by EPCSE in V79 cells. Consistently, the extract induced increase lipid peroxidation (TBARS), superoxide dismutase (SOD) and catalase (CAT) activities in V79 cells. In addition, EPCSE induced mutations in S. typhimurium TA98 and TA100 strains, confirming a mutagenic potential. Taken together, our results suggest that EPCSE is cytotoxic and genotoxic to V79 cells and mutagenic to S. typhimurium. These properties can be related to the pro-oxidant ability of the extract and induction of DNA lesions. Additionally, EPCSE could inhibit the growth of tumor cells, especially human colorectal adenocarcinoma (HT29) cell line, and can constitute a possible source of antitumor natural agents., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The activity of two chlorinated isocyanurates (NaDCC and TCCA) and peroxymonosulphate (OXONE) was evaluated against biofilms of Stenotrophomonas maltophilia , an emerging pathogen isolated from drinking water (DW), and for the prevention of biofilm regrowth. After disinfection of pre-formed 48 h-old biofilms, the culturability was reduced up to 7 log, with OXONE, TCCA, and NaDCC showing more efficiency than free chlorine against biofilms formed on stainless steel. The regrowth of biofilms previously exposed to OXONE was reduced by 5 and 4 log CFU cm -2 in comparison to the unexposed biofilms and biofilms exposed to free chlorine, respectively. Rheometry analysis showed that biofilms presented properties of viscoelastic solid materials, regardless of the treatment. OXONE reduced the cohesiveness of the biofilm, given the significant decrease in the complex shear modulus (G*). AFM analysis revealed that biofilms had a fractured appearance and smaller bacterial aggregates dispersed throughout the surface after OXONE exposure than the control sample. In general, OXONE has been demonstrated to be a promising disinfectant to control DW biofilms, with a higher activity than chlorine. The results also show the impact of the biofilm mechanical properties on the efficacy of the disinfectants in biofilm control.

Diphenyl ditelluride (DPDT) is an organotellurium (OT) compound with pharmacological properties, including antioxidant, antigenotoxic and antimutagenic activities when applied at low concentrations. However, DPDT as well as other OT compounds also show cytotoxicity against mammalian cells when treatments occur at higher drug concentrations. Considering that the underlying mechanisms of toxicity of DPDT against tumor cells have been poorly explored, the objective of our study was to investigate the effects of DPDT against both human cancer and non-tumorigenic cells. As a model, we used the colonic HCT116 cancer cells and the MRC5 fibroblasts. Our results showed that DPDT preferentially targets HCT116 cancer cells when compared to MRC5 cells with IC 50 values of 2.4 and 10.1 μM, respectively. This effect was accompanied by the induction of apoptosis and a pronounced G2/M cell cycle arrest in HCT116 cells. Furthermore, DPDT induces DNA strand breaks at concentrations below 5 μM in HCT116 cells and promotes the occurrence of DNA double strand breaks mostly during S-phase as measured by γ-H2AX/EdU double staining. Finally, DPDT forms covalent complexes with DNA topoisomerase I, as observed by the TARDIS assay, with a more prominent effect observed in HCT116 than in MRC5 cells. Taken together, our results show that DPDT preferentially targets HCT116 colon cancer cells likely through DNA topoisomerase I poisoning. This makes DPDT an interesting molecule for further development as an anti-proliferative compound in the context of cancer.

Exposure to endocrine-disrupting chemicals during critical windows of development may lead to functional abnormalities in adulthood. Isoflavones are a flavonoid group of phytoestrogens that are recognized by their estrogenic activity and are highly abundant in soybean. Since the thyroid gland presents estrogen receptors and infants, toddlers and teenagers may consume isoflavones from soy-based infant formula and beverages as alternatives to animal milk, we propose to investigate the potential effects of relevant concentrations of soy isoflavones in the regulation of the hypothalamic-pituitary (HP) thyroid axis using peripubertal male rats as an experimental model. Thirty-two 23-day-old male rats were exposed to 0.5, 5, or 50 mg of soy isoflavones/kg from weaning to 60 days of age, when they were euthanized, and the tissues were collected to evaluate the mRNA expression of genes involved in the regulation of the HP thyroid axis and dosages of thyroid hormones (THs). Serum TSH concentrations were increased, while alterations were not observed in serum concentrations of triiodothyronine and thyroxine. Regarding mRNA gene expression, Mct-8 was increased in the hypothalamus, Mct-8 , Thra1 , and Thrb2 were decreased in the pituitary, and Nis and Pds were reduced in the thyroid. In the heart, Mct8 and Thrb2 were increased, and Thra1 was decreased. In the liver, Mct8 , Thra1 , and Thrb2 were decreased. These results suggest that the consumption of relevant doses of soy isoflavones during the peripubertal period in males may induce subclinical hypothyroidism, with alterations in the regulation of the HP thyroid axis, modulation of TH synthesis, and peripheral alterations in TH target organs.

Alzheimer's disease (AD) is a common form of dementia that leads to multiple repercussions in the patient's life. This condition's clinical characteristics include loss of memory, temporal and spatial disorientation, language or executive dysfunction, and subsequent decline of social function. Dysexecutive syndrome (DS), the second most frequent neuropsychological dysfunction in AD, affects multiple brain areas and causes cognitive, behavioral, and emotional difficulties. We aimed to analyze the association between DS and AD and elucidate possible lack of evidence that may urge further research on this theme. Especially when dealing with such a disabling disease, where new findings can directly imply a better prognosis., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Cryptococcosis therapy is often limited by toxicity problems, antifungal tolerance, and high costs. Studies approaching chalcogen compounds, especially those containing selenium, have shown promising antifungal activity against pathogenic species. This work aimed to evaluate the in vitro and in vivo antifungal potential of organoselenium compounds against Cryptococcus neoformans. The lead compound LQA&#95;78 had an inhibitory effect on C. neoformans planktonic cells and dispersed cells from mature biofilms at similar concentrations. The fungal growth inhibition led to an increase in budding cells arrested in the G 2 /M phase, but the compound did not significantly affect structural cell wall components or chitinase activity, an enzyme that regulates the dynamics of the cell wall. The compound also inhibited titan cell (Tc) and enlarged capsule yeast (NcC) growth and reduced the body diameter and capsule thickness associated with increased capsular permeability of both virulent morphotypes. LQA&#95;78 also reduced fungal melanization through laccase activity inhibition. The fungicidal activity was observed at higher concentrations (16 to 64 μg/mL) and may be associated with augmented plasma membrane permeability, ROS production, and loss of mitochondrial membrane potential. While LQA&#95;78 is a nonhemolytic compound, its cytotoxic effects were cell type dependent, exhibiting no toxicity on Galleria mellonella larvae at a dose ≤46.5 mg/kg. LQA&#95;78 treatment of larvae infected with C. neoformans effectively reduced the fungal burden and inhibited virulent morphotype formation. To conclude, LQA&#95;78 displays fungicidal action and inhibits virulence factors of C. neoformans. Our results highlight the potential use of LQA&#95;78 as a lead molecule for developing novel pharmaceuticals for treating cryptococcosis.

Despite extensive research on overweight and obesity, there are few studies that present longitudinal statistical analyses among non-institutionalized older adults, particularly in low- and middle-income countries. This study aimed to assess the prevalence and factors associated with excess weight in older adults from the same cohort over a period of fifteen years. A total of 264 subjects aged (≥60 years) from the SABE survey (Health, Wellbeing and Aging) in the years 2000, 2006, 2010, and 2015 in the city of São Paulo, Brazil, were evaluated. Overweight was assessed by a BMI of ≥28 kg/m 2 . Multinomial logistic regression models adjusted for sociodemographic and health data were used to assess factors associated with excess weight. After normal weight, overweight was the most prevalent nutritional status in all evaluated periods: 34.02% in 2000 (95%CI: 28.29-40.26); 34.86% in 2006 (95%CI: 28.77-41.49%); 41.38% in 2010 (95%CI: 35.25-47.79); 33.75% in 2015 (95%CI: 28.02-40.01). Being male was negatively associated with being overweight in all years (OR: 0.34 in 2000; OR: 0.36 in 2006; OR: 0.27 in 2010; and OR: 0.43 in 2015). A greater number of chronic diseases and worse functionality were the main factors associated with overweight, regardless of gender, age, marital status, education, physical activity, and alcohol or tobacco consumption. Older adults with overweight and obesity, a greater number of chronic diseases, and difficulties in carrying out daily tasks required a greater commitment to healthcare. Health services must be prepared to accommodate this rapidly growing population in low- and middle-income countries.

The main objective of this research was to analyse the efficacy of lower body strength assessment tests in the Armed Forces Physical Assessment System. Secondly, it was to determine what relationship exists between the physical evaluation system of the Spanish Armed forces and standardized evaluation protocols (Gold standard). A total of 905 students enrolled in the military/civil bachelor’s degree (813 male and 92 female) participated in this study. The influence of the sex of the participants was studied through the student’s t-test for independent data, and the degree of association between variables was defined by Pearson’s correlation coefficient. The results present moderate correlations (r = 0.67, r = 0.66; p < 0.001) between the vertical jump test used by the Army and the power or elastic force tests commonly used in practice and in research. The results obtained reflect a moderate relationship between the gold standard tests and the tests used by the Army, which suggests that the tests currently used to assess lower body strength should be adapted to more objective measurement tools which would allow a better comparison between samples from different armed forces.

Background and Objectives: Parkinson disease may present difficulties in performing dual tasks. The use of dual tasks during training can improve different abilities. Therefore, the objective of this study is creating a protocol, based on standard protocol items recommendations for interventional trials compliant, for a clinical trial study conduct, review, reporting, and interpretation. This protocol will provide the framework and a guide to a randomized double-blind study, that will be conducted to assess the influence of a cycling exercise program combined with a cognitive task, on cognitive and physical Parkinson disease aspects., Methods: Designed a protocol for a double-blind randomized study, where participants will perform a dual tasks intervention with cycling and a cognitive task. The revised version of the unified Parkinson disease rating scale, the Parkinson disease questionnaire, the timed up and go Test, the 30 seconds chair sit to stand test, the Stroop and the trail making test will be used to measure outcomes., Discussion: Research in Parkinson disease suggests that an improvement of motor and cognitive functions of Parkinson disease patients can be achieved by modifying different motor and cognitive pathways. The results of the present study will yield findings on both the physical and cognitive response to an intervention that combines a cognitive task with a motor task in Parkinson disease patients and will be essential tool for a better conducting of the clinical trial study., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

The ongoing COVID-19 pandemic caused a significant loss of human lives and a worldwide decline in quality of life. Treatment of COVID-19 patients is challenging, and specific treatments to reduce COVID-19 aggravation and mortality are still necessary. Here, we describe the discovery of a novel class of epiandrosterone steroidal compounds with cationic amphiphilic properties that present antiviral activity against SARS-CoV-2 in the low micromolar range. Compounds were identified in screening campaigns using a cytopathic effect-based assay in Vero CCL81 cells, followed by hit compound validation and characterization. Compounds LNB167 and LNB169 were selected due to their ability to reduce the levels of infectious viral progeny and viral RNA levels in Vero CCL81, HEK293, and HuH7.5 cell lines. Mechanistic studies in Vero CCL81 cells indicated that LNB167 and LNB169 inhibited the initial phase of viral replication through mechanisms involving modulation of membrane lipids and cholesterol in host cells. Selection of viral variants resistant to steroidal compound treatment revealed single mutations on transmembrane, lipid membrane-interacting Spike and Envelope proteins. Finally, in vivo testing using the hACE2 transgenic mouse model indicated that SARS-CoV-2 infection could not be ameliorated by LNB167 treatment. We conclude that anti-SARS-CoV-2 activities of steroidal compounds LNB167 and LNB169 are likely host-targeted, consistent with the properties of cationic amphiphilic compounds that modulate host cell lipid biology. Although effective in vitro, protective effects were cell-type specific and did not translate to protection in vivo, indicating that subversion of lipid membrane physiology is an important, yet complex mechanism involved in SARS-CoV-2 replication and pathogenesis.

Gastroesophageal cancer (GEC) is an aggressive disease characterized by a high frequency of metastasis and poor overall survival rates. GEC presents HER2 overexpression in 5 to 25% of tumors eligible for HER2-targeted therapy. HER2 evaluation requires protein levels and copy number alteration analyses by immunohistochemistry (IHC) and in situ hybridization (FISH or SISH), respectively. These are semiquantitative methodologies that need an expert and well-trained pathologist. Therefore, the use of new surrogate methods for HER2 evaluation in cancer, such as gene expression analysis, might improve GEC HER2 classification. We evaluated HER2 positivity in GEC through conventional IHC and SISH analyses and investigated the potential application of HER2 mRNA expression by quantitative PCR to categorize GEC samples as HER2-positive or HER2-negative. Among 270 GEC samples, 10.9% were HER2-positive by IHC and SISH analyses. HER2 mRNA was overexpressed in HER2-positive GEC samples and presented high accuracy in distinguishing those tumors from HER2-negative GEC. Nevertheless, HER2 mRNA analysis was not capable of classifying HER2-equivocal GEC samples into HER2-positive or -negative according to SISH data. Quantitative PCR analysis showed HER2 overexpression in HER2-positive GEC samples. Nevertheless, HER2 mRNA analysis failed to classify HER2-equivocal GEC according to SISH data.

Background: Although aging correlates with a worse prognosis for Covid-19, super elderly still unvaccinated individuals presenting mild or no symptoms have been reported worldwide. Most of the reported genetic variants responsible for increased disease susceptibility are associated with immune response, involving type I IFN immunity and modulation; HLA cluster genes; inflammasome activation; genes of interleukins; and chemokines receptors. On the other hand, little is known about the resistance mechanisms against SARS-CoV-2 infection. Here, we addressed polymorphisms in the MHC region associated with Covid-19 outcome in super elderly resilient patients as compared to younger patients with a severe outcome., Methods: SARS-CoV-2 infection was confirmed by RT-PCR test. Aiming to identify candidate genes associated with host resistance, we investigated 87 individuals older than 90 years who recovered from Covid-19 with mild symptoms or who remained asymptomatic following positive test for SARS-CoV-2 as compared to 55 individuals younger than 60 years who had a severe disease or died due to Covid-19, as well as to the general elderly population from the same city. Whole-exome sequencing and an in-depth analysis of the MHC region was performed. All samples were collected in early 2020 and before the local vaccination programs started., Results: We found that the resilient super elderly group displayed a higher frequency of some missense variants in the MUC22 gene (a member of the mucins' family) as one of the strongest signals in the MHC region as compared to the severe Covid-19 group and the general elderly control population. For example, the missense variant rs62399430 at MUC22 is two times more frequent among the resilient super elderly (p = 0.00002, OR = 2.24)., Conclusion: Since the pro-inflammatory basal state in the elderly may enhance the susceptibility to severe Covid-19, we hypothesized that MUC22 might play an important protective role against severe Covid-19, by reducing overactive immune responses in the senior population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Castelli, de Castro, Naslavsky, Scliar, Silva, Pereira, Ciriaco, Castro, Mendes-Junior, Silveira, de Oliveira, Antonio, Vieira, Meyer, Nunes, Matos, Silva, Wang, Esposito, Cória, Magawa, Santos, Cunha-Neto, Kalil, Bortolin, Hirata, Dell’Aquila, Razuk-Filho, Batista-Júnior, Duarte-Neto, Dolhnikoff, Saldiva, Passos-Bueno and Zatz.)

Objective: The Brazilian state of Paraná has suffered from COVID-19 effects, understanding predictors of increased mortality in health system interventions prevent hospitalisation of patients. We selected the best models to evaluate the association of death with demographic characteristics, symptoms and comorbidities based on three levels of clinical severity for COVID-19: non-hospitalised, hospitalised non-ICU ward and ICU ward., Design: Cross-sectional survey using binomial mixed models., Setting: COVID-19-positive cases diagnosed by reverse transcription-PCR of municipalities located in Paraná State., Patients: Cases of anonymous datasets of electronic medical records from 1 April 2020 to 31 December 2020., Primary and Secondary Outcome Measures: The best prediction factors were chosen based on criteria after a stepwise analysis using multicollinearity measure, lower Akaike information criterion and goodness-of-fit χ 2 tests from univariate to multivariate contexts., Results: Male sex was associated with increased mortality among non-hospitalised patients (OR 1.76, 95% CI 1.47 to 2.11) and non-ICU patients (OR 1.22, 95% CI 1.05 to 1.43) for symptoms and for comorbidities (OR 1.89, 95% CI 1.59 to 2.25, and OR 1.30, 95% CI 1.11 to 1.52, respectively). Higher mortality occurred in patients older than 35 years in non-hospitalised (for symptoms: OR 4.05, 95% CI 1.55 to 10.54; and for comorbidities: OR 3.00, 95% CI 1.24 to 7.27) and in hospitalised over 40 years (for symptoms: OR 2.72, 95% CI 1.08 to 6.87; and for comorbidities: OR 2.66, 95% CI 1.22 to 5.79). Dyspnoea was associated with increased mortality in non-hospitalised (OR 4.14, 95% CI 3.45 to 4.96), non-ICU (OR 2.41, 95% CI 2.04 to 2.84) and ICU (OR 1.38, 95% CI 1.10 to 1.72) patients. Neurological disorders (OR 2.16, 95% CI 1.35 to 3.46), neoplastic (OR 3.22, 95% CI 1.75 to 5.93) and kidney diseases (OR 2.13, 95% CI 1.36 to 3.35) showed the majority of increased mortality for ICU as well in the three levels of severity jointly with heart disease, diabetes and CPOD., Conclusions: These findings highlight the importance of the predictor's assessment for the implementation of public healthcare policy in response to the COVID-19 pandemic, mainly to understand how non-pharmaceutical measures could mitigate the virus impact over the population., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Isoflavones are phytoestrogens with recognized estrogenic activity but may also affect testosterone, corticosterone and thyroid hormone levels in experimental models. However, the molecular mechanisms involved in these alterations are still unclear. Isoflavones are present in soy-based infant formula, in breast milk after the consumption of soy by the mother and are widely used for the preparation of beverages consumed by toddlers and teenagers. In this sense, we proposed to investigate the effects of soy isoflavone exposure during the prepubertal period, a recognized window of sensitivity for endocrine disruption, over the hypothalamic-pituitary-testicular (HPT) axis. For this, 42 3-week-old male Wistar rats were exposed to 0.5, 5 or 50 mg of soy isoflavones/kg from postnatal day (PND) 23 to PND60. We evaluated body growth, age at puberty, serum concentrations of LH, FSH, testosterone and estradiol, and the expression of the transcripts (mRNA) of genes encoding key genes controlling the hypothalamic-pituitary-testicular (HPT) axis. In the hypothalamus, we observed an increase in Esr1 mRNA expression (0.5 and 5 mg). In the pituitary, we observed an increase in Gnrhr mRNA expression (50 mg), a reduction in Lhb mRNA expression (0.5 mg), and a reduction in Ar mRNA expression. In the testis, we observed an increase in Lhcgr mRNA expression (50 mg) and a reduction in Star mRNA expression (0.5 and 5 mg). The serum levels of LH (5 and 50 mg) and FSH (0.5 mg) were increased, while testosterone and estradiol were reduced. Puberty was delayed in all groups. Taken together, these results suggest that prepubertal consumption of relevant levels of soy isoflavones disrupts the HPT axis, causing hypergonadotropic hypogonadism and altered expression levels of key genes regulating the axis., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest to disclose., (Copyright © 2022 Elsevier B.V. All rights reserved.)

INDUCTION: chemotherapy (IC) followed by chemoradiation (CRT) is an attractive approach in high-risk locally advanced rectal cancer. Additionally, ASA has shown potential to improve outcomes alongside CRT in rectal cancer. The ICAR trial aimed to evaluate the safety and efficacy of IC followed by CRT with or without ASA on MRI tumor response., Methods: Single-center, double-blind, randomized phase II trial to evaluate induction treatment with CAPOX, followed by capecitabine-based chemoradiotherapy with ASA (arm 1) or placebo (arm 2) in high-risk stage II-III rectal adenocarcinoma staged by MRI. The primary endpoint was MRI tumor regression grade (mrTRG). Secondary endpoints were pathological response, surgical outcomes, postoperative complications, treatment tolerance, DFS, and OS., Results: Between January 2018 and August 2019, 27 patients were eligible, 25 (92.5%) completed IC, and 23 patients were randomly assigned (12 to ASA group; 11 to placebo group). In the ASA arm, 3 pts (25%) presented distant disease progression at restaging. Seven patients (30.4%) had cCR after neoadjuvant treatment. All 13 patients submitted to surgery after neoadjuvant treatment underwent R0 resections except for 1 patient with positive CRM, and 12 patients (92.3%) had sphincter preservation. After a median follow-up of 34.9 months, the 2-year DFS was 83.1% and 3-year OS was 81.5%., Conclusion: There was good compliance in both treatment arms and encouraging cCR rate. ASA during CRT was safe but failed to improve on MRI tumor response. The study was closed due to the absence of benefits., (Copyright © 2022. Published by Elsevier Inc.)

The National Policy on Integrative and Complementary Practices (NPICP) was published 15 years ago, and between 2017 and 2018 it saw two phases of growth and increased from 5 to 29 modalities of Integrative and Complementary Practices (ICP), namely an increase of 24 new practices within a year. The scope of this article is to understand the conditions for such transformations in the ICPs in the Unified Health System (SUS), reflecting upon how social actors interpret these changes. Thus, semi-structured interviews were conducted with eight interlocutors, analyzed in the light of Pierre Bourdieu's field theory. The results show that the expansion of the NPICP, motivated by political-institutional factors, is comprehended in two matrices of thought that are related to the cultural and scientific legitimation of the ICPs in the SUS. The conclusion drawn is that the rapid expansion of the NPICP generated a crisis in the field, showing the need for a restructuring dialogue with its social bases.

Gliomas represent 80% of all primary malignant brain tumors in adults. In view of this public health problem, the early detection through sensitive and specific molecular tumor markers analysis can help to improve gliomas diagnosis and prognosis as well as their staging, assessment of therapeutic response and detection of recurrence. Therefore, this review focuses in current gliomas tumor markers, IDH-1/2, 1p/19q, MGMT, ATRX, TERT, H3, EGFR, BRAF and Ki67 used in clinic worldwide and their importance to early detection, glioma histological and molecular classification as well as in predicting patient's therapeutic response. In addition, we present what are the steps in the requesting process for this type of examination in the Brazilian Public Health System (SUS) scope, which attends most of the Brazilian population. Thereby, this article is useful in demonstrating which markers are used in the clinical practice for glioma patients and can be performed in the SUS through partnerships/agreements between specialized health centers and clinical analysis laboratories. It is hoped that this work clarifies, the necessary subsidies to carry out the research of tumor markers in all institutions that serve SUS users, providing a service with equal conditions.

(1) Background: Those with Parkinson's disease (PD) may present difficulties in performing dual tasks (DT). The use of DT during training can improve different abilities. Therefore, the objective of this study is to verify the influence of a cycling exercise program combined with a cognitive task on cognitive and physical PD aspects; (2) Methods: A double-blind, randomized pilot study was undertaken. Participants performed a DT intervention composed of cycling and a cognitive task. The cycling parameters, MDS-UPDRS, PDQ-39, TUG Test, 30 s Chair Sit to Stand test and Stroop were used to measure outcomes; (3) Results: DT generated impairment in performing the cycling task, with significant differences in cycling parameters, active and passive distance (m), total work (W) and active speed (rpm). At the cognitive level, there was a trend of improvement in the group that performed the training with DT, which improved by 211%; (4) Conclusions: Combining cycling with a cognitive task caused impairment in the performance of the physical task and an improvement at the cognitive level. Therefore, combining cycling with a cognitive task in a presumably safer environment for patients with PD can be a good way to train these patients for the dual-task challenges with practical applications.

This article aims to identify factors associated with undiagnosed systemic arterial hypertension (SAH) among elderly adults in Brazil. A total of 5,416 hypertensive participants in the Longitudinal Study of the Health of Elderly Brazilians (ELSI-BRAZIL) were evaluated. Undiagnosed SAH was identified by mean blood pressure (BP) ≥140/90 mmHg without previous SAH diagnosis. Logistic regression was used to verify factors associated with undiagnosed SAH. In this study, 19.8% of the hypertensive patients evaluated did not report a previous diagnosis of SAH. Age between 60 to 69 (OR: 0.68, 95%CI 0.55-0.85) and 70 to79 (OR: 0.67, 95%CI 0.51-0.89), being black (OR: 0.67, 95%CI 0.49-0.91), obese (OR: 0.51, 95%CI 0.40-0.65), having one chronic disease (OR: 0.54, 95%CI 0.44-0.66) or more (OR: 0.32, 95%CI 0.25-0.42) and medical consultations in the last year (OR: 0.47, 95%CI 0.38-0.58) were factors associated with lower chances of undiagnosed SAH, while being male (OR: 1.27, 95%CI 1,05-1,54), presenting low body weight (OR: 1.33, 95%CI 1,00-1,78) and alcohol consumption (OR: 1.36, 95%CI 1,09-1,68) increased the chances of having the undiagnosed condition. The characteristics identified in this study needs to be observed in health services, expanding early diagnosis and preventing the progression of BP and its future consequences.

The understanding of microbial susceptibility to disinfectants is an important step to provide drinking water (DW) of adequate microbiological quality. In drinking water distribution systems (DWDS) the application of disinfectants is the main approach to control microorganisms. Although chlorine has been commonly used for DW treatment, the increase of microbial resistance and the production of harmful disinfection by-products promote the necessity to seek new alternatives. This study evaluated the antimicrobial activity of sodium dichloroisocyanurate (NaDCC), trichloroisocyanuric acid (TCCA), and pentapotassium bis(peroxymonosulphate) bis(sulphate) (OXONE) against two emerging pathogens isolated from DW, Acinetobacter calcoaceticus and Stenotrophomonas maltophilia. Free chlorine from calcium hypochlorite was used for comparison. The dose and time-responses against planktonic bacteria were performed as well as the assessment of the effects on membrane integrity. Moreover, the effects against 48 h-old biofilms formed on polyvinyl chloride and stainless steel were evaluated in terms of biofilm culturability and removal. Minimum bactericidal concentrations of 2.1 and 3.1 mg/L for NaDCC, 2.5 and 3.8 mg/L for TCCA, 340 and 690 mg/L for OXONE, and 0.80 and 1.0 mg/L for free chlorine alone were obtained against S. maltophilia and A. calcoaceticus, respectively. The kinetic modeling revealed that NaDCC and TCCA caused similar inactivation rates and the time for first log reduction by OXONE was less than 10 min, for both bacteria. All the disinfectants triggered significant bacterial cytoplasmic membrane destabilization, even at sub-lethal concentrations. A 30 min treatment with the disinfectants allowed a reduction in the biofilm culturability up to 5 log. OXONE was the disinfectant with the best efficiency against both bacterial biofilms. However, none of the disinfectants caused significant biofilm removal (reduction < 1 log cells/cm 2 ). This study highlights NaDCC, TCCA, and OXONE as promising alternatives to free chlorine for DW disinfection, particularly for planktonic growth control and biofilm culturability reduction., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The increasing incidence of implant-associated infections has prompted the development of effective strategies to prevent biofilm formation on these devices. In this work, pristine graphene nanoplatelet/polydimethylsiloxane (GNP/PDMS) surfaces containing different GNP loadings (1, 2, 3, 4, and 5 wt%) were produced and evaluated on their ability to mitigate biofilm development. After GNP loading optimization, the most promising surface was tested against single- and dual-species biofilms of Staphylococcus aureus and Pseudomonas aeruginosa . The antibiofilm activity of GNP/PDMS surfaces was determined by the quantification of total, viable, culturable, and viable but nonculturable (VBNC) cells, as well as by confocal laser scanning microscopy (CLSM). Results showed that 5 wt% GNP loading reduced the number of total (57%), viable (69%), culturable (55%), and VBNC cells (85%) of S. aureus biofilms compared to PDMS. A decrease of 25% in total cells and about 52% in viable, culturable, and VBNC cells was observed for P. aeruginosa biofilms. Dual-species biofilms demonstrated higher resistance to the antimicrobial activity of GNP surfaces, with lower biofilm cell reductions (of up to 29% when compared to single-species biofilms). Still, the effectiveness of these surfaces in suppressing single- and dual-species biofilm formation was confirmed by CLSM analysis, where a decrease in biofilm biovolume (83% for S. aureus biofilms and 42% for P. aeruginosa and dual-species biofilms) and thickness (on average 72%) was obtained. Overall, these results showed that pristine GNPs dispersed into the PDMS matrix were able to inhibit biofilm growth, being a starting point for the fabrication of novel surface coatings based on functionalized GNP/PDMS composites.

Cerebral venous thrombosis (CVT) is an uncommon condition that is potentially reversible if properly diagnosed and promptly treated. Although CVT can occur at any age, it most commonly affects neonates and young adults. Clinical diagnosis is difficult because the clinical manifestations of CVT are nonspecific, including headache, seizures, decreased level of consciousness, and focal neurologic deficits. Therefore, imaging is crucial for the diagnosis. Radiologists should be able to identify the findings of CVT and to recognize potential imaging pitfalls that may lead to misdiagnosis. Thus, the appropriate treatment (anticoagulation therapy) can be started early, thereby avoiding complications and unfavorable outcomes.

Objective: To analyze the evolution of syphilis during pregnancy notification regarding clinical classification, diagnosis and treatment in the state of Goiás, Brazil, between 2007 and 2017., Methods: This is a time-series study, analyzing data provided by the Health Secretariat of the state of Goiás. The variables related to the diagnosis and treatment of pregnant women and their partners were analyzed, and their evolution trend during the years. Descriptive statistics and percentage calculation were used. Cochran-Armitage test with a significance level α = 0.05 was used to determine increase and decrease trends., Results: During the period, 7,774 cases were notified. The highest percentage of notifications occurred in the second trimester of pregnancy (39.8%) and corresponded to primary syphilis (34.1%). The most frequent treatment prescribed was benzathine benzylpenicillin with a dosage of 7.2 million (43.8%). Between 2007 and 2017, there was an increasing trend in the notification percentage of latent (14.1% to 30.7%), secondary (5.2% to 19%), and tertiary syphilis (4.4% to 11.4%). The treatment with benzathine benzylpenicillin with a dosage of 7.2 million also increased (19.3% to 59.6%). The percentages of primary syphilis decreased (43.4% to 22.1%), as well as other treatments' percentages., Conclusions: Latent syphilis notification of pregnant women and treatment with penicillin at the dosage of 7,200,000 IU increased. Notification forms' data completeness also increased for the variables clinical classification and treatment, suggesting improvements in the notification process.

Objectives: This study aimed to evaluate the effects on bone repair of different concentrations of mineral trioxide aggregate (MTA) added to AH Plus., Materials and Methods: Bone tissue reactions were evaluated in 30 rats ( Rattus norvegicus ) after 7 and 30 days. In the AH + MTA10, AH + MTA20, and AH + MTA30 groups, defects in the tibiae were filled with AH Plus with MTA in proportions of 10%, 20% and 30%, respectively; in the MTA-FILL group, MTA Fillapex was used; and in the control group, no sealer was used. The samples were histologically analyzed to assess bone union and maturation. The Kruskal-Wallis and Mann-Whitney tests were performed for multiple pairwise comparisons ( p ≤ 0.05)., Results: At the 7-day time point, AH + MTA10 was superior to MTA-FILL with respect to bone union, and AH + MTA20 was superior to MTA-FILL with respect to bone maturity ( p < 0.05). At the 30-day time point, both the AH + MTA10 and AH + MTA20 experimental sealers were superior not only to MTA-FILL, but also to AH + MTA30 with respect to both parameters ( p < 0.05). The results of the AH + MTA10 and AH + MTA20 groups were superior to those of the control group for both parameters and experimental time points ( p < 0.05)., Conclusions: The results suggest the potential benefit of using a combination of these materials in situations requiring bone repair., Competing Interests: Conflict of Interest: No potential conflict of interest relevant to this article was reported., (Copyright © 2021. The Korean Academy of Conservative Dentistry.)